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Conserved domains on  [gi|974005246|ref|NP_001305690|]
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ephrin type-A receptor 5 isoform f [Homo sapiens]

Protein Classification

ephrin type-A receptor 5( domain architecture ID 10917950)

ephrin type-A receptor 5 (EPHA5) is a receptor tyrosine kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates; EphA receptors bind GPI-anchored ephrin-A ligands

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
602-868 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 603.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05066    1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd05066  161 EAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQ 240
                        250       260
                 ....*....|....*....|....*..
gi 974005246 842 LMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05066  241 LMLDCWQKDRNERPKFEQIVSILDKLI 267
EphR_LBD super family cl02704
Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest ...
1-163 7.65e-120

Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). They are subdivided into 2 groups, A and B type receptors, depending on their ligand ephrin-A or ephrin-B, respectively. In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


The actual alignment was detected with superfamily member cd10483:

Pssm-ID: 470656  Cd Length: 173  Bit Score: 362.81  E-value: 7.65e-120
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10483   11 MGDLGWIAYPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10483   91 TFNVYYFESNDEDGRNIRENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLTKKGFYLAFQDLGACIALVSVRVY 170

                 ...
gi 974005246 161 YKK 163
Cdd:cd10483  171 YKK 173
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
897-962 6.24e-41

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


:

Pssm-ID: 188945  Cd Length: 66  Bit Score: 144.30  E-value: 6.24e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 897 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09546    1 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
507-604 1.67e-26

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


:

Pssm-ID: 464211  Cd Length: 72  Bit Score: 103.45  E-value: 1.67e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  507 IAVSVTVGVILLAVVIGVLLSGSCCecgcgrasslcavahpsliwrCGYSKAKQDPEEEKMHFhnghiKLPGVRTYIDPH 586
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRC---------------------CGRKKSQDDDEEEFHQY-----KPPGRKTYIDPH 54
                          90
                  ....*....|....*...
gi 974005246  587 TYEDPNQAVHEFAKEIEA 604
Cdd:pfam14575  55 TYEDPNQAVLEFAKEIDA 72
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
400-490 1.77e-19

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


:

Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 84.09  E-value: 1.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 400 PSPVTNVKKGKIAKNSISLSWQEPDRPNGIILEYEIKYFEKDQETSYTIIK--SKETTITAEGLKPASVYVFQIRARTAA 477
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGG 80
                         90
                 ....*....|...
gi 974005246 478 GYGVFSRRFEFET 490
Cdd:cd00063   81 GESPPSESVTVTT 93
FN3 super family cl27307
Fibronectin type 3 domain [General function prediction only];
286-529 6.58e-13

Fibronectin type 3 domain [General function prediction only];


The actual alignment was detected with superfamily member COG3401:

Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 72.73  E-value: 6.58e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 286 TRPPSAPRN-AISNVNETSVFLEWIPPADtggrKDVSYYIACKKCNShagvceecGGHVRYLprqSGLKNTSVMMVDLLA 364
Cdd:COG3401  230 TTPPSAPTGlTATADTPGSVTLSWDPVTE----SDATGYRVYRSNSG--------DGPFTKV---ATVTTTSYTDTGLTN 294
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 365 HTNYTFEIEAVNGVSDLSPGArqyVSVNVTTNQAAPSPVTNVKKGKIAKNSISLSWQEPDrpNGIILEYEIkYFEKDQET 444
Cdd:COG3401  295 GTTYYYRVTAVDAAGNESAPS---NVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASS--DADVTGYNV-YRSTSGGG 368
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 445 SYTIIKS--KETTITAEGLKPASVYVFQIRARTAAGygvfsrRFEFETTPVSVAASSDQSQIPVIAVSVTVGVILLAVVI 522
Cdd:COG3401  369 TYTKIAEtvTTTSYTDTGLTPGTTYYYKVTAVDAAG------NESAPSEEVSATTASAASGESLTASVDAVPLTDVAGAT 442

                 ....*..
gi 974005246 523 GVLLSGS 529
Cdd:COG3401  443 AAASAAS 449
 
Name Accession Description Interval E-value
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
602-868 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 603.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05066    1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd05066  161 EAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQ 240
                        250       260
                 ....*....|....*....|....*..
gi 974005246 842 LMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05066  241 LMLDCWQKDRNERPKFEQIVSILDKLI 267
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
607-864 6.21e-140

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 418.05  E-value: 6.21e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  607 ITIERVIGAGEFGEVCSGRLK-LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaAY 765
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDY-YR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:pfam07714 160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                         250
                  ....*....|....*....
gi 974005246  846 CWQKERNSRPKFDEIVNML 864
Cdd:pfam07714 240 CWAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
607-864 1.05e-134

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 404.61  E-value: 1.05e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   607 ITIERVIGAGEFGEVCSGRLK-LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKgKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaaY 765
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY--Y 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:smart00219 159 RKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQ 238
                          250
                   ....*....|....*....
gi 974005246   846 CWQKERNSRPKFDEIVNML 864
Cdd:smart00219 239 CWAEDPEDRPTFSELVEIL 257
EphR_LBD_A5 cd10483
Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the ...
1-163 7.65e-120

Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA5 is almost exclusively expressed in the nervous system. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198451  Cd Length: 173  Bit Score: 362.81  E-value: 7.65e-120
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10483   11 MGDLGWIAYPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10483   91 TFNVYYFESNDEDGRNIRENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLTKKGFYLAFQDLGACIALVSVRVY 170

                 ...
gi 974005246 161 YKK 163
Cdd:cd10483  171 YKK 173
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
1-163 6.76e-96

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 299.97  E-value: 6.76e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246     1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:smart00615  11 TGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSSLPGVGGSCKE 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246    81 TFNMYYFESDDQNGRNIK----ENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVS 156
Cdd:smart00615  91 TFNLYYYESDTDTATNTLpnwmENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQDQGACVALVS 170

                   ....*..
gi 974005246   157 VRVYYKK 163
Cdd:smart00615 171 VRVFYKK 177
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
2-164 1.31e-87

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 277.62  E-value: 1.31e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246    2 GDLGWIAFPK-NGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:pfam01404  11 SDLGWTTYPYdGGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSSIPGVSGTCKE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   81 TFNMYYFESDDQNG----RNIKENQYIKIDTIAADESFTELDlGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVS 156
Cdd:pfam01404  91 TFNLYYYESDADAAtatpPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQDQGACIALLS 169

                  ....*...
gi 974005246  157 VRVYYKKC 164
Cdd:pfam01404 170 VRVFYKKC 177
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
897-962 6.24e-41

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 144.30  E-value: 6.24e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 897 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09546    1 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
608-855 2.16e-38

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 150.16  E-value: 2.16e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYT--EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:COG0515   10 RILRLLGRGGMGVVYLARDLRLGR---PVALKVLRPELAadPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:COG0515   87 EYVEGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQT 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLPSP---MDCPAALYQL 842
Cdd:COG0515  166 GTVVGTPG--YMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPPPSelrPDLPPALDAI 242
                        250
                 ....*....|...
gi 974005246 843 MLDCWQKERNSRP 855
Cdd:COG0515  243 VLRALAKDPEERY 255
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
507-604 1.67e-26

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 103.45  E-value: 1.67e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  507 IAVSVTVGVILLAVVIGVLLSGSCCecgcgrasslcavahpsliwrCGYSKAKQDPEEEKMHFhnghiKLPGVRTYIDPH 586
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRC---------------------CGRKKSQDDDEEEFHQY-----KPPGRKTYIDPH 54
                          90
                  ....*....|....*...
gi 974005246  587 TYEDPNQAVHEFAKEIEA 604
Cdd:pfam14575  55 TYEDPNQAVLEFAKEIDA 72
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
895-959 5.66e-22

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 90.02  E-value: 5.66e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246  895 GSGAYRSVGEWLEAIKMGRYTEIFMeNGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
901-959 6.33e-20

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 84.27  E-value: 6.33e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246   901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:smart00454   8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLK 66
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
400-490 1.77e-19

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 84.09  E-value: 1.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 400 PSPVTNVKKGKIAKNSISLSWQEPDRPNGIILEYEIKYFEKDQETSYTIIK--SKETTITAEGLKPASVYVFQIRARTAA 477
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGG 80
                         90
                 ....*....|...
gi 974005246 478 GYGVFSRRFEFET 490
Cdd:cd00063   81 GESPPSESVTVTT 93
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
597-806 3.13e-17

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 84.54  E-value: 3.13e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 597 EFAKEIEASC-ITIERVIGAGEFGEVCSGRLklPGKRElPVaikTLKVGytekQRRDFLGEASIMGQFDHPNIIHL-EGV 674
Cdd:PHA03209  57 QKAREVVASLgYTVIKTLTPGSEGRVFVATK--PGQPD-PV---VLKIG----QKGTTLIEAMLLQNVNHPSVIRMkDTL 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 675 VTKSKPVMIVTEYmeNGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS-NLVCkVSDFGL 753
Cdd:PHA03209 127 VSGAITCMVLPHY--SSDLYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDvDQVC-IGDLGA 203
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 754 SRVleddPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY 806
Cdd:PHA03209 204 AQF----PVVAPAFLGLAGTVETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
400-480 5.21e-16

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 73.80  E-value: 5.21e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   400 PSPVTNVKKGKIAKNSISLSWQEPDRPNGI--ILEYEIKYFEKDQETSYTIIKSKETTITAEGLKPASVYVFQIRARTAA 477
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80

                   ...
gi 974005246   478 GYG 480
Cdd:smart00060  81 GEG 83
fn3 pfam00041
Fibronectin type III domain;
401-483 5.82e-14

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 68.21  E-value: 5.82e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  401 SPVTNVKKGKIAKNSISLSWQEPDRPNGIILEYEIKYFEKDQETS--YTIIKSKETTITAEGLKPASVYVFQIRARTAAG 478
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPwnEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80

                  ....*
gi 974005246  479 YGVFS 483
Cdd:pfam00041  81 EGPPS 85
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
286-529 6.58e-13

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 72.73  E-value: 6.58e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 286 TRPPSAPRN-AISNVNETSVFLEWIPPADtggrKDVSYYIACKKCNShagvceecGGHVRYLprqSGLKNTSVMMVDLLA 364
Cdd:COG3401  230 TTPPSAPTGlTATADTPGSVTLSWDPVTE----SDATGYRVYRSNSG--------DGPFTKV---ATVTTTSYTDTGLTN 294
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 365 HTNYTFEIEAVNGVSDLSPGArqyVSVNVTTNQAAPSPVTNVKKGKIAKNSISLSWQEPDrpNGIILEYEIkYFEKDQET 444
Cdd:COG3401  295 GTTYYYRVTAVDAAGNESAPS---NVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASS--DADVTGYNV-YRSTSGGG 368
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 445 SYTIIKS--KETTITAEGLKPASVYVFQIRARTAAGygvfsrRFEFETTPVSVAASSDQSQIPVIAVSVTVGVILLAVVI 522
Cdd:COG3401  369 TYTKIAEtvTTTSYTDTGLTPGTTYYYKVTAVDAAG------NESAPSEEVSATTASAASGESLTASVDAVPLTDVAGAT 442

                 ....*..
gi 974005246 523 GVLLSGS 529
Cdd:COG3401  443 AAASAAS 449
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
609-811 9.12e-11

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 65.59  E-value: 9.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGR-LKLpgKRElpVAIKTLKVGYTEK---QRRdFLGEASIMGQFDHPNIIHL-----EGVVtksk 679
Cdd:NF033483  11 IGERIGRGGMAEVYLAKdTRL--DRD--VAVKVLRPDLARDpefVAR-FRREAQSAASLSHPNIVSVydvgeDGGI---- 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 pVMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:NF033483  82 -PYIVMEYVDGRTLKDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSS 159
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 760 D----------------PEAAyttRGGKIPIRwtapeaiafrkftsaSDVWSYGIVMWEVVSyGERPY 811
Cdd:NF033483 160 TtmtqtnsvlgtvhylsPEQA---RGGTVDAR---------------SDIYSLGIVLYEMLT-GRPPF 208
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
366-524 1.07e-10

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 65.41  E-value: 1.07e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 366 TNYTFEIEAVN--GVSDLSPgarqyvSVNVTTNQAAPSPVTNVKKGKIAKNSISLSWQEPDRPNgiILEYEIkYFEKDQE 443
Cdd:COG3401  203 TTYYYRVAATDtgGESAPSN------EVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRV-YRSNSGD 273
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 444 TSYTII-KSKETTITAEGLKPASVYVFQIRARTAAGygvfsrrfefettpvsvaASSDQSQIpviaVSVTVGVILLAVVI 522
Cdd:COG3401  274 GPFTKVaTVTTTSYTDTGLTNGTTYYYRVTAVDAAG------------------NESAPSNV----VSVTTDLTPPAAPS 331

                 ..
gi 974005246 523 GV 524
Cdd:COG3401  332 GL 333
fn3 pfam00041
Fibronectin type III domain;
290-378 1.15e-09

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 55.88  E-value: 1.15e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  290 SAPRN-AISNVNETSVFLEWIPPaDTGGRKDVSYYIACKKCNShagvceecGGHVRY--LPRQSglknTSVMMVDLLAHT 366
Cdd:pfam00041   1 SAPSNlTVTDVTSTSLTVSWTPP-PDGNGPITGYEVEYRPKNS--------GEPWNEitVPGTT----TSVTLTGLKPGT 67
                          90
                  ....*....|..
gi 974005246  367 NYTFEIEAVNGV 378
Cdd:pfam00041  68 EYEVRVQAVNGG 79
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
289-395 2.30e-09

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 55.20  E-value: 2.30e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 289 PSAPRN-AISNVNETSVFLEWIPPADTGGRkDVSYYIACKKCNSHAGvcEECGGHVrylprqsgLKNTSVMMVDLLAHTN 367
Cdd:cd00063    1 PSPPTNlRVTDVTSTSVTLSWTPPEDDGGP-ITGYVVEYREKGSGDW--KEVEVTP--------GSETSYTLTGLKPGTE 69
                         90       100       110
                 ....*....|....*....|....*....|
gi 974005246 368 YTFEIEAVN--GVSDLSPgarqyvSVNVTT 395
Cdd:cd00063   70 YEFRVRAVNggGESPPSE------SVTVTT 93
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
289-378 1.16e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 53.00  E-value: 1.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   289 PSAPRN-AISNVNETSVFLEWIPPADTGGRKDVSYYIACKKcnshagvceecGGHVRYLPRQSGLKNTSVMMVDLLAHTN 367
Cdd:smart00060   1 PSPPSNlRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYR-----------EEGSEWKEVNVTPSSTSYTLTGLKPGTE 69
                           90
                   ....*....|.
gi 974005246   368 YTFEIEAVNGV 378
Cdd:smart00060  70 YEFRVRAVNGA 80
 
Name Accession Description Interval E-value
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
602-868 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 603.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05066    1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd05066  161 EAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQ 240
                        250       260
                 ....*....|....*....|....*..
gi 974005246 842 LMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05066  241 LMLDCWQKDRNERPKFEQIVSILDKLI 267
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
602-868 0e+00

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 572.78  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05033    1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKKEIDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEdDP 761
Cdd:cd05033   81 MIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLE-DS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd05033  160 EATYTTKGGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQ 239
                        250       260
                 ....*....|....*....|....*..
gi 974005246 842 LMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05033  240 LMLDCWQKDRNERPTFSQIVSTLDKMI 266
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
602-868 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 542.15  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05065    1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd05065   81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 -EAAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAAL 839
Cdd:cd05065  161 sDPTYTSSlGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTAL 240
                        250       260
                 ....*....|....*....|....*....
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05065  241 HQLMLDCWQKDRNLRPKFGQIVNTLDKMI 269
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
601-868 8.28e-178

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 516.45  E-value: 8.28e-178
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd05063    1 EIHPSHITKQKVIGAGEFGEVFRGILKMPGRKEVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd05063   81 AMIITEYMENGALDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05063  161 PEGTYTTSGGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVY 240
                        250       260
                 ....*....|....*....|....*...
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05063  241 QLMLQCWQQDRARRPRFVDIVNLLDKLL 268
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
601-868 4.42e-141

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 421.64  E-value: 4.42e-141
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd05064    1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGlsRVLEDD 760
Cdd:cd05064   81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFR--RLQEDK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05064  159 SEAIYTTMSGKSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLH 238
                        250       260
                 ....*....|....*....|....*...
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05064  239 QLMLDCWQKERGERPRFSQIHSILSKMV 266
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
607-864 6.21e-140

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 418.05  E-value: 6.21e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  607 ITIERVIGAGEFGEVCSGRLK-LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaAY 765
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDY-YR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:pfam07714 160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                         250
                  ....*....|....*....
gi 974005246  846 CWQKERNSRPKFDEIVNML 864
Cdd:pfam07714 240 CWAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
607-864 1.05e-134

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 404.61  E-value: 1.05e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   607 ITIERVIGAGEFGEVCSGRLK-LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKgKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaaY 765
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY--Y 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:smart00219 159 RKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQ 238
                          250
                   ....*....|....*....
gi 974005246   846 CWQKERNSRPKFDEIVNML 864
Cdd:smart00219 239 CWAEDPEDRPTFSELVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
607-864 2.22e-133

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 401.16  E-value: 2.22e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   607 ITIERVIGAGEFGEVCSGRLK-LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKgKGDGKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   686 EYMENGSLDTFLKKNDGQF-TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaa 764
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKElSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY-- 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   765 YTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLML 844
Cdd:smart00221 159 YKVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLML 238
                          250       260
                   ....*....|....*....|
gi 974005246   845 DCWQKERNSRPKFDEIVNML 864
Cdd:smart00221 239 QCWAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
611-865 1.83e-126

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 383.43  E-value: 1.83e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd00192    1 KKLGEGAFGEVYKGKLKGGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKN--------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpE 762
Cdd:cd00192   81 GDLLDFLRKSrpvfpspePSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDD-D 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQL 842
Cdd:cd00192  160 YYRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYEL 239
                        250       260
                 ....*....|....*....|...
gi 974005246 843 MLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd00192  240 MLSCWQLDPEDRPTFSELVERLE 262
EphR_LBD_A5 cd10483
Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the ...
1-163 7.65e-120

Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA5 is almost exclusively expressed in the nervous system. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198451  Cd Length: 173  Bit Score: 362.81  E-value: 7.65e-120
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10483   11 MGDLGWIAYPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10483   91 TFNVYYFESNDEDGRNIRENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLTKKGFYLAFQDLGACIALVSVRVY 170

                 ...
gi 974005246 161 YKK 163
Cdd:cd10483  171 YKK 173
EphR_LBD_A cd10473
Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the ...
1-163 6.53e-111

Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198441  Cd Length: 173  Bit Score: 339.41  E-value: 6.53e-111
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10473   11 QGELGWITYPPNGWEEISEMDEDYTPIRTYQVCNVMEPNQNNWLRTNWIYRGEAQRIYIELKFTLRDCNSFPGVLGTCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10473   91 TFNLYYMESDLDLGRNIRENQFTKIDTIAADESFTQGDLGDRIMKLNTEVREVGPLTKKGFYLAFQDVGACVALVSVRVY 170

                 ...
gi 974005246 161 YKK 163
Cdd:cd10473  171 YKK 173
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
611-865 1.95e-102

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 320.00  E-value: 1.95e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd05034    1 KKLGAGQFGEVWMGVWN----GTTKVAVKTLKPGTMSPE--AFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSK 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGQFTVI-QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeaAYTTR- 768
Cdd:cd05034   75 GSLLDYLRTGEGRALRLpQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDD---EYTARe 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd05034  152 GAKFPIKWTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWK 231
                        250
                 ....*....|....*..
gi 974005246 849 KERNSRPKFDEIVNMLD 865
Cdd:cd05034  232 KEPEERPTFEYLQSFLE 248
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
601-858 3.04e-98

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 309.72  E-value: 3.04e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd05068    4 EIDRKSLKLLRKLGSGQFGEVWEGLWN----NTTPVAVKTLKPGTMDPE--DFLREAQIMKKLRHPKLIQLYAVCTLEEP 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd05068   78 IYIITELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEaaYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAAL 839
Cdd:cd05068  158 DE--YEAReGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQL 235
                        250
                 ....*....|....*....
gi 974005246 840 YQLMLDCWQKERNSRPKFD 858
Cdd:cd05068  236 YDIMLECWKADPMERPTFE 254
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
1-163 6.76e-96

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 299.97  E-value: 6.76e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246     1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:smart00615  11 TGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSSLPGVGGSCKE 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246    81 TFNMYYFESDDQNGRNIK----ENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVS 156
Cdd:smart00615  91 TFNLYYYESDTDTATNTLpnwmENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQDQGACVALVS 170

                   ....*..
gi 974005246   157 VRVYYKK 163
Cdd:smart00615 171 VRVFYKK 177
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
613-865 8.07e-94

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 297.05  E-value: 8.07e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05041    3 IGRGNFGDVYRGVLKPDN---TEVAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEaaYTTRGG-- 770
Cdd:cd05041   80 LLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSRE-EEDGE--YTVSDGlk 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd05041  157 QIPIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYD 236
                        250
                 ....*....|....*
gi 974005246 851 RNSRPKFDEIVNMLD 865
Cdd:cd05041  237 PENRPSFSEIYNELQ 251
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
613-864 1.95e-93

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 296.57  E-value: 1.95e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVvTKSKPVMIVTEYMENGS 692
Cdd:cd05060    3 LGHGNFGSVRKGVYLMKSGKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGV-CKGEPLMLVMELAPLGP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI 772
Cdd:cd05060   82 LLKYLKKR-REIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSDYYRATTAGRW 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 773 PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERN 852
Cdd:cd05060  161 PLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPE 240
                        250
                 ....*....|..
gi 974005246 853 SRPKFDEIVNML 864
Cdd:cd05060  241 DRPTFSELESTF 252
EphR_LBD_A7 cd10485
Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the ...
3-164 4.68e-93

Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA7 has been implicated in various cancers, including prostate, gastic and colorectal cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198453  Cd Length: 177  Bit Score: 292.32  E-value: 4.68e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKETF 82
Cdd:cd10485   15 ELEWISSPPSGWEEISGLDENYTPIRTYQVCQVMEPNQNNWLRTNWISKGNAQRIFVELKFTLRDCNSLPGVLGTCKETF 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  83 NMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVYYK 162
Cdd:cd10485   95 NLYYYETDYDTGRNIRENQYVKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSKKGFYLAFQDVGACIALVSVKVYYK 174

                 ..
gi 974005246 163 KC 164
Cdd:cd10485  175 KC 176
EphR_LBD_A10 cd10487
Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the ...
3-163 4.56e-90

Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction results in cell-cell repulsion or adhesion.


Pssm-ID: 198455  Cd Length: 173  Bit Score: 284.22  E-value: 4.56e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKETF 82
Cdd:cd10487   13 ELGWTSLPSNGWEEISGVDEHYKPIRTYQVCNVMEPNQNNWLQTGWISRGRGQRIFIELQFTLRDCNSIPGVAGTCKETF 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  83 NMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVYYK 162
Cdd:cd10487   93 NLYYAESDADLGRRLRESRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGHLSRRGFHLAFQDVGACVALVSVRVYYK 172

                 .
gi 974005246 163 K 163
Cdd:cd10487  173 Q 173
EphR_LBD_A3 cd10481
Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the ...
2-163 1.37e-89

Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA3 has been implicated in leukemia, lung and other cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198449  Cd Length: 173  Bit Score: 283.10  E-value: 1.37e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKET 81
Cdd:cd10481   12 GELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWIPRNSAQKIYVELKFTLRDCNSIPLVLGTCKET 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  82 FNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVYY 161
Cdd:cd10481   92 FNLYYMESDEDQGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEVREVGPVSKKGFYLAFQDVGACVALVSVRVYF 171

                 ..
gi 974005246 162 KK 163
Cdd:cd10481  172 KK 173
EphR_LBD_A8 cd10486
Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the ...
2-163 2.13e-89

Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA8 has been implicated in various cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198454  Cd Length: 173  Bit Score: 282.31  E-value: 2.13e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKET 81
Cdd:cd10486   12 GDWGWLTYPSHGWDSINEMDEYFSPIHTYQVCNVMSPNQNNWLRTNWVQRDGARRVYAEIKFTLRDCNSMPGVLGTCKET 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  82 FNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVYY 161
Cdd:cd10486   92 FNLYYYESDRDLGTSTWESQFLKIDTIAADESFTNVDLGVRRLKLNTEVRGVGPLSKRGFYLAFQDIGACIAIVSVRVYY 171

                 ..
gi 974005246 162 KK 163
Cdd:cd10486  172 KK 173
EphR_LBD_A6 cd10484
Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the ...
1-163 2.42e-89

Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA6, like other Eph receptors and their ephrin ligands, seems to play a role in neural development, underlying learning and memory. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198452  Cd Length: 173  Bit Score: 282.29  E-value: 2.42e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   1 MGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10484   11 LGELNWKTYPCNGWDAITEMDEYNRPIHTYQVCNVMEPNQNNWLRTNWISRDAAQKIYVEMKFTLRDCNSIPWVVGTCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10484   91 TFNLHYMESDEAHAVKFKPNQYSKIDTIAADESFTQMDLGDRILKLNTEVREVGPITRKGFYLAFQDIGACIALVSVRVY 170

                 ...
gi 974005246 161 YKK 163
Cdd:cd10484  171 YKK 173
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
2-164 1.31e-87

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 277.62  E-value: 1.31e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246    2 GDLGWIAFPK-NGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:pfam01404  11 SDLGWTTYPYdGGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSSIPGVSGTCKE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   81 TFNMYYFESDDQNG----RNIKENQYIKIDTIAADESFTELDlGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVS 156
Cdd:pfam01404  91 TFNLYYYESDADAAtatpPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQDQGACIALLS 169

                  ....*...
gi 974005246  157 VRVYYKKC 164
Cdd:pfam01404 170 VRVFYKKC 177
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
613-864 1.01e-85

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 275.77  E-value: 1.01e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpGKRelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05039   14 IGKGEFGDVMLGDYR--GQK---VAVKCLKDDSTAAQA--FLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKGS 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvleddpEAAYTTRGGK 771
Cdd:cd05039   87 LVDYLRSRGRAvITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAK------EASSNQDGGK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKER 851
Cdd:cd05039  161 LPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELDP 240
                        250
                 ....*....|...
gi 974005246 852 NSRPKFDEIVNML 864
Cdd:cd05039  241 AKRPTFKQLREKL 253
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
601-864 2.58e-85

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 275.07  E-value: 2.58e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSkP 680
Cdd:cd05056    2 EIQREDITLGRCIGEGQFGDVYQGVYMSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITEN-P 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDd 760
Cdd:cd05056   81 VWIVMELAPLGELRSYLQVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMED- 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 pEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05056  160 -ESYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLY 238
                        250       260
                 ....*....|....*....|....
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05056  239 SLMTKCWAYDPSKRPRFTELKAQL 262
EphR_LBD_A4 cd10482
Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the ...
2-163 2.90e-85

Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. A loss of EphA4, as well as EphB2, precedes memory decline in a murine model of Alzheimers disease. EphA4 has been shown to have a negative effect on axon regeneration and functional restoration in corticospinal lesions and is downregulated in some cervical cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198450  Cd Length: 174  Bit Score: 271.53  E-value: 2.90e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFP-KNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10482   12 GELGWIASPlEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWIPREGAQRVYIEIKFTLRDCNSLPGVMGTCKE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10482   92 TFNLYYYESNNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVF 171

                 ...
gi 974005246 161 YKK 163
Cdd:cd10482  172 YKK 174
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
608-865 1.06e-83

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 270.46  E-value: 1.06e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQRrDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05148    9 TLERKLGSGYFGEVWEGLWK----NRVRVAIKILKSDDLLKQQ-DFQKEVQALKRLRHKHLISLFAVCSVGEPVYIITEL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeaAYT 766
Cdd:cd05148   84 MEKGSLLAFLRSPEGQvLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKED---VYL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDC 846
Cdd:cd05148  161 SSDKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLEC 240
                        250
                 ....*....|....*....
gi 974005246 847 WQKERNSRPKFDEIVNMLD 865
Cdd:cd05148  241 WAAEPEDRPSFKALREELD 259
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
602-864 4.49e-83

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 268.55  E-value: 4.49e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKlpGKRElpVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05059    1 IDPSELTFLKELGSGQFGVVHLGKWR--GKID--VAIKMIKEGSMSED--DFIEEAKVMMKLSHPKLVQLYGVCTKQRPI 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDp 761
Cdd:cd05059   75 FIVTEYMANGCLLNYLRERRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDD- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 eaAYTTRGG-KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05059  154 --EYTSSVGtKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVY 231
                        250       260
                 ....*....|....*....|....
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05059  232 TIMYSCWHEKPEERPTFKILLSQL 255
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
613-864 1.64e-82

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 266.71  E-value: 1.64e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpGKrelPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd13999    1 IGSGSFGEVYKGKWR--GT---DVAIKKLKVEDdNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGG 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGk 771
Cdd:cd13999   76 SLYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTEKMTGVVGT- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 ipIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd13999  155 --PRWMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPiQIAAAVVQKGLRPPIPPDCPPELSKLIKRCWNED 231
                        250
                 ....*....|....
gi 974005246 851 RNSRPKFDEIVNML 864
Cdd:cd13999  232 PEKRPSFSEIVKRL 245
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
601-865 6.66e-82

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 265.98  E-value: 6.66e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKsKP 680
Cdd:cd05067    3 EVPRETLKLVERLGAGQFGEVWMGYYNGHTK----VAIKSLKQGSMSPDA--FLAEANLMKQLQHQRLVRLYAVVTQ-EP 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd05067   76 IYIITEYMENGSLVDFLKTPSGiKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIED 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAA 838
Cdd:cd05067  156 N---EYTAReGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEE 232
                        250       260
                 ....*....|....*....|....*..
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05067  233 LYQLMRLCWKERPEDRPTFEYLRSVLE 259
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
601-865 7.71e-81

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 263.43  E-value: 7.71e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05032    2 ELPREKITLIRELGQGSFGMVYEGLAKgvVKGEPETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKK-------NDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd05032   82 QPTLVVMELMAKGDLKSYLRSrrpeaenNPGLgpPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd05032  162 DFGMTR---DIYETDYYRKGGKglLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGG 238
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05032  239 HLDLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLK 276
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
599-865 4.02e-80

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 261.51  E-value: 4.02e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 599 AKEIEASCITIERVIGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05072    1 AWEIPRESIKLVKKLGAGQFGEVWMGYYNNSTK----VAVKTLKPGTMSVQA--FLEEANLMKTLQHDKLVRLYAVVTKE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd05072   75 EPIYIITEYMAKGSLLDFLKSDEGgKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EDDpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCP 836
Cdd:cd05072  155 EDN---EYTAReGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCP 231
                        250       260
                 ....*....|....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05072  232 DELYDIMKTCWKEKAEERPTFDYLQSVLD 260
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
601-864 3.57e-78

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 256.53  E-value: 3.57e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKRELP--VAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05048    1 EIPLSAVRFLEELGEGAFGKVYKGELLGPSSEESAisVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKN------------DGQFTVIQLVGMLR---GISAGMKYLSDMGYVHRDLAARNILINSN 743
Cdd:cd05048   81 QPQCMLFEYMAHGDLHEFLVRHsphsdvgvssddDGTASSLDQSDFLHiaiQIAAGMEYLSSHHYVHRDLAARNCLVGDG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 744 LVCKVSDFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIK 821
Cdd:cd05048  161 LTVKISDFGLSR---DIYSSDYYRVQSKslLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIE 237
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 974005246 822 AVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05048  238 MIRSRQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRL 280
EphR_LBD_B cd10472
Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the ...
3-163 6.78e-78

Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. They play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphB receptors are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198440  Cd Length: 176  Bit Score: 251.72  E-value: 6.78e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKETF 82
Cdd:cd10472   12 ELGWTAHPPSGWEEVSGYDENMNTIRTYQVCNVFESNQNNWLRTKFIRRRGAHRVYVEMKFTVRDCSSIPNVPGSCKETF 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  83 NMYYFESD----DQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVR 158
Cdd:cd10472   92 NLYYYESDsdiaTKTSPFWMENPYVKVDTIAADESFSQVDLGGRVMKVNTEVRSFGPLSRNGFYLAFQDYGACMSLISVR 171

                 ....*
gi 974005246 159 VYYKK 163
Cdd:cd10472  172 VFYKK 176
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
613-865 1.34e-77

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 253.69  E-value: 1.34e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKsKPVMIVTEYMENGS 692
Cdd:cd14203    3 LGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMSPEA--FLEEAQIMKKLRHDKLVQLYAVVSE-EPIYIVTEFMSKGS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVI-QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeaAYTTR-GG 770
Cdd:cd14203   76 LLDFLKDGEGKYLKLpQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDN---EYTARqGA 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd14203  153 KFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKD 232
                        250
                 ....*....|....*
gi 974005246 851 RNSRPKFDEIVNMLD 865
Cdd:cd14203  233 PEERPTFEYLQSFLE 247
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
601-866 3.54e-77

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 253.54  E-value: 3.54e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05049    1 HIKRDTIVLKRELGEGAFGKVFLGECYnlEPEQDKMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKND-------------GQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV 745
Cdd:cd05049   81 DPLLMVFEYMEHGDLNKFLRSHGpdaaflasedsapGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 746 CKVSDFGLSR-VLEDDpeaaYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKA 822
Cdd:cd05049  161 VKIGDFGMSRdIYSTD----YYRVGGHtmLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIEC 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 974005246 823 VEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd05049  237 ITQGRLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRLQE 280
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
601-868 4.41e-77

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 252.73  E-value: 4.41e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKlpgKRELPVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd05052    2 EIERTDITMKHKLGGGQYGEVYEGVWK---KYNLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPP 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd05052   77 FYIITEFMPYGNLLDYLRECNREeLNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAA 838
Cdd:cd05052  157 D---TYTAHaGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPK 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05052  234 VYELMRACWQWNPSDRPSFAEIHQALETMF 263
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
613-864 5.00e-77

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 252.26  E-value: 5.00e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQR--RDFLGEASIMGQFDHPNIIHLEGVVTkSKPVMIVTEYMEN 690
Cdd:cd05040    3 LGDGSFGVVRRGEWTTPSGKVIQVAVKCLKSDVLSQPNamDDFLKEVNAMHSLDHPNLIRLYGVVL-SSPLMMVTELAPL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGG 770
Cdd:cd05040   82 GSLLDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDHYVMQEHR 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVE-EGYRLPSPMDCPAALYQLMLDCWQK 849
Cdd:cd05040  162 KVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDkEGERLERPDDCPQDIYNVMLQCWAH 241
                        250
                 ....*....|....*
gi 974005246 850 ERNSRPKFDEIVNML 864
Cdd:cd05040  242 KPADRPTFVALRDFL 256
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
611-864 5.96e-76

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 250.03  E-value: 5.96e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLK---LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05044    1 KFLGSGAFGEVFEGTAKdilGDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILEL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKN------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN----LVCKVSDFGLSR-V 756
Cdd:cd05044   81 MEGGDLLSYLRAArptaftPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKdyreRVVKIGDFGLARdI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDpeaAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDC 835
Cdd:cd05044  161 YKND---YYRKEGeGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNC 237
                        250       260
                 ....*....|....*....|....*....
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05044  238 PDDLYELMLRCWSTDPEERPSFARILEQL 266
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
611-872 1.81e-75

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 248.87  E-value: 1.81e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR-ELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTkSKPVMIVTEYME 689
Cdd:cd05057   13 KVLGSGAFGTVYKGVWIPEGEKvKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICL-SSQVQLITQLMP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS-NLVcKVSDFGLSRVLEDDpEAAYTTR 768
Cdd:cd05057   92 LGCLLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTpNHV-KITDFGLAKLLDVD-EKEYHAE 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd05057  170 GGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLVKCWM 249
                        250       260
                 ....*....|....*....|....
gi 974005246 849 KERNSRPKFDEIVNMLDKLIRNPS 872
Cdd:cd05057  250 IDAESRPTFKELANEFSKMARDPQ 273
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
613-860 6.54e-74

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 243.68  E-value: 6.54e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpgKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05084    4 IGRGNFGEVFSGRLR---ADNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpeAAYTTRGG-- 770
Cdd:cd05084   81 FLTFLRTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEED---GVYAATGGmk 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd05084  158 QIPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYD 237
                        250
                 ....*....|
gi 974005246 851 RNSRPKFDEI 860
Cdd:cd05084  238 PRKRPSFSTV 247
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
611-867 1.01e-73

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 244.60  E-value: 1.01e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPG--KRELpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS--KPVMIVTE 686
Cdd:cd05038   10 KQLGEGHFGSVELCRYDPLGdnTGEQ-VAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPgrRSLRLIME 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd05038   89 YLPSGSLRDYLQRHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKEYYYV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPY--------------WEMTNQDVIKAVEEGYRLPSP 832
Cdd:cd05038  169 KEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQsppalflrmigiaqGQMIVTRLLELLKSGERLPRP 248
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 974005246 833 MDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05038  249 PSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDRL 283
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
600-866 2.09e-73

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 243.45  E-value: 2.09e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 600 KEIEASCITIERVIGAGEFGEVCSGRLK-LPG-KRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK 677
Cdd:cd05036    1 KEVPRKNLTLIRALGQGAFGEVYEGTVSgMPGdPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 678 SKPVMIVTEYMENGSLDTFLKKN------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNL---VCKV 748
Cdd:cd05036   81 RLPRFILLELMAGGDLKSFLRENrprpeqPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKGpgrVAKI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 749 SDFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEG 826
Cdd:cd05036  161 GDFGMAR---DIYRADYYRKGGKamLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSG 237
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 827 YRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd05036  238 GRMDPPKNCPGPVYRIMTQCWQHIPEDRPNFSTILERLNY 277
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
612-860 7.79e-73

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 240.68  E-value: 7.79e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd05085    3 LLGKGNFGEVYKGTLK----DKTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGG 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvLEDDpeAAYTTRGGK 771
Cdd:cd05085   79 DFLSFLRKKKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSR-QEDD--GVYSSSGLK 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 -IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd05085  156 qIPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYN 235
                        250
                 ....*....|
gi 974005246 851 RNSRPKFDEI 860
Cdd:cd05085  236 PENRPKFSEL 245
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
611-860 2.00e-72

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 241.47  E-value: 2.00e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEV--C-------SGRLKLPGKRELP----VAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK 677
Cdd:cd05051   11 EKLGEGQFGEVhlCeanglsdLTSDDFIGNDNKDepvlVAVKMLRPDASKNAREDFLKEVKIMSQLKDPNIVRLLGVCTR 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 678 SKPVMIVTEYMENGSLDTFLKKNDGQFTVIQ-----------LVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVC 746
Cdd:cd05051   91 DEPLCMIVEYMENGDLNQFLQKHEAETQGASatnsktlsygtLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPNYTI 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 747 KVSDFGLSRVL-EDDpeaAYTTRGGKI-PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYG-ERPYWEMTNQDVIKAV 823
Cdd:cd05051  171 KIADFGMSRNLySGD---YYRIEGRAVlPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTDEQVIENA 247
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 974005246 824 EEGYR-------LPSPMDCPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd05051  248 GEFFRddgmevyLSRPPNCPKEIYELMLECWRRDEEDRPTFREI 291
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
613-864 2.86e-72

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 239.85  E-value: 2.86e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPgKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVtKSKPVMIVTEYMENGS 692
Cdd:cd05115   12 LGSGNFGCVKKGVYKMR-KKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVC-EAEALMLVMEMASGGP 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTR-GGK 771
Cdd:cd05115   90 LNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGAD-DSYYKARsAGK 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKER 851
Cdd:cd05115  169 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKW 248
                        250
                 ....*....|...
gi 974005246 852 NSRPKFDEIVNML 864
Cdd:cd05115  249 EDRPNFLTVEQRM 261
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
607-866 4.43e-72

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 240.12  E-value: 4.43e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd05050    7 IEYVRDIGQGAFGRVFQARAPglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCAVGKPMCLL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNDG---------------------QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN 743
Cdd:cd05050   87 FEYMAYGDLNEFLRHRSPraqcslshstssarkcglnplPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGEN 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 744 LVCKVSDFGLSRvledDPEAAYTTRGGK---IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVI 820
Cdd:cd05050  167 MVVKIADFGLSR----NIYSADYYKASEndaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVI 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 821 KAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd05050  243 YYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQR 288
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
599-865 9.64e-72

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 238.39  E-value: 9.64e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 599 AKEIEASCITIERVIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKs 678
Cdd:cd05073    5 AWEIPRESLKLEKKLGAGQFGEVWMATYN----KHTKVAVKTMKPGSMSVEA--FLAEANVMKTLQHDKLVKLHAVVTK- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd05073   78 EPIYIITEFMAKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVI 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EDDpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCP 836
Cdd:cd05073  158 EDN---EYTAReGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCP 234
                        250       260
                 ....*....|....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05073  235 EELYNIMMRCWKNRPEERPTFEYIQSVLD 263
EphR_LBD_B1 cd10476
Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the ...
2-163 9.74e-71

Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. Using EphB1 knockout-mice, EphB1 has been shown to be essential to the development of long-term potentiation (LTP), a cellular model of synaptic plasticity, learning and memory formation. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198444  Cd Length: 176  Bit Score: 232.25  E-value: 9.74e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKET 81
Cdd:cd10476   11 AELGWTANPASGWEEVSGYDENLNTIRTYQVCNVFEPNQNNWLLTTFINRRGAHRIYTEMRFTVRDCSSLPNVPGSCKET 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  82 FNMYYFESDDQNGRNIK----ENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSV 157
Cdd:cd10476   91 FNLYYYETDSVIATKKSafwtEAPYLKVDTIAADESFSQVDFGGRLMKVNTEVRSFGPLTRNGFYLAFQDYGACMSLLSV 170

                 ....*.
gi 974005246 158 RVYYKK 163
Cdd:cd10476  171 RVFFKK 176
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
602-864 1.61e-70

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 234.84  E-value: 1.61e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKlpGKRElpVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05112    1 IDPSELTFVQEIGSGQFGLVHLGYWL--NKDK--VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDp 761
Cdd:cd05112   75 CLVFEFMEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDD- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 eaAYT-TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05112  154 --QYTsSTGTKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVY 231
                        250       260
                 ....*....|....*....|....
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05112  232 EIMNHCWKERPEDRPSFSLLLRQL 255
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
601-865 6.51e-70

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 233.81  E-value: 6.51e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKsKP 680
Cdd:cd05070    5 EIPRESLQLIKRLGNGQFGEVWMGTWNGNTK----VAIKTLKPGTMSPE--SFLEEAQIMKKLKHDKLVQLYAVVSE-EP 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd05070   78 IYIVTEYMSKGSLLDFLKDGEGRaLKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIED 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAA 838
Cdd:cd05070  158 N---EYTARqGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPIS 234
                        250       260
                 ....*....|....*....|....*..
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05070  235 LHELMIHCWKKDPEERPTFEYLQGFLE 261
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
599-865 6.94e-70

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 233.81  E-value: 6.94e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 599 AKEIEASCITIERVIGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKs 678
Cdd:cd05069    6 AWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSE- 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKNDGQFTVI-QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd05069   79 EPIYIVTEFMGKGSLLDFLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EDDpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCP 836
Cdd:cd05069  159 EDN---EYTARqGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCP 235
                        250       260
                 ....*....|....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05069  236 ESLHELMKLCWKKDPDERPTFEYIQSFLE 264
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
599-865 6.77e-69

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 231.11  E-value: 6.77e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 599 AKEIEASCITIERVIGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKs 678
Cdd:cd05071    3 AWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTR----VAIKTLKPGTMSPEA--FLQEAQVMKKLRHEKLVQLYAVVSE- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKNDGQFTVI-QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd05071   76 EPIYIVTEYMSKGSLLDFLKGEMGKYLRLpQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EDDpeaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCP 836
Cdd:cd05071  156 EDN---EYTARqGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECP 232
                        250       260
                 ....*....|....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05071  233 ESLHDLMCQCWRKEPEERPTFEYLQAFLE 261
EphR_LBD_B3 cd10478
Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the ...
3-163 9.35e-69

Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB3 plays a role in cell positioning in the gastrointestinal tract by being preferentially expressed in Paneth cells. It also has been implicated in early colorectal cancer and early stage squamous cell lung cancer. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198446  Cd Length: 173  Bit Score: 226.43  E-value: 9.35e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKETF 82
Cdd:cd10478   13 ELAWTTHPESGWEEVSGYDEAMNPIRTYQVCNVRESNQNNWLRTGFIPRRDVQRVYVELKFTVRDCNSIPNIPGSCKETF 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  83 NMYYFESDDQ----NGRNIKENQYIKIDTIAADESFTELDLGdrvmKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVR 158
Cdd:cd10478   93 NLFYYESDSDsasaSSPFWMENPYVKVDTIAPDESFSRLDSG----RVNTKVRSFGPLSKAGFYLAFQDLGACMSLISVR 168

                 ....*
gi 974005246 159 VYYKK 163
Cdd:cd10478  169 AFFKK 173
EphR_LBD_B2 cd10477
Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the ...
2-163 2.62e-68

Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells. It also has been implicated in colorectal cancer. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198445  Cd Length: 178  Bit Score: 225.71  E-value: 2.62e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKET 81
Cdd:cd10477   13 AELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKYIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKET 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  82 FNMYYFESDDQNGR----NIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSV 157
Cdd:cd10477   93 FNLYYYESDFDSATktfpNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRNGFYLAFQDYGGCMSLIAV 172

                 ....*.
gi 974005246 158 RVYYKK 163
Cdd:cd10477  173 RVFYRK 178
EphR_LBD cd10319
Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest ...
2-163 3.10e-68

Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). They are subdivided into 2 groups, A and B type receptors, depending on their ligand ephrin-A or ephrin-B, respectively. In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198439  Cd Length: 177  Bit Score: 225.36  E-value: 3.10e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFP--KNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCK 79
Cdd:cd10319   11 SDLGWLTYPygHGGWDEESGLDPDGANIRTYVVCNVAMPNQDNWLRTPFIERRGAQRIYVELKFTVRDCESFPGNARSCK 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  80 ETFNMYYFESDDQNGR----NIKENQYIKIDTIAADESFTELDlGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALV 155
Cdd:cd10319   91 ETFNLYYYESDHDTATkefpPWNEDPYTKIDTIAADESFKSSN-EDTTEKLNTETRSIGPLTKRGFYLAFQDQGACMSLL 169

                 ....*...
gi 974005246 156 SVRVYYKK 163
Cdd:cd10319  170 SVKVYYKK 177
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
607-861 4.44e-68

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 227.84  E-value: 4.44e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpGKRElpVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05113    6 LTFLKELGTGQFGVVKYGKWR--GQYD--VAIKMIKEGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeaAYT 766
Cdd:cd05113   80 YMANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDD---EYT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:cd05113  157 SSvGSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYS 236
                        250
                 ....*....|....*.
gi 974005246 846 CWQKERNSRPKFDEIV 861
Cdd:cd05113  237 CWHEKADERPTFKILL 252
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
602-868 2.66e-67

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 225.90  E-value: 2.66e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQrrDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05114    1 INPSELTFMKELGSGLFGVVRLGKWR----AQYKVAIKAIREGAMSEE--DFIEEAKVMMKLTHPKLVQLYGVCTQQKPI 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDp 761
Cdd:cd05114   75 YIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDD- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 eaAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd05114  154 --QYTSSsGAKFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVY 231
                        250       260
                 ....*....|....*....|....*...
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05114  232 EVMYSCWHEKPEGRPTFADLLRTITEIA 259
EphR_LBD_A2 cd10480
Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of ...
2-164 1.74e-66

Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA2 negatively regulates cell differentiation and has been shown to be overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198448  Cd Length: 174  Bit Score: 220.49  E-value: 1.74e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFPK-NGWEEIGEVdENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10480   12 GELGWLTHPYgKGWDLMQNV-MNDSPIYMYSVCNVMSGEQDNWLRTNWIYRSEAERIFIELKFTVRDCNSFPGGAGSCKE 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVY 160
Cdd:cd10480   91 TFNLYYAESDVDYGTNFQKRQFRKIDTIAPDEITVSSDFETRNVKLNVEERSVGPLTRKGFYLAFQDIGACVALLSVRVY 170

                 ....
gi 974005246 161 YKKC 164
Cdd:cd10480  171 YKKC 174
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
607-866 3.10e-66

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 222.83  E-value: 3.10e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGrlKLPGKrelPVAIKTLKVGYTEKQrrdFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVTE 686
Cdd:cd05083    8 LTLGEIIGEGEFGAVLQG--EYMGQ---KVAVKNIKCDVTAQA---FLEETAVMTKLQHKNLVRLLGVILHNG-LYIVME 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNdGQFTV--IQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVledDPEAA 764
Cdd:cd05083   79 LMSKGNLVNFLRSR-GRALVpvIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKV---GSMGV 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRggkIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLML 844
Cdd:cd05083  155 DNSR---LPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMT 231
                        250       260
                 ....*....|....*....|..
gi 974005246 845 DCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd05083  232 SCWEAEPGKRPSFKKLREKLEK 253
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
607-864 4.13e-64

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 217.91  E-value: 4.13e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEV----CSGRLklPGKRELPVAIKTLKVGyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd05092    7 IVLKWELGEGAFGKVflaeCHNLL--PEQDKMLVAVKALKEA-TESARQDFQREAELLTVLQHQHIVRFYGVCTEGEPLI 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKND--------------GQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKV 748
Cdd:cd05092   84 MVFEYMRHGDLNRFLRSHGpdakildggegqapGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKI 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 749 SDFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEG 826
Cdd:cd05092  164 GDFGMSR---DIYSTDYYRVGGRtmLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQG 240
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 827 YRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05092  241 RELERPRTCPPEVYAIMQGCWQREPQQRHSIKDIHSRL 278
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
613-857 5.09e-64

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 216.75  E-value: 5.09e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPgKRELPVAIKTLKVGYTEKQRRD-FLGEASIMGQFDHPNIIHLEGVVtKSKPVMIVTEYMENG 691
Cdd:cd05116    3 LGSGNFGTVKKGYYQMK-KVVKTVAVKILKNEANDPALKDeLLREANVMQQLDNPYIVRMIGIC-EAESWMLVMEMAELG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTRG-G 770
Cdd:cd05116   81 PLNKFLQKNR-HVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRAD-ENYYKAQThG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKE 850
Cdd:cd05116  159 KWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYD 238

                 ....*..
gi 974005246 851 RNSRPKF 857
Cdd:cd05116  239 VDERPGF 245
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
607-870 6.66e-64

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 217.52  E-value: 6.66e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSG---RLK-LPGKRElpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd05045    2 LVLGKTLGEGEFGKVVKAtafRLKgRAGYTT--VAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKK---------------------NDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL 739
Cdd:cd05045   80 LIVEYAKYGSLRSFLREsrkvgpsylgsdgnrnssyldNPDEraLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 740 INSNLVCKVSDFGLSR-VLEDDpeaAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQ 817
Cdd:cd05045  160 VAEGRKMKISDFGLSRdVYEED---SYVKRSkGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPE 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 818 DVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRN 870
Cdd:cd05045  237 RLFNLLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKMMVK 289
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
601-868 3.38e-63

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 215.74  E-value: 3.38e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLK-LPGKRELP--VAIKTLKVGYTEKQRRDFLGEASIM---GQfdHPNIIHLEGV 674
Cdd:cd05053    8 ELPRDRLTLGKPLGEGAFGQVVKAEAVgLDNKPNEVvtVAVKMLKDDATEKDLSDLVSEMEMMkmiGK--HKNIINLLGA 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 675 VTKSKPVMIVTEYMENGSLDTFLKKN---------------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL 739
Cdd:cd05053   86 CTQDGPLYVVVEYASKGNLREFLRARrppgeeaspddprvpEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVL 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 740 INSNLVCKVSDFGLSRVLEDDPEAAYTTRGgKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDV 819
Cdd:cd05053  166 VTEDNVMKIADFGLARDIHHIDYYRKTTNG-RLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEEL 244
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 820 IKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05053  245 FKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRIL 293
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
601-860 5.65e-63

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 214.88  E-value: 5.65e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLKLPGKRELP-VAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSK 679
Cdd:cd05090    1 ELPLSAVRFMEELGECAFGKIYKGHLYLPGMDHAQlVAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENGSLDTFL------------KKNDGQFTVI----QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN 743
Cdd:cd05090   81 PVCMLFEFMNQGDLHEFLimrsphsdvgcsSDEDGTVKSSldhgDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 744 LVCKVSDFGLSRVLEddpEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIK 821
Cdd:cd05090  161 LHVKISDLGLSREIY---SSDYYRVQNKslLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIE 237
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 822 AVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd05090  238 MVRKRQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDI 276
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
601-864 6.07e-63

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 214.83  E-value: 6.07e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05061    2 EVSREKITLLRELGQGSFGMVYEGNARdiIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLK-------KNDGQF--TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd05061   82 QPTLVVMELMAHGDLKSYLRslrpeaeNNPGRPppTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd05061  162 DFGMTR---DIYETDYYRKGGKglLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGG 238
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05061  239 YLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLL 275
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
597-864 8.32e-63

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 214.86  E-value: 8.32e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 597 EFAKEIeascITIERVIGAGEFGEV--CSGR-----------LKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05095    1 EFPRKL----LTFKEKLGEGQFGEVhlCEAEgmekfmdkdfaLEVSENQPVLVAVKMLRADANKNARNDFLKEIKIMSRL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN--DGQFTVI---------QLVGMLRGISAGMKYLSDMGYVHRD 732
Cdd:cd05095   77 KDPNIIRLLAVCITDDPLCMITEYMENGDLNQFLSRQqpEGQLALPsnaltvsysDLRFMAAQIASGMKYLSSLNFVHRD 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 733 LAARNILINSNLVCKVSDFGLSRVLEDDPeaAYTTRGGKI-PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY-GERP 810
Cdd:cd05095  157 LATRNCLVGKNYTIKIADFGMSRNLYSGD--YYRIQGRAVlPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQP 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 811 YWEMTNQDVIKAVEEGYR-------LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05095  235 YSQLSDEQVIENTGEFFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLL 295
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
611-872 9.29e-63

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 214.12  E-value: 9.29e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR-ELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVTEYME 689
Cdd:cd05109   13 KVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTST-VQLVTQLMP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTRG 769
Cdd:cd05109   92 YGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID-ETEYHADG 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQK 849
Cdd:cd05109  171 GKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 250
                        250       260
                 ....*....|....*....|...
gi 974005246 850 ERNSRPKFDEIVNMLDKLIRNPS 872
Cdd:cd05109  251 DSECRPRFRELVDEFSRMARDPS 273
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
600-864 9.93e-63

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 214.11  E-value: 9.93e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 600 KEIEASCITIERVIGAGEFGEVCSGRL--KLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK 677
Cdd:cd05091    1 KEINLSAVRFMEELGEDRFGKVYKGHLfgTAPGEQTQAVAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 678 SKPVMIVTEYMENGSLDTFL---------KKNDGQFTV------IQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS 742
Cdd:cd05091   81 EQPMSMIFSYCSHGDLHEFLvmrsphsdvGSTDDDKTVkstlepADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 743 NLVCKVSDFGLSR-VLEDDpeaAYTTRGGK-IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVI 820
Cdd:cd05091  161 KLNVKISDLGLFReVYAAD---YYKLMGNSlLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVI 237
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 974005246 821 KAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05091  238 EMIRNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRL 281
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
607-867 1.20e-62

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 212.92  E-value: 1.20e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpGKRelpVAIKTLKVGYTEKQrrdFLGEASIMGQFDHPNIIHLEGVVTKSK-PVMIVT 685
Cdd:cd05082    8 LKLLQTIGKGEFGDVMLGDYR--GNK---VAVKCIKNDATAQA---FLAEASVMTQLRHSNLVQLLGVIVEEKgGLYIVT 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQfTVI---QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvleddpE 762
Cdd:cd05082   80 EYMAKGSLVDYLRSR-GR-SVLggdCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTK------E 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQL 842
Cdd:cd05082  152 ASSTQDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDV 231
                        250       260
                 ....*....|....*....|....*
gi 974005246 843 MLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05082  232 MKNCWHLDAAMRPSFLQLREQLEHI 256
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
611-861 9.22e-62

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 210.79  E-value: 9.22e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV-MIVTEYME 689
Cdd:cd05058    1 EVIGKGHFGCVYHGTLIDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSEGSpLVVLPYMK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR-VLEDDPEAAYTTR 768
Cdd:cd05058   81 HGDLRNFIRSETHNPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARdIYDKEYYSVHNHT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd05058  161 GAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCWH 240
                        250
                 ....*....|...
gi 974005246 849 KERNSRPKFDEIV 861
Cdd:cd05058  241 PKPEMRPTFSELV 253
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
611-872 3.96e-61

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 210.65  E-value: 3.96e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR-ELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVTEYME 689
Cdd:cd05108   13 KVLGSGAFGTVYKGLWIPEGEKvKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTST-VQLITQLMP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTRG 769
Cdd:cd05108   92 FGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAE-EKEYHAEG 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQK 849
Cdd:cd05108  171 GKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMI 250
                        250       260
                 ....*....|....*....|...
gi 974005246 850 ERNSRPKFDEIVNMLDKLIRNPS 872
Cdd:cd05108  251 DADSRPKFRELIIEFSKMARDPQ 273
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
607-870 1.44e-60

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 207.94  E-value: 1.44e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKReLPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS------- 678
Cdd:cd05075    2 LALGKTLGEGEFGSVMEGQLNQDDSV-LKVAVKTMKIAIcTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLQNtesegyp 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTeYMENGSLDTFLKKND-GQFTVI----QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd05075   81 SPVVILP-FMKHGDLHSFLLYSRlGDCPVYlptqMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLEDdpeAAYTTRG--GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPS 831
Cdd:cd05075  160 SKKIYN---GDYYRQGriSKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQ 236
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 832 PMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRN 870
Cdd:cd05075  237 PPDCLDGLYELMSSCWLLNPKDRPSFETLRCELEKILKD 275
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
607-868 1.81e-60

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 207.39  E-value: 1.81e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV---- 681
Cdd:cd05035    1 LKLGKILGEGEFGSVMEAQLKQDDGSQLKVAVKTMKVdIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkpp 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 --MIVTEYMENGSLDTFL-----KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS 754
Cdd:cd05035   81 spMVILPFMKHGDLHSYLlysrlGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 755 RVLEDdpEAAY-TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPM 833
Cdd:cd05035  161 RKIYS--GDYYrQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPE 238
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 974005246 834 DCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05035  239 DCLDEVYFLMYFCWTVDPKDRPTFTKLREVLENIL 273
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
607-869 6.37e-60

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 206.43  E-value: 6.37e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd05093    7 IVLKRELGEGAFGKVFLAECYnlCPEQDKILVAVKTLKDA-SDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKN--------DGQ----FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFG 752
Cdd:cd05093   86 FEYMKHGDLNKFLRAHgpdavlmaEGNrpaeLTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 753 LSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLP 830
Cdd:cd05093  166 MSR---DVYSTDYYRVGGHtmLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQ 242
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 831 SPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd05093  243 RPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAK 281
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
613-864 1.01e-59

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 206.37  E-value: 1.01e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEV----CSGRLKLPGK-------RELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05097   13 LGEGQFGEVhlceAEGLAEFLGEgapefdgQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGVCVSDDPL 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKND--GQFTVIQ---------LVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSD 750
Cdd:cd05097   93 CMITEYMENGDLNQFLSQREieSTFTHANnipsvsianLLYMAVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIAD 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 751 FGLSRVLEDDPeaAYTTRGGKI-PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY-GERPYWEMTNQDVIKAVEEGYR 828
Cdd:cd05097  173 FGMSRNLYSGD--YYRIQGRAVlPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQVIENTGEFFR 250
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 974005246 829 -------LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05097  251 nqgrqiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
601-864 1.42e-59

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 205.94  E-value: 1.42e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEV--CS-------GRLKLP----GKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPN 667
Cdd:cd05096    1 KFPRGHLLFKEKLGEGQFGEVhlCEvvnpqdlPTLQFPfnvrKGRPLLVAVKILRPDANKNARNDFLKEVKILSRLKDPN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 668 IIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN---------------DGQFTVIQ---LVGMLRGISAGMKYLSDMGYV 729
Cdd:cd05096   81 IIRLLGVCVDEDPLCMITEYMENGDLNQFLSSHhlddkeengndavppAHCLPAISyssLLHVALQIASGMKYLSSLNFV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 730 HRDLAARNILINSNLVCKVSDFGLSRVLEDDPeaAYTTRGGKI-PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY-G 807
Cdd:cd05096  161 HRDLATRNCLVGENLTIKIADFGMSRNLYAGD--YYRIQGRAVlPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLcK 238
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 808 ERPYWEMTNQDVIKAVEEGYR-------LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05096  239 EQPYGELTDEQVIENAGEFFRdqgrqvyLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIHAFL 302
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
612-866 3.65e-59

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 203.85  E-value: 3.65e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLP--GKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd05046   12 TLGRGEFGEVFLAKAKGIeeEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYTD 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQ--------FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR-VLEDD 760
Cdd:cd05046   92 LGDLKQFLRATKSKdeklkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKdVYNSE 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 peaAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEG-YRLPSPMDCPAAL 839
Cdd:cd05046  172 ---YYKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGkLELPVPEGCPSRL 248
                        250       260
                 ....*....|....*....|....*..
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd05046  249 YKLMTRCWAVNPKDRPSFSELVSALGE 275
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
602-868 9.53e-59

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 203.24  E-value: 9.53e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK--- 677
Cdd:cd14204    4 IDRNLLSLGKVLGEGEFGSVMEGELQQPDGTNHKVAVKTMKLdNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLEvgs 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 678 ---SKPvMIVTEYMENGSLDTFLKKN----DGQFTVIQ-LVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd14204   84 qriPKP-MVILPFMKYGDLHSFLLRSrlgsGPQHVPLQtLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRVLEddpEAAYTTRG--GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd14204  163 DFGLSKKIY---SGDYYRQGriAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGH 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd14204  240 RLKQPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLL 280
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
611-871 1.11e-58

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 203.76  E-value: 1.11e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR-ELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTkSKPVMIVTEYME 689
Cdd:cd05110   13 KVLGSGAFGTVYKGIWVPEGETvKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCL-SPTIQLVTQLMP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTRG 769
Cdd:cd05110   92 HGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGD-EKEYNADG 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQK 849
Cdd:cd05110  171 GKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMI 250
                        250       260
                 ....*....|....*....|..
gi 974005246 850 ERNSRPKFDEIVNMLDKLIRNP 871
Cdd:cd05110  251 DADSRPKFKELAAEFSRMARDP 272
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
612-867 2.69e-58

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 201.42  E-value: 2.69e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKReLPVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd05047    2 VIGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPH 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKN-----DGQF----------TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR 755
Cdd:cd05047   81 GNLLDFLRKSrvletDPAFaianstastlSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 756 vleddPEAAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMD 834
Cdd:cd05047  161 -----GQEVYVKKTmGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLN 235
                        250       260       270
                 ....*....|....*....|....*....|...
gi 974005246 835 CPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05047  236 CDDEVYDLMRQCWREKPYERPSFAQILVSLNRM 268
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
608-863 5.59e-58

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 199.68  E-value: 5.59e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:smart00220   2 EILEKLGEGSFGKVYLARDKKTGKL---VAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEY 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   688 MENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeDDPEAAYTT 767
Cdd:smart00220  79 CEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQL-DPGEKLTTF 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   768 RGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVI--KAVEEGYRLPSPM-DCPAALYQLML 844
Cdd:smart00220 157 VG---TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELfkKIGKPKPPFPPPEwDISPEAKDLIR 232
                          250
                   ....*....|....*....
gi 974005246   845 DCWQKERNSRPKFDEIVNM 863
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQH 251
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
602-867 3.83e-57

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 198.60  E-value: 3.83e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 602 IEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVG-YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd05074    6 IQEQQFTLGRMLGKGEFGSVREAQLKSEDGSFQKVAVKMLKADiFSSSDIEEFLREAACMKEFDHPNVIKLIGVSLRSRA 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 V------MIVTEYMENGSLDTFL---KKNDGQFTVIQ--LVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd05074   86 KgrlpipMVILPFMKHGDLHTFLlmsRIGEEPFTLPLqtLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVA 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRVLEddpEAAYTTRG--GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd05074  166 DFGLSKKIY---SGDYYRQGcaSKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGN 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05074  243 RLKQPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQLELI 282
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
607-881 4.43e-56

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 195.99  E-value: 4.43e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKReLPVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd05089    4 IKFEDVIGEGNFGQVIKAMIKKDGLK-MNAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGYLYIAI 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKN-----DGQF----------TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSD 750
Cdd:cd05089   83 EYAPYGNLLDFLRKSrvletDPAFakehgtastlTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIAD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 751 FGLSRvleddPEAAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRL 829
Cdd:cd05089  163 FGLSR-----GEEVYVKKTmGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRM 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 830 PSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIrnpSSLKTLVNAS 881
Cdd:cd05089  238 EKPRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRML---EARKAYVNMA 286
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
607-867 8.44e-56

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 194.84  E-value: 8.44e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKvGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd05094    7 IVLKRELGEGAFGKVFLAECYnlSPTKDKMLVAVKTLK-DPTLAARKDFQREAELLTNLQHDHIVKFYGVCGDGDPLIMV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLK---------------KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd05094   86 FEYMKHGDLNKFLRahgpdamilvdgqprQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd05094  166 DFGMSR---DVYSTDYYRVGGHtmLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQGR 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05094  243 VLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHAL 282
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
588-868 1.76e-55

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 194.85  E-value: 1.76e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 588 YEDPNQAVHEFAKEIeascITIERVIGAGEFGEVCS----GRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05101   11 YELPEDPKWEFPRDK----LTLGKPLGEGCFGQVVMaeavGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMI 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 -DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN---------------DGQFTVIQLVGMLRGISAGMKYLSDMG 727
Cdd:cd05101   87 gKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARrppgmeysydinrvpEEQMTFKDLVSCTYQLARGMEYLASQK 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 728 YVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTrGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYG 807
Cdd:cd05101  167 CIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTT-NGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLG 245
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 808 ERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05101  246 GSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIL 306
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
591-868 2.01e-55

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 194.80  E-value: 2.01e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 591 PNQAVHEFAKEIeascITIERVIGAGEFGEVCS----GRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFD-H 665
Cdd:cd05099    2 PLDPKWEFPRDR----LVLGKPLGEGCFGQVVRaeayGIDKSRPDQTVTVAVKMLKDNATDKDLADLISEMELMKLIGkH 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 666 PNIIHLEGVVTKSKPVMIVTEYMENGSLDTFL---------------KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVH 730
Cdd:cd05099   78 KNIINLLGVCTQEGPLYVIVEYAAKGNLREFLrarrppgpdytfditKVPEEQLSFKDLVSCAYQVARGMEYLESRRCIH 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 731 RDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTrGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERP 810
Cdd:cd05099  158 RDLAARNVLVTEDNVMKIADFGLARGVHDIDYYKKTS-NGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSP 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 811 YWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05099  237 YPGIPVEELFKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVL 294
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
601-862 2.98e-55

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 192.94  E-value: 2.98e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd05062    2 EVAREKITMSRELGQGSFGMVYEGIAKgvVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKK-------NDGQF--TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd05062   82 QPTLVIMELMTRGDLKSYLRSlrpemenNPVQAppSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRvleDDPEAAYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGY 827
Cdd:cd05062  162 DFGMTR---DIYETDYYRKGGKglLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGG 238
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 974005246 828 RLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd05062  239 LLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIIS 273
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
586-868 5.32e-55

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 193.09  E-value: 5.32e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 586 HTYEDPNQAVHEFAKEIEASCITIERVIGAGEFGEVCSGRLKLPGKRE--LPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05055   16 YVYIDPTQLPYDLKWEFPRNNLSFGKTLGAGAFGKVVEATAYGLSKSDavMKVAVKMLKPTAHSSEREALMSELKIMSHL 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 -DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQF-TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILIN 741
Cdd:cd05055   96 gNHENIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKRESFlTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLT 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 742 SNLVCKVSDFGLSRVLEDDpeAAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEM-TNQDV 819
Cdd:cd05055  176 HGKIVKICDFGLARDIMND--SNYVVKGnARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMpVDSKF 253
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 820 IKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05055  254 YKLIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQL 302
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
611-871 9.53e-55

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 191.71  E-value: 9.53e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR-ELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVTEYME 689
Cdd:cd05111   13 KVLGSGVFGTVHKGIWIPEGDSiKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGAS-LQLVTQLLP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTRG 769
Cdd:cd05111   92 LGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLYPD-DKKYFYSE 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQK 849
Cdd:cd05111  171 AKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMI 250
                        250       260
                 ....*....|....*....|..
gi 974005246 850 ERNSRPKFDEIVNMLDKLIRNP 871
Cdd:cd05111  251 DENIRPTFKELANEFTRMARDP 272
EphR_LBD_A1 cd10479
Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the ...
2-163 3.68e-54

Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA1 is downregulated in some advanced colorectal and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198447  Cd Length: 177  Bit Score: 186.01  E-value: 3.68e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   2 GDLGWIAFP-KNGWEEIGEVdENYAPIHTYQVCKVMEQ-NQNNWLLTSWI-SNEGASRIFIELKFTLRDCNSLPGGLG-- 76
Cdd:cd10479   12 GELGWLLDPpEVGWSEVQQM-LNGTPLYMYQDCPVQSEgDTDHWLRSNWIyRGEEASRIYVELQFTVRDCKSFPGGAGpl 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  77 TCKETFNMYYFESDDQNGRNIKENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVS 156
Cdd:cd10479   91 GCKETFNLYYMESDQDVGIQLRRPLFQKVTTVAADQSFTIRDLASGSVKLNVERCSLGKLTRRGLYLAFHNPGACVALVS 170

                 ....*..
gi 974005246 157 VRVYYKK 163
Cdd:cd10479  171 VRVFYQR 177
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
607-881 4.71e-53

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 187.90  E-value: 4.71e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKReLPVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd05088    9 IKFQDVIGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAI 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKN-----DGQFTVI----------QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSD 750
Cdd:cd05088   88 EYAPHGNLLDFLRKSrvletDPAFAIAnstastlssqQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIAD 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 751 FGLSRvledDPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLP 830
Cdd:cd05088  168 FGLSR----GQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLE 243
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 831 SPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRnpsSLKTLVNAS 881
Cdd:cd05088  244 KPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLE---ERKTYVNTT 291
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
597-867 3.09e-52

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 185.00  E-value: 3.09e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 597 EFAKEIeascITIERVIGAGEFGEVCS----GRLKLPGKRElpVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHL 671
Cdd:cd05054    3 EFPRDR----LKLGKPLGRGAFGKVIQasafGIDKSATCRT--VAVKMLKEGATASEHKALMTELKILIHIgHHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 672 EGVVTKS-KPVMIVTEYMENGSLDTFLK-------------------------KNDGQFTVIQLVGMLRGISAGMKYLSD 725
Cdd:cd05054   77 LGACTKPgGPLMVIVEFCKFGNLSNYLRskreefvpyrdkgardveeeedddeLYKEPLTLEDLICYSFQVARGMEFLAS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 726 MGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaaYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd05054  157 RKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPD--YVRKGdARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIF 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 805 SYGERPYWEMT-NQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05054  235 SLGASPYPGVQmDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKLGDL 298
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
613-864 7.42e-52

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 180.93  E-value: 7.42e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd00180    1 LGKGSFGKVYKARDKETGK---KVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeDDPEAAYTTRGGKI 772
Cdd:cd00180   78 LKDLLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDL-DSDDSLLKTTGGTT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 773 PIRWTAPEAIAFRKFTSASDVWSYGIVMWEvvsygerpywemtnqdvikaveegyrlpspMDCpaaLYQLMLDCWQKERN 852
Cdd:cd00180  157 PPYYAPPELLGGRYYGPKVDIWSLGVILYE------------------------------LEE---LKDLIRRMLQYDPK 203
                        250
                 ....*....|..
gi 974005246 853 SRPKFDEIVNML 864
Cdd:cd00180  204 KRPSAKELLEHL 215
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
613-867 8.00e-52

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 183.68  E-value: 8.00e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLK-LPGKRELPVAIKTLKvGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS--KPVMIVTEYME 689
Cdd:cd14205   12 LGKGNFGSVEMCRYDpLQDNTGEVVAVKKLQ-HSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNLRLIMEYLP 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRG 769
Cdd:cd14205   91 YGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEP 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERP------YWEMTNQD---------VIKAVEEGYRLPSPMD 834
Cdd:cd14205  171 GESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSksppaeFMRMIGNDkqgqmivfhLIELLKNNGRLPRPDG 250
                        250       260       270
                 ....*....|....*....|....*....|...
gi 974005246 835 CPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14205  251 CPDEIYMIMTECWNNNVNQRPSFRDLALRVDQI 283
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
601-868 3.14e-51

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 182.52  E-value: 3.14e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEV----CSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVV 675
Cdd:cd05098    9 ELPRDRLVLGKPLGEGCFGQVvlaeAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNIINLLGAC 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 676 TKSKPVMIVTEYMENGSLDTFLKKN---------------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI 740
Cdd:cd05098   89 TQDGPLYVIVEYASKGNLREYLQARrppgmeycynpshnpEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 741 NSNLVCKVSDFGLSRVLEDDPEAAYTTRGgKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVI 820
Cdd:cd05098  169 TEDNVMKIADFGLARDIHHIDYYKKTTNG-RLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELF 247
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 821 KAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05098  248 KLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIV 295
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
601-873 7.63e-51

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 182.53  E-value: 7.63e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCS----GRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVV 675
Cdd:cd05100    8 ELSRTRLTLGKPLGEGCFGQVVMaeaiGIDKDKPNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIgKHKNIINLLGAC 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 676 TKSKPVMIVTEYMENGSLDTFLKKN---------------DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI 740
Cdd:cd05100   88 TQDGPLYVLVEYASKGNLREYLRARrppgmdysfdtcklpEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLV 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 741 NSNLVCKVSDFGLSRVLEDDPEAAYTTrGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVI 820
Cdd:cd05100  168 TEDNVMKIADFGLARDVHNIDYYKKTT-NGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELF 246
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 821 KAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRNPSS 873
Cdd:cd05100  247 KLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTST 299
EphR_LBD_B6 cd10475
Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the ...
3-163 7.78e-50

Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB6, a kinase-defective member of this family, is downregulated in MDA-MB-231-breast cancer cells and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198443  Cd Length: 180  Bit Score: 173.96  E-value: 7.78e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQ--NQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCKE 80
Cdd:cd10475   13 EIGWLTYPPGGWDEVSVLDDQRRLTRTFEVCNVAAQgpGQDNWLRTHFIERRGAHRVHVRLHFSVRDCASLGVPGGTCRE 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  81 TFNMYYFESDDQNGRNIK----ENQYIKIDTIAADESFTELDL-GDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALV 155
Cdd:cd10475   93 TFTLYYRQADEPDEPADKsewhEGPWTKVDTIAADESFPASLGkGGQGLQMNVKERSFGPLTQRGFYLAFQDSGACLSLV 172

                 ....*...
gi 974005246 156 SVRVYYKK 163
Cdd:cd10475  173 AVKVFFYK 180
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
611-868 6.62e-49

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 175.12  E-value: 6.62e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKR--ELpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS--KPVMIVTE 686
Cdd:cd05079   10 RDLGEGHFGKVELCRYDPEGDNtgEQ-VAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDggNGIKLIME 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaAYT 766
Cdd:cd05079   89 FLPSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKE-YYT 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGK-IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPY--------------WEMTNQDVIKAVEEGYRLPS 831
Cdd:cd05079  168 VKDDLdSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESspmtlflkmigpthGQMTVTRLVRVLEEGKRLPR 247
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 974005246 832 PMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05079  248 PPNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAIL 284
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
607-864 1.15e-48

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 174.18  E-value: 1.15e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK-SKPVMIVT 685
Cdd:cd05043    8 VTLSDLLQEGTFGRIFHGILRDEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCIEdGEKPMVLY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKK------NDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR-VL 757
Cdd:cd05043   88 PYMNWGNLKLFLQQcrlseaNNPQaLSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRdLF 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EDDpeaaYTTRGGK--IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDC 835
Cdd:cd05043  168 PMD----YHCLGDNenRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINC 243
                        250       260
                 ....*....|....*....|....*....
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05043  244 PDELFAVMACCWALDPEERPSFQQLVQCL 272
EphR_LBD_B4 cd10474
Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the ...
3-163 1.00e-47

Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB4 plays a role in osteoblast differentiation and has been linked to multiple myeloma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198442  Cd Length: 180  Bit Score: 167.83  E-value: 1.00e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   3 DLGWIAFPK--NGWEEIGEVDENYAPIHTYQVCKVMEQ-NQNNWLLTSWISNEGASRIFIELKFTLRDCNSLPGGLGTCK 79
Cdd:cd10474   13 DLKWVTYPQvdGQWEELSGLDEEQHSVRTYEVCDAQRAgGQAHWLRTGWVPRRGAVHVYATLRFTMLECLSLPRAGRSCK 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  80 ETFNMYYFESDDQNGRNIK----ENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALV 155
Cdd:cd10474   93 ETFTVFYYESDADTATAHTpawmENPYIKVDTVAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYLAFQDQGACMALL 172

                 ....*...
gi 974005246 156 SVRVYYKK 163
Cdd:cd10474  173 SLHLFYKK 180
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
597-867 4.49e-47

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 171.72  E-value: 4.49e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 597 EFAKEIeascITIERVIGAGEFGEVCS----GRLKLPGKRelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHP-NIIHL 671
Cdd:cd14207    3 EFARER----LKLGKSLGRGAFGKVVQasafGIKKSPTCR--VVAVKMLKEGATASEYKALMTELKILIHIGHHlNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 672 EGVVTKSK-PVMIVTEYMENGSLDTFLKKNDGQF---------------------------------------------- 704
Cdd:cd14207   77 LGACTKSGgPLMVIVEYCKYGNLSNYLKSKRDFFvtnkdtslqeelikekkeaeptggkkkrlesvtssesfassgfqed 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 705 ---------------------TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEa 763
Cdd:cd14207  157 kslsdveeeeedsgdfykrplTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPD- 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 aYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMT-NQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd14207  236 -YVRKGdARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQiDEDFCSKLKEGIRMRAPEFATSEIYQ 314
                        330       340
                 ....*....|....*....|....*.
gi 974005246 842 LMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14207  315 IMLDCWQGDPNERPRFSELVERLGDL 340
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
612-867 9.53e-46

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 166.22  E-value: 9.53e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKR--ELpVAIKTLKvGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS--KPVMIVTEY 687
Cdd:cd05081   11 QLGKGNFGSVELCRYDPLGDNtgAL-VAVKQLQ-HSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLRLVMEY 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd05081   89 LPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVR 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERP------YWEMTNQD--------VIKAVEEGYRLPSPM 833
Cdd:cd05081  169 EPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKScspsaeFLRMMGCErdvpalcrLLELLEEGQRLPAPP 248
                        250       260       270
                 ....*....|....*....|....*....|....
gi 974005246 834 DCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd05081  249 ACPAEVHELMKLCWAPSPQDRPSFSALGPQLDML 282
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
611-869 9.97e-46

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 168.24  E-value: 9.97e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCS----GRLKLPGKRElpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHP-NIIHLEGVVTK-SKPVMIV 684
Cdd:cd05103   13 KPLGRGAFGQVIEadafGIDKTATCRT--VAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGPLMVI 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNDGQF------------------------------------------------------------ 704
Cdd:cd05103   91 VEFCKFGNLSAYLRSKRSEFvpyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfveekslsdveeeeagqed 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 705 ------TVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaaYTTRG-GKIPIRWT 777
Cdd:cd05103  171 lykdflTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPD--YVRKGdARLPLKWM 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 778 APEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEM-TNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPK 856
Cdd:cd05103  249 APETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPT 328
                        330
                 ....*....|...
gi 974005246 857 FDEIVNMLDKLIR 869
Cdd:cd05103  329 FSELVEHLGNLLQ 341
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
613-869 1.96e-45

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 164.15  E-value: 1.96e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLklpgkRELPVAIKTLKvgyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14058    1 VGRGSFGVVCKARW-----RNQIVAVKIIE---SESEKKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGS 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFL--KKNDGQFTVIQLVGMLRGISAGMKYLSDM---GYVHRDLAARNILI-NSNLVCKVSDFGLSRvledDPEAAYT 766
Cdd:cd14058   73 LYNVLhgKEPKPIYTAAHAMSWALQCAKGVAYLHSMkpkALIHRDLKPPNLLLtNGGTVLKICDFGTAC----DISTHMT 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQD--VIKAVEEGYRLPSPMDCPAALYQLML 844
Cdd:cd14058  149 NNKGSAA--WMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIGGPAfrIMWAVHNGERPPLIKNCPKPIESLMT 225
                        250       260
                 ....*....|....*....|....*
gi 974005246 845 DCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd14058  226 RCWSKDPEKRPSMKEIVKIMSHLMQ 250
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
611-864 6.79e-45

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 163.53  E-value: 6.79e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlP---GKRELpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS--KPVMIVT 685
Cdd:cd05080   10 RDLGEGHFGKVSLYCYD-PtndGTGEM-VAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQggKSLQLIM 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:cd05080   88 EYVPLGSLRDYLPKH--SIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYR 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGErPY---------------WEMTNQDVIKAVEEGYRLP 830
Cdd:cd05080  166 VREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCD-SSqspptkflemigiaqGQMTVVRLIELLERGERLP 244
                        250       260       270
                 ....*....|....*....|....*....|....
gi 974005246 831 SPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05080  245 CPDKCPQEVYHLMKNCWETEASFRPTFENLIPIL 278
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
611-869 2.73e-44

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 163.61  E-value: 2.73e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKREL--PVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSK-PVMIVTE 686
Cdd:cd05102   13 KVLGHGAFGKVVEASAFGIDKSSSceTVAVKMLKEGATASEHKALMSELKILIHIgNHLNVVNLLGACTKPNgPLMVIVE 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLK-KNDG-----------QFTVIQLVGMLRG--------------------------------------- 715
Cdd:cd05102   93 FCKYGNLSNFLRaKREGfspyrersprtRSQVRSMVEAVRAdrrsrqgsdrvasftestsstnqprqevddlwqspltme 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 716 --------ISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEaaYTTRG-GKIPIRWTAPEAIAFRK 786
Cdd:cd05102  173 dlicysfqVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPD--YVRKGsARLPLKWMAPESIFDKV 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 787 FTSASDVWSYGIVMWEVVSYGERPYWEMT-NQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05102  251 YTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERPTFSDLVEILG 330

                 ....
gi 974005246 866 KLIR 869
Cdd:cd05102  331 DLLQ 334
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
608-856 6.62e-44

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 160.06  E-value: 6.62e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYT--EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14014    3 RLVRLLGRGGMGEVYRARDTLLGR---PVAIKVLRPELAedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:cd14014   80 EYVEGGSLADLLRER-GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwEMTNQDVIKAVEEGYRLPSP----MDCPAALYQ 841
Cdd:cd14014  159 GSVLGTPA--YMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPF-DGDSPAAVLAKHLQEAPPPPsplnPDVPPALDA 234
                        250
                 ....*....|....*
gi 974005246 842 LMLDCWQKERNSRPK 856
Cdd:cd14014  235 IILRALAKDPEERPQ 249
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
586-869 9.45e-43

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 160.40  E-value: 9.45e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 586 HTYEDPNQAVHEFAKEIEASCITIERVIGAGEFGEVCSGRLKLPGKRE--LPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05106   19 YTFIDPTQLPYNEKWEFPRDNLQFGKTLGAGAFGKVVEATAFGLGKEDnvLRVAVKMLKASAHTDEREALMSELKILSHL 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 -DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKK------------------------------------------- 699
Cdd:cd05106   99 gQHKNIVNLLGACTHGGPVLVITEYCCYGDLLNFLRKkaetflnfvmalpeisetssdyknitlekkyirsdsgfssqgs 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 700 -------------NDGQFTV----------IQLVGMLR---GISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd05106  179 dtyvemrpvssssSQSSDSKdeedtedswpLDLDDLLRfssQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGL 258
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLEDDpeAAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEM-TNQDVIKAVEEGYRLPS 831
Cdd:cd05106  259 ARDIMND--SNYVVKGnARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGIlVNSKFYKMVKRGYQMSR 336
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 974005246 832 PMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd05106  337 PDFAPPEIYSIMKMCWNLEPTERPTFSQISQLIQRQLG 374
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
612-867 4.00e-41

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 151.78  E-value: 4.00e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLklpgkRELPVAIKTLKVGYTE---KQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14061    1 VIGVGGFGKVYRGIW-----RGEEVAVKAARQDPDEdisVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYA 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQFTViqLVGMLRGISAGMKYLSDMGYV---HRDLAARNILIN--------SNLVCKVSDFGLSRvl 757
Cdd:cd14061   76 RGGALNRVLAGRKIPPHV--LVDWAIQIARGMNYLHNEAPVpiiHRDLKSSNILILeaienedlENKTLKITDFGLAR-- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 eddpEAAYTTR---GGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEmtnqdvIKAVEEGYR------ 828
Cdd:cd14061  152 ----EWHKTTRmsaAGTYA--WMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKG------IDGLAVAYGvavnkl 218
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 829 -LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14061  219 tLPIPSTCPEPFAQLMKDCWQPDPHDRPSFADILKQLENI 258
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
897-962 6.24e-41

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 144.30  E-value: 6.24e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 897 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09546    1 GAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
586-868 8.60e-41

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 155.57  E-value: 8.60e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 586 HTYEDPNQAVHEFAKEIEASCITIERVIGAGEFGEVCSGRLKLPGKRE--LPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05105   18 YIYVDPMQLPYDSRWEFPRDGLVLGRILGSGAFGKVVEGTAYGLSRSQpvMKVAVKMLKPTARSSEKQALMSELKIMTHL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 D-HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQF-------------------------------------- 704
Cdd:cd05105   98 GpHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDNFlsrhpekpkkdldifginpadestrsyvilsfenkgdy 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 705 ---------------------------------------------------------TVIQLVGMLRGISAGMKYLSDMG 727
Cdd:cd05105  178 mdmkqadttqyvpmleikeaskysdiqrsnydrpasykgsndsevknllsddgseglTTLDLLSFTYQVARGMEFLASKN 257
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 728 YVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYTTRGGK-IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY 806
Cdd:cd05105  258 CVHRDLAARNVLLAQGKIVKICDFGLARDIMHD--SNYVSKGSTfLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSL 335
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 974005246 807 GERPYWEM-TNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05105  336 GGTPYPGMiVDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESLL 398
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
586-868 1.13e-40

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 155.17  E-value: 1.13e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 586 HTYEDPNQAVHEFAKEIEASCITIERVIGAGEFGEVCSGRLK--LPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQF 663
Cdd:cd05107   18 YIYVDPMQLPYDSAWEMPRDNLVLGRTLGSGAFGRVVEATAHglSHSQSTMKVAVKMLKSTARSSEKQALMSELKIMSHL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 D-HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN---------------------------------------DGQ 703
Cdd:cd05107   98 GpHLNIVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNkhtflqyyldknrddgslisggstplsqrkshvslgsesDGG 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 704 F-------------------------------------------------TVIQ---------LVGMLRGISAGMKYLSD 725
Cdd:cd05107  178 YmdmskdesadyvpmqdmkgtvkyadiessnyespydqylpsapertrrdTLINespalsymdLVGFSYQVANGMEFLAS 257
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 726 MGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYTTRGGK-IPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd05107  258 KNCVHRDLAARNVLICEGKLVKICDFGLARDIMRD--SNYISKGSTfLPLKWMAPESIFNNLYTTLSDVWSFGILLWEIF 335
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 805 SYGERPYWEM-TNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05107  336 TLGGTPYPELpMNEQFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLVHLVGDLL 400
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
613-865 2.70e-39

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 146.38  E-value: 2.70e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpGkrelPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVTEYMENG 691
Cdd:cd14062    1 IGSGSFGTVYKGRWH--G----DVAVKKLNVTDpTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGS 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVleddpeaayTTRGGK 771
Cdd:cd14062   74 SLYKHLHVLETKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATV---------KTRWSG 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 IP--------IRWTAPEAIAFRK---FTSASDVWSYGIVMWEVVSyGERPYWEMTNQD-VIKAVEEGYRLPS----PMDC 835
Cdd:cd14062  145 SQqfeqptgsILWMAPEVIRMQDenpYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDqILFMVGRGYLRPDlskvRSDT 223
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd14062  224 PKALRRLMEDCIKFQRDERPLFPQILASLE 253
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
586-868 3.64e-39

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 150.05  E-value: 3.64e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 586 HTYEDPNQAVHEFAKEIEASCITIERVIGAGEFGEVCS----GRLKlpGKRELPVAIKTLKVGYTEKQRRDFLGEASIMG 661
Cdd:cd05104   16 YVYIDPTQLPYDHKWEFPRDRLRFGKTLGAGAFGKVVEatayGLAK--ADSAMTVAVKMLKPSAHSTEREALMSELKVLS 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 662 QF-DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFL------------------------------------------- 697
Cdd:cd05104   94 YLgNHINIVNLLGACTVGGPTLVITEYCCYGDLLNFLrrkrdsficpkfedlaeaalyrnllhqremacdslneymdmkp 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 698 -------KKND-------GQFT-----------------VIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVC 746
Cdd:cd05104  174 svsyvvpTKADkrrgvrsGSYVdqdvtseileedelaldTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRIT 253
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 747 KVSDFGLSRVLEDDpeAAYTTRG-GKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEM-TNQDVIKAVE 824
Cdd:cd05104  254 KICDFGLARDIRND--SNYVVKGnARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMpVDSKFYKMIK 331
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 974005246 825 EGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd05104  332 EGYRMDSPEFAPSEMYDIMRSCWDADPLKRPTFKQIVQLIEQQL 375
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
613-867 5.33e-39

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 146.26  E-value: 5.33e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPgkreLPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14066    1 IGSGGFGTVYKGVLENG----TVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDMGY---VHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd14066   77 LEDRLHCHKGSppLPWPQRLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 --RGGkipIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY----WEMTNQDVIKAVEEGYR------------- 828
Cdd:cd14066  157 avKGT---IGYLAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAVdenrENASRKDLVEWVESKGKeeledildkrlvd 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 829 -LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14066  233 dDGVEEEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
613-867 6.71e-39

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 146.11  E-value: 6.71e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVcsgrLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14154    1 LGKGFFGQA----IKVTHRETGEVMVMKELIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE------AAYT 766
Cdd:cd14154   77 LKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLpsgnmsPSET 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPIR-----------WTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDC 835
Cdd:cd14154  157 LRHLKSPDRkkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEIIGRVEADPDYLPRTKDFGLNVDSFREKFCAGC 236
                        250       260       270
                 ....*....|....*....|....*....|..
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14154  237 PPPFFKLAFLCCDLDPEKRPPFETLEEWLEAL 268
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
613-857 2.08e-38

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 144.13  E-value: 2.08e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYT-EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd13978    1 LGSGGFGTVSKARHVSWF---GMVAIKCLHSSPNcIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDM--GYVHRDLAARNILINSNLVCKVSDFGLSRV----LEDDPEAAY 765
Cdd:cd13978   78 SLKSLLEREIQDVPWSLRFRIIHEIALGMNFLHNMdpPLLHHDLKPENILLDNHFHVKISDFGLSKLgmksISANRRRGT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKipIRWTAPEAI--AFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKA-VEEGYR-------LPSPMDC 835
Cdd:cd13978  158 ENLGGT--PIYMAPEAFddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLIMQiVSKGDRpslddigRLKQIEN 234
                        250       260
                 ....*....|....*....|..
gi 974005246 836 PAALYQLMLDCWQKERNSRPKF 857
Cdd:cd13978  235 VQELISLMIRCWDGNPDARPTF 256
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
608-855 2.16e-38

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 150.16  E-value: 2.16e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYT--EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:COG0515   10 RILRLLGRGGMGVVYLARDLRLGR---PVALKVLRPELAadPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:COG0515   87 EYVEGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQT 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLPSP---MDCPAALYQL 842
Cdd:COG0515  166 GTVVGTPG--YMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPPPSelrPDLPPALDAI 242
                        250
                 ....*....|...
gi 974005246 843 MLDCWQKERNSRP 855
Cdd:COG0515  243 VLRALAKDPEERY 255
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
608-855 7.40e-38

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 142.34  E-value: 7.40e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgYTEKQRRDFLG-EASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05122    3 EILEKIGKGGFGVVYKARHKKTGQI---VAIKKIN--LESKEKKESILnEIAILKKCKHPNIVKYYGSYLKKDELWIVME 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAayT 766
Cdd:cd05122   78 FCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTR--N 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIK--AVEEGYRLPSPMDCPAALYQLML 844
Cdd:cd05122  156 TFVGTPY--WMAPEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSELPPMKALFliATNGPPGLRNPKKWSKEFKDFLK 232
                        250
                 ....*....|.
gi 974005246 845 DCWQKERNSRP 855
Cdd:cd05122  233 KCLQKDPEKRP 243
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
613-865 3.41e-37

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 139.94  E-value: 3.41e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLklpgkRELPVAIKtlKVgytekqrRDfLGEASI--MGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd14059    1 LGSGAQGAVFLGKF-----RGEEVAVK--KV-------RD-EKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPY 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKknDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpEAAYTTRG 769
Cdd:cd14059   66 GQLYEVLR--AGReITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSE--KSTKMSFA 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV-EEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd14059  142 GTVA--WMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCWN 218
                        250
                 ....*....|....*..
gi 974005246 849 KERNSRPKFDEIVNMLD 865
Cdd:cd14059  219 SKPRNRPSFRQILMHLD 235
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
611-859 3.44e-37

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 140.73  E-value: 3.44e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd06606    6 ELLGKGSFGSVYLALNLDTGEL---MAVKEVELSGDSEEELEALeREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVP 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNdGQF--TVIQLVgmLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD--PEAAY 765
Cdd:cd06606   83 GGSLASLLKKF-GKLpePVVRKY--TRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIatGEGTK 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQ-DVIKAVEEGYRLPS-PMDCPAALYQLM 843
Cdd:cd06606  160 SLRG---TPYWMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELGNPvAALFKIGSSGEPPPiPEHLSEEAKDFL 235
                        250
                 ....*....|....*.
gi 974005246 844 LDCWQKERNSRPKFDE 859
Cdd:cd06606  236 RKCLQRDPKKRPTADE 251
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
601-867 2.39e-36

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 139.01  E-value: 2.39e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVcsgrlkLPGKRELPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSK 679
Cdd:cd14149    8 EIEASEVMLSTRIGSGSFGTV------YKGKWHGDVAVKILKVvDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 pVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlED 759
Cdd:cd14149   82 -LAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATV-KS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DPEAAYTTRGGKIPIRWTAPEAIAFRK---FTSASDVWSYGIVMWEVVSyGERPYWEMTNQD-VIKAVEEGYRLPSP--- 832
Cdd:cd14149  160 RWSGSQQVEQPTGSILWMAPEVIRMQDnnpFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqIIFMVGRGYASPDLskl 238
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 974005246 833 -MDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14149  239 yKNCPKAMKRLVADCIKKVKEERPLFPQILSSIELL 274
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
601-870 8.69e-36

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 137.11  E-value: 8.69e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVcsgrlkLPGKRELPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSK 679
Cdd:cd14151    4 EIPDGQITVGQRIGSGSFGTV------YKGKWHGDVAVKMLNVtAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 pVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlED 759
Cdd:cd14151   78 -LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV-KS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DPEAAYTTRGGKIPIRWTAPEAIAFRK---FTSASDVWSYGIVMWEVVSyGERPYWEMTNQD-VIKAVEEGYRLPS---- 831
Cdd:cd14151  156 RWSGSHQFEQLSGSILWMAPEVIRMQDknpYSFQSDVYAFGIVLYELMT-GQLPYSNINNRDqIIFMVGRGYLSPDlskv 234
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 832 PMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRN 870
Cdd:cd14151  235 RSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS 273
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
607-869 1.55e-35

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 135.91  E-value: 1.55e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVcsgrlkLPGKRELPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKpVMIVT 685
Cdd:cd14150    2 VSMLKRIGTGSFGTV------FRGKWHGDVAVKILKVTEpTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPN-FAIIT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAY 765
Cdd:cd14150   75 QWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATV-KTRWSGSQ 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPIRWTAPEAIAFRK---FTSASDVWSYGIVMWEVVSyGERPYWEMTNQD-VIKAVEEGYRLPS----PMDCPA 837
Cdd:cd14150  154 QVEQPSGSILWMAPEVIRMQDtnpYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDqIIFMVGRGYLSPDlsklSSNCPK 232
                        250       260       270
                 ....*....|....*....|....*....|..
gi 974005246 838 ALYQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd14150  233 AMKRLLIDCLKFKREERPLFPQILVSIELLQR 264
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
601-867 1.99e-35

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 135.94  E-value: 1.99e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 601 EIEASCITIERVIGAGEFGEVCSGrlkLPGKRElpVAIKTLK------VGYTEKQRRDflgEASIMGQFDHPNIIHLEGV 674
Cdd:cd14145    2 EIDFSELVLEEIIGIGGFGKVYRA---IWIGDE--VAVKAARhdpdedISQTIENVRQ---EAKLFAMLKHPNIIALRGV 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 675 VTKSKPVMIVTEYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYV---HRDLAARNILIN--------SN 743
Cdd:cd14145   74 CLKEPNLCLVMEFARGGPLNRVLSGK--RIPPDILVNWAVQIARGMNYLHCEAIVpviHRDLKSSNILILekvengdlSN 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 744 LVCKVSDFGLSRvleddpEAAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKA 822
Cdd:cd14145  152 KILKITDFGLAR------EWHRTTKmSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYG 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 823 VE-EGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFdeiVNMLDKL 867
Cdd:cd14145  225 VAmNKLSLPIPSTCPEPFARLMEDCWNPDPHSRPPF---TNILDQL 267
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
612-867 3.15e-35

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 135.11  E-value: 3.15e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLklpgkRELPVAIKTLK------VGYTEKQRRDflgEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14148    1 IIGVGGFGKVYKGLW-----RGEEVAVKAARqdpdedIAVTAENVRQ---EARLFWMLQHPNIIALRGVCLNPPHLCLVM 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTViqLVGMLRGISAGMKYLSDMGYV---HRDLAARNILI-----NSNL---VCKVSDFGLS 754
Cdd:cd14148   73 EYARGGALNRALAGKKVPPHV--LVNWAVQIARGMNYLHNEAIVpiiHRDLKSSNILIlepieNDDLsgkTLKITDFGLA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 755 RvleddpEAAYTTR-GGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVE-EGYRLPSP 832
Cdd:cd14148  151 R------EWHKTTKmSAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAmNKLTLPIP 223
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 974005246 833 MDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14148  224 STCPEPFARLLEECWDPDPHGRPDFGSILKRLEDI 258
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
613-855 5.04e-35

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 134.27  E-value: 5.04e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06627    8 IGRGAFGSVYKGLNLNTG---EFVAIKQISLeKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQF----TVIQLVGMLRgisaGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL---EDDPEAA 764
Cdd:cd06627   85 SLASIIKKF-GKFpeslVAVYIYQVLE----GLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLnevEKDENSV 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTrggkiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTnqdvikAVEEGYRL------PSPMDCPAA 838
Cdd:cd06627  160 VGT-----P-YWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYYDLQ------PMAALFRIvqddhpPLPENISPE 226
                        250
                 ....*....|....*..
gi 974005246 839 LYQLMLDCWQKERNSRP 855
Cdd:cd06627  227 LRDFLLQCFQKDPTLRP 243
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
614-867 2.31e-34

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 132.00  E-value: 2.31e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 614 GAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKqrrdflgEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSL 693
Cdd:cd14060    2 GGGSFGSVYRAIWVSQDKE---VAVK--KLLKIEK-------EAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSL 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 694 DTFLKKNDGQ-FTVIQLVGMLRGISAGMKYL---SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddpEAAYTTRG 769
Cdd:cd14060   70 FDYLNSNESEeMDMDQIMTWATDIAKGMHYLhmeAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHS---HTTHMSLV 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVI-KAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd14060  147 GTFP--WMAPEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQVAwLVVEKNERPTIPSSCPRSFAELMRRCWE 223
                        250
                 ....*....|....*....
gi 974005246 849 KERNSRPKFDEIVNMLDKL 867
Cdd:cd14060  224 ADVKERPSFKQIIGILESM 242
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
608-863 3.23e-34

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 131.82  E-value: 3.23e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKpVMIVT 685
Cdd:cd08215    3 EKIRVIGKGSFGSAYLVRRKSDGK---LYVLKEIDLSNmSEKEREEALNEVKLLSKLKHPNIVkYYESFEENGK-LCIVM 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKK---NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd08215   79 EYADGGDLAQKIKKqkkKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLESTTD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGgkipirwT----APEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwEMTNQD--VIKAVEEGYR-LPSPMDc 835
Cdd:cd08215  159 LAKTVVG-------TpyylSPELCENKPYNYKSDIWALGCVLYELCT-LKHPF-EANNLPalVYKIVKGQYPpIPSQYS- 228
                        250       260
                 ....*....|....*....|....*...
gi 974005246 836 pAALYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd08215  229 -SELRDLVNSMLQKDPEKRPSANEILSS 255
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
608-862 3.83e-34

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 131.49  E-value: 3.83e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIK-----TLKVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14003    3 ELGKTLGEGSFGKVKLARHKLTGEK---VAIKiidksKLKEEIEEKIKR----EIEIMKLLNHPNIIKLYEVIETENKIY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNDG------QFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV 756
Cdd:cd14003   76 LVMEYASGGELFDYIVNNGRlsedeaRRFFQQLI-------SAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNE 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDPEAayTTRGGKIPirWTAPEAIAFRKF-TSASDVWSYGIVMWEVVsYGERPyWEMTNQDVI--KAVEEGYRLPS-- 831
Cdd:cd14003  149 FRGGSLL--KTFCGTPA--YAAPEVLLGRKYdGPKADVWSLGVILYAML-TGYLP-FDDDNDSKLfrKILKGKYPIPShl 222
                        250       260       270
                 ....*....|....*....|....*....|.
gi 974005246 832 PMDCPAALYQLMldcwQKERNSRPKFDEIVN 862
Cdd:cd14003  223 SPDARDLIRRML----VVDPSKRITIEEILN 249
Pkinase pfam00069
Protein kinase domain;
608-863 5.42e-34

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 130.06  E-value: 5.42e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:pfam00069   2 EVLRKLGSGSFGTVYKAKHRDTGK---IVAIKKIkKEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  687 YMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMgyvhrdlaarnilinSNLVCkvsdfglsrvleddpeaayt 766
Cdd:pfam00069  79 YVEGGSLFDLLSEK-GAFSEREAKFIMKQILEGLESGSSL---------------TTFVG-------------------- 122
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  767 TRGgkipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW-EMTNQDVIKAVEEGYRLPS-PMDCPAALYQLML 844
Cdd:pfam00069 123 TPW------YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPgINGNEIYELIIDQPYAFPElPSNLSEEAKDLLK 195
                         250
                  ....*....|....*....
gi 974005246  845 DCWQKERNSRPKFDEIVNM 863
Cdd:pfam00069 196 KLLKKDPSKRLTATQALQH 214
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
898-958 6.05e-34

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 124.26  E-value: 6.05e-34
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEM 958
Cdd:cd09488    1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
612-864 1.41e-33

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 130.54  E-value: 1.41e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLpgkRElpVAIKTLK-------VGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd14146    1 IIGVGGFGKVYRATWKG---QE--VAVKAARqdpdediKATAESVRQ----EAKLFSMLRHPNIIKLEGVCLEEPNLCLV 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNDGQFTVIQ--------LVGMLRGISAGMKYLSDMGYV---HRDLAARNIL----INSNLVC--- 746
Cdd:cd14146   72 MEFARGGTLNRALAAANAAPGPRRarripphiLVNWAVQIARGMLYLHEEAVVpilHRDLKSSNILllekIEHDDICnkt 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 747 -KVSDFGLSRvleddpEAAYTTRGGKI-PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVE 824
Cdd:cd14146  152 lKITDFGLAR------EWHRTTKMSAAgTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVA 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 974005246 825 -EGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd14146  225 vNKLTLPIPSTCPEPFAKLMKECWEQDPHIRPSFALILEQL 265
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
613-870 2.33e-33

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 129.69  E-value: 2.33e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVcsgrLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14221    1 LGKGCFGQA----IKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI 772
Cdd:cd14221   77 LRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKK 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 773 PIR-----------WTAPEAIAFRKFTSASDVWSYGIVMWEVVS-YGERPYWEMTNQDV---IKAVEEGYrlpSPMDCPA 837
Cdd:cd14221  157 PDRkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEIIGrVNADPDYLPRTMDFglnVRGFLDRY---CPPNCPP 233
                        250       260       270
                 ....*....|....*....|....*....|...
gi 974005246 838 ALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRN 870
Cdd:cd14221  234 SFFPIAVLCCDLDPEKRPSFSKLEHWLETLRMH 266
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
613-864 1.63e-32

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 126.84  E-value: 1.63e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelpvaIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14065    1 LGKGFFGEVYKVTHRETGK------VMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRVLEDDPEA------ 763
Cdd:cd14065   75 LEELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreaNRGRNAVVADFGLAREMPDEKTKkpdrkk 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY-----GERPYWEMTNQDVikaveEGYRLPSPMDCPAA 838
Cdd:cd14065  155 RLTVVGSPY---WMAPEMLRGESYDEKVDVFSFGIVLCEIIGRvpadpDYLPRTMDFGLDV-----RAFRTLYVPDCPPS 226
                        250       260
                 ....*....|....*....|....*.
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd14065  227 FLPLAIRCCQLDPEKRPSFVELEHHL 252
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
613-867 1.10e-31

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 125.06  E-value: 1.10e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14222    1 LGKGFFGQAIKVTHKATGK----VMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR-VLEDDPEAA------- 764
Cdd:cd14222   77 LKDFLRADD-PFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRlIVEEKKKPPpdkpttk 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 ------------YTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVS--YGE--------------RPYWEmtn 816
Cdd:cd14222  156 krtlrkndrkkrYTVVGNPY---WMAPEMLNGKSYDEKVDIFSFGIVLCEIIGqvYADpdclprtldfglnvRLFWE--- 229
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 817 qdviKAVeegyrlpsPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14222  230 ----KFV--------PKDCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEAL 268
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
613-860 1.80e-31

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 124.68  E-value: 1.80e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14206    5 IGNGWFGKVILGEI-FSDYTPAQVVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQLGD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFL---KKNDG--------QFTVIQLVGMlrGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDP 761
Cdd:cd14206   84 LKRYLraqRKADGmtpdlptrDLRTLQRMAY--EITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSH--NNYK 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGK-IPIRWTAPE-------AIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAV--EEGYRLPS 831
Cdd:cd14206  160 EDYYLTPDRLwIPLRWVAPElldelhgNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVvrEQQMKLAK 239
                        250       260       270
                 ....*....|....*....|....*....|..
gi 974005246 832 P-MDCPAA--LYQLMLDCWQKErNSRPKFDEI 860
Cdd:cd14206  240 PrLKLPYAdyWYEIMQSCWLPP-SQRPSVEEL 270
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
607-867 3.27e-31

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 123.60  E-value: 3.27e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpgkRELpVAIKTLK------VGYTEKQRRDflgEASIMGQFDHPNIIHLEGVVTKSKP 680
Cdd:cd14147    5 LRLEEVIGIGGFGKVYRGSWR----GEL-VAVKAARqdpdedISVTAESVRQ---EARLFAMLAHPNIIALKAVCLEEPN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNDGQFTViqLVGMLRGISAGMKYLSDMGYV---HRDLAARNILINSNLV--------CKVS 749
Cdd:cd14147   77 LCLVMEYAAGGPLSRALAGRRVPPHV--LVNWAVQIARGMHYLHCEALVpviHRDLKSNNILLLQPIEnddmehktLKIT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 750 DFGLSRvlEDDPEAAYTTRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVE-EGYR 828
Cdd:cd14147  155 DFGLAR--EWHKTTQMSAAG---TYAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAvNKLT 228
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 829 LPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14147  229 LPIPSTCPEPFAQLMADCWAQDPHRRPDFASILQQLEAL 267
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
613-865 4.54e-31

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 122.64  E-value: 4.54e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLklpgkRELPVAIKTLKV-GYTEKQRRD-FLGEASIMGQFDHPNIIHLEGV-VTKSKPVMIVTEYME 689
Cdd:cd14064    1 IGSGSFGKVYKGRC-----RNKIVAIKRYRAnTYCSKSDVDmFCREVSILCRLNHPCVIQFVGAcLDDPSQFAIVTQYVS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLkknDGQFTVIQLVGMLR---GISAGMKYLSDMGY--VHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAA 764
Cdd:cd14064   76 GGSLFSLL---HEQKRVIDLQSKLIiavDVAKGMEYLHNLTQpiIHRDLNSHNILLYEDGHAVVADFGESRFLQSLDEDN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGKipIRWTAPEAIA-FRKFTSASDVWSYGIVMWEVVSyGERPYWEMtnQDVIKAVEEGY---RLPSPMDCPAALY 840
Cdd:cd14064  153 MTKQPGN--LRWMAPEVFTqCTRYSIKADVFSYALCLWELLT-GEIPFAHL--KPAAAAADMAYhhiRPPIGYSIPKPIS 227
                        250       260
                 ....*....|....*....|....*
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd14064  228 SLLMRGWNAEPESRPSFVEIVALLE 252
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
607-864 3.89e-30

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 120.28  E-value: 3.89e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVgyTEKQRRD----FLGEASIMGQFDHPNIIHLEGVvTKSKPVM 682
Cdd:cd05037    1 ITFHEHLGQGTFTNIYDGILREVGDGRVQEVEVLLKV--LDSDHRDisesFFETASLMSQISHKHLVKLYGV-CVADENI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI------NSNLVCKVSDFGLSRV 756
Cdd:cd05037   78 MVQEYVRYGPLDKYLRRMGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPIT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDPEaayttRGGKIPirWTAPEAI--AFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPmD 834
Cdd:cd05037  158 VLSREE-----RVDRIP--WIAPECLrnLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAP-D 229
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 835 CpAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05037  230 C-AELAELIMQCWTYEPTKRPSFRAILRDL 258
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
613-864 5.06e-30

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 120.36  E-value: 5.06e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05086    5 IGNGWFGKVLLGEI-YTGTSVARVVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCDLGD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKND----GQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL--SRVLEDDPEaayT 766
Cdd:cd05086   84 LKTYLANQQeklrGDSQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIgfSRYKEDYIE---T 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPIRWTAPEAIAFRK-------FTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAV--EEGYRLPSP-MDCP 836
Cdd:cd05086  161 DDKKYAPLRWTAPELVTSFQdgllaaeQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFKPhLEQP 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 837 AA--LYQLMLDCWQKErNSRPKFDEIVNML 864
Cdd:cd05086  241 YSdrWYEVLQFCWLSP-EKRPTAEEVHRLL 269
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
613-860 7.41e-30

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 119.61  E-value: 7.41e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05042    3 IGNGWFGKVLLGEI-YSGTSVAQVVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDLGD 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLK------KNDGQFTVIQLVGMlrGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL--SRVLEDdpeaA 764
Cdd:cd05042   82 LKAYLRsereheRGDSDTRTLQRMAC--EVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLahSRYKED----Y 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGK-IPIRWTAPEAIA-------FRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAV--EEGYRLPSP-M 833
Cdd:cd05042  156 IETDDKLwFPLRWTAPELVTefhdrllVVDQTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPqL 235
                        250       260
                 ....*....|....*....|....*....
gi 974005246 834 DCPAA--LYQLMLDCWQKERNsRPKFDEI 860
Cdd:cd05042  236 ELPYSdrWYEVLQFCWLSPEQ-RPAAEDV 263
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
608-832 9.09e-30

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 119.12  E-value: 9.09e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05117    3 ELGKVLGRGSFGVVRLAVHKKTGEE---YAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVME 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS---NLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd05117   80 LCTGGELFDRIVKK-GSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASkdpDSPIKIIDFGLAKIFEEGEKL 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 764 ayTTRGGkipirwT----APEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd05117  159 --KTVCG------TpyyvAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKILKGkYSFDSP 223
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
613-869 1.21e-28

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 115.65  E-value: 1.21e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelpvaIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14155    1 IGSGFFSEVYKVRHRTSGQ------VMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGN 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRVLEDdpeaaYTTRG 769
Cdd:cd14155   75 LEQLLDSNE-PLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAEKIPD-----YSDGK 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPI----RWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGErpywemTNQDVIKAVEE------GYRLPSPmDCPAAL 839
Cdd:cd14155  149 EKLAVvgspYWMAPEVLRGEPYNEKADVFSYGIILCEIIARIQ------ADPDYLPRTEDfgldydAFQHMVG-DCPPDF 221
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd14155  222 LQLAFNCCNMDPKSRPSFHDIVKTLEEILE 251
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
613-860 6.30e-28

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 114.19  E-value: 6.30e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRR-------------DFLGEASIMGQFDHPNIIHLEGVVT--K 677
Cdd:cd14008    1 LGRGSFGKVKLALDTETGQL---YAIKIFNKSRLRKRREgkndrgkiknaldDVRREIAIMKKLDHPNIVRLYEVIDdpE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 678 SKPVMIVTEYMENGSLDTFL-KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV 756
Cdd:cd14008   78 SDKLYLVLEYCEGGPVMELDsGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEM 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDPEAAYTTRGgkipirwT----APEAIAFRKFT---SASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAV-EEGYR 828
Cdd:cd14008  158 FEDGNDTLQKTAG-------TpaflAPELCDGDSKTysgKAADIWALGVTLYCLV-FGRLPFNGDNILELYEAIqNQNDE 229
                        250       260       270
                 ....*....|....*....|....*....|..
gi 974005246 829 LPSPMDCPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd14008  230 FPIPPELSPELKDLLRRMLEKDPEKRITLKEI 261
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
613-862 1.02e-27

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 113.09  E-value: 1.02e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14009    1 IGRGSFATVWKGRHKQTG---EVVAIKEISRkKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVgMLRGISAGMKYLSDMGYVHRDLAARNILINS---NLVCKVSDFGLSRVLEDDPEAAyTTR 768
Cdd:cd14009   78 DLSQYIRKRGRLPEAVARH-FMQQLASGLKFLRSKNIIHRDLKPQNLLLSTsgdDPVLKIADFGFARSLQPASMAE-TLC 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGkiPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDV---IKAVEEGYRLPSPM----DCPAALYQ 841
Cdd:cd14009  156 GS--PL-YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGSNHVQLlrnIERSDAVIPFPIAAqlspDCKDLLRR 231
                        250       260
                 ....*....|....*....|...
gi 974005246 842 LMldcwqkERN--SRPKFDEIVN 862
Cdd:cd14009  232 LL------RRDpaERISFEEFFA 248
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
608-804 1.20e-27

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 114.93  E-value: 1.20e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRD---FLGEASIMGQFDHPNIIHLEGVVTKSKP---- 680
Cdd:cd07834    3 ELLKPIGSGAYGVVCSAYDKRTGRK---VAIK--KISNVFDDLIDakrILREIKILRHLKHENIIGLLDILRPPSPeefn 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 -VMIVTEYMEngsldTFLKK---------ND-GQFTVIQlvgMLRGIsagmKYLSDMGYVHRDLAARNILINSNLVCKVS 749
Cdd:cd07834   78 dVYIVTELME-----TDLHKvikspqpltDDhIQYFLYQ---ILRGL----KYLHSAGVIHRDLKPSNILVNSNCDLKIC 145
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 750 DFGLSRVLEDDPEAAYTTrgGKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07834  146 DFGLARGVDPDEDKGFLT--EYVVTRWyRAPELLlSSKKYTKAIDIWSVGCIFAELL 200
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
612-873 1.24e-27

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 113.07  E-value: 1.24e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06623    8 VLGQGSSGVVYKVRHKPTGK---IYALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTVIQLVGMLRGISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGg 770
Cdd:cd06623   85 SLADLLKKV-GKIPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENTLDQCNTFVG- 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 kipirwTA----PEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY--------WEMtnqdvIKAV--EEGYRLPsPMDCP 836
Cdd:cd06623  163 ------TVtymsPERIQGESYSYAADIWSLGLTLLECAL-GKFPFlppgqpsfFEL-----MQAIcdGPPPSLP-AEEFS 229
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEivnMLD-KLIRNPSS 873
Cdd:cd06623  230 PEFRDFISACLQKDPKKRPSAAE---LLQhPFIKKADN 264
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
636-867 1.47e-27

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 112.87  E-value: 1.47e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKtlKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRG 715
Cdd:cd13992   28 VAIK--HITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKMDWMFKSSFIKD 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 716 ISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTAPEAI----AFRKFTSA 790
Cdd:cd13992  106 IVKGMNYLhSSSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDEDAQHKKLLWTAPELLrgslLEVRGTQK 185
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 791 SDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMD------CPAALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd13992  186 GDVYSFAIILYEILFRSDPFALEREVAIVEKVISGGNKPFRPELavlldeFPPRLVLLVKQCWAENPEKRPSFKQIKKTL 265

                 ...
gi 974005246 865 DKL 867
Cdd:cd13992  266 TEN 268
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
613-860 2.04e-27

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 112.77  E-value: 2.04e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd05087    5 IGHGWFGKVFLGEVN-SGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCPLGD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTV----IQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV-LEDDpeaAYTT 767
Cdd:cd05087   84 LKGYLRSCRAAESMapdpLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCkYKED---YFVT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGK-IPIRWTAPEAI-------AFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAV--EEGYRLPSPMdCPA 837
Cdd:cd05087  161 ADQLwVPLRWIAPELVdevhgnlLVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPQ-LKL 239
                        250       260
                 ....*....|....*....|....*...
gi 974005246 838 AL----YQLMLDCW-QKERnsRPKFDEI 860
Cdd:cd05087  240 SLaerwYEVMQFCWlQPEQ--RPTAEEV 265
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
612-815 1.46e-26

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 109.61  E-value: 1.46e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgytEKQRRDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd06614    7 KIGEGASGEVYKATDRATGKE---VAIKKMRL---RKQNKELIiNEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSrvleddpeAAYTTRGG 770
Cdd:cd06614   81 GSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFA--------AQLTKEKS 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 771 KipiR--------WTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMT 815
Cdd:cd06614  153 K---RnsvvgtpyWMAPEVIKRKDYGPKVDIWSLGIMCIEMAE-GEPPYLEEP 201
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
507-604 1.67e-26

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 103.45  E-value: 1.67e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  507 IAVSVTVGVILLAVVIGVLLSGSCCecgcgrasslcavahpsliwrCGYSKAKQDPEEEKMHFhnghiKLPGVRTYIDPH 586
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRC---------------------CGRKKSQDDDEEEFHQY-----KPPGRKTYIDPH 54
                          90
                  ....*....|....*...
gi 974005246  587 TYEDPNQAVHEFAKEIEA 604
Cdd:pfam14575  55 TYEDPNQAVLEFAKEIDA 72
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
611-869 1.86e-26

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 110.39  E-value: 1.86e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRlklPGKRELPVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14026    3 RYLSRGAFGTVSRAR---HADWRVTVAIKCLKLDspVGDSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVTEYM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQFTVIQLV--GMLRGISAGMKYLSDMG--YVHRDLAARNILINSNLVCKVSDFGLS--RVLEDDPE 762
Cdd:cd14026   80 TNGSLNELLHEKDIYPDVAWPLrlRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSkwRQLSISQS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTT--RGGKIPirWTAPEAIAFRKFTSAS---DVWSYGIVMWEVVSYgERPYWEMTNQ-DVIKAVEEGYRLPS----- 831
Cdd:cd14026  160 RSSKSapEGGTII--YMPPEEYEPSQKRRASvkhDIYSYAIIMWEVLSR-KIPFEEVTNPlQIMYSVSQGHRPDTgedsl 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 832 PMDCP--AALYQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd14026  237 PVDIPhrATLINLIESGWAQNPDERPSFLKCLIELEPVLR 276
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
613-805 7.09e-26

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 108.81  E-value: 7.09e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgyTEKQRRDF----LGEASIMGQFDHPNIIHLEGVVTKSKP------VM 682
Cdd:cd07840    7 IGEGTYGQVYKARNKKTGEL---VALKKIR---MENEKEGFpitaIREIKLLQKLDHPNVVRLKEIVTSKGSakykgsIY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd07840   81 MVFEYMDH-DLTGLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKENN 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 974005246 763 AAYTTRggKIPIRWTAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07840  160 ADYTNR--VITLWYRPPELLlGATRYGPEVDMWSVGCILAELFT 201
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
608-862 8.61e-26

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 107.65  E-value: 8.61e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRELpVAIKTLKvgyTEKQRRDFLG-----EASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14080    3 RLGKTIGEGSYSKVKLAEYTKSGLKEK-VACKIID---KKKAPKDFLEkflprELEILRKLRHPNIIQVYSIFERGSKVF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd14080   79 IFMEYAEHGDLLEYIQKR-GALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDDG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 ----------AAYttrggkipirwTAPEAIAFRKFTS-ASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKA-VEEGYRLP 830
Cdd:cd14080  158 dvlsktfcgsAAY-----------AAPEILQGIPYDPkKYDIWSLGVILYIMLC-GSMPFDDSNIKKMLKDqQNRKVRFP 225
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 974005246 831 SPM-----DCPAALYQLMldcwQKERNSRPKFDEIVN 862
Cdd:cd14080  226 SSVkklspECKDLIDQLL----EPDPTKRATIEEILN 258
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
613-873 1.07e-25

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 107.11  E-value: 1.07e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKpVMIVTEYMEN 690
Cdd:cd08529    8 LGKGSFGVVYKVVRKVDGR---VYALKQIDIsRMSRKMREEAIDEARVLSKLNSPYVIkYYDSFVDKGK-LNIVMEYAEN 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRG 769
Cdd:cd08529   84 GDLHSLIKSQRGRpLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNFAQTIVG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 gkIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwEMTNQD-VIKAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd08529  164 --TPY-YLSPELCEDKPYNEKSDVWALGCVLYELCT-GKHPF-EAQNQGaLILKIVRGKYPPISASYSQDLSQLIDSCLT 238
                        250       260
                 ....*....|....*....|....*
gi 974005246 849 KERNSRPKFDEivnmldkLIRNPSS 873
Cdd:cd08529  239 KDYRQRPDTTE-------LLRNPSL 256
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
609-862 1.10e-25

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 107.51  E-value: 1.10e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEV--CSGrLKLPGKRELPVaIKTLKVG-YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd08222    4 VVRKLGSGNFGTVylVSD-LKATADEELKV-LKEISVGeLQPDETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVT 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFL---KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVcKVSDFGLSRVLEDDPE 762
Cdd:cd08222   82 EYCEGGDLDDKIseyKKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNVI-KVGDFGISRILMGTSD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGyRLPSPMDC-PAALYQ 841
Cdd:cd08222  161 LATTFTG--TP-YYMSPEVLKHEGYNSKSDIWSLGCILYEMCCL-KHAFDGQNLLSVMYKIVEG-ETPSLPDKySKELNA 235
                        250       260
                 ....*....|....*....|.
gi 974005246 842 LMLDCWQKERNSRPKFDEIVN 862
Cdd:cd08222  236 IYSRMLNKDPALRPSAAEILK 256
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
609-814 1.38e-25

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 106.97  E-value: 1.38e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVgytEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd06612    7 ILEKLGEGSYGSVYKAIHKETGQ---VVAIKVVPV---EEDLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpeaAYTTR 768
Cdd:cd06612   81 GAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTD----TMAKR 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 769 GGKI--PIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06612  157 NTVIgtPF-WMAPEVIQEIGYNNKADIWSLGITAIEMAE-GKPPYSDI 202
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
611-872 3.11e-25

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 106.42  E-value: 3.11e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpgKRELPVAIK---TLKVgyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVtkSKPVMIVTEY 687
Cdd:cd14025    2 EKVGSGGFGQVYKVRHK---HWKTWLAIKcppSLHV--DDSERMELLEEAKKMEMAKFRHILPVYGIC--SEPVGLVMEY 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKN----DGQFTVIQlvgmlrGISAGMKYLSDMG--YVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd14025   75 METGSLEKLLASEplpwELRFRIIH------ETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKWNGLSH 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAI--AFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTN-QDVIKAVEEGYRlPS------- 831
Cdd:cd14025  149 SHDLSRDGLRGTIAYLPPERFkeKNRCPDTKHDVYSFAIVIWGILTQ-KKPFAGENNiLHIMVKVVKGHR-PSlspiprq 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 974005246 832 -PMDCpAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRNPS 872
Cdd:cd14025  227 rPSEC-QQMICLMKRCWDQDPRKRPTFQDITSETENLLSLLE 267
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
611-861 6.30e-25

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 105.31  E-value: 6.30e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGkrELpVAIKTLKV----GYTEKQRRDFL----GEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd06628    6 ALIGSGSFGSVYLGMNASSG--EL-MAVKQVELpsvsAENKDRKKSMLdalqREIALLRELQHENIVQYLGSSSDANHLN 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpe 762
Cdd:cd06628   83 IFLEYVPGGSVATLLN-NYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEAN-- 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKIP-----IRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLPSPMDCPA 837
Cdd:cd06628  160 SLSTKNNGARPslqgsVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISS 238
                        250       260
                 ....*....|....*....|....
gi 974005246 838 ALYQLMLDCWQKERNSRPKFDEIV 861
Cdd:cd06628  239 EARDFLEKTFEIDHNKRPTADELL 262
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
612-859 9.01e-25

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 105.09  E-value: 9.01e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14202    9 LIGHGAFAVVFKGRHK--EKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI--------NSNLVC-KVSDFGLSRVLEDDPE 762
Cdd:cd14202   87 DLADYLHTM-RTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLsysggrksNPNNIRiKIADFGFARYLQNNMM 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAyTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRL-PS-PMDCPAALY 840
Cdd:cd14202  166 AA-TLCGSPM---YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKSLsPNiPRETSSHLR 240
                        250
                 ....*....|....*....
gi 974005246 841 QLMLDCWQKERNSRPKFDE 859
Cdd:cd14202  241 QLLLGLLQRNQKDRMDFDE 259
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
608-814 9.75e-25

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 105.02  E-value: 9.75e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd06609    4 TLLERIGKGSFGEVYKGIDKRTNQ---VVAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd06609   81 CGGGSVLDLLKP--GPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNTF 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 768 RGgkIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06609  159 VG--TPF-WMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPLSDL 201
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
611-862 1.03e-24

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 104.56  E-value: 1.03e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL--KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14099    7 KFLGKGGFAKCYEVTDMSTGKV---YAGKVVpkSSLTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTR 768
Cdd:cd14099   84 SNGSLMELLKRR-KALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDGERKKTLC 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GgkipirwT----APEAIAFRKFTS-ASDVWSYGIVMWEVVsYGERPYwEMTNQDV----IKAVEegYRLPSPMDCPAAL 839
Cdd:cd14099  163 G-------TpnyiAPEVLEKKKGHSfEVDIWSLGVILYTLL-VGKPPF-ETSDVKEtykrIKKNE--YSFPSHLSISDEA 231
                        250       260
                 ....*....|....*....|...
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14099  232 KDLIRSMLQPDPTKRPSLDEILS 254
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
612-803 1.12e-24

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 105.52  E-value: 1.12e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgkrELPVAIKTlkvgYTEKQRRDFLGEASIMGQF--DHPNIIHL----EGVVTKSKP-VMIV 684
Cdd:cd14054    2 LIGQGRYGTVWKGSLD-----ERPVAVKV----FPARHRQNFQNEKDIYELPlmEHSNILRFigadERPTADGRMeYLLV 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNDGQFTviQLVGMLRGISAGMKYL-SDM--------GYVHRDLAARNILINSNLVCKVSDFGLSR 755
Cdd:cd14054   73 LEYAPKGSLCSYLRENTLDWM--SSCRMALSLTRGLAYLhTDLrrgdqykpAIAHRDLNSRNVLVKADGSCVICDFGLAM 150
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 756 VL----------EDDPEAAYTTRGgkiPIRWTAPE----AIAFRKFTSA---SDVWSYGIVMWEV 803
Cdd:cd14054  151 VLrgsslvrgrpGAAENASISEVG---TLRYMAPEvlegAVNLRDCESAlkqVDVYALGLVLWEI 212
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
613-865 1.19e-24

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 104.26  E-value: 1.19e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGK----RELPVAIKTL-KV--GYTEKqrrdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd05078    7 LGQGTFTKIFKGIRREVGDygqlHETEVLLKVLdKAhrNYSES----FFEAASMMSQLSHKHLVLNYGVCVCGDENILVQ 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-------NSNL-VCKVSDFGLSRVL 757
Cdd:cd05078   83 EYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrkTGNPpFIKLSDPGISITV 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 EddPEAAYTTRggkipIRWTAPEAIAF-RKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMdcP 836
Cdd:cd05078  163 L--PKDILLER-----IPWVPPECIENpKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPK--W 233
                        250       260
                 ....*....|....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd05078  234 TELANLINNCMDYEPDHRPSFRAIIRDLN 262
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
613-865 1.24e-24

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 104.50  E-value: 1.24e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpgkRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14664    1 IGRGGAGTVYKGVMP----NGTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLR---GISAGMKYL---SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd14664   77 LGELLHSRPESQPPLDWETRQRialGSARGLAYLhhdCSPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQD-------VIKAVEEG------------- 826
Cdd:cd14664  157 SVAGSYG--YIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFDEAFLDDgvdivdwVRGLLEEKkvealvdpdlqgv 233
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 827 YRLPSPMDcpaaLYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd14664  234 YKLEEVEQ----VFQVALLCTQSSPMERPTMREVVRMLE 268
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
615-862 1.58e-24

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 104.12  E-value: 1.58e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 615 AGEFGEVCSGRLKLPGKrelpVAIKTLKVGYTEKQRRD-FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSL 693
Cdd:cd14027    3 SGGFGKVSLCFHRTQGL----VVLKTVYTGPNCIEHNEaLLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 694 DTFLKKNDGQFTVIQLVgmLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL------SRVLEDDP------ 761
Cdd:cd14027   79 MHVLKKVSVPLSVKGRI--ILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLasfkmwSKLTKEEHneqrev 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKipIRWTAPEAI--AFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQD-VIKAVEEGYRlPS----PMD 834
Cdd:cd14027  157 DGTAKKNAGT--LYYMAPEHLndVNAKPTEKSDVYSFAIVLW-AIFANKEPYENAINEDqIIMCIKSGNR-PDvddiTEY 232
                        250       260
                 ....*....|....*....|....*...
gi 974005246 835 CPAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14027  233 CPREIIDLMKLCWEANPEARPTFPGIEE 260
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
613-804 1.64e-24

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 104.49  E-value: 1.64e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKqrrdflG-------EASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd07829    7 LGEGTYGVVYKAKDKKTGE---IVALKKIRLDNEEE------GipstalrEISLLKELKHPNIVKLLDVIHTENKLYLVF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEdDPEAAY 765
Cdd:cd07829   78 EYCDQ-DLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFG-IPLRTY 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 766 TTRggkIPIRW-TAPEaIAF--RKFTSASDVWSYGIVMWEVV 804
Cdd:cd07829  156 THE---VVTLWyRAPE-ILLgsKHYSTAVDIWSVGCIFAELI 193
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-961 3.23e-24

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 96.47  E-value: 3.23e-24
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQ 961
Cdd:cd09554    2 SCGSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
609-862 3.56e-24

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 102.55  E-value: 3.56e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIK-----TLKVGYTEKQ-RRdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14007    4 IGKPLGKGKFGNVYLAREKKSGFI---VALKvisksQLQKSGLEHQlRR----EIEIQSHLRHPNILRLYGYFEDKKRIY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd14007   77 LILEYAPNGELYKELKKQ-KRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHAPSNRR 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AayTTRGgkipirwT----APEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVEEG-YRLPSPMDCPA 837
Cdd:cd14007  156 K--TFCG-------TldylPPEMVEGKEYDYKVDIWSLGVLCYELL-VGKPPFESKSHQETYKRIQNVdIKFPSSVSPEA 225
                        250       260
                 ....*....|....*....|....*
gi 974005246 838 AlyQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14007  226 K--DLISKLLQKDPSKRLSLEQVLN 248
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
612-859 6.37e-24

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 102.46  E-value: 6.37e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRelpVAIKTLK-VGYTEKQRRDFLGEASIMgQFDHPNIIHL---EGVVTKSKPVMIVTEY 687
Cdd:cd13979   10 PLGSGGFGSVYKATYK--GET---VAVKIVRrRRKNRASRQSFWAELNAA-RLRHENIVRVlaaETGTDFASLGLIIMEY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd13979   84 CGNGTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGTPR 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwEMTNQDVIKAV---------------EEGYRLPSP 832
Cdd:cd13979  164 SHIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLT-RELPY-AGLRQHVLYAVvakdlrpdlsgledsEFGQRLRSL 241
                        250       260
                 ....*....|....*....|....*..
gi 974005246 833 MDCpaalyqlmldCWQKERNSRPKFDE 859
Cdd:cd13979  242 ISR----------CWSAQPAERPNADE 258
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
611-834 9.60e-24

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 101.56  E-value: 9.60e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIK-TLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14002    7 ELIGEGSFGKVYKGRRKYTGQV---VALKfIPKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQ 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 nGSL------DTFLKKNDGQFTVIQLVGMLRgisagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd14002   84 -GELfqiledDGTLPEEEVRSIAKQLVSALH-------YLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTLV 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 764 AYTTRGgkIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWemTN---QDVIKAVEEGYRLPSPMD 834
Cdd:cd14002  156 LTSIKG--TPL-YMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPFY--TNsiyQLVQMIVKDPVKWPSNMS 223
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
608-805 9.87e-24

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 101.16  E-value: 9.87e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKvGYTEKQRRDfLGEASIMGQF----DHPNIIHLEGVVT--KSKPV 681
Cdd:cd05118    2 EVLRKIGEGAFGTVWLARDKVTGEK---VAIKKIK-NDFRHPKAA-LREIKLLKHLndveGHPNIVKLLDVFEhrGGNHL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNL-VCKVSDFGLSRVLEDD 760
Cdd:cd05118   77 CLVFELMGM-NLYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSFTSP 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 761 PeaaYTTRGGKIPIRwtAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd05118  156 P---YTPYVATRWYR--APEVLlGAKPYGSSIDIWSLGCILAELLT 196
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
608-855 1.07e-23

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 102.23  E-value: 1.07e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEA-SIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd07830    2 KVIKQLGDGTFGSVYLARNKETGEL---VAIKKMKKKFYSWEECMNLREVkSLRKLNEHPNIVKLKEVFRENDELYFVFE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMEnGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPeaAY 765
Cdd:cd07830   79 YME-GNLYQLMKDRKGKpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSRP--PY 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRggkIPIRW-TAPEaIAFR--KFTSASDVWSYGIVMWEVVSYgeRPYWEMTNQ-DVI-KAVE-----------EGYRL 829
Cdd:cd07830  156 TDY---VSTRWyRAPE-ILLRstSYSSPVDIWALGCIMAELYTL--RPLFPGSSEiDQLyKICSvlgtptkqdwpEGYKL 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 974005246 830 ------------PSPMD-----CPAALYQLMLDCWQKERNSRP 855
Cdd:cd07830  230 asklgfrfpqfaPTSLHqlipnASPEAIDLIKDMLRWDPKKRP 272
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
611-863 1.07e-23

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 101.65  E-value: 1.07e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd06605    7 GELGEGNGGVVSKVRHRPSGQI---MAVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGqftvI---QLVGMLRGISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYT 766
Cdd:cd06605   84 GSLDKILKEVGR----IperILGKIAVAVVKGLIYLhEKHKIIHRDVKPSNILVNSRGQVKLCDFGVSGQLVDS--LAKT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEvVSYGERPY------WEMTNQDVIKAV--EEGYRLPSPMdCPAA 838
Cdd:cd06605  158 FVGTR---SYMAPERISGGKYTVKSDIWSLGLSLVE-LATGRFPYpppnakPSMMIFELLSYIvdEPPPLLPSGK-FSPD 232
                        250       260
                 ....*....|....*....|....*
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd06605  233 FQDFVSQCLQKDPTERPSYKELMEH 257
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
613-855 1.75e-23

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 101.30  E-value: 1.75e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFL---------GEASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd06629    9 IGKGTYGRVYLAMNATTGE---MLAVKQVELPKTSSDRADSRqktvvdalkSEIDTLKDLDHPNIVQYLGFEETEDYFSI 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKKNdGQFTViQLV-GMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED--D 760
Cdd:cd06629   86 FLEYVPGGSIGSCLRKY-GKFEE-DLVrFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSDDiyG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEAAYTTRGGkipIRWTAPEAI-AFRKFTSAS-DVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRLPSPMD--- 834
Cdd:cd06629  164 NNGATSMQGS---VFWMAPEVIhSQGQGYSAKvDIWSLGCVVLEMLA-GRRPWSDDEAiAAMFKLGNKRSAPPVPEDvnl 239
                        250       260
                 ....*....|....*....|.
gi 974005246 835 CPAALyQLMLDCWQKERNSRP 855
Cdd:cd06629  240 SPEAL-DFLNACFAIDPRDRP 259
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
610-860 2.06e-23

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 100.58  E-value: 2.06e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd08220    5 IRVVGRGAYGTVYLCRRKDDNKL---VIIKQIPVeQMTKEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQF----TVIQLVGMlrgISAGMKYLSDMGYVHRDLAARNILINSN-LVCKVSDFGLSRVLEDDPEa 763
Cdd:cd08220   82 PGGTLFEYIQQRKGSLlseeEILHFFVQ---ILLALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFGISKILSSKSK- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIPIrwtAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLM 843
Cdd:cd08220  158 AYTVVGTPCYI---SPELCEGKPYNQKSDIWALGCVLYELASL-KRAFEAANLPALVLKIMRGTFAPISDRYSEELRHLI 233
                        250
                 ....*....|....*..
gi 974005246 844 LDCWQKERNSRPKFDEI 860
Cdd:cd08220  234 LSMLHLDPNKRPTLSEI 250
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
613-863 2.22e-23

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 101.36  E-value: 2.22e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVcSGRLKLPGKRElpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGV-VTKSKPVMIVTEYMENG 691
Cdd:cd06620   13 LGAGNGGSV-SKVLHIPTGTI--MAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAfLNENNNIIICMEYMDCG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTViQLVGMLR-GISAGMKYLSDMGY-VHRDLAARNILINSNLVCKVSDFGLSRVLEDdpEAAYTTRG 769
Cdd:cd06620   90 SLDKILKKK-GPFPE-EVLGKIAvAVLEGLTYLYNVHRiIHRDIKPSNILVNSKGQIKLCDFGVSGELIN--SIADTFVG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWeMTNQDVIKAV--------------EEGYRLPSPMDC 835
Cdd:cd06620  166 TST---YMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFA-GSNDDDDGYNgpmgildllqrivnEPPPRLPKDRIF 240
                        250       260
                 ....*....|....*....|....*...
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd06620  241 PKDLRDFVDRCLLKDPRERPSPQLLLDH 268
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
611-861 2.35e-23

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 100.42  E-value: 2.35e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDflGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd08225    6 KKIGEGSFGKIYLAKAKSDSEHCVIKEIDLTKMPVKEKEASK--KEVILLAKMKHPNIVTFFASFQENGRLFIVMEYCDG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN-LVCKVSDFGLSRVLEDDPEAAYTTR 768
Cdd:cd08225   84 GDLMKRINRQRGvLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNgMVAKLGDFGIARQLNDSMELAYTCV 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQ 848
Cdd:cd08225  164 GTPY---YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLISQLFK 239
                        250
                 ....*....|...
gi 974005246 849 KERNSRPKFDEIV 861
Cdd:cd08225  240 VSPRDRPSITSIL 252
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
611-867 3.21e-23

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 101.04  E-value: 3.21e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpgkrELPVAIKTLKV---GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd14158   21 NKLGEGGFGVVFKGYIN-----DKNVAVKKLAAmvdISTEDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTY 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSL-DTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:cd14158   96 MPNGSLlDRLACLNDTpPLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFSQTIM 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRggkipIRWT----APEAIAfRKFTSASDVWSYGIVMWEVVS------YGERPYWEMTNQDVIKAVE---EGYRLPSP 832
Cdd:cd14158  176 TER-----IVGTtaymAPEALR-GEITPKSDIFSFGVVLLEIITglppvdENRDPQLLLDIKEEIEDEEktiEDYVDKKM 249
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 833 MDCPA----ALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14158  250 GDWDStsieAMYSVASQCLNDKKNRRPDIAKVQQLLQEL 288
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
608-800 3.34e-23

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 100.55  E-value: 3.34e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVcsgRLKLPGKRELPVAIKTLKvgyteKQR------------RDFLGEASIMGQFDHPNIIHLEGVV 675
Cdd:cd14084    9 IMSRTLGSGACGEV---KLAYDKSTCKKVAIKIIN-----KRKftigsrreinkpRNIETEIEILKKLSHPCIIKIEDFF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 676 TKSKPVMIVTEYMENGSL------DTFLKKNDGQFTVIQlvgMLRGIsagmKYLSDMGYVHRDLAARNILINSN---LVC 746
Cdd:cd14084   81 DAEDDYYIVLELMEGGELfdrvvsNKRLKEAICKLYFYQ---MLLAV----KYLHSNGIIHRDLKPENVLLSSQeeeCLI 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 747 KVSDFGLSRVLEDDpeAAYTTRGGKipIRWTAPEAIAF---RKFTSASDVWSYGIVM 800
Cdd:cd14084  154 KITDFGLSKILGET--SLMKTLCGT--PTYLAPEVLRSfgtEGYTRAVDCWSLGVIL 206
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
613-861 4.01e-23

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 100.51  E-value: 4.01e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06640   12 IGKGSFGEVFKG---IDNRTQQVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI 772
Cdd:cd06640   89 ALDLLRA--GPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPF 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 773 pirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEegyRLPSPM---DCPAALYQLMLDCWQK 849
Cdd:cd06640  167 ---WMAPEVIQQSAYDSKADIWSLGITAIELAK-GEPPNSDMHPMRVLFLIP---KNNPPTlvgDFSKPFKEFIDACLNK 239
                        250
                 ....*....|..
gi 974005246 850 ERNSRPKFDEIV 861
Cdd:cd06640  240 DPSFRPTAKELL 251
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
613-862 5.40e-23

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 99.37  E-value: 5.40e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpGKRELPVAIKTL-KVGYTEKQrrDFLG-EASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd14120    1 IGHGAFAVVFKGRHR--KKPDLPVAIKCItKKNLSKSQ--NLLGkEIKILKELSHENVVALLDCQETSSSVYLVMEYCNG 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFL-KKNDGQFTVIQLvgMLRGISAGMKYLSDMGYVHRDLAARNILIN---------SNLVCKVSDFGLSRVLEDD 760
Cdd:cd14120   77 GDLADYLqAKGTLSEDTIRV--FLQQIAAAMKALHSKGIVHRDLKPQNILLShnsgrkpspNDIRLKIADFGFARFLQDG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEAAyTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRL-PS-PMDCPAA 838
Cdd:cd14120  155 MMAA-TLCGSPM---YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFQAQTPQELKAFYEKNANLrPNiPSGTSPA 229
                        250       260
                 ....*....|....*....|....
gi 974005246 839 LYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14120  230 LKDLLLGLLKRNPKDRIDFEDFFS 253
SAM_EPH-B3 cd09553
SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
899-962 6.20e-23

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.


Pssm-ID: 188952  Cd Length: 69  Bit Score: 93.17  E-value: 6.20e-23
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 899 YRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09553    6 FTTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMRLQM 69
SAM_EPH-A7 cd09548
SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-962 6.58e-23

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188947  Cd Length: 70  Bit Score: 93.17  E-value: 6.58e-23
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09548    6 SFCSVGEWLEAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMRAQM 70
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
607-869 6.63e-23

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 99.35  E-value: 6.63e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpGKrelpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14063    2 LEIKEVIGKGRFGRVHRGRWH--GD----VAIKLLNIDYlNEEQLEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCkVSDFGLSRV--LEDDPEA 763
Cdd:cd14063   76 SLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGLFSLsgLLQPGRR 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRggkIPIRWT---APEAI-AFR---------KFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLP 830
Cdd:cd14063  155 EDTLV---IPNGWLcylAPEIIrALSpdldfeeslPFTKASDVYAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGKKQS 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 974005246 831 -SPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIR 869
Cdd:cd14063  231 lSQLDIGREVKDILMQCWAYDPEKRPTFSDLLRMLERLPK 270
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
611-862 7.48e-23

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 99.01  E-value: 7.48e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFL----GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd06632    6 QLLGSGSFGSVYEGFNGDTGDF---FAVKEVSLVDDDKKSRESVkqleQEIALLSKLRHPNIVQYYGTEREEDNLYIFLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNdGQFT--VIQLvgMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddpEAA 764
Cdd:cd06632   83 YVPGGSIHKLLQRY-GAFEepVIRL--YTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHV----EAF 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGKIPIRWTAPEAIAfRK---FTSASDVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRLPSPMDCPAALY 840
Cdd:cd06632  156 SFAKSFKGSPYWMAPEVIM-QKnsgYGLAVDIWSLGCTVLEMAT-GKPPWSQYEGvAAIFKIGNSGELPPIPDHLSPDAK 233
                        250       260
                 ....*....|....*....|..
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd06632  234 DFIRLCLQRDPEDRPTASQLLE 255
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
611-831 7.85e-23

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 99.02  E-value: 7.85e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKrelPVAIKTL------KVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVV-TKSKpVMI 683
Cdd:cd14663    6 RTLGEGTFAKVKFARNTKTGE---SVAIKIIdkeqvaREGMVEQIKR----EIAIMKLLRHPNIVELHEVMaTKTK-IFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSL------DTFLKKNDGQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd14663   78 VMELVTGGELfskiakNGRLKEDKARKYFQQLI-------DAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALS 150
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 758 E--DDPEAAYTTRGgkIPiRWTAPEAIAFRKFTSA-SDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEG-YRLPS 831
Cdd:cd14663  151 EqfRQDGLLHTTCG--TP-NYVAPEVLARRGYDGAkADIWSCGVILF-VLLAGYLPFDDENLMALYRKIMKGeFEYPR 224
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
613-812 8.58e-23

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 99.05  E-value: 8.58e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06648   15 IGEGSTGIVCIATDKSTGRQ---VAVK--KMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLD---TFLKKNDGQF-TVIQLVgmLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeaaytt 767
Cdd:cd06648   90 ALTdivTHTRMNEEQIaTVCRAV--LKALS----FLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKE------- 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 768 rggkIPIR--------WTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW 812
Cdd:cd06648  157 ----VPRRkslvgtpyWMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPYF 204
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
610-861 9.90e-23

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 98.61  E-value: 9.90e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVG-YTEKQRRDFLGEASI---MGQfdHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd13997    5 LEQIGSGSFSEVFKVRSKVDG---CLYAVKKSKKPfRGPKERARALREVEAhaaLGQ--HPNIVRYYSSWEEGGHLYIQM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKN--DGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEa 763
Cdd:cd13997   80 ELCENGSLQDALEELspISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLETSGD- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 aytTRGGKipIRWTAPEAIA-FRKFTSASDVWSYGIVMWEVVSYGERPywemTNQDVIKAVEEGYRLPSPMDC-PAALYQ 841
Cdd:cd13997  159 ---VEEGD--SRYLAPELLNeNYTHLPKADIFSLGVTVYEAATGEPLP----RNGQQWQQLRQGKLPLPPGLVlSQELTR 229
                        250       260
                 ....*....|....*....|
gi 974005246 842 LMLDCWQKERNSRPKFDEIV 861
Cdd:cd13997  230 LLKVMLDPDPTRRPTADQLL 249
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
612-805 1.17e-22

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 99.32  E-value: 1.17e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgKRElpVAIKTLKvgytEKQRRDFLGEASIMG--QFDHPNIIHLEGV--VTKSKPV--MIVT 685
Cdd:cd14053    2 IKARGRFGAVWKAQYL---NRL--VAVKIFP----LQEKQSWLTEREIYSlpGMKHENILQFIGAekHGESLEAeyWLIT 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdgqftVIQLVGMLR---GISAGMKYL-SDMGY---------VHRDLAARNILINSNLVCKVSDFG 752
Cdd:cd14053   73 EFHERGSLCDYLKGN-----VISWNELCKiaeSMARGLAYLhEDIPAtngghkpsiAHRDFKSKNVLLKSDLTACIADFG 147
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 753 LSRVLEDD--PEAAYTTRGGKipiRWTAPE----AIAFRK--FTsASDVWSYGIVMWEVVS 805
Cdd:cd14053  148 LALKFEPGksCGDTHGQVGTR---RYMAPEvlegAINFTRdaFL-RIDMYAMGLVLWELLS 204
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
683-860 1.87e-22

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 98.25  E-value: 1.87e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLK----KNDGQFTVIQLVGMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE 758
Cdd:cd14043   73 IVSEHCSRGSLEDLLRnddmKLDWMFKSSLLLDLIKG----MRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILE 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 759 --------DDPEAAYttrggkipirWTAPE----AIAFRKFTSASDVWSYGIVMWEVVSYGErPY--WEMTNQDVIKAVe 824
Cdd:cd14043  149 aqnlplpePAPEELL----------WTAPEllrdPRLERRGTFPGDVFSFAIIMQEVIVRGA-PYcmLGLSPEEIIEKV- 216
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 974005246 825 egyRLPSP-------MD-CPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd14043  217 ---RSPPPlcrpsvsMDqAPLECIQLMKQCWSEAPERRPTFDQI 257
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
613-810 2.15e-22

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 98.93  E-value: 2.15e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgYTEK-------QRrdflgEASIMGQFDHPNIIHLEGVV-------TKS 678
Cdd:cd07866   16 LGEGTFGEVYKARQIKTGRV---VALKKILM-HNEKdgfpitaLR-----EIKILKKLKHPNVVPLIDMAverpdksKRK 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVM-IVTEYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd07866   87 RGSVyMVTPYMDH-DLSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPY 165
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 758 EDDP----------EAAYTtrgGKIPIRW-TAPEAIA-FRKFTSASDVWSYGIVMWEVvsYGERP 810
Cdd:cd07866  166 DGPPpnpkggggggTRKYT---NLVVTRWyRPPELLLgERRYTTAVDIWGIGCVFAEM--FTRRP 225
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
608-862 2.34e-22

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 97.46  E-value: 2.34e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG-YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd08530    3 KVLKKLGKGSYGSVYKVKRLSDNQV---YALKEVNLGsLSQKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVME 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQ-------LVGMLRGISAgmkyLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd08530   80 YAPFGDLSKLISKRKKKRRLFPeddiwriFIQMLRGLKA----LHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKK 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DpeAAYTTRGgkIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAAL 839
Cdd:cd08530  156 N--LAKTQIG--TPL-YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQDL 229
                        250       260
                 ....*....|....*....|...
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd08530  230 QQIIRSLLQVNPKKRPSCDKLLQ 252
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-962 3.92e-22

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


Pssm-ID: 188951  Cd Length: 71  Bit Score: 90.84  E-value: 3.92e-22
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09552    5 SFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMRAQM 69
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
613-861 4.10e-22

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 97.45  E-value: 4.10e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06641   12 IGKGSFGEVFKG---IDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI 772
Cdd:cd06641   89 ALDLLEP--GPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRN*FVGTPF 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 773 pirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERN 852
Cdd:cd06641  167 ---WMAPEVIKQSAYDSKADIWSLGITAIELAR-GEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKEFVEACLNKEPS 242

                 ....*....
gi 974005246 853 SRPKFDEIV 861
Cdd:cd06641  243 FRPTAKELL 251
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
611-847 5.50e-22

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 96.43  E-value: 5.50e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14072    6 KTIGKGNFAKVKLARHVLTGRE---VAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYAS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPEAAYTTRG 769
Cdd:cd14072   83 GGEVFDYLV-AHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSN--EFTPGNKLDTFC 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPirWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSPM--DCP--------- 836
Cdd:cd14072  160 GSPP--YAAPELFQGKKYDGPEvDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRGkYRIPFYMstDCEnllkkflvl 236
                        250
                 ....*....|....*.
gi 974005246 837 -----AALYQLMLDCW 847
Cdd:cd14072  237 npskrGTLEQIMKDRW 252
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
895-959 5.66e-22

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 90.02  E-value: 5.66e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246  895 GSGAYRSVGEWLEAIKMGRYTEIFMeNGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
612-862 5.99e-22

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 96.62  E-value: 5.99e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14201   13 LVGHGAFAVVFKGRHR--KKTDWEVAIKSINKKNLSKSQILLGKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGG 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILIN---------SNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd14201   91 DLADYLQAK-GTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADFGFARYLQSNMM 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAyTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVEEGYRL-PS-PMDCPAALY 840
Cdd:cd14201  170 AA-TLCGSPM---YMAPEVIMSQHYDAKADLWSIGTVIYQCL-VGKPPFQANSPQDLRMFYEKNKNLqPSiPRETSPYLA 244
                        250       260
                 ....*....|....*....|..
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14201  245 DLLLGLLQRNQKDRMDFEAFFS 266
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
612-854 9.90e-22

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 96.74  E-value: 9.90e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgkrELPVAIKTLKVGytekQRRDFLGEASIMG--QFDHPNIIHL----EGVVTKSKPVMIVT 685
Cdd:cd13998    2 VIGKGRFGEVWKASLK-----NEPVAVKIFSSR----DKQSWFREKEIYRtpMLKHENILQFiaadERDTALRTELWLVT 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdgqftVIQLVGMLR---GISAGMKYL-SDM--------GYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd13998   73 AFHPNGSL*DYLSLH-----TIDWVSLCRlalSVARGLAHLhSEIpgctqgkpAIAHRDLKSKNILVKNDGTCCIADFGL 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLE---DDPEAAYTTRGGKipIRWTAPE----AIAFRKFTS--ASDVWSYGIVMWEVVS-----YGERPYWEMTNQDV 819
Cdd:cd13998  148 AVRLSpstGEEDNANNGQVGT--KRYMAPEvlegAINLRDFESfkRVDIYAMGLVLWEMASrctdlFGIVEEYKPPFYSE 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 820 IK---AVEEGYRL-----------PSPMDCPA--ALYQLMLDCWQKERNSR 854
Cdd:cd13998  226 VPnhpSFEDMQEVvvrdkqrpnipNRWLSHPGlqSLAETIEECWDHDAEAR 276
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
607-864 9.93e-22

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 96.13  E-value: 9.93e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPG----------------KRELPVAIKTLkvgytEKQRRD----FLGEASIMGQFDHP 666
Cdd:cd05076    1 ITQLSHLGQGTRTNIYEGRLLVEGsgepeedkelvpgrdrGQELRVVLKVL-----DPSHHDialaFFETASLMSQVSHT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 667 NIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI------ 740
Cdd:cd05076   76 HLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNLVHGNVCAKNILLarlgle 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 741 -NSNLVCKVSDFGLSRVLEDDPEaayttRGGKIPirWTAPEAI-AFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQD 818
Cdd:cd05076  156 eGTSPFIKLSDPGVGLGVLSREE-----RVERIP--WIAPECVpGGNSLSTAADKWGFGATLLEICFNGEAPLQSRTPSE 228
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 819 VIKAVEEGYRLPSPmDCPaALYQLMLDCWQKERNSRPKFDEIVNML 864
Cdd:cd05076  229 KERFYQRQHRLPEP-SCP-ELATLISQCLTYEPTQRPSFRTILRDL 272
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
608-805 1.19e-21

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 97.37  E-value: 1.19e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQ---RRDfLGEASIMGQFDHPNIIHLEGVVTKS-----K 679
Cdd:cd07849    8 QNLSYIGEGAYGMVCSAVHKPTGQK---VAIK--KISPFEHQtycLRT-LREIKILLRFKHENIIGILDIQRPPtfesfK 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMEngsldTFLKK--------NDG-QFTVIQlvgMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSD 750
Cdd:cd07849   82 DVYIVQELME-----TDLYKliktqhlsNDHiQYFLYQ---ILRG----LKYIHSANVLHRDLKPSNLLLNTNCDLKICD 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 751 FGLSRVleDDPEAAYTtrgGK----IPIRW-TAPE-AIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07849  150 FGLARI--ADPEHDHT---GFlteyVATRWyRAPEiMLNSKGYTKAIDIWSVGCILAEMLS 205
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
608-855 1.20e-21

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 95.80  E-value: 1.20e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd08224    3 EIEKKIGKGQFSVVYRARCLLDGR---LVALKKVQIFemMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLR---GISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd08224   80 ELADAGDLSRLIKHFKKQKRLIPERTIWKyfvQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGgkIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVS-----YGErpywEMTNQDVIKAVEEGYRLPSPMDC-P 836
Cdd:cd08224  160 AAHSLVG--TPY-YMSPERIREQGYDFKSDIWSLGCLLYEMAAlqspfYGE----KMNLYSLCKKIEKCEYPPLPADLyS 232
                        250
                 ....*....|....*....
gi 974005246 837 AALYQLMLDCWQKERNSRP 855
Cdd:cd08224  233 QELRDLVAACIQPDPEKRP 251
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-961 1.81e-21

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 88.94  E-value: 1.81e-21
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQ 961
Cdd:cd09551    5 AFTSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSMRVQ 68
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
613-811 2.10e-21

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 94.60  E-value: 2.10e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14103    1 LGRGKFGTVYRCVEKATGKE---LAAKFIKC-RKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LdtFLKKNDGQFTVIQLVGML--RGISAGMKYLSDMGYVHRDLAARNILI---NSNLVcKVSDFGLSRVLEDD------- 760
Cdd:cd14103   77 L--FERVVDDDFELTERDCILfmRQICEGVQYMHKQGILHLDLKPENILCvsrTGNQI-KIIDFGLARKYDPDkklkvlf 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 761 --PEaayttrggkipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14103  154 gtPE-------------FVAPEVVNYEPISYATDMWSVGVICYVLLS-GLSPF 192
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
607-802 2.41e-21

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 95.65  E-value: 2.41e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKrelPVAIKtlKV----GYteKQRrdflgEASIMGQFDHPNIIHLEG---VVTKSK 679
Cdd:cd14137    6 YTIEKVIGSGSFGVVYQAKLLETGE---VVAIK--KVlqdkRY--KNR-----ELQIMRRLKHPNIVKLKYffySSGEKK 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVM---IVTEYMENgSLDTFLKKNDGQFTVIQLV-------GMLRGISagmkYLSDMGYVHRDLAARNILIN-SNLVCKV 748
Cdd:cd14137   74 DEVylnLVMEYMPE-TLYRVIRHYSKNKQTIPIIyvklysyQLFRGLA----YLHSLGICHRDIKPQNLLVDpETGVLKL 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 749 SDFGLSRVLE-DDPEAAY-TTRggkiPIRwtAPEAIA-FRKFTSASDVWSYGIVMWE 802
Cdd:cd14137  149 CDFGSAKRLVpGEPNVSYiCSR----YYR--APELIFgATDYTTAIDIWSAGCVLAE 199
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
612-863 2.41e-21

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 94.92  E-value: 2.41e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG-YTEKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKPVM-IVTEYM 688
Cdd:cd08217    7 TIGKGSFGTVRKVRRKSDGKI---LVWKEIDYGkMSEKEKQQLVSEVNILRELKHPNIVrYYDRIVDRANTTLyIVMEYC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLK--KNDGQF----TVI----QLVGML----RGISAGMKYLsdmgyvHRDLAARNILINSNLVCKVSDFGLS 754
Cdd:cd08217   84 EGGDLAQLIKkcKKENQYipeeFIWkiftQLLLALyechNRSVGGGKIL------HRDLKPANIFLDSDNNVKLGDFGLA 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 755 RVLEDDPEAAYTTRGgkIPIRWtAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwEMTNQDVIKA-VEEGYRLPSPM 833
Cdd:cd08217  158 RVLSHDSSFAKTYVG--TPYYM-SPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPF-QAANQLELAKkIKEGKFPRIPS 232
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 834 DCPAALYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd08217  233 RYSSELNEVIKSMLNVDPDKRPSVEELLQL 262
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
612-860 2.62e-21

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 94.73  E-value: 2.62e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLkLPGKRElpVAIKTLKVgytEKQRRDF---LGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd06610    8 VIGSGATAVVYAAYC-LPKKEK--VAIKRIDL---EKCQTSMdelRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLK---KNDGQFTVIqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD----P 761
Cdd:cd06610   82 SGGSLLDIMKssyPRGGLDEAI-IATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATGgdrtR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGgkIPIrWTAPEAIA-FRKFTSASDVWSYGIVMWEvVSYGERPYWE--------MTNQDVIKAVEEGyrlPSP 832
Cdd:cd06610  161 KVRKTFVG--TPC-WMAPEVMEqVRGYDFKADIWSFGITAIE-LATGAAPYSKyppmkvlmLTLQNDPPSLETG---ADY 233
                        250       260
                 ....*....|....*....|....*...
gi 974005246 833 MDCPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd06610  234 KKYSKSFRKMISLCLQKDPSKRPTAEEL 261
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
636-867 2.71e-21

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 94.48  E-value: 2.71e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKTLKVG-YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGqFTV--IQLVGM 712
Cdd:cd14057   21 IVAKILKVRdVTTRISRDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEGTG-VVVdqSQAVKF 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 713 LRGISAGMKYLSDMGYV--HRDLAARNILINSNLVCKVSdFGLSRVLEDDPEAAYTTrggkipiRWTAPEAIAfRKFTS- 789
Cdd:cd14057  100 ALDIARGMAFLHTLEPLipRHHLNSKHVMIDEDMTARIN-MADVKFSFQEPGKMYNP-------AWMAPEALQ-KKPEDi 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 790 ---ASDVWSYGIVMWEVVSYgERPYWEMTNQDV-IKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd14057  171 nrrSADMWSFAILLWELVTR-EVPFADLSNMEIgMKIALEGLRVTIPPGISPHMCKLMKICMNEDPGKRPKFDMIVPILE 249

                 ..
gi 974005246 866 KL 867
Cdd:cd14057  250 KM 251
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
608-802 3.47e-21

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 94.95  E-value: 3.47e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQR----RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd07841    3 EKGKKLGEGTYAVVYKARDKETGR---IVAIKKIKLGERKEAKdginFTALREIKLLQELKHPNIIGLLDVFGHKSNINL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMEnGSLDTFLKKNDGQFTVIQ----LVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd07841   80 VFEFME-TDLEKVIKDKSIVLTPADiksyMLMTLRGLE----YLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFGS 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 760 DPEaAYTTrggKIPIRW-TAPEaIAF--RKFTSASDVWSYGIVMWE 802
Cdd:cd07841  155 PNR-KMTH---QVVTRWyRAPE-LLFgaRHYGVGVDMWSVGCIFAE 195
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
608-805 3.94e-21

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 96.00  E-value: 3.94e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRD---FLGEASIMGQFDHPNIIHLEGVVTKSKP---- 680
Cdd:cd07859    3 KIQEVIGKGSYGVVCSAIDTHTGEK---VAIK--KINDVFEHVSDatrILREIKLLRLLRHPDIVEIKHIMLPPSRrefk 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 -VMIVTEYMENgSLDTFLKKNDG------QFTVIQLvgmLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd07859   78 dIYVVFELMES-DLHQVIKANDDltpehhQFFLYQL---LRA----LKYIHTANVFHRDLKPKNILANADCKLKICDFGL 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 754 SRV-LEDDPEAAYTTrgGKIPIRW-TAPEAIA--FRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07859  150 ARVaFNDTPTAIFWT--DYVATRWyRAPELCGsfFSKYTPAIDIWSIGCIFAEVLT 203
SAM_EPH-A8 cd09550
SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
900-962 4.43e-21

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.


Pssm-ID: 188949  Cd Length: 65  Bit Score: 87.61  E-value: 4.43e-21
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 974005246 900 RSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09550    3 LSVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQVMRAQL 65
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
609-835 5.05e-21

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 93.61  E-value: 5.05e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPgKRElpVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd14071    4 IERTIGKGNFAVVKLARHRIT-KTE--VAIKIIdKSQLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTT 767
Cdd:cd14071   81 ASNGEIFDYLAQH-GRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFK--PGELLKT 157
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 768 RGGKIPirWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSPM--DC 835
Cdd:cd14071  158 WCGSPP--YAAPEVFEGKEYEGPQlDIWSLGVVLYVLVC-GALPFDGSTLQTLRDRVLSGrFRIPFFMstDC 226
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
613-805 5.69e-21

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 94.21  E-value: 5.69e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVgytEKQRRDF----LGEASIMGQFDHPNIIHLEGVVTKSK--PVMIVTE 686
Cdd:cd07843   13 IEEGTYGVVYRARDKKTGE---IVALKKLKM---EKEKEGFpitsLREINILLKLQHPNIVTVKEVVVGSNldKIYMVME 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEdDPEAAYT 766
Cdd:cd07843   87 YVEH-DLKSLMETMKQPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREYG-SPLKPYT 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 767 TrggKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07843  165 Q---LVVTLWyRAPELLlGAKEYSTAIDMWSVGCIFAELLT 202
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
608-813 5.98e-21

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 93.55  E-value: 5.98e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVcsgRLKLPGKRELPVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14069    4 DLVQTLGEGAFGEV---FLAVNRNTEEAVAVKFVDMkRAPGDCPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSL------DTFLKKNDGQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE-D 759
Cdd:cd14069   81 YASGGELfdkiepDVGMPEDVAQFYFQQLM-------AGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFRyK 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 760 DPEAAYTTRGGKIPirWTAPEAIAFRKF-TSASDVWSYGIVMWEVVSyGERPyWE 813
Cdd:cd14069  154 GKERLLNKMCGTLP--YVAPELLAKKKYrAEPVDVWSCGIVLFAMLA-GELP-WD 204
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
609-802 6.26e-21

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 93.90  E-value: 6.26e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd13996   10 EIELLGSGGFGSVYKVRNKVDGVT---YAIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELC 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFL----KKNDGQFTVIqlVGMLRGISAGMKYLSDMGYVHRDLAARNILI-NSNLVCKVSDFGLSRVLEDDPE- 762
Cdd:cd13996   87 EGGTLRDWIdrrnSSSKNDRKLA--LELFKQILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIGNQKRe 164
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 763 ------------AAYTTRGGKipIRWTAPEAIAFRKFTSASDVWSYGIVMWE 802
Cdd:cd13996  165 lnnlnnnnngntSNNSVGIGT--PLYASPEQLDGENYNEKADIYSLGIILFE 214
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
609-851 8.79e-21

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 92.84  E-value: 8.79e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY--TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14073    5 LLETLGKGTYGKVKLAIERATGRE---VAIKSIKKDKieDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYT 766
Cdd:cd14073   82 YASGGELYDYIS-ERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKD--KLLQ 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKiPIrWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVEEG-YRLPSPMDCPAALYQLML 844
Cdd:cd14073  159 TFCGS-PL-YASPEIVNGTPYQGPEvDCWSLGVLLYTLV-YGTMPFDGSDFKRLVKQISSGdYREPTQPSDASGLIRWML 235

                 ....*..
gi 974005246 845 DCWQKER 851
Cdd:cd14073  236 TVNPKRR 242
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
613-862 9.00e-21

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 93.14  E-value: 9.00e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELpVAIKTLKVGYTEKQRRDF----LGEASIMGQFDHPNIIH-LEGVVTKSKPVMIVTEY 687
Cdd:cd13994    1 IGKGATSVVRIVTKKNPRSGVL-YAVKEYRRRDDESKRKDYvkrlTSEYIISSKLHHPNIVKvLDLCQDLHGKWCLVMEY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED--DPEAAY 765
Cdd:cd13994   80 CPGGDLFTLIEK-ADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFGMpaEKESPM 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTR-GGKIPirWTAPEAIAFRKFT-SASDVWSYGIVMweVVSYGERPYWEM---TNQDVIKAVEEG---------YRLPS 831
Cdd:cd13994  159 SAGlCGSEP--YMAPEVFTSGSYDgRAVDVWSCGIVL--FALFTGRFPWRSakkSDSAYKAYEKSGdftngpyepIENLL 234
                        250       260       270
                 ....*....|....*....|....*....|.
gi 974005246 832 PMDCPAALYQlMLDcwQKERNsRPKFDEIVN 862
Cdd:cd13994  235 PSECRRLIYR-MLH--PDPEK-RITIDEALN 261
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
901-959 9.32e-21

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 86.55  E-value: 9.32e-21
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246  901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:pfam07647   8 SVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
613-879 9.91e-21

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 93.27  E-value: 9.91e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGyTEKQRRDFLGEASIMGQFDHPNIIHL-EGVVTKSKPVMIVtEYMENG 691
Cdd:cd06611   13 LGDGAFGKVYKAQHKETG---LFAAAKIIQIE-SEEELEDFMVEIDILSECKHPNIVGLyEAYFYENKLWILI-EFCDGG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGK 771
Cdd:cd06611   88 ALDSIMLELERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKSTLQKRDTFIGTP 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 ipiRWTAPEAIAFRKFTSA-----SDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGyrlPSP-MDCP----AALYQ 841
Cdd:cd06611  168 ---YWMAPEVVACETFKDNpydykADIWSLGITLIELAQ-MEPPHHELNPMRVLLKILKS---EPPtLDQPskwsSSFND 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 974005246 842 LMLDCWQKERNSRPKFDEIvnMLDKLIRNPSS---LKTLVN 879
Cdd:cd06611  241 FLKSCLVKDPDDRPTAAEL--LKHPFVSDQSDnkaIKDLLA 279
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
613-862 1.55e-20

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 92.02  E-value: 1.55e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14075   10 LGSGNFSQVKLGIHQLTKEK---VAIKILdKTKLDQKTQRLLSREISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLedDPEAAYTTRGGK 771
Cdd:cd14075   87 ELYTKIS-TEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHA--KRGETLNTFCGS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 IPirWTAPEAiafrkFTSAS------DVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPS--PMDCpAALYQL 842
Cdd:cd14075  164 PP--YAAPEL-----FKDEHyigiyvDIWALGVLLYFMVT-GVMPFRAETVAKLKKCILEGtYTIPSyvSEPC-QELIRG 234
                        250       260
                 ....*....|....*....|
gi 974005246 843 MLdcwQKERNSRPKFDEIVN 862
Cdd:cd14075  235 IL---QPVPSDRYSIDEIKN 251
SAM_EPH-B6 cd09555
SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
904-962 2.25e-20

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.


Pssm-ID: 188954  Cd Length: 69  Bit Score: 85.75  E-value: 2.25e-20
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 904 EWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09555   11 AWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQQHL 69
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
612-847 2.81e-20

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 92.34  E-value: 2.81e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLklpgkRELPVAIKTlkvgYTEKQRRDFLGEASI----MGQfdHPNI-------IHLEGVVTKskp 680
Cdd:cd14056    2 TIGKGRYGEVWLGKY-----RGEKVAVKI----FSSRDEDSWFRETEIyqtvMLR--HENIlgfiaadIKSTGSWTQ--- 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSD--MGY------VHRDLAARNILINSNLVCKVSDFG 752
Cdd:cd14056   68 LWLITEYHEHGSLYDYLQRN--TLDTEEALRLAYSAASGLAHLHTeiVGTqgkpaiAHRDLKSKNILVKRDGTCCIADLG 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 753 LSRVLEDD----PEAAYTTRGGKipiRWTAPE----AIAFRKFTS--ASDVWSYGIVMWEVVSYGER---------PYWE 813
Cdd:cd14056  146 LAVRYDSDtntiDIPPNPRVGTK---RYMAPEvlddSINPKSFESfkMADIYSFGLVLWEIARRCEIggiaeeyqlPYFG 222
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 814 MTNQD--------VIkaVEEGYRLPSP---MDCP--AALYQLMLDCW 847
Cdd:cd14056  223 MVPSDpsfeemrkVV--CVEKLRPPIPnrwKSDPvlRSMVKLMQECW 267
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
899-962 3.05e-20

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 85.27  E-value: 3.05e-20
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 899 YRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09543    5 FRTVAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKEQV 68
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
613-814 4.15e-20

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 91.66  E-value: 4.15e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06642   12 IGKGSFGEVYKG---IDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI 772
Cdd:cd06642   89 ALDLLKP--GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPF 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 773 pirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06642  167 ---WMAPEVIKQSAYDFKADIWSLGITAIELAK-GEPPNSDL 204
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
607-851 4.59e-20

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 90.82  E-value: 4.59e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpgKRELPVAIKTL-KVGYTEKQRRDFLG-EASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd14162    2 YIVGKTLGHGSYAVVKKAYST---KHKCKVAIKIVsKKKAPEDYLQKFLPrEIEVIKGLKHPNLICFYEAIETTSRVYII 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvleDDPEAA 764
Cdd:cd14162   79 MELAENGDLLDYIRKN-GALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR---GVMKTK 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 yttrGGKIPIRWT--------APE---AIAFRKFtsASDVWSYGIVMWEVVsYGERPYwEMTNQDVI-KAVEEGYRLPS- 831
Cdd:cd14162  155 ----DGKPKLSETycgsyayaSPEilrGIPYDPF--LSDIWSMGVVLYTMV-YGRLPF-DDSNLKVLlKQVQRRVVFPKn 226
                        250       260
                 ....*....|....*....|...
gi 974005246 832 ---PMDCPAALYQLMLdcWQKER 851
Cdd:cd14162  227 ptvSEECKDLILRMLS--PVKKR 247
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
613-803 5.46e-20

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 91.33  E-value: 5.46e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGR-LKLPGKRelpVAIKTLKV---GYTEKQRRdfLGEASIMGQFD---HPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14052    8 IGSGEFSQVYKVSeRVPTGKV---YAVKKLKPnyaGAKDRLRR--LEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVI---QLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpe 762
Cdd:cd14052   83 ELCENGSLDVFLSEL-GLLGRLdefRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLI-- 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 763 AAYTTRGGKIPIrwtAPEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd14052  160 RGIEREGDREYI---APEILSEHMYDKPADIFSLGLILLEA 197
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
612-832 5.62e-20

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 90.86  E-value: 5.62e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14167   10 VLGTGAFSEVVLAEEK---RTQKLVAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL---INSNLVCKVSDFGLSRVleDDPEAAYTT 767
Cdd:cd14167   87 ELfDRIVEK--GFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKI--EGSGSVMST 162
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 768 RGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14167  163 ACGT-P-GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDAKLFEQILKAeYEFDSP 225
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
901-959 6.33e-20

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 84.27  E-value: 6.33e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246   901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:smart00454   8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLK 66
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
636-867 6.57e-20

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 91.12  E-value: 6.57e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKtlkvgYTEKQR----RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKkNDGqftvIQLVG 711
Cdd:cd14042   33 VAIK-----KVNKKRidltREVLKELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILE-NED----IKLDW 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 712 MLRG-----ISAGMKYL--SDMGYvHRDLAARNILINSNLVCKVSDFGLS--RVLEDDPEAAYTTRGGKIpirWTAPEAI 782
Cdd:cd14042  103 MFRYslihdIVKGMHYLhdSEIKS-HGNLKSSNCVVDSRFVLKITDFGLHsfRSGQEPPDDSHAYYAKLL---WTAPELL 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 783 afRKF------TSASDVWSYGIVMWEVVSYgERPYWE-----MTNQDVIKAVEEGYRLP-----SPMDCPAALYQLMLDC 846
Cdd:cd14042  179 --RDPnppppgTQKGDVYSFGIILQEIATR-QGPFYEegpdlSPKEIIKKKVRNGEKPPfrpslDELECPDEVLSLMQRC 255
                        250       260
                 ....*....|....*....|.
gi 974005246 847 WQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14042  256 WAEDPEERPDFSTLRNKLKKL 276
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
613-867 6.67e-20

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 90.27  E-value: 6.67e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelpvaIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14156    1 IGSGFFSKVYKVTHGATGK------VMVVKIYKNDVDQHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGC 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN---LVCKVSDFGLSRVLED----DPEAAY 765
Cdd:cd14156   75 LEELLAREELPLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIRVTprgREAVVTDFGLAREVGEmpanDPERKL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVsyGERPywemTNQDVIKAVEE------GYRLPSPmDCPAAL 839
Cdd:cd14156  155 SLVGSAF---WMAPEMLRGEPYDRKVDVFSFGIVLCEIL--ARIP----ADPEVLPRTGDfgldvqAFKEMVP-GCPEPF 224
                        250       260
                 ....*....|....*....|....*...
gi 974005246 840 YQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14156  225 LDLAASCCRMDAFKRPSFAELLDELEDI 252
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
613-834 9.43e-20

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 89.88  E-value: 9.43e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVV-TKSKPVMiVTEYME 689
Cdd:cd05123    1 LGKGSFGKVLLVRKKDTGKL---YAMKVLRKKeiIKRKEVEHTLNERNILERVNHPFIVKLHYAFqTEEKLYL-VLDYVP 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNdGQFTViqlvGMLRGISA----GMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:cd05123   77 GGELFSHLSKE-GRFPE----ERARFYAAeivlALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDRTY 151
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 766 TTRGgkipirwT----APEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYW---EMTNQDVIKavEEGYRLPSPMD 834
Cdd:cd05123  152 TFCG-------TpeylAPEVLLGKGYGKAVDWWSLGVLLYEML-TGKPPFYaenRKEIYEKIL--KSPLKFPEYVS 217
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
613-859 9.78e-20

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 89.65  E-value: 9.78e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlPGKRELpVAIK-TLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14121    3 LGSGTYATVYKAYRK-SGAREV-VAVKcVSKSSLNKASTENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS--NLVCKVSDFGLSRVLEDDpEAAYTTRG 769
Cdd:cd14121   81 DLSRFIRSR-RTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSryNPVLKLADFGFAQHLKPN-DEAHSLRG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GkiPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTnqdvIKAVEEGYRLPSPMDCPAALyQLMLDC--- 846
Cdd:cd14121  159 S--PL-YMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRS----FEELEEKIRSSKPIEIPTRP-ELSADCrdl 229
                        250
                 ....*....|....*..
gi 974005246 847 ----WQKERNSRPKFDE 859
Cdd:cd14121  230 llrlLQRDPDRRISFEE 246
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
613-804 1.24e-19

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 91.09  E-value: 1.24e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGV-VTKSKPVMIVTEYMEN 690
Cdd:cd07856   18 VGMGAFGLVCSARDQLTGQ---NVAVKKImKPFSTPVLAKRTYRELKLLKHLRHENIISLSDIfISPLEDIYFVTELLGT 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 gSLDTFLKKN--DGQFTVIQLVGMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTR 768
Cdd:cd07856   95 -DLHRLLTSRplEKQFIQYFLYQILRG----LKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIQDPQMTGYVSTR 169
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 974005246 769 ggkipiRWTAPE-AIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07856  170 ------YYRAPEiMLTWQKYDVEVDIWSAGCIFAEML 200
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
613-863 1.36e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 89.48  E-value: 1.36e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVgyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd08218    8 IGEGSFGKALLVKSKEDGKQYVIKEINISKM--SPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYCDGGD 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGK 771
Cdd:cd08218   86 LYKRINAQRGvLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTCIGTP 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 772 IpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgeRPYWEMTNQD--VIKAVEEGYRlPSPMDCPAALYQLMLDCWQK 849
Cdd:cd08218  166 Y---YLSPEICENKPYNNKSDIWALGCVLYEMCTL--KHAFEAGNMKnlVLKIIRGSYP-PVPSRYSYDLRSLVSQLFKR 239
                        250
                 ....*....|....
gi 974005246 850 ERNSRPKFDEIVNM 863
Cdd:cd08218  240 NPRDRPSINSILEK 253
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
611-826 1.44e-19

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 89.53  E-value: 1.44e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRElpvAIK--------TLKVGYTEKqrrdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14097    7 RKLGQGSFGVVIEATHKETQTKW---AIKkinrekagSSAVKLLER-------EVDILKHVNHAHIIHLEEVFETPKRMY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV-------CKVSDFGLSR 755
Cdd:cd14097   77 LVMELCEDGELKELLLR-KGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLSV 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 756 VLEDDPEAAYTTRGGKiPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG 826
Cdd:cd14097  156 QKYGLGEDMLQETCGT-PI-YMAPEVISAHGYSQQCDIWSIGVIMYMLLC-GEPPFVAKSEEKLFEEIRKG 223
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
400-490 1.77e-19

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 84.09  E-value: 1.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 400 PSPVTNVKKGKIAKNSISLSWQEPDRPNGIILEYEIKYFEKDQETSYTIIK--SKETTITAEGLKPASVYVFQIRARTAA 477
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGG 80
                         90
                 ....*....|...
gi 974005246 478 GYGVFSRRFEFET 490
Cdd:cd00063   81 GESPPSESVTVTT 93
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
607-811 1.92e-19

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 89.21  E-value: 1.92e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTlkvgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14190    6 IHSKEVLGGGKFGKVHTCTEKRTGLKLAAKVINK----QNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVcKVSDFGLSRvlEDDPEA 763
Cdd:cd14190   82 YVEGGELFERIVDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnrTGHQV-KIIDFGLAR--RYNPRE 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 764 AYTTRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14190  159 KLKVNFGT-P-EFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPF 203
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
579-812 2.47e-19

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 89.66  E-value: 2.47e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 579 VRTYIDPHtyeDPNQAVHEFAKeieascitiervIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgyTEKQRRDFL-GEA 657
Cdd:cd06659   10 LRMVVDQG---DPRQLLENYVK------------IGEGSTGVVCIAREKHSGRQ---VAVKMMDL--RKQQRRELLfNEV 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 658 SIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARN 737
Cdd:cd06659   70 VIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTDIVSQT--RLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDS 147
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 738 ILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW 812
Cdd:cd06659  148 ILLTLDGRVKLSDFGFCAQISKDVPKRKSLVGTPY---WMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPYF 218
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
632-865 3.52e-19

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 88.42  E-value: 3.52e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 632 RELPVAIKTLKVGYTEKQRrDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMiVTEYMENGSLDTFLKKN--DGQFTVIQL 709
Cdd:cd14208   29 CETEVLLKVMDPTHGNCQE-SFLEAASIMSQISHKHLVLLHGVCVGKDSIM-VQEFVCHGALDLYLKKQqqKGPVAISWK 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 710 VGMLRGISAGMKYLSDMGYVHRDLAARNILI------NSNLVCKVSDFGLS-RVLEDDPEAAyttrggKIPirWTAPEAI 782
Cdd:cd14208  107 LQVVKQLAYALNYLEDKQLVHGNVSAKKVLLsregdkGSPPFIKLSDPGVSiKVLDEELLAE------RIP--WVAPECL 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 783 A-FRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALyqLMLDCWQKERNSRPKFDEIV 861
Cdd:cd14208  179 SdPQNLALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYNDRKQLPAPHWIELAS--LIQQCMSYNPLLRPSFRAII 256

                 ....
gi 974005246 862 NMLD 865
Cdd:cd14208  257 RDLN 260
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
609-837 4.77e-19

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 88.79  E-value: 4.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKlpgKRELPVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05580    5 FLKTLGTGSFGRVRLVKHK---DSGKYYALKILKKAkiIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKND------GQFTVIQLVGMLrgisagmKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd05580   82 YVPGGELFSLLRRSGrfpndvAKFYAAEVVLAL-------EYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVKDR 154
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 761 peaAYTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSPMDCPA 837
Cdd:cd05580  155 ---TYTLCG--TP-EYLAPEIILSKGHGKAVDWWALGILIYEMLA-GYPPFFDENPMKIYEKILEGkIRFPSFFDPDA 225
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
608-845 6.25e-19

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 87.32  E-value: 6.25e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTL------KVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd14079    5 ILGKTLGVGSFGKVKLAEHELTGHK---VAVKILnrqkikSLDMEEKIRR----EIQILKLFRHPHIIRLYEVIETPTDI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDp 761
Cdd:cd14079   78 FMVMEYVSGGELFDYIVQK-GRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMRDG- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGkiPiRWTAPEAIAFRKFT-SASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEG-YRLPSPMDCPAA- 838
Cdd:cd14079  156 EFLKTSCGS--P-NYAAPEVISGKLYAgPEVDVWSCGVILY-ALLCGSLPFDDEHIPNLFKKIKSGiYTIPSHLSPGARd 231

                 ....*..
gi 974005246 839 LYQLMLD 845
Cdd:cd14079  232 LIKRMLV 238
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
901-960 6.28e-19

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 81.47  E-value: 6.28e-19
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKV 960
Cdd:cd09547    5 TVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLRL 64
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
612-802 6.77e-19

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 88.14  E-value: 6.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd07833    8 VVGEGAYGVVLKCRNKATGEI---VAIKKFKESEdDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVER 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDtFLKKNDG-------QFTVIQLvgmLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd07833   85 TLLE-LLEASPGglppdavRSYIWQL---LQAIA----YCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPAS 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 764 AYTTrggKIPIRW-TAPEA-IAFRKFTSASDVWSYGIVMWE 802
Cdd:cd07833  157 PLTD---YVATRWyRAPELlVGDTNYGKPVDVWAIGCIMAE 194
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
609-798 7.30e-19

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 87.36  E-value: 7.30e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERvIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEkQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd06613    5 IQR-IGSGTYGDVYKARNIATGEL---AAVKVIKLEPGD-DFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYC 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddpEAAYTTR 768
Cdd:cd06613   80 GGGSLQDIYQVT-GPLSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQL----TATIAKR 154
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 974005246 769 GGKI--PIrWTAPEAIAFRK---FTSASDVWSYGI 798
Cdd:cd06613  155 KSFIgtPY-WMAPEVAAVERkggYDGKCDIWALGI 188
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
631-861 7.32e-19

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 87.68  E-value: 7.32e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 631 KRELPVAIKTLKVGYtekqrRD----FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQFTV 706
Cdd:cd05077   34 EKEIKVILKVLDPSH-----RDislaFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSDVLTT 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 707 IQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV-------CKVSDFGLSRVLEDDPEaayttRGGKIPirWTAP 779
Cdd:cd05077  109 PWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLSDPGIPITVLSRQE-----CVERIP--WIAP 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 780 EAIA-FRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPmDCpAALYQLMLDCWQKERNSRPKFD 858
Cdd:cd05077  182 ECVEdSKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYEGQCMLVTP-SC-KELADLMTHCMNYDPNQRPFFR 259

                 ...
gi 974005246 859 EIV 861
Cdd:cd05077  260 AIM 262
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
638-840 8.64e-19

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 87.28  E-value: 8.64e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 638 IKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGV-VTKSKPVMI-VTEYMENGSLDTFLKKndgqFTVIQ---LVGM 712
Cdd:cd13983   34 IKLRKLPKAERQR--FKQEIEILKSLKHPNIIKFYDSwESKSKKEVIfITELMTSGTLKQYLKR----FKRLKlkvIKSW 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 713 LRGISAGMKYL--SDMGYVHRDLAARNILINSNL-VCKVSDFGLSRVLEDDpeAAYTTRGgkIPiRWTAPEaIAFRKFTS 789
Cdd:cd13983  108 CRQILEGLNYLhtRDPPIIHRDLKCDNIFINGNTgEVKIGDLGLATLLRQS--FAKSVIG--TP-EFMAPE-MYEEHYDE 181
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 790 ASDVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRlpspmdcPAALY 840
Cdd:cd13983  182 KVDIYAFGMCLLEMAT-GEYPYSECTNaAQIYKKVTSGIK-------PESLS 225
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
608-802 8.76e-19

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 88.89  E-value: 8.76e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY--TEKQRRDFLgEASIMGQFDHPNIIHLEGVVTKSKPVM--- 682
Cdd:cd07851   18 QNLSPVGSGAYGQVCSAFDTKTGRK---VAIKKLSRPFqsAIHAKRTYR-ELRLLKHMKHENVIGLLDVFTPASSLEdfq 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 ---IVTEYMeNGSLDTFLKK---NDG--QFTVIQlvgMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS 754
Cdd:cd07851   94 dvyLVTHLM-GADLNNIVKCqklSDDhiQFLVYQ---ILRG----LKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLA 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 755 RVLEDDPEAAYTTrggkipiRW-TAPEAI-AFRKFTSASDVWSYGIVMWE 802
Cdd:cd07851  166 RHTDDEMTGYVAT-------RWyRAPEIMlNWMHYNQTVDIWSVGCIMAE 208
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
662-867 1.01e-18

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 87.22  E-value: 1.01e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 662 QFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgqftvIQLVGMLR-----GISAGMKYLSDMGYVHRDLAAR 736
Cdd:cd14045   58 ELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNED-----IPLNWGFRfsfatDIARGMAYLHQHKIYHGRLKSS 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 737 NILINSNLVCKVSDFGLSRVLEDD-PEAAYTTRGGKIPIrWTAPEAIAFRKF--TSASDVWSYGIVMWEVVSYGErpywe 813
Cdd:cd14045  133 NCVIDDRWVCKIADYGLTTYRKEDgSENASGYQQRLMQV-YLPPENHSNTDTepTQATDVYSYAIILLEIATRND----- 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 814 mTNQDVIKAVEEGYRLPSP----------MDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14045  207 -PVPEDDYSLDEAWCPPLPelisgktensCPCPADYVELIRRCRKNNPAQRPTFEQIKKTLHKI 269
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
613-802 1.11e-18

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 87.38  E-value: 1.11e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTL----KVGYTEKQrrdFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd07832    8 IGEGAHGIVFKAKDRETGE---TVALKKValrkLEGGIPNQ---ALREIKALQACqGHPYVVKLRDVFPHGTGFVLVFEY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MEnGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd07832   82 ML-SSLSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDPRLYSH 160
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 974005246 768 RggkIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWE 802
Cdd:cd07832  161 Q---VATRWyRAPELLyGSRKYDEGVDLWAVGCIFAE 194
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
590-812 1.39e-18

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 87.40  E-value: 1.39e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 590 DPNQAVHEFAKeieascitiervIGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRDFL-GEASIMGQFDHPNI 668
Cdd:cd06658   19 DPREYLDSFIK------------IGEGSTGIVCIATEKHTGKQ---VAVK--KMDLRKQQRRELLfNEVVIMRDYHHENV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 669 IHLEGVVTKSKPVMIVTEYMENGSLD---TFLKKNDGQFTVIQLvGMLRGISagmkYLSDMGYVHRDLAARNILINSNLV 745
Cdd:cd06658   82 VDMYNSYLVGDELWVVMEFLEGGALTdivTHTRMNEEQIATVCL-SVLRALS----YLHNQGVIHRDIKSDSILLTSDGR 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 746 CKVSDFGLSRVLEDDPEAAYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW 812
Cdd:cd06658  157 IKLSDFGFCAQVSKEVPKRKSLVGTPY---WMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPYF 219
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
635-867 1.62e-18

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 86.86  E-value: 1.62e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 635 PVAIKTLKVG---YTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN----DGQFTVI 707
Cdd:cd14044   33 VVILKDLKNNegnFTEKQKI----ELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVLNDKisypDGTFMDW 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 708 QL-VGMLRGISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAayttrggkipirWTAPEAIAFR 785
Cdd:cd14044  109 EFkISVMYDIAKGMSYLhSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSKDL------------WTAPEHLRQA 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 786 KFTSASDVWSYGIVMWEVVSYGERPY-----------WEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSR 854
Cdd:cd14044  177 GTSQKGDVYSYGIIAQEIILRKETFYtaacsdrkekiYRVQNPKGMKPFRPDLNLESAGEREREVYGLVKNCWEEDPEKR 256
                        250
                 ....*....|...
gi 974005246 855 PKFDEIVNMLDKL 867
Cdd:cd14044  257 PDFKKIENTLAKI 269
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
609-851 2.68e-18

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 85.77  E-value: 2.68e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14081    5 LGKTLGKGQTGLVKLAKHCVTGQK---VAIKIVNKEklSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvLEDDPEAAYT 766
Cdd:cd14081   82 YVSGGELFDYLVKK-GRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMAS-LQPEGSLLET 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGkiPiRWTAPEAIAFRKFT-SASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPS--PMDCpAALYQL 842
Cdd:cd14081  160 SCGS--P-HYACPEVIKGEKYDgRKADIWSCGVILYALLV-GALPFDDDNLRQLLEKVKRGvFHIPHfiSPDA-QDLLRR 234

                 ....*....
gi 974005246 843 MLDCWQKER 851
Cdd:cd14081  235 MLEVNPEKR 243
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
609-810 2.71e-18

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 87.42  E-value: 2.71e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQ--RRDfLGEASIMGQFDHPNIIHLEGVVTKSKP------ 680
Cdd:cd07855    9 PIETIGSGAYGVVCSAIDTKSGQK---VAIKKIPNAFDVVTtaKRT-LRELKILRHFKHDNIIAIRDILRPKVPyadfkd 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENgSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd07855   85 VYVVLDLMES-DLHHIIH-SDQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGLCTS 162
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 761 PEAAYTTRGGKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVVsyGERP 810
Cdd:cd07855  163 PEEHKYFMTEYVATRWyRAPELMlSLPEYTQAIDMWSVGCIFAEML--GRRQ 212
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
609-832 3.18e-18

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 85.39  E-value: 3.18e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQR-RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05578    4 ILRVIGKGSFGKVCIVQKKDTKKM---FAMKYMnKQKCIEKDSvRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAayT 766
Cdd:cd05578   81 LLLGGDLRYHLQQK-VKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTLA--T 157
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQ--DVIKAVEEGYRLPSP 832
Cdd:cd05578  158 STSGTKP--YMAPEVFMRAGYSFAVDWWSLGVTAYEML-RGKRPYEIHSRTsiEEIRAKFETASVLYP 222
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
608-860 3.50e-18

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 85.30  E-value: 3.50e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVcsgRLKLPGKRELPVAIKTL--KVGYTEKQRRDFLGEASIMGQFDHPNIIHL-EGVVTKSKPVMIV 684
Cdd:cd14164    3 TLGTTIGEGSFSKV---KLATSQKYCCKVAIKIVdrRRASPDFVQKFLPRELSILRRVNHPNIVQMfECIEVANGRLYIV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENgSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN-LVCKVSDFGLSRVLEDDPEA 763
Cdd:cd14164   80 MEAAAT-DLLQKIQEV-HHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSADdRKIKIADFGFARFVEDYPEL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIpirWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVSyGERPYWEmTNQDVIKAVEEGYRLPSPMD----CPAA 838
Cdd:cd14164  158 STTFCGSRA---YTPPEVILGTPYDPKKyDVWSLGVVLYVMVT-GTMPFDE-TNVRRLRLQQRGVLYPSGVAleepCRAL 232
                        250       260
                 ....*....|....*....|..
gi 974005246 839 LYQLMldcwQKERNSRPKFDEI 860
Cdd:cd14164  233 IRTLL----QFNPSTRPSIQQV 250
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
611-863 4.31e-18

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 85.17  E-value: 4.31e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRlklpgKRELPVAIKTLKVGYT---EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd08221    6 RVLGRGAFGEAVLYR-----KTEDNSLVVWKEVNLSrlsEKERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNI-LINSNLVcKVSDFGLSRVLEDDPEAAY 765
Cdd:cd08221   81 CNGGNLHDKIAQQKNQlFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIfLTKADLV-KLGDFGISKVLDSESSMAE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgeRPYWEMTNQ--DVIKAVEEGYRLPSPmDCPAALYQLM 843
Cdd:cd08221  160 SIVGTPY---YMSPELVQGVKYNFKSDIWAVGCVLYELLTL--KRTFDATNPlrLAVKIVQGEYEDIDE-QYSEEIIQLV 233
                        250       260
                 ....*....|....*....|
gi 974005246 844 LDCWQKERNSRPKFDEIVNM 863
Cdd:cd08221  234 HDCLHQDPEDRPTAEELLER 253
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
609-811 4.33e-18

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 85.22  E-value: 4.33e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSG---RLKLPgkrelpVAIKTLKvgyTEKQRRDFLG-----EASIMGQFDHPNIIHL-EGVVTKSK 679
Cdd:cd14165    5 LGINLGEGSYAKVKSAyseRLKCN------VAIKIID---KKKAPDDFVEkflprELEILARLNHKSIIKTyEIFETSDG 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd14165   76 KVYIVMELGVQGDLLEFIKLR-GALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLR 154
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 760 DPEaayttrgGKIPIRWT--------APEAIAFRKFT-SASDVWSYGIVMWeVVSYGERPY 811
Cdd:cd14165  155 DEN-------GRIVLSKTfcgsaayaAPEVLQGIPYDpRIYDIWSLGVILY-IMVCGSMPY 207
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
609-831 4.35e-18

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 84.91  E-value: 4.35e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGkreLPVAIKTL------KVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14186    5 VLNLLGKGSFACVYRARSLHTG---LEVAIKMIdkkamqKAGMVQRVRN----EVEIHCQLKHPSILELYNYFEDSNYVY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd14186   78 LVLEMCHNGEMSRYLKNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHE 157
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVI-KAVEEGYRLPS 831
Cdd:cd14186  158 KHFTMCGTP---NYISPEIATRSAHGLESDVWSLGCMFYTLLV-GRPPFDTDTVKNTLnKVVLADYEMPA 223
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
637-864 4.35e-18

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 85.36  E-value: 4.35e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 637 AIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKskPVMIVTEYMENGSLDTFLKKNDGQFtvIQLVGMLR-- 714
Cdd:cd14000   41 MLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGIH--PLMLVLELAPLGSLDHLLQQDSRSF--ASLGRTLQqr 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 715 ---GISAGMKYLSDMGYVHRDLAARNILI-----NSNLVCKVSDFGLSRvlEDDPEAAYTTRGGKipiRWTAPEAIAFR- 785
Cdd:cd14000  117 ialQVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIIIKIADYGISR--QCCRMGAKGSEGTP---GFRAPEIARGNv 191
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 786 KFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYRLP-SPMDC--PAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14000  192 IYNEKVDVFSFGMLLYEILS-GGAPMVGHLKFPNEFDIHGGLRPPlKQYECapWPEVEVLMKKCWKENPQQRPTAVTVVS 270

                 ..
gi 974005246 863 ML 864
Cdd:cd14000  271 IL 272
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
612-805 4.75e-18

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 85.89  E-value: 4.75e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKL-PGKRELPVAIKTLKvgYTE----KQRRDFLGEASImgqfDHPNIIHL----EGVVTKSKPVM 682
Cdd:cd14055    2 LVGKGRFAEVWKAKLKQnASGQYETVAVKIFP--YEEyaswKNEKDIFTDASL----KHENILQFltaeERGVGLDRQYW 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYL-SD--------MGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd14055   76 LITAYHENGSLQDYLTRH--ILSWEDLCKMAGSLARGLAHLhSDrtpcgrpkIPIAHRDLKSSNILVKNDGTCVLADFGL 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 754 SRVLedDP-----EAAYTTRGGKipIRWTAPEAIAFR-------KFTSAsDVWSYGIVMWEVVS 805
Cdd:cd14055  154 ALRL--DPslsvdELANSGQVGT--ARYMAPEALESRvnledleSFKQI-DVYSMALVLWEMAS 212
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
613-845 6.29e-18

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 84.62  E-value: 6.29e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEV-----CSGRLklpgkrelpVAIKTLKVGYTeKQRRDFLG---EASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd14161   11 LGKGTYGRVkkardSSGRL---------VAIKSIRKDRI-KDEQDLLHirrEIEIMSSLNHPHIISVYEVFENSSKIVIV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAA 764
Cdd:cd14161   81 MEYASRGDLYDYISERQ-RLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQD--KF 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGKiPIrWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVEEG-YRLPS-PMD-CPAALY 840
Cdd:cd14161  158 LQTYCGS-PL-YASPEIVNGRPYIGPEvDSWSLGVLLYILV-HGTMPFDGHDYKILVKQISSGaYREPTkPSDaCGLIRW 234

                 ....*
gi 974005246 841 QLMLD 845
Cdd:cd14161  235 LLMVN 239
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
611-817 6.46e-18

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 84.66  E-value: 6.46e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVC------SGRLklpgkrelpVAIKTLK-VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd06626    6 NKIGEGTFGKVYtavnldTGEL---------MAMKEIRfQDNDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYI 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKKNDGQ-FTVIQL--VGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED- 759
Cdd:cd06626   77 FMEYCQEGTLEELLRHGRILdEAVIRVytLQLLEGLA----YLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNn 152
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 760 ----DPEAAYTTRGGKIpirWTAPEAIAFRKFTS---ASDVWSYGIVMWEVVSyGERPYWEMTNQ 817
Cdd:cd06626  153 tttmAPGEVNSLVGTPA---YMAPEVITGNKGEGhgrAADIWSLGCVVLEMAT-GKRPWSELDNE 213
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
612-832 1.24e-17

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 84.27  E-value: 1.24e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRrDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14166   10 VLGSGAFSEVYLVKQRSTGKL---YALKCIKKSPLSRDS-SLENEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSGG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRVLEDD-PEAAYT 766
Cdd:cd14166   86 ELfDRILER--GVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSKMEQNGiMSTACG 163
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 767 TRGgkipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14166  164 TPG------YVAPEVLAQKPYSKAVDCWSIGVITYILLC-GYPPFYEETESRLFEKIKEGyYEFESP 223
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
609-811 1.35e-17

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 84.07  E-value: 1.35e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRELP--VAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd14076    5 LGRTLGEGEFGKVKLGWPLPKANHRSGvqVAIKLIRRDtqQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIGIV 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSL------DTFLKKNDGQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL- 757
Cdd:cd14076   85 LEFVSGGELfdyilaRRRLKDSVACRLFAQLI-------SGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFd 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 758 EDDPEAAYTTRGGKIpirWTAPEAIAFRKFTSAS--DVWSYGIVMWEVVSyGERPY 811
Cdd:cd14076  158 HFNGDLMSTSCGSPC---YAAPELVVSDSMYAGRkaDIWSCGVILYAMLA-GYLPF 209
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
612-879 1.38e-17

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 84.06  E-value: 1.38e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDH---PNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd06917    8 LVGRGSYGAVYRGYHVKTGR---VVALKVLNLDTDDDDVSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYC 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQFTVIQLVgmLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTR 768
Cdd:cd06917   85 EGGSIRTLMRAGPIAERYIAVI--MREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKRSTFV 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GgkIPIrWTAPEAIA-FRKFTSASDVWSYGIVMWEVVsYGERPYwemTNQDVIKAV-----EEGYRLPSPMDCPaALYQL 842
Cdd:cd06917  163 G--TPY-WMAPEVITeGKYYDTKADIWSLGITTYEMA-TGNPPY---SDVDALRAVmlipkSKPPRLEGNGYSP-LLKEF 234
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 974005246 843 MLDCWQKERNSRPKFDEIVNMldKLIRN-----PSSLKTLVN 879
Cdd:cd06917  235 VAACLDEEPKDRLSADELLKS--KWIKQhsktpTSVLKELIS 274
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
609-855 1.93e-17

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 83.10  E-value: 1.93e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd08219    4 VLRVVGEGSFGRALLVQHVNSDQK---YAMKEIRLPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd08219   81 DGGDLMQKIKLQRGKlFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAYACTY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCW 847
Cdd:cd08219  161 VGTPY---YVPPEIWENMPYNNKSDIWSLGCILYELCTL-KHPFQANSWKNLILKVCQGSYKPLPSHYSYELRSLIKQMF 236

                 ....*...
gi 974005246 848 QKERNSRP 855
Cdd:cd08219  237 KRNPRSRP 244
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
613-802 2.24e-17

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 83.11  E-value: 2.24e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpGKRELpVAIKTlkvgyTEKQRRD-FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14010    8 IGRGKHSVVYKGRRK--GTIEF-VAIKC-----VDKSKRPeVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDG-QFTVIQLVGmlRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGG 770
Cdd:cd14010   80 DLETLLRQDGNlPESSVRKFG--RDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGEILKELFGQFSD 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 771 ---------KIPIR----WTAPEAIAFRKFTSASDVWSYGIVMWE 802
Cdd:cd14010  158 egnvnkvskKQAKRgtpyYMAPELFQGGVHSFASDLWALGCVLYE 202
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
608-868 2.25e-17

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 83.50  E-value: 2.25e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEkQRRDFLGEASIMGQFDHPNIIHLE--GVVTK---SKPVM 682
Cdd:cd13986    3 RIQRLLGEGGFSFVYLVEDLSTGR---LYALKKILCHSKE-DVKEAMREIENYRLFNHPNILRLLdsQIVKEaggKKEVY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSL----DTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDM---GYVHRDLAARNILINSNLVCKVSDFG--- 752
Cdd:cd13986   79 LLLPYYKRGSLqdeiERRLVKGT-FFPEDRILHIFLGICRGLKAMHEPelvPYAHRDIKPGNVLLSEDDEPILMDLGsmn 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 753 LSRV-LEDDPEA----AYTTRGGKIPirWTAPEAIAFRK---FTSASDVWSYGIVMWEVVsYGERPYwEMTNQ---DVIK 821
Cdd:cd13986  158 PARIeIEGRREAlalqDWAAEHCTMP--YRAPELFDVKShctIDEKTDIWSLGCTLYALM-YGESPF-ERIFQkgdSLAL 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 822 AVEEG-YRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLI 868
Cdd:cd13986  234 AVLSGnYSFPDNSRYSEELHQLVKSMLVVNPAERPSIDDLLSRVHDLI 281
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
597-806 3.13e-17

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 84.54  E-value: 3.13e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 597 EFAKEIEASC-ITIERVIGAGEFGEVCSGRLklPGKRElPVaikTLKVGytekQRRDFLGEASIMGQFDHPNIIHL-EGV 674
Cdd:PHA03209  57 QKAREVVASLgYTVIKTLTPGSEGRVFVATK--PGQPD-PV---VLKIG----QKGTTLIEAMLLQNVNHPSVIRMkDTL 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 675 VTKSKPVMIVTEYmeNGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS-NLVCkVSDFGL 753
Cdd:PHA03209 127 VSGAITCMVLPHY--SSDLYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDvDQVC-IGDLGA 203
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 754 SRVleddPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSY 806
Cdd:PHA03209 204 AQF----PVVAPAFLGLAGTVETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
649-861 3.88e-17

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 82.37  E-value: 3.88e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 649 QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGY 728
Cdd:cd14188   44 QREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARK-VLTEPEVRYYLRQIVSGLKYLHEQEI 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 729 VHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSygE 808
Cdd:cd14188  123 LHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRTICGTP---NYLSPEVLNKQGHGCESDIWALGCVMYTMLL--G 197
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 809 RPYWEMTN-QDVIKAVEEG-YRLPSPMDCPAAlyQLMLDCWQKERNSRPKFDEIV 861
Cdd:cd14188  198 RPPFETTNlKETYRCIREArYSLPSSLLAPAK--HLIASMLSKNPEDRPSLDEII 250
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
611-803 3.90e-17

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 82.10  E-value: 3.90e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRELpvaIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKPVMIVTEYM 688
Cdd:cd08223    6 RVIGKGSYGEVWLVRHKRDRKQYV---IKKLNLkNASKRERKAAEQEAKLLSKLKHPNIVsYKESFEGEDGFLYIVMGFC 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd08223   83 EGGDLYTRLKEQKGVlLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSSDMATTL 162
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 974005246 768 RGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd08223  163 IGTPY---YMSPELFSNKPYNHKSDVWALGCCVYEM 195
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
613-811 3.98e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 82.88  E-value: 3.98e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpgKRELPVAIKTLKV--GYTEKQRRDFLGEASIMGQFDHPNII-------HLEGVVTKSKPVMI 683
Cdd:cd13989    1 LGSGGFGYVTLWKHQ---DTGEYVAIKKCRQelSPSDKNRERWCLEVQIMKKLNHPNVVsardvppELEKLSPNDLPLLA 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VtEYMENGSLDTFLK--KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRVLe 758
Cdd:cd13989   78 M-EYCSGGDLRKVLNqpENCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLqqgGGRVIYKLIDLGYAKEL- 155
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 759 DDPEAAYTTRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd13989  156 DQGSLCTSFVG---TLQYLAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPF 204
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
612-814 3.99e-17

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 82.74  E-value: 3.99e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKP------VMIV 684
Cdd:cd06608   13 VIGEGTYGKVYKARHKKTGQL---AAIKIMD--IIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPpggddqLWLV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGS---LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd06608   88 MEYCGGGSvtdLVKGLRKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQLDSTL 167
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 762 EAAYTTRGgkIPIrWTAPEAIAFRK-----FTSASDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06608  168 GRRNTFIG--TPY-WMAPEVIACDQqpdasYDARCDVWSLGITAIELAD-GKPPLCDM 221
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
636-863 4.03e-17

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 82.86  E-value: 4.03e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKTLKVGYTEKQRRDFLGEASI-MGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgSLDTFLKK--NDGQFTVIQLVG- 711
Cdd:cd06617   29 MAVKRIRATVNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICMEVMDT-SLDKFYKKvyDKGLTIPEDILGk 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 712 MLRGISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYTTRGGKIPirWTAPEAI----AFRK 786
Cdd:cd06617  108 IAVSIVKALEYLhSKLSVIHRDVKPSNVLINRNGQVKLCDFGISGYLVDS--VAKTIDAGCKP--YMAPERInpelNQKG 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 787 FTSASDVWSYGIVMWEVVSyGERPY--WEMTNQDVIKAVEEgyrlPSPmDCPAALYQLMLD-----CWQKERNSRPKFDE 859
Cdd:cd06617  184 YDVKSDVWSLGITMIELAT-GRFPYdsWKTPFQQLKQVVEE----PSP-QLPAEKFSPEFQdfvnkCLKKNYKERPNYPE 257

                 ....
gi 974005246 860 IVNM 863
Cdd:cd06617  258 LLQH 261
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
612-832 4.56e-17

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 82.03  E-value: 4.56e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14083   10 VLGTGAFSEVVLAEDKATGKL---VAIKCIDKKALKGKEDSLENEIAVLRKIKHPNIVQLLDIYESKSHLYLVMELVTGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVckVSDFGLSRVleDDPEAAY 765
Cdd:cd14083   87 ELfDRIVEK--GSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYyspdeDSKIM--ISDFGLSKM--EDSGVMS 160
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 766 T---TRGgkipirWTAPEAIAFRKFTSASDVWSYGivmweVVSY----GERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14083  161 TacgTPG------YVAPEVLAQKPYGKAVDCWSIG-----VISYillcGYPPFYDENDSKLFAQILKAeYEFDSP 224
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
609-811 5.13e-17

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 82.26  E-value: 5.13e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKrelPVAIKTL---------KVGYTEKQRRdflgeasIMGQFDHPNIIHLEGVVTKSK 679
Cdd:cd05581    5 FGKPLGEGSYSTVVLAKEKETGK---EYAIKVLdkrhiikekKVKYVTIEKE-------VLSRLAHPGIVKLYYTFQDES 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENGSLDTFLKKN------DGQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd05581   75 KLYFVLEYAPNGDLLEYIRKYgsldekCTRFYTAEIV-------LALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGT 147
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 754 SRVL--EDDPEAAYTTRGGKIPI------------RWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPY 811
Cdd:cd05581  148 AKVLgpDSSPESTKGDADSQIAYnqaraasfvgtaEYVSPELLNEKPAGKSSDLWALGCIIYQML-TGKPPF 218
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
607-867 5.31e-17

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 82.32  E-value: 5.31e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpGKrelpVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14152    2 IELGELIGQGRWGKVHRGRWH--GE----VAIRLLEIdGNNQDHLKLFKKEVMNYRQTRHENVVLFMGACMHPPHLAIIT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCkVSDFGL---SRVLEDDPE 762
Cdd:cd14152   76 SFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLfgiSGVVQEGRR 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTtrggKIPIRWT---APEAIafRK-----------FTSASDVWSYGIVMWEVvsygERPYWEMTNQDV------IKA 822
Cdd:cd14152  155 ENEL----KLPHDWLcylAPEIV--REmtpgkdedclpFSKAADVYAFGTIWYEL----QARDWPLKNQPAealiwqIGS 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 823 VEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14152  225 GEGMKQVLTTISLGKEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
901-962 5.67e-17

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 76.14  E-value: 5.67e-17
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09545    5 SVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMRSQM 66
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
608-872 5.82e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 82.54  E-value: 5.82e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgyTEKQRRDF----LGEASIMGQFDHPNIIHLEGVVTKSKPVM- 682
Cdd:cd07864   10 DIIGIIGEGTYGQVYKAKDKDTGEL---VALKKVR---LDNEKEGFpitaIREIKILRQLNHRSVVNLKEIVTDKQDALd 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 ---------IVTEYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd07864   84 fkkdkgafyLVFEYMDH-DLMGLLESGLVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGL 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLEDDPEAAYTTRggKIPIRWTAPE-AIAFRKFTSASDVWSYGIVMWEVvsYGERPYW----EMTNQDVIKAVeegyr 828
Cdd:cd07864  163 ARLYNSEESRPYTNK--VITLWYRPPElLLGEERYGPAIDVWSCGCILGEL--FTKKPIFqanqELAQLELISRL----- 233
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 829 LPSPmdCPAA--------LYQLMLDCWQKERNSRPKFD----EIVNMLDKLIR-NPS 872
Cdd:cd07864  234 CGSP--CPAVwpdviklpYFNTMKPKKQYRRRLREEFSfiptPALDLLDHMLTlDPS 288
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
612-816 7.66e-17

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 81.69  E-value: 7.66e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEkQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06624   15 VLGKGTFGVVYAARDLSTQVR---IAIKEIPERDSR-EVQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGG 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQF----TVIQLVGmlRGISAGMKYLSDMGYVHRDLAARNILINS-NLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd06624   91 SLSALLRSKWGPLkdneNTIGYYT--KQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGTSKRLAGINPCTET 168
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 767 TRGgkiPIRWTAPEAIA--FRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN 816
Cdd:cd06624  169 FTG---TLQYMAPEVIDkgQRGYGPPADIWSLGCTIIEMAT-GKPPFIELGE 216
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
613-840 1.29e-16

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 82.12  E-value: 1.29e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQR---RDFLG----------EASIMGQFDHPNIIHLEGVVTKSK 679
Cdd:PTZ00024  17 LGEGTYGKVEKAYDTLTGKI---VAIKKVKIIEISNDVtkdRQLVGmcgihfttlrELKIMNEIKHENIMGLVDVYVEGD 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENGsldtfLKK---NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV 756
Cdd:PTZ00024  94 FINLVMDIMASD-----LKKvvdRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARR 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDPEAAYTTRG----------GKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVVSygERPYWEMTNQdvIKAVE 824
Cdd:PTZ00024 169 YGYPPYSDTLSKDetmqrreemtSKVVTLWyRAPELLmGAEKYHFAVDMWSVGCIFAELLT--GKPLFPGENE--IDQLG 244
                        250
                 ....*....|....*....
gi 974005246 825 EGYRL---PSPMDCPAALY 840
Cdd:PTZ00024 245 RIFELlgtPNEDNWPQAKK 263
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
610-813 1.37e-16

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 80.92  E-value: 1.37e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKrelPVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14082    8 DEVLGSGQFGIVYGGKHRKTGR---DVAIKVIdKLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDG-------QFTVIQlvgmlrgISAGMKYLSDMGYVHRDLAARNILINSNL---VCKVSDFGLSRVLe 758
Cdd:cd14082   85 HGDMLEMILSSEKGrlperitKFLVTQ-------ILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARII- 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 759 ddPEAAYTTRGGKIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWE 813
Cdd:cd14082  157 --GEKSFRRSVVGTPA-YLAPEVLRNKGYNRSLDMWSVGVIIYVSLS-GTFPFNE 207
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
613-867 1.38e-16

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 81.08  E-value: 1.38e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLklpgkRELPVAIKTLKVGYT---EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14160    1 IGEGEIFEVYRVRI-----GNRSYAVKLFKQEKKmqwKKHWKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQ 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDM---GYVHRDLAARNILINSNLVCKVSDFGLSRV---LEDDP 761
Cdd:cd14160   76 NGTLFDRLQCHGVTkpLSWHERINILIGIAKAIHYLHNSqpcTVICGNISSANILLDDQMQPKLTDFALAHFrphLEDQS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN----QDVIKAVEEGYRL-------- 829
Cdd:cd14160  156 CTINMTTALHKHLWYMPEEYIRQGKLSVKTDVYSFGIVIMEVLT-GCKVVLDDPKhlqlRDLLHELMEKRGLdsclsfld 234
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 974005246 830 ----PSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14160  235 lkfpPCPRNFSAKLFRLAGRCTATKAKLRPDMDEVLQRLEST 276
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
609-802 1.42e-16

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 82.56  E-value: 1.42e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERV--IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:PLN00034  76 LERVnrIGSGAGGTVYKVIHRPTGR---LYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLE 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTfLKKNDGQFtviqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:PLN00034 153 FMDGGSLEG-THIADEQF----LADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRILAQTMDPCNS 227
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 974005246 767 TRGgkiPIRWTAPEAI-------AFRKFtsASDVWSYGIVMWE 802
Cdd:PLN00034 228 SVG---TIAYMSPERIntdlnhgAYDGY--AGDIWSLGVSILE 265
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
613-803 1.47e-16

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 82.03  E-value: 1.47e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRD---FLGEASIMGQFDHPNIIHLEGVVTKS-----KPVMIV 684
Cdd:cd07858   13 IGRGAYGIVCSAKNSETNEK---VAIK--KIANAFDNRIDakrTLREIKLLRHLDHENVIAIKDIMPPPhreafNDVYIV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENgSLDTFLKKNDG------QFTVIQLvgmLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE 758
Cdd:cd07858   88 YELMDT-DLHQIIRSSQTlsddhcQYFLYQL---LRG----LKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTS 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 759 DDPE---AAYTTRggkipiRWTAPEAI-AFRKFTSASDVWSYGIVMWEV 803
Cdd:cd07858  160 EKGDfmtEYVVTR------WYRAPELLlNCSEYTTAIDVWSVGCIFAEL 202
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
611-862 1.48e-16

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 80.48  E-value: 1.48e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEV--CsgrLKLPGKRELpvAIKTLKVGY----TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd06625    6 KLLGQGAFGQVylC---YDADTGREL--AVKQVEIDPinteASKEVKALECEIQLLKNLQHERIVQYYGCLQDEKSLSIF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddpeaA 764
Cdd:cd06625   81 MEYMPGGSVKDEIKAY-GALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQ-----T 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGKIPIR----WTAPEAIAFRKFTSASDVWSYGIVMWEVVSygERPYW----EMTNQDVIKAVEEGYRLPSpmDCP 836
Cdd:cd06625  155 ICSSTGMKSVTgtpyWMSPEVINGEGYGRKADIWSVGCTVVEMLT--TKPPWaefePMAAIFKIATQPTNPQLPP--HVS 230
                        250       260
                 ....*....|....*....|....*.
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd06625  231 EDARDFLSLIFVRNKKQRPSAEELLS 256
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
609-811 1.95e-16

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 80.43  E-value: 1.95e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVcsgrLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14191    6 IEERLGSGKFGQV----FRLVEKKTKKVWAGKFFKAYSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI--NSNLVCKVSDFGLSRVLEDdpeaayt 766
Cdd:cd14191   82 SGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCvnKTGTKIKLIDFGLARRLEN------- 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 trGGKIPI-----RWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14191  155 --AGSLKVlfgtpEFVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPF 201
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
609-867 2.04e-16

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 80.85  E-value: 2.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd08229   28 IEKKIGRGQFSEVYRATCLLDG---VPVALKKVQIFdlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLR---GISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd08229  105 LADAGDLSRMIKHFKKQKRLIPEKTVWKyfvQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTA 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYW--EMTNQDVIKAVEEGYRLPSPMD-CPAALY 840
Cdd:cd08229  185 AHSLVGTPY---YMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYgdKMNLYSLCKKIEQCDYPPLPSDhYSEELR 260
                        250       260
                 ....*....|....*....|....*..
gi 974005246 841 QLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd08229  261 QLVNMCINPDPEKRPDITYVYDVAKRM 287
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
613-865 2.48e-16

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 80.78  E-value: 2.48e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNII-------HLEGVVTKSKPvMIVT 685
Cdd:cd14038    2 LGTGGFGNVLRWINQETGEQ---VAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVVaardvpeGLQKLAPNDLP-LLAM 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLK--KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILIN---SNLVCKVSDFGLSRVLedD 760
Cdd:cd14038   78 EYCQGGDLRKYLNqfENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQqgeQRLIHKIIDLGYAKEL--D 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 761 PEAAYTTRGGKIpiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY---WE----------------MTNQDVIK 821
Cdd:cd14038  156 QGSLCTSFVGTL--QYLAPELLEQQKYTVTVDYWSFGTLAFECIT-GFRPFlpnWQpvqwhgkvrqksnediVVYEDLTG 232
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 822 AVEEGYRLPSPMDCPAAL-------YQLMLDCWQKERNSRPK------FDEIVNMLD 865
Cdd:cd14038  233 AVKFSSVLPTPNNLNGILagklerwLQCMLMWHPRQRGTDPPqnpngcFQALDSILN 289
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
609-826 2.95e-16

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 79.83  E-value: 2.95e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14098    4 IIDRLGSGTFAEVKKAVEVETGKMRAIKQIVKRKVAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDGqftVIQLVG--MLRGISAGMKYLSDMGYVHRDLAARNILINSN--LVCKVSDFGLSRVLEDDpeAA 764
Cdd:cd14098   84 EGGDLMDFIMAWGA---IPEQHAreLTKQILEAMAYTHSMGITHRDLKPENILITQDdpVIVKISDFGLAKVIHTG--TF 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 765 YTTRGGKipIRWTAPEAIAFRK------FTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEG 826
Cdd:cd14098  159 LVTFCGT--MAYLAPEILMSKEqnlqggYSNLVDMWSVGCLVY-VMLTGALPFDGSSQLPVEKRIRKG 223
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
613-802 3.63e-16

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 80.49  E-value: 3.63e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgyteKQRRD-----FLGEASIMGQFDHPNIIHLEGVVTKSK--PVMIVT 685
Cdd:cd07845   15 IGEGTYGIVYRARDTTSGEI---VALKKVRM----DNERDgipisSLREITLLLNLRHPNIVELKEVVVGKHldSIFLVM 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEdDPEAAY 765
Cdd:cd07845   88 EYCEQ-DLASLLDNMPTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYG-LPAKPM 165
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 974005246 766 TTRggKIPIRWTAPEAI-AFRKFTSASDVWSYGIVMWE 802
Cdd:cd07845  166 TPK--VVTLWYRAPELLlGCTTYTTAIDMWAVGCILAE 201
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
613-824 3.80e-16

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 80.07  E-value: 3.80e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQRRDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06657   28 IGEGSTGIVCIATVKSSGKL---VAVK--KMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGG 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLD---TFLKKNDGQFTVIqLVGMLRGISAgmkyLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTR 768
Cdd:cd06657  103 ALTdivTHTRMNEEQIAAV-CLAVLKALSV----LHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLV 177
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 769 GGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWemtNQDVIKAVE 824
Cdd:cd06657  178 GTPY---WMAPELISRLPYGPEVDIWSLGIMVIEMVD-GEPPYF---NEPPLKAMK 226
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
612-823 3.86e-16

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 79.62  E-value: 3.86e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14192   11 VLGGGRFGQVHKCTELSTG---LTLAAKIIKVK-GAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL-INS--NLVcKVSDFGLSRVLEddPEAAYTTR 768
Cdd:cd14192   87 ELFDRITDESYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILcVNStgNQI-KIIDFGLARRYK--PREKLKVN 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 769 GGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV 823
Cdd:cd14192  164 FGT-P-EFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
607-811 4.31e-16

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 79.54  E-value: 4.31e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGrLKLPGKRELpvAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd06619    3 IQYQEILGHGNGGTVYKA-YHLLTRRIL--AVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQlVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd06619   80 FMDGGSLDVYRKIPEHVLGRIA-VAVVKGLT----YLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIAKTYV 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 767 TRGGkipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd06619  155 GTNA-----YMAPERISGEQYGIHSDVWSLGISFMELAL-GRFPY 193
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
613-820 4.71e-16

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 79.67  E-value: 4.71e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrLKLPGKRELPVAIKTLKVGYTEKQRRDF----LGEASIMGQFDHPNIIHLEGVVTKSKPVMI-VTEY 687
Cdd:cd13990    8 LGKGGFSEVYKA-FDLVEQRYVACKIHQLNKDWSEEKKQNYikhaLREYEIHKSLDHPRIVKLYDVFEIDTDSFCtVLEY 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLS--DMGYVHRDLAARNILINSNLVC---KVSDFGLSRVLEDDPE 762
Cdd:cd13990   87 CDGNDLDFYLKQH-KSIPEREARSIIMQVVSALKYLNeiKPPIIHYDLKPGNILLHSGNVSgeiKITDFGLSKIMDDESY 165
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 763 AAYT---TRGGKIPIRWTAPEAI----AFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVI 820
Cdd:cd13990  166 NSDGmelTSQGAGTYWYLPPECFvvgkTPPKISSKVDVWSVGVIFYQML-YGRKPFGHNQSQEAI 229
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
400-480 5.21e-16

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 73.80  E-value: 5.21e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   400 PSPVTNVKKGKIAKNSISLSWQEPDRPNGI--ILEYEIKYFEKDQETSYTIIKSKETTITAEGLKPASVYVFQIRARTAA 477
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80

                   ...
gi 974005246   478 GYG 480
Cdd:smart00060  81 GEG 83
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
613-854 5.37e-16

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 79.69  E-value: 5.37e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTlkvgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06643   13 LGDGAFGKVYKAQNKETGILAAAKVIDT----KSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGA 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS----RVLEDDPEAAYTTr 768
Cdd:cd06643   89 VDAVMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSakntRTLQRRDSFIGTP- 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 ggkipiRWTAPEAIAF-----RKFTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIK--AVEEGYRLPSPMDCPAALYQ 841
Cdd:cd06643  168 ------YWMAPEVVMCetskdRPYDYKADVWSLGVTLIEMAQI-EPPHHELNPMRVLLkiAKSEPPTLAQPSRWSPEFKD 240
                        250
                 ....*....|...
gi 974005246 842 LMLDCWQKERNSR 854
Cdd:cd06643  241 FLRKCLEKNVDAR 253
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
655-860 5.78e-16

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 79.01  E-value: 5.78e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 655 GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLA 734
Cdd:cd06630   52 EEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLLSKY-GAFSENVIINYTLQILRGLAYLHDNQIIHRDLK 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 735 ARNILINSN-LVCKVSDFGLSRVLeddpeAAYTTRGGKI------PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyg 807
Cdd:cd06630  131 GANLLVDSTgQRLRIADFGAAARL-----ASKGTGAGEFqgqllgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMAT-- 203
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 808 ERPYWEMTNQD----VIKAVEEGYRLPS-PMDCPAALYQLMLDCWQKERNSRPKFDEI 860
Cdd:cd06630  204 AKPPWNAEKISnhlaLIFKIASATTPPPiPEHLSPGLRDVTLRCLELQPEDRPPAREL 261
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
607-856 5.82e-16

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 79.39  E-value: 5.82e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlPGKRELpvAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVT--KSKPVMIV 684
Cdd:cd06621    3 IVELSSLGEGAGGSVTKCRLR-NTKTIF--ALKTITTDPNPDVQKQILRELEINKSCASPYIVKYYGAFLdeQDSSIGIA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLK---KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd06621   80 MEYCEGGSLDSIYKkvkKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELVNSL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTtrGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEvVSYGERPYWEMTNQDV--IKAVEEGYRLPSPM--DCPA 837
Cdd:cd06621  160 AGTFT--GTSY---YMAPERIQGGPYSITSDVWSLGLTLLE-VAQNRFPFPPEGEPPLgpIELLSYIVNMPNPElkDEPE 233
                        250       260
                 ....*....|....*....|....*.
gi 974005246 838 -------ALYQLMLDCWQKERNSRPK 856
Cdd:cd06621  234 ngikwseSFKDFIEKCLEKDGTRRPG 259
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
606-810 6.12e-16

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 78.50  E-value: 6.12e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 606 CITIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY-TEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMI 683
Cdd:cd14050    2 CFTILSKLGEGSFGEVFKVRSREDGKL---YAVKRSRSRFrGEKDRKRKLEEVERHEKLgEHPNCVRFIKAWEEKGILYI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMEnGSLDTFLKKND--GQFTVIQ-LVGMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLsrVLE-D 759
Cdd:cd14050   79 QTELCD-TSLQQYCEETHslPESEVWNiLLDLLKG----LKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGL--VVElD 151
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 760 DPEAAYTTRGGKipiRWTAPEAIAfRKFTSASDVWSYGIVMWEVVSYGERP 810
Cdd:cd14050  152 KEDIHDAQEGDP---RYMAPELLQ-GSFTKAADIFSLGITILELACNLELP 198
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
649-861 6.44e-16

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 78.82  E-value: 6.44e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 649 QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGY 728
Cdd:cd14189   44 QREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSLAHIWKARH-TLLEPEVRYYLKQIISGLKYLHLKGI 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 729 VHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGE 808
Cdd:cd14189  123 LHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICGTP---NYLAPEVLLRQGHGPESDVWSLGCVMYTLLC-GN 198
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005246 809 RPYWEMTNQDVIKAVEE-GYRLPSPMDCPAAlyQLMLDCWQKERNSRPKFDEIV 861
Cdd:cd14189  199 PPFETLDLKETYRCIKQvKYTLPASLSLPAR--HLLAGILKRNPGDRLTLDQIL 250
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
635-866 7.32e-16

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 79.37  E-value: 7.32e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 635 PVAIKTLKVGYTEKQRRDFLG----EASIMGQFDHPNIIHLEGVvTKSK--PVMIVTEYME---NGSLDTFLKKNDGQFT 705
Cdd:cd14001   30 PWAVKKINSKCDKGQRSLYQErlkeEAKILKSLNHPNIVGFRAF-TKSEdgSLCLAMEYGGkslNDLIEERYEAGLGPFP 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 706 VIQLVGMLRGISAGMKYL-SDMGYVHRDLAARNILINSNL-VCKVSDFGLSRVLED------DPEAAYTtrgGKIPirWT 777
Cdd:cd14001  109 AATILKVALSIARALEYLhNEKKILHGDIKSGNVLIKGDFeSVKLCDFGVSLPLTEnlevdsDPKAQYV---GTEP--WK 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 778 APEAI-AFRKFTSASDVWSYGIVMWEVVS--------------YGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQL 842
Cdd:cd14001  184 AKEALeEGGVITDKADIFAYGLVLWEMMTlsvphlnlldieddDEDESFDEDEEDEEAYYGTLGTRPALNLGELDDSYQK 263
                        250       260
                 ....*....|....*....|....*...
gi 974005246 843 MLD----CWQKERNSRPKFDEIVNMLDK 866
Cdd:cd14001  264 VIElfyaCTQEDPKDRPSAAHIVEALEA 291
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
613-863 7.89e-16

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 78.70  E-value: 7.89e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELpvAIKTLKV-----GYTEKQR----RDFLGEASIMG-QFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd08528    8 LGSGAFGCVYKVRKKSNGQTLL--ALKEINMtnpafGRTEQERdksvGDIISEVNIIKeQLRHPNIVRYYKTFLENDRLY 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSL-DTF--LKKNDGQFTVIQLVGMLRGISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlE 758
Cdd:cd08528   86 IVMELIEGAPLgEHFssLKEKNEHFTEDRIWNIFVQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAK--Q 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 759 DDPEAAYTTRGGKIpIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgeRPYWEMTNQDVI--KAVEEGYR-LPSPMdC 835
Cdd:cd08528  164 KGPESSKMTSVVGT-ILYSCPEIVQNEPYGEKADIWALGCILYQMCTL--QPPFYSTNMLTLatKIVEAEYEpLPEGM-Y 239
                        250       260
                 ....*....|....*....|....*...
gi 974005246 836 PAALYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd08528  240 SDDITFVIRSCLTPDPEARPDIVEVSSM 267
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
609-811 1.24e-15

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 77.96  E-value: 1.24e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCsgRLKLPGKRElPVAIKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14087    5 IKALIGRGSFSRVV--RVEHRVTRQ-PYAIKMIETKCRGREV--CESELNVLRRVRHTNIIQLIEVFETKERVYMVMELA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL-----INSNLVckVSDFGLSRVLEDDPE 762
Cdd:cd14087   80 TGGELfDRIIAK--GSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLyyhpgPDSKIM--ITDFGLASTRKKGPN 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 763 AAYTTRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14087  156 CLMKTTCGT-P-EYIAPEILLRKPYTQSVDMWAVGVIAYILLS-GTMPF 201
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
899-956 1.31e-15

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 71.96  E-value: 1.31e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 899 YRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQ 956
Cdd:cd09542    4 YRSVSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQ 61
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
613-867 1.42e-15

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 78.33  E-value: 1.42e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLklpgkRELPVAIKTLKVGYT---EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14159    1 IGEGGFGCVYQAVM-----RNTEYAVKRLKEDSEldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLP 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDG--QFTVIQLVGMLRGISAGMKYL-SDM-GYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAY 765
Cdd:cd14159   76 NGSLEDRLHCQVScpCLSWSQRLHVLLGTARAIQYLhSDSpSLIHGDVKSSNILLDAALNPKLGDFGLARFSRRPKQPGM 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 T-----TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERP-------------------------YWEMT 815
Cdd:cd14159  156 SstlarTQTVRGTLAYLPEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRAmevdscsptkylkdlvkeeeeaqhtPTTMT 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 816 NQDVIKAVEEGYRL------PSPMDCPA----ALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14159  235 HSAEAQAAQLATSIcqkhldPQAGPCPPelgiEISQLACRCLHRRAKKRPPMTEVFQELERL 296
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
609-855 1.51e-15

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 77.76  E-value: 1.51e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKV--GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd08228    6 IEKKIGRGQFSEVYRATCLLDRK---PVALKKVQIfeMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLR---GISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd08228   83 LADAGDLSQMIKYFKKQKRLIPERTVWKyfvQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYgERPYW--EMTNQDVIKAVEEGYRLPSPMD-CPAALY 840
Cdd:cd08228  163 AHSLVGTPY---YMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYgdKMNLFSLCQKIEQCDYPPLPTEhYSEKLR 238
                        250
                 ....*....|....*
gi 974005246 841 QLMLDCWQKERNSRP 855
Cdd:cd08228  239 ELVSMCIYPDPDQRP 253
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
611-811 1.56e-15

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 78.60  E-value: 1.56e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRlKLPGKRELPV-AIK-----TLKVgyteKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIV 684
Cdd:cd05582    1 KVLGQGSFGKVFLVR-KITGPDAGTLyAMKvlkkaTLKV----RDRVRTKMERDILADVNHPFIVKLHYAFQTEGKLYLI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAA 764
Cdd:cd05582   76 LDFLRGGDLFTRLSK-EVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKA 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 765 YTTRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05582  155 YSFCG---TVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPF 197
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
611-814 1.59e-15

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 77.49  E-value: 1.59e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLpgKRELpVAIKtlKVGYTEKQR----RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd06607    7 REIGHGSFGAVYYARNKR--TSEV-VAIK--KMSYSGKQStekwQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMEnGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLedDPeaAYT 766
Cdd:cd06607   82 YCL-GSASDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV--CP--ANS 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 767 TRGgkIPIrWTAPEAIAFR---KFTSASDVWSYGIVMWEVvsyGER--PYWEM 814
Cdd:cd06607  157 FVG--TPY-WMAPEVILAMdegQYDGKVDVWSLGITCIEL---AERkpPLFNM 203
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
613-860 2.31e-15

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 77.80  E-value: 2.31e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENg 691
Cdd:cd06618   23 IGSGTCGQVYKMRHKKTGH---VMAVKQMrRSGNKEENKRILMDLDVVLKSHDCPYIVKCYGYFITDSDVFICMELMST- 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDM-GYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYTTRGG 770
Cdd:cd06618   99 CLDKLLKRIQGPIPEDILGKMTVSIVKALHYLKEKhGVIHRDVKPSNILLDESGNVKLCDFGISGRLVDS--KAKTRSAG 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 771 KIPirWTAPEAI---AFRKFTSASDVWSYGIVMWEVVSyGERPYWEM-TNQDVIKAV--EEGYRLPSPMDCPAALYQLML 844
Cdd:cd06618  177 CAA--YMAPERIdppDNPKYDIRADVWSLGISLVELAT-GQFPYRNCkTEFEVLTKIlnEEPPSLPPNEGFSPDFCSFVD 253
                        250
                 ....*....|....*.
gi 974005246 845 DCWQKERNSRPKFDEI 860
Cdd:cd06618  254 LCLTKDHRYRPKYREL 269
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
613-837 2.59e-15

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 77.76  E-value: 2.59e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTlkvgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06644   20 LGDGAFGKVYKAKNKETGALAAAKVIET----KSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGGA 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS----RVLEDDPEAAYTTr 768
Cdd:cd06644   96 VDAIMLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSaknvKTLQRRDSFIGTP- 174
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 769 ggkipiRWTAPEAIAFRKFTSA-----SDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGYrlPSPMDCPA 837
Cdd:cd06644  175 ------YWMAPEVVMCETMKDTpydykADIWSLGITLIEMAQI-EPPHHELNPMRVLLKIAKSE--PPTLSQPS 239
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
611-867 3.16e-15

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 77.39  E-value: 3.16e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRelpVAIKTlkvgYTEKQRRDFLGEASIMGQ--FDHPNIIHLEGVVTK----SKPVMIV 684
Cdd:cd14220    1 RQIGKGRYGEVWMGKWR--GEK---VAVKV----FFTTEEASWFRETEIYQTvlMRHENILGFIAADIKgtgsWTQLYLI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKkndgqFTVIQLVGMLR---GISAGMKYLSDMGY--------VHRDLAARNILINSNLVCKVSDFGL 753
Cdd:cd14220   72 TDYHENGSLYDFLK-----CTTLDTRALLKlaySAACGLCHLHTEIYgtqgkpaiAHRDLKSKNILIKKNGTCCIADLGL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLEDDP---EAAYTTRGGKipIRWTAPEAI-------AFRKFTSAsDVWSYGIVMWE---------VVSYGERPYWEM 814
Cdd:cd14220  147 AVKFNSDTnevDVPLNTRVGT--KRYMAPEVLdeslnknHFQAYIMA-DIYSFGLIIWEmarrcvtggIVEEYQLPYYDM 223
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 815 -----TNQDVIKAVEEGYRLPSPM------DCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14220  224 vpsdpSYEDMREVVCVKRLRPTVSnrwnsdECLRAVLKLMSECWAHNPASRLTALRIKKTLAKM 287
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
607-811 3.17e-15

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 76.88  E-value: 3.17e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14193    6 VNKEEILGGGRFGQVHKCEEKSSG---LKLAAKIIKA-RSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV--CKVSDFGLSRVLEddPEAA 764
Cdd:cd14193   82 YVDGGELFDRIIDENYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSREAnqVKIIDFGLARRYK--PREK 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 765 YTTRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14193  160 LRVNFGT-P-EFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPF 203
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
613-805 3.32e-15

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 77.14  E-value: 3.32e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkrELpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN-- 690
Cdd:cd07836    8 LGEGTYATVYKGRNRTTG--EI-VALKEIHLDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKdl 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 ----------GSLDTFLKKNdgqFTvIQLvgmLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLedd 760
Cdd:cd07836   85 kkymdthgvrGALDPNTVKS---FT-YQL---LKGIA----FCHENRVLHRDLKPQNLLINKRGELKLADFGLARAF--- 150
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 761 peaayttrggKIPIR----------WTAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07836  151 ----------GIPVNtfsnevvtlwYRAPDVLlGSRTYSTSIDIWSVGCIMAEMIT 196
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-962 3.39e-15

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188948  Cd Length: 70  Bit Score: 71.05  E-value: 3.39e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKVQL 962
Cdd:cd09549    6 SFGSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
611-854 4.11e-15

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 76.75  E-value: 4.11e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRelpVAIKTlkvgYTEKQRRDFLGEASIMGQ--FDHPNI-------IHLEGVVTKskpV 681
Cdd:cd14144    1 RSVGKGRYGEVWKGKWR--GEK---VAVKI----FFTTEEASWFRETEIYQTvlMRHENIlgfiaadIKGTGSWTQ---L 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKNdgqftVIQLVGMLR---GISAGMKYLSDMGY--------VHRDLAARNILINSNLVCKVSD 750
Cdd:cd14144   69 YLITDYHENGSLYDFLRGN-----TLDTQSMLKlaySAACGLAHLHTEIFgtqgkpaiAHRDIKSKNILVKKNGTCCIAD 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 751 FGLS-RVLEDDPEA--AYTTRGGKipIRWTAPEAI-------AFRKFTSAsDVWSYGIVMWEV----VSYG-----ERPY 811
Cdd:cd14144  144 LGLAvKFISETNEVdlPPNTRVGT--KRYMAPEVLdeslnrnHFDAYKMA-DMYSFGLVLWEIarrcISGGiveeyQLPY 220
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005246 812 WEM-----TNQDVIKAV-EEGYRLPSPM-----DCPAALYQLMLDCWQKERNSR 854
Cdd:cd14144  221 YDAvpsdpSYEDMRRVVcVERRRPSIPNrwssdEVLRTMSKLMSECWAHNPAAR 274
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
609-805 5.41e-15

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 76.38  E-value: 5.41e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERvIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRrdflgEASIMGQFDHPNIIHLEGV-------------- 674
Cdd:cd14047   11 IEL-IGSGGFGQVFKAKHRIDGKT---YAIKRVKLNNEKAER-----EVKALAKLDHPNIVRYNGCwdgfdydpetsssn 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 675 --VTKSKPVMIVTEYMENGSLDTFLKKNDG-QFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDF 751
Cdd:cd14047   82 ssRSKTKCLFIQMEFCEKGTLESWIEKRNGeKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDF 161
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005246 752 GLSRVLEDDPEaayTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd14047  162 GLVTSLKNDGK---RTKSKGTL-SYMSPEQISSQDYGKEVDIYALGLILFELLH 211
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
613-802 5.56e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 77.02  E-value: 5.56e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgytEKQRRDF----LGEASIMGQFDHPNIIHL-EGVVTKSKP------- 680
Cdd:cd07865   20 IGQGTFGEVFKARHRKTGQI---VALKKVLM---ENEKEGFpitaLREIKILQLLKHENVVNLiEICRTKATPynrykgs 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENgSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL--- 757
Cdd:cd07865   94 IYLVFEFCEH-DLAGLLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAFsla 172
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 758 EDDPEAAYTTRggKIPIRWTAPE-AIAFRKFTSASDVWSYGIVMWE 802
Cdd:cd07865  173 KNSQPNRYTNR--VVTLWYRPPElLLGERDYGPPIDMWGAGCIMAE 216
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
613-862 5.94e-15

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 76.43  E-value: 5.94e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06622    9 LGKGNYGSVYKVLHRPTGV---TMAMKEIRLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLkkNDGQFTVIQLVGMLRGISA----GMKYLSD-MGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTT 767
Cdd:cd06622   86 LDKLY--AGGVATEGIPEDVLRRITYavvkGLKFLKEeHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLV--ASLAKTN 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGKipiRWTAPEAI------AFRKFTSASDVWSYGIVMWEvVSYGERPYWEMTNQDV---IKAVEEGY--RLPSPMDCP 836
Cdd:cd06622  162 IGCQ---SYMAPERIksggpnQNPTYTVQSDVWSLGLSILE-MALGRYPYPPETYANIfaqLSAIVDGDppTLPSGYSDD 237
                        250       260
                 ....*....|....*....|....*.
gi 974005246 837 AAlyQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd06622  238 AQ--DFVAKCLNKIPNRRPTYAQLLE 261
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
609-823 5.98e-15

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 75.76  E-value: 5.98e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKlpgKRELPVAIKTL------KVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14116    9 IGRPLGKGKFGNVYLAREK---QSKFILALKVLfkaqleKAGVEHQLRR----EVEIQSHLRHPNILRLYGYFHDATRVY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSrvlEDDPE 762
Cdd:cd14116   82 LILEYAPLGTVYRELQKL-SKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWS---VHAPS 157
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 763 AAYTTRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAV 823
Cdd:cd14116  158 SRRTTLCGTLD--YLPPEMIEGRMHDEKVDLWSLGVLCYEFL-VGKPPFEANTYQETYKRI 215
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
608-862 7.42e-15

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 75.50  E-value: 7.42e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKRelpVAIKtlkvgYTEKQR-------RD-FLG----EASIMGQ---FDHPNIIHLE 672
Cdd:cd14004    3 TILKEMGEGAYGQVNLAIYKSKGKE---VVIK-----FIFKERilvdtwvRDrKLGtvplEIHILDTlnkRSHPNIVKLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 673 GVVTKSKPVMIVTEYMENGsLDTF----LKKNDGQFTVIQLvgmLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKV 748
Cdd:cd14004   75 DFFEDDEFYYLVMEKHGSG-MDLFdfieRKPNMDEKEAKYI---FRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 749 SDFGLSRVLEDDPeaAYTTRGgkiPIRWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVsYGERPYWEmtnqdvikaVEEGy 827
Cdd:cd14004  151 IDFGSAAYIKSGP--FDTFVG---TIDYAAPEVLRGNPYGGKEqDIWALGVLLYTLV-FKENPFYN---------IEEI- 214
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 828 rLPSPMDCPAALYQ----LMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14004  215 -LEADLRIPYAVSEdlidLISRMLNRDVGDRPTIEELLT 252
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
613-811 9.45e-15

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 75.72  E-value: 9.45e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgytekqRRDFLG---------EASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd05579    1 ISRGAYGRVYLAKKKSTGDL---YAIKVIK-------KRDMIRknqvdsvlaERNILSQAQNPFVVKLYYSFQGKKNLYL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKkNDGQFTViqlvGMLRGISA----GMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV-LE 758
Cdd:cd05579   71 VMEYLPGGDLYSLLE-NVGALDE----DVARIYIAeivlALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVgLV 145
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 759 DDPEAAYTTRGGKIPIR-----------WTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05579  146 RRQIKLSIQKKSNGAPEkedrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLV-GIPPF 208
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
613-811 9.49e-15

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 75.72  E-value: 9.49e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGV------VTKSKPvMIVTE 686
Cdd:cd14039    1 LGTGGFGNVCLYQNQETGEK---IAIKSCRLELSVKNKDRWCHEIQIMKKLNHPNVVKACDVpeemnfLVNDVP-LLAME 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKK--NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNIL---INSNLVCKVSDFGLSRVLedDP 761
Cdd:cd14039   77 YCSGGDLRKLLNKpeNCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAKDL--DQ 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKipIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14039  155 GSLCTSFVGT--LQYLAPELFENKSYTVTVDYWSFGTMVFECIA-GFRPF 201
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
613-823 1.03e-14

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 75.44  E-value: 1.03e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRR-----DFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd14194   13 LGSGQFAVVKKCREKSTGLQ---YAAKFIKKRRTKSSRRgvsreDIEREVSILKEIQHPNVITLHEVYENKTDVILILEL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNI-LINSNLV---CKVSDFGLSRVLE--DDP 761
Cdd:cd14194   90 VAGGELFDFLAEKE-SLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENImLLDRNVPkprIKIIDFGLAHKIDfgNEF 168
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 762 EAAYTTRggkipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV 823
Cdd:cd14194  169 KNIFGTP------EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANV 223
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
613-815 1.16e-14

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 76.40  E-value: 1.16e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG--YTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:PTZ00263  26 LGTGSFGRVRIAKHKGTGEY---YAIKCLKKReiLKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVG 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKK-----ND-GQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddPEAA 764
Cdd:PTZ00263 103 GELFTHLRKagrfpNDvAKFYHAELV-------LAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKV---PDRT 172
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 765 YTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMT 815
Cdd:PTZ00263 173 FTLCG--TP-EYLAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPFFDDT 219
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
613-811 1.40e-14

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 75.99  E-value: 1.40e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLK-VGY---TEKQRRDFlgeaSIMGQFDHPNIIHLEGVVTK--SKPVMIVTE 686
Cdd:cd13988    1 LGQGATANVFRGRHKKTGDL---YAVKVFNnLSFmrpLDVQMREF----EVLKKLNHKNIVKLFAIEEEltTRHKVLVME 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFTVIQ--LVGMLRGISAGMKYLSDMGYVHRDLAARNILI----NSNLVCKVSDFGLSRVLEDD 760
Cdd:cd13988   74 LCPCGSLYTVLEEPSNAYGLPEseFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRvigeDGQSVYKLTDFGAARELEDD 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 761 PEAA--YTTRGGKIPIRWtapEAIAFRK-----FTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd13988  154 EQFVslYGTEEYLHPDMY---ERAVLRKdhqkkYGATVDLWSIGVTFYHAAT-GSLPF 207
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
613-823 1.40e-14

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 74.83  E-value: 1.40e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEK--QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd14105   13 LGSGQFAVVKKCREKSTGLEYAAKFIKKRRSKASRRgvSREDIEREVSILRQVLHPNIITLHDVFENKTDVVLILELVAG 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDGqFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV----CKVSDFGLSRVLEDDPEaaYT 766
Cdd:cd14105   93 GELFDFLAEKES-LSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIEDGNE--FK 169
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 767 TRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV 823
Cdd:cd14105  170 NIFGT-P-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANI 223
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
664-802 1.50e-14

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 76.06  E-value: 1.50e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 DHPNIIHLEGVV--TKSKPVMIVTEYMENgSLDTFLKKN-----DGQFTVIQLvgmLRGIsagmKYLSDMGYVHRDLAAR 736
Cdd:cd07852   65 DHPNIIKLLNVIraENDKDIYLVFEYMET-DLHAVIRANilediHKQYIMYQL---LKAL----KYLHSGGVIHRDLKPS 136
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 737 NILINSNLVCKVSDFGLSRVLEDDPEAAyttrggKIPI-------RW-TAPEA-IAFRKFTSASDVWSYGIVMWE 802
Cdd:cd07852  137 NILLNSDCRVKLADFGLARSLSQLEEDD------ENPVltdyvatRWyRAPEIlLGSTRYTKGVDMWSVGCILGE 205
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
607-867 1.59e-14

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 75.04  E-value: 1.59e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKlpGKrelpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14153    2 LEIGELIGKGRFGQVYHGRWH--GE----VAIRLIDIERdNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIIT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCkVSDFGL---SRVLEddpe 762
Cdd:cd14153   76 SLCKGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLftiSGVLQ---- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKIPIRWT---APEAIAFRK---------FTSASDVWSYGIVMWEVVSYgERPYWEMTNQDVIKAVEEGYR-L 829
Cdd:cd14153  151 AGRREDKLRIQSGWLchlAPEIIRQLSpeteedklpFSKHSDVFAFGTIWYELHAR-EWPFKTQPAEAIIWQVGSGMKpN 229
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 830 PSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14153  230 LSQIGMGKEISDILLFCWAYEQEERPTFSKLMEMLEKL 267
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
613-804 2.11e-14

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 75.86  E-value: 2.11e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTE--KQRRDFLgEASIMGQFDHPNIIHLEGVVTKS------KPVMIV 684
Cdd:cd07878   23 VGSGAYGSVCSA---YDTRLRQKVAVKKLSRPFQSliHARRTYR-ELRLLKHMKHENVIGLLDVFTPAtsienfNEVYLV 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMeNGSLDTFLK-----KNDGQFTVIQLvgmLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd07878   99 TNLM-GADLNNIVKcqklsDEHVQFLIYQL---LRG----LKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADD 170
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 760 DpeaayttRGGKIPIRW-TAPE-AIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07878  171 E-------MTGYVATRWyRAPEiMLNWMHYNQTVDIWSVGCIMAELL 210
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
612-847 2.42e-14

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 74.79  E-value: 2.42e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLklpgkRELPVAIKTlkvgYTEKQRRDFLGEASIMG--QFDHPNIIHLEGVVTK----SKPVMIVT 685
Cdd:cd14143    2 SIGKGRFGEVWRGRW-----RGEDVAVKI----FSSREERSWFREAEIYQtvMLRHENILGFIAADNKdngtWTQLWLVS 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYL--------SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd14143   73 DYHEHGSLFDYLNRY--TVTVEGMIKLALSIASGLAHLhmeivgtqGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRH 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 758 E---DDPEAAYTTRGGKipIRWTAPE----AIAFRKFTS--ASDVWSYGIVMWEVV---SYG------ERPYWEM----- 814
Cdd:cd14143  151 DsatDTIDIAPNHRVGT--KRYMAPEvlddTINMKHFESfkRADIYALGLVFWEIArrcSIGgihedyQLPYYDLvpsdp 228
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 974005246 815 TNQDVIKAV-EEGYRLPSP---MDCPA--ALYQLMLDCW 847
Cdd:cd14143  229 SIEEMRKVVcEQKLRPNIPnrwQSCEAlrVMAKIMRECW 267
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
649-862 2.50e-14

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 74.20  E-value: 2.50e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 649 QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGY 728
Cdd:cd14187   50 QKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSL-LELHKRRKALTEPEARYYLRQIILGCQYLHRNRV 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 729 VHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGE 808
Cdd:cd14187  129 IHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGERKKTLCGTP---NYIAPEVLSKKGHSFEVDIWSIGCIMYTLL-VGK 204
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 809 RPY-WEMTNQDVIKAVEEGYRLPSPMD-CPAALYQLMLdcwQKERNSRPKFDEIVN 862
Cdd:cd14187  205 PPFeTSCLKETYLRIKKNEYSIPKHINpVAASLIQKML---QTDPTARPTINELLN 257
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
613-805 2.82e-14

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 75.46  E-value: 2.82e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTE--KQRRDFLgEASIMGQFDHPNIIHLEGVVTKSKP------VMIV 684
Cdd:cd07877   25 VGSGAYGSVCAA---FDTKTGLRVAVKKLSRPFQSiiHAKRTYR-ELRLLKHMKHENVIGLLDVFTPARSleefndVYLV 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMeNGSLDTFLK-----KNDGQFTVIQLvgmLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd07877  101 THLM-GADLNNIVKcqkltDDHVQFLIYQI---LRG----LKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDD 172
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 760 DpeaayttRGGKIPIRW-TAPE-AIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07877  173 E-------MTGYVATRWyRAPEiMLNWMHYNQTVDIWSVGCIMAELLT 213
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
606-801 2.83e-14

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 73.90  E-value: 2.83e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 606 CITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDflgEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14095    1 KYDIGRVIGDGNFAVVKECRDKATDKEYALKIIDKAKCKGKEHMIEN---EVAILRRVKHPNIVQLIEEYDTDTELYLVM 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSL-DTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN----LVCKVSDFGLSRVLedd 760
Cdd:cd14095   78 ELVKGGDLfDAITSST--KFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHedgsKSLKLADFGLATEV--- 152
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 761 PEAAYTTRGgkIPIrWTAPEAIAFRKFTSASDVWSYGIVMW 801
Cdd:cd14095  153 KEPLFTVCG--TPT-YVAPEILAETGYGLKVDIWAAGVITY 190
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
608-811 3.22e-14

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 74.29  E-value: 3.22e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFgEVCSGRLKLPGKRELPVAIktlkvgyTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14175    4 VVKETIGVGSY-SVCKRCVHKATNMEYAVKV-------IDKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTE 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGS-LDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVC-KVSDFGLSRVLEDDP 761
Cdd:cd14175   76 LMRGGElLDKILRQK--FFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYvdeSGNPESlRICDFGFAKQLRAEN 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005246 762 ----EAAYTTrggkipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14175  154 gllmTPCYTA-------NFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPF 199
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
638-855 3.22e-14

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 74.23  E-value: 3.22e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 638 IKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVvtKSKPVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLR--- 714
Cdd:cd14067   42 LKHLRAADAMKNFSEFRQEASMLHSLQHPCIVYLIGI--SIHPLCFALELAPLGSLNTVLEENHKGSSFMPLGHMLTfki 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 715 --GISAGMKYLSDMGYVHRDLAARNILINS-----NLVCKVSDFGLSRvlEDDPEAAYTTRGGKipiRWTAPEAIAFRKF 787
Cdd:cd14067  120 ayQIAAGLAYLHKKNIIFCDLKSDNILVWSldvqeHINIKLSDYGISR--QSFHEGALGVEGTP---GYQAPEIRPRIVY 194
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 788 TSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGYR--LPSPMDCPAALYQ-LMLDCWQKERNSRP 855
Cdd:cd14067  195 DEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLSKGIRpvLGQPEEVQFFRLQaLMMECWDTKPEKRP 264
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
587-874 3.54e-14

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 74.70  E-value: 3.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 587 TYEDPNQAvHEFAKEIEASCITIERVIGAGEFGEVCSGRlklPGKRELPVAIKtlKVGYTEKQR----RDFLGEASIMGQ 662
Cdd:cd06635    8 SLKDPDIA-ELFFKEDPEKLFSDLREIGHGSFGAVYFAR---DVRTSEVVAIK--KMSYSGKQSnekwQDIIKEVKFLQR 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 663 FDHPNIIHLEGVVTKSKPVMIVTEYMEnGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS 742
Cdd:cd06635   82 IKHPNSIEYKGCYLREHTAWLVMEYCL-GSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 743 NLVCKVSDFGLSRVLEddPEAAYTtrggKIPIrWTAPEAIAFR---KFTSASDVWSYGIVMWEVvsyGER--PYWEMTNQ 817
Cdd:cd06635  161 PGQVKLADFGSASIAS--PANSFV----GTPY-WMAPEVILAMdegQYDGKVDVWSLGITCIEL---AERkpPLFNMNAM 230
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 818 DVIKAVEEGyRLPSPMDCPAALY--QLMLDCWQKERNSRPKFDEIVNMLDKLIRNPSSL 874
Cdd:cd06635  231 SALYHIAQN-ESPTLQSNEWSDYfrNFVDSCLQKIPQDRPTSEELLKHMFVLRERPETV 288
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
613-805 3.94e-14

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 73.89  E-value: 3.94e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgS 692
Cdd:cd07871   13 LGEGTYATVFKGRSKLTENL---VALKEIRLEHEEGAPCTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEYLDS-D 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTV----IQLVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAYTTr 768
Cdd:cd07871   89 LKQYLDNCGNLMSMhnvkIFMFQLLRGLS----YCHKRKILHRDLKPQNLLINEKGELKLADFGLARA-KSVPTKTYSN- 162
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 974005246 769 ggKIPIRWTAPEAIAF--RKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07871  163 --EVVTLWYRPPDVLLgsTEYSTPIDMWGVGCILYEMAT 199
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
613-813 4.20e-14

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 74.75  E-value: 4.20e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlPGKRELPVAIKTLKVGYTEK--QRRDfLGEASIMGQF-DHPNIIHL--EGVVTKSK--PVMIVT 685
Cdd:cd07857    8 LGQGAYGIVCSARNA-ETSEEETVAIKKITNVFSKKilAKRA-LRELKLLRHFrGHKNITCLydMDIVFPGNfnELYLYE 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMEnGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE--A 763
Cdd:cd07857   86 ELME-ADLHQIIR-SGQPLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPGenA 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 764 AYTTrgGKIPIRW-TAPE-AIAFRKFTSASDVWSYGIVMWEVvsYGERPYWE 813
Cdd:cd07857  164 GFMT--EYVATRWyRAPEiMLSFQSYTKAIDVWSVGCILAEL--LGRKPVFK 211
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
613-834 4.62e-14

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 73.07  E-value: 4.62e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14006    1 LGRGRFGVVKRCIEKATGRE---FAAKFIP--KRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGE 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVcKVSDFGLSRVLEDD--------- 760
Cdd:cd14006   76 LLDRLA-ERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLadrPSPQI-KIIDFGLARKLNPGeelkeifgt 153
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 761 PEAAyttrggkipirwtAPEAIAFRKFTSASDVWSYGivmweVVSY----GERPYWEMTNQDVIKAVEEG-YRLPSPMD 834
Cdd:cd14006  154 PEFV-------------APEIVNGEPVSLATDMWSIG-----VLTYvllsGLSPFLGEDDQETLANISACrVDFSEEYF 214
fn3 pfam00041
Fibronectin type III domain;
401-483 5.82e-14

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 68.21  E-value: 5.82e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  401 SPVTNVKKGKIAKNSISLSWQEPDRPNGIILEYEIKYFEKDQETS--YTIIKSKETTITAEGLKPASVYVFQIRARTAAG 478
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPwnEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80

                  ....*
gi 974005246  479 YGVFS 483
Cdd:pfam00041  81 EGPPS 85
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
613-805 6.04e-14

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 73.31  E-value: 6.04e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMeNG 691
Cdd:cd07860    8 IGEGTYGVVYKARNKLTGEV---VALKKIRLDTeTEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFL-HQ 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLV-GMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeDDPEAAYTTRgg 770
Cdd:cd07860   84 DLKKFMDASALTGIPLPLIkSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAF-GVPVRTYTHE-- 160
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 974005246 771 KIPIRWTAPEAIAFRKF-TSASDVWSYGIVMWEVVS 805
Cdd:cd07860  161 VVTLWYRAPEILLGCKYySTAVDIWSLGCIFAEMVT 196
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
613-803 7.04e-14

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 73.53  E-value: 7.04e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKtlKVGYTEKQR----RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd06633   29 IGHGSFGAVYFATNSHTNE---VVAIK--KMSYSGKQTnekwQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYC 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 EnGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTtr 768
Cdd:cd06633  104 L-GSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS--PANSFV-- 178
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 974005246 769 ggKIPIrWTAPEAIAFR---KFTSASDVWSYGIVMWEV 803
Cdd:cd06633  179 --GTPY-WMAPEVILAMdegQYDGKVDIWSLGITCIEL 213
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
613-802 7.17e-14

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 73.08  E-value: 7.17e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDF-LGEASIMGQ---FDHPNIIHLEGV-----VTKSKPVMI 683
Cdd:cd07838    7 IGEGAYGTVYKARDLQDGRF---VALKKVRVPLSEEGIPLStIREIALLKQlesFEHPNVVRLLDVchgprTDRELKLTL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENgSLDTFLKK-NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpE 762
Cdd:cd07838   84 VFEHVDQ-DLATYLDKcPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIYSF--E 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 974005246 763 AAYTtrggkiPIRWT----APEAIAFRKFTSASDVWSYGIVMWE 802
Cdd:cd07838  161 MALT------SVVVTlwyrAPEVLLQSSYATPVDMWSVGCIFAE 198
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
610-818 9.00e-14

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 72.38  E-value: 9.00e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgyteKQRR--DFLGE-----ASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14106   13 STPLGRGKFAVVRKCIHKETGKE---YAAKFLR-----KRRRgqDCRNEilheiAVLELCKDCPRVVNLHEVYETRSELI 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVC---KVSDFGLSRVLED 759
Cdd:cd14106   85 LILELAAGGELQTLLD-EEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPLgdiKLCDFGISRVIGE 163
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 760 DPEaayttrggkipIR-------WTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQD 818
Cdd:cd14106  164 GEE-----------IReilgtpdYVAPEILSYEPISLATDMWSIGVLTYVLLT-GHSPFGGDDKQE 217
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
590-823 9.14e-14

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 72.27  E-value: 9.14e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 590 DPNQAVHEFAKeieascitiervIGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGYTEKQRRdFLGEASIMGQFDHPNII 669
Cdd:cd06647    4 DPKKKYTRFEK------------IGQGASGTVYTA---IDVATGQEVAIKQMNLQQQPKKEL-IINEILVMRENKNPNIV 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 670 HLEGVVTKSKPVMIVTEYMENGSLDTFLKK---NDGQftviqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVC 746
Cdd:cd06647   68 NYLDSYLVGDELWVVMEYLAGGSLTDVVTEtcmDEGQ-----IAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSV 142
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 747 KVSDFGLSRVLEddPEAAYTTRGGKIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwemTNQDVIKAV 823
Cdd:cd06647  143 KLTDFGFCAQIT--PEQSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY---LNENPLRAL 212
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
611-804 9.92e-14

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 73.48  E-value: 9.92e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRELPVAIKTLKVGYTEKQRR--DFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:PTZ00426  36 RTLGTGSFGRVILATYK--NEDFPPVAIKRFEKSKIIKQKQvdHVFSERKILNYINHPFCVNLYGSFKDESYLYLVLEFV 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKND------GQFTVIQLVGMLrgisagmKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddpE 762
Cdd:PTZ00426 114 IGGEFFTFLRRNKrfpndvGCFYAAQIVLIF-------EYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVD---T 183
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 763 AAYTTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:PTZ00426 184 RTYTLCGTP---EYIAPEILLNVGHGKAADWWTLGIFIYEIL 222
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
613-826 1.00e-13

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 72.51  E-value: 1.00e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVG--YTEKQRRDFLGEASI-MGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd05611    4 ISKGAFGSVYLAKKRSTGDY---FAIKVLKKSdmIAKNQVTNVKAERAImMIQGESPYVAKLYYSFQSKDYLYLVMEYLN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDG-------QFTVIQLVGMlrgisagmKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddpE 762
Cdd:cd05611   81 GGDCASLIKTLGGlpedwakQYIAEVVLGV--------EDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGL---E 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 763 AAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVEEG 826
Cdd:cd05611  150 KRHNKKFVGTP-DYLAPETILGVGDDKMSDWWSLGCVIFEFL-FGYPPFHAETPDAVFDNILSR 211
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
613-811 1.06e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 72.74  E-value: 1.06e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFgEVCSGRLKLPGKRELPVAIktlkvgyTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14177   12 IGVGSY-SVCKRCIHRATNMEFAVKI-------IDKSKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVTELMKGG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 S-LDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVcKVSDFGLSRVLEDDP---- 761
Cdd:cd14177   84 ElLDRILRQK--FFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYmddsaNADSI-RICDFGFAKQLRGENglll 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTrggkipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14177  161 TPCYTA-------NFVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPF 202
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
609-811 1.09e-13

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 72.16  E-value: 1.09e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTL------KVGYTEKQRRDflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14070    6 IGRKLGEGSFAKVREGLHAVTGEK---VAIKVIdkkkakKDSYVTKNLRR---EGRIQQMIRHPNITQLLDILETENSYY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSL-DTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRV--LED 759
Cdd:cd14070   80 LVMELCPGGNLmHRIYDKK--RLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCagILG 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 760 DPEAAYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14070  158 YSDPFSTQCGSPA---YAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPF 205
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
901-960 1.17e-13

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 66.55  E-value: 1.17e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMKV 960
Cdd:cd09498    9 DLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKD 68
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
612-838 1.35e-13

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 72.79  E-value: 1.35e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGrLKLPGKRELPVAIKTLKVGYTEKQRRDF----LGEASIMGQFDHPNIIHLEGVVT-KSKPVMIVTE 686
Cdd:cd14041   13 LLGRGGFSEVYKA-FDLTEQRYVAVKIHQLNKNWRDEKKENYhkhaCREYRIHKELDHPRIVKLYDYFSlDTDSFCTVLE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKN------DGQFTVIQLVGMLrgisagmKYLSDMG--YVHRDLAARNILINSNLVC---KVSDFGLSR 755
Cdd:cd14041   92 YCEGNDLDFYLKQHklmsekEARSIIMQIVNAL-------KYLNEIKppIIHYDLKPGNILLVNGTACgeiKITDFGLSK 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 756 VLEDDP----EAAYTTRGGKIPIRWTAPEAIAF----RKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQD-------VI 820
Cdd:cd14041  165 IMDDDSynsvDGMELTSQGAGTYWYLPPECFVVgkepPKISNKVDVWSVGVIFYQCL-YGRKPFGHNQSQQdilqentIL 243
                        250
                 ....*....|....*...
gi 974005246 821 KAVEEGYRlPSPMDCPAA 838
Cdd:cd14041  244 KATEVQFP-PKPVVTPEA 260
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
612-809 1.36e-13

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 72.40  E-value: 1.36e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14046   13 VLGKGAFGQVVKVRNKLDGRY---YAIKKIKLRSESKNNSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEKS 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQfTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGK 771
Cdd:cd14046   90 TLRDLIDSGLFQ-DTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSNKLNVELATQDINKS 168
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 772 IPIR---------------WTAPE--AIAFRKFTSASDVWSYGIV---MWEVVSYG-ER 809
Cdd:cd14046  169 TSAAlgssgdltgnvgtalYVAPEvqSGTKSTYNEKVDMYSLGIIffeMCYPFSTGmER 227
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
613-836 1.40e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 72.37  E-value: 1.40e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGR-LKLPGKRelpVAIKTLKVGYTEK-QRRDFLGEASIMGQ---FDHPNIIHLEGVVTKSK-----PVM 682
Cdd:cd07862    9 IGEGAYGKVFKARdLKNGGRF---VALKRVRVQTGEEgMPLSTIREVAVLRHletFEHPNVVRLFDVCTVSRtdretKLT 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENgSLDTFLKK-NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddp 761
Cdd:cd07862   86 LVFEHVDQ-DLTTYLDKvPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIY---- 160
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 762 EAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVvsYGERPYWEmTNQDV--IKAVEEGYRLPSPMDCP 836
Cdd:cd07862  161 SFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEM--FRRKPLFR-GSSDVdqLGKILDVIGLPGEEDWP 234
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
610-805 1.69e-13

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 73.24  E-value: 1.69e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP-----VMI 683
Cdd:cd07853    5 DRPIGYGAFGVVWSVTDPRDGKR---VALKKMpNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIdpfeeIYV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMEngsldTFLKK---NDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd07853   82 VTELMQ-----SDLHKiivSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPD 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 761 pEAAYTTRgGKIPIRWTAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07853  157 -ESKHMTQ-EVVTQYYRAPEILmGSRHYTSAVDIWSVGCIFAELLG 200
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
609-851 1.69e-13

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 71.60  E-value: 1.69e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14184    5 IGKVIGDGNFAVVKECVERSTGKE---FALKIIDKAKCCGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMELV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI----NSNLVCKVSDFGLSRVLEDdpeAA 764
Cdd:cd14184   82 KGGDLFDAITSST-KYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVceypDGTKSLKLGDFGLATVVEG---PL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTN--QDVIKAVEEGY-RLPSPM-----DCP 836
Cdd:cd14184  158 YTVCGTPT---YVAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPFRSENNlqEDLFDQILLGKlEFPSPYwdnitDSA 233
                        250
                 ....*....|....*
gi 974005246 837 AALYQLMLDCWQKER 851
Cdd:cd14184  234 KELISHMLQVNVEAR 248
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
611-862 1.70e-13

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 72.36  E-value: 1.70e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRlklPGKRELPVAIKtlKVGYTEKQR----RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd06634   21 REIGHGSFGAVYFAR---DVRNNEVVAIK--KMSYSGKQSnekwQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVME 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMEnGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYT 766
Cdd:cd06634   96 YCL-GSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMA--PANSFV 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 trggKIPIrWTAPEAIAFR---KFTSASDVWSYGIVMWEVvsyGER--PYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd06634  173 ----GTPY-WMAPEVILAMdegQYDGKVDVWSLGITCIEL---AERkpPLFNMNAMSALYHIAQNESPALQSGHWSEYFR 244
                        250       260
                 ....*....|....*....|..
gi 974005246 842 LMLD-CWQKERNSRPKFDEIVN 862
Cdd:cd06634  245 NFVDsCLQKIPQDRPTSDVLLK 266
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
589-805 1.76e-13

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 73.01  E-value: 1.76e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 589 EDPNQAVHEFAKEIEASCItiervIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEK--QRRDFLgEASIMGQFDHP 666
Cdd:cd07879    4 EEVNKTVWELPERYTSLKQ-----VGSGAYGSVCSAIDKRTGEK---VAIKKLSRPFQSEifAKRAYR-ELTLLKHMQHE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 667 NIIHLEGVVTKS------KPVMIVTEYMEngsldTFLKKNDG--------QFTVIQLVgmlrgisAGMKYLSDMGYVHRD 732
Cdd:cd07879   75 NVIGLLDVFTSAvsgdefQDFYLVMPYMQ-----TDLQKIMGhplsedkvQYLVYQML-------CGLKYIHSAGIIHRD 142
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 733 LAARNILINSNLVCKVSDFGLSRvlEDDPEAAyttrgGKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07879  143 LKPGNLAVNEDCELKILDFGLAR--HADAEMT-----GYVVTRWyRAPEVIlNWMHYNQTVDIWSVGCIMAEMLT 210
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
610-832 1.93e-13

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 71.56  E-value: 1.93e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASimgqfDHPNIIHL----EGVVTKSKPVMIVT 685
Cdd:cd14172    9 KQVLGLGVNGKVLECFHRRTGQK---CALKLLYDSPKARREVEHHWRAS-----GGPHIVHIldvyENMHHGKRCLLIIM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFL-KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRvlEDDP 761
Cdd:cd14172   81 ECMEGGELFSRIqERGDQAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYtskEKDAVLKLTDFGFAK--ETTV 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 762 EAAYTTrggkiPIR---WTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEGYRL-----PSP 832
Cdd:cd14172  159 QNALQT-----PCYtpyYVAPEVLGPEKYDKSCDMWSLGVIMY-ILLCGFPPFYSNTGQAISPGMKRRIRMgqygfPNP 231
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
612-862 2.29e-13

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 71.31  E-value: 2.29e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGrlkLPGKREL----PVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd06631    8 VLGKGAYGTVYCG---LTSTGQLiavkQVELDTSDKEKAEKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddpeAAYTT 767
Cdd:cd06631   85 VPGGSIASILARF-GALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRL-----CINLS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 768 RGGKIPI--------RWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEGY----RLPSPMDC 835
Cdd:cd06631  159 SGSQSQLlksmrgtpYWMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNPMAAIFAIGSGRkpvpRLPDKFSP 237
                        250       260
                 ....*....|....*....|....*..
gi 974005246 836 PAALYQLMldCWQKERNSRPKFDEIVN 862
Cdd:cd06631  238 EARDFVHA--CLTRDQDERPSAEQLLK 262
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
613-805 2.33e-13

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 72.68  E-value: 2.33e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLkvgYTEKQRRDFLGEA----SIMGQFDHPNIIHLEGVVT------KSKPVM 682
Cdd:cd07880   23 VGSGAYGTVCSA---LDRRTGAKVAIKKL---YRPFQSELFAKRAyrelRLLKHMKHENVIGLLDVFTpdlsldRFHDFY 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYM--ENGSLDTF--LKKNDGQFTVIQlvgMLRGisagMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlE 758
Cdd:cd07880   97 LVMPFMgtDLGKLMKHekLSEDRIQFLVYQ---MLKG----LKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLAR--Q 167
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 759 DDPEAAyttrgGKIPIRW-TAPEAI-AFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07880  168 TDSEMT-----GYVVTRWyRAPEVIlNWMHYTQTVDIWSVGCIMAEMLT 211
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
604-867 2.42e-13

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 71.70  E-value: 2.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 604 ASCITIERVIGAGEFGEVCSGRLKlpGKrelPVAIKTlkvgYTEKQRRDFLGEASIMGQ--FDHPNIIHLEGVVTKSK-- 679
Cdd:cd14142    4 ARQITLVECIGKGRYGEVWRGQWQ--GE---SVAVKI----FSSRDEKSWFRETEIYNTvlLRHENILGFIASDMTSRns 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 --PVMIVTEYMENGSLDTFLkkndgQFTVIQLVGMLR---GISAGMKYL--------SDMGYVHRDLAARNILINSNLVC 746
Cdd:cd14142   75 ctQLWLITHYHENGSLYDYL-----QRTTLDHQEMLRlalSAASGLVHLhteifgtqGKPAIAHRDLKSKNILVKSNGQC 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 747 KVSDFGLS---RVLEDDPEAAYTTR-GGKipiRWTAPEAI-------AFRKFTSAsDVWSYGIVMWEV----VSYG---- 807
Cdd:cd14142  150 CIADLGLAvthSQETNQLDVGNNPRvGTK---RYMAPEVLdetintdCFESYKRV-DIYAFGLVLWEVarrcVSGGivee 225
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 808 -ERPYWEMTNQD-----VIKAV-EEGYR--LP---SPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKL 867
Cdd:cd14142  226 yKPPFYDVVPSDpsfedMRKVVcVDQQRpnIPnrwSSDPTLTAMAKLMKECWYQNPSARLTALRIKKTLLKI 297
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
612-821 2.43e-13

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 72.01  E-value: 2.43e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGrLKLPGKRELPVAIKTLKVGYTEKQRRDF----LGEASIMGQFDHPNIIHLEGVVT-KSKPVMIVTE 686
Cdd:cd14040   13 LLGRGGFSEVYKA-FDLYEQRYAAVKIHQLNKSWRDEKKENYhkhaCREYRIHKELDHPRIVKLYDYFSlDTDTFCTVLE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKN------DGQFTVIQLVGMLRgisagmkYLSDMG--YVHRDLAARNILINSNLVC---KVSDFGLSR 755
Cdd:cd14040   92 YCEGNDLDFYLKQHklmsekEARSIVMQIVNALR-------YLNEIKppIIHYDLKPGNILLVDGTACgeiKITDFGLSK 164
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 756 VLEDDP---EAAYTTRGGKIPIRWTAPEAIAF----RKFTSASDVWSYGIVMWEVVsYGERPY-WEMTNQDVIK 821
Cdd:cd14040  165 IMDDDSygvDGMDLTSQGAGTYWYLPPECFVVgkepPKISNKVDVWSVGVIFFQCL-YGRKPFgHNQSQQDILQ 237
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
609-800 2.45e-13

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 71.23  E-value: 2.45e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGR-LKLPGKrelpVAIKTL-KVGYTEK-----QRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKP 680
Cdd:cd13993    4 LISPIGEGAYGVVYLAVdLRTGRK----YAIKCLyKSGPNSKdgndfQKLPQLREIDLHRRVsRHPNIITLHDVFETEVA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYMENGSLDTFLKKND---GQFTVIQLVgMLRGISAgMKYLSDMGYVHRDLAARNILINSN-LVCKVSDFGLSRV 756
Cdd:cd13993   80 IYIVLEYCPNGDLFEAITENRiyvGKTELIKNV-FLQLIDA-VKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLATT 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 757 LEDDPEAAyttRGGKipiRWTAPEAIAF----RKF--TSASDVWSYGIVM 800
Cdd:cd13993  158 EKISMDFG---VGSE---FYMAPECFDEvgrsLKGypCAAGDIWSLGIIL 201
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
609-820 2.51e-13

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 71.14  E-value: 2.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYTEKQRRDFLG-----EASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd14196    9 IGEELGSGQFAIVKKCREKSTG---LEYAAKFIKKRQSRASRRGVSReeierEVSILRQVLHPNIITLHDVYENRTDVVL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNI-LINSNLV---CKVSDFGLSRVLED 759
Cdd:cd14196   86 ILELVSGGELFDFLAQKE-SLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENImLLDKNIPiphIKLIDFGLAHEIED 164
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 760 DPEaaYTTRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVI 820
Cdd:cd14196  165 GVE--FKNIFGT-P-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETL 220
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
643-811 2.79e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 72.36  E-value: 2.79e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 643 VGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEYMENGS-LDTFLKKNdgQFTVIQLVGMLRGISAGM 720
Cdd:cd14176   49 VKIIDKSKRDPTEEIEILLRYgQHPNIITLKDVYDDGKYVYVVTELMKGGElLDKILRQK--FFSEREASAVLFTITKTV 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 721 KYLSDMGYVHRDLAARNILI-----NSNLVcKVSDFGLSRVLEDDP----EAAYTTrggkipiRWTAPEAIAFRKFTSAS 791
Cdd:cd14176  127 EYLHAQGVVHRDLKPSNILYvdesgNPESI-RICDFGFAKQLRAENgllmTPCYTA-------NFVAPEVLERQGYDAAC 198
                        170       180
                 ....*....|....*....|
gi 974005246 792 DVWSYGIVMWEVVSyGERPY 811
Cdd:cd14176  199 DIWSLGVLLYTMLT-GYTPF 217
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
611-834 2.79e-13

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 71.70  E-value: 2.79e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgyTE----KQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05612    7 KTIGTGTFGRVHLVRDRISEHY---YALKVMAI--PEvirlKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpeAAYT 766
Cdd:cd05612   82 YVPGGELFSYLR-NSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKLRD---RTWT 157
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 767 TRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSPMD 834
Cdd:cd05612  158 LCG--TP-EYLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPFFDDNPFGIYEKILAGkLEFPRHLD 222
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
611-814 3.21e-13

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 71.19  E-value: 3.21e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgyTEKQRRDFLGEASIMGQFDH-PNIIHLEGVVTKSKP------VMI 683
Cdd:cd06636   22 EVVGNGTYGQVYKGRHVKTGQL---AAIKVMDV--TEDEEEEIKLEINMLKKYSHhRNIATYYGAFIKKSPpghddqLWL 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd06636   97 VMEFCGAGSVTDLVKNTKGNaLKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVG 176
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 763 AAYTTRGGKIpirWTAPEAIAFRKFTSA-----SDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06636  177 RRNTFIGTPY---WMAPEVIACDENPDAtydyrSDIWSLGITAIEMAE-GAPPLCDM 229
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
613-863 3.23e-13

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 71.24  E-value: 3.23e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlPGKRELpvAIKTLKVGYTEKQRRDFLGEA-SIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENg 691
Cdd:cd06616   14 IGRGAFGTVNKMLHK-PSGTIM--AVKRIRSTVDEKEQKRLLMDLdVVMRSSDCPYIVKFYGALFREGDCWICMELMDI- 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKK-NDGQFTVI--QLVGMLR-GISAGMKYL-SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpEAAYT 766
Cdd:cd06616   90 SLDKFYKYvYEVLDSVIpeEILGKIAvATVKALNYLkEELKIIHRDVKPSNILLDRNGNIKLCDFGISGQLVD--SIAKT 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPirWTAPEAI----AFRKFTSASDVWSYGIVMWEvVSYGERPY--WeMTNQDVIKAVEEGY--RLP--SPMDCP 836
Cdd:cd06616  168 RDAGCRP--YMAPERIdpsaSRDGYDVRSDVWSLGITLYE-VATGKFPYpkW-NSVFDQLTQVVKGDppILSnsEEREFS 243
                        250       260
                 ....*....|....*....|....*..
gi 974005246 837 AALYQLMLDCWQKERNSRPKFDEIVNM 863
Cdd:cd06616  244 PSFVNFVNLCLIKDESKRPKYKELLKH 270
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
612-880 3.77e-13

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 71.31  E-value: 3.77e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd06615    8 ELGAGNGGVVTKVLHRPSG---LIMARKLIHLEIKPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSD-MGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT-TRG 769
Cdd:cd06615   85 SLDQVLKKA-GRIPENILGKISIAVLRGLTYLREkHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVgTRS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 gkipirWTAPEAIAFRKFTSASDVWSYGIVMWEvVSYGERPY-------WEMTNQDVIKAVEEGYRL----PSPMDCPA- 837
Cdd:cd06615  164 ------YMSPERLQGTHYTVQSDIWSLGLSLVE-MAIGRYPIpppdakeLEAMFGRPVSEGEAKESHrpvsGHPPDSPRp 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 838 -ALYQLmLDCWQKERNSR-PK--F-DEIVNMLDK-LIRNPS---SLKTLVNA 880
Cdd:cd06615  237 mAIFEL-LDYIVNEPPPKlPSgaFsDEFQDFVDKcLKKNPKeraDLKELTKH 287
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
611-804 3.97e-13

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 71.68  E-value: 3.97e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK-----VGYTEKQRRDFLgeasIMGQFDHPNIIHLEGVVTKSKP----- 680
Cdd:cd07850    6 KPIGSGAQGIVCAAYDTVTGQN---VAIKKLSrpfqnVTHAKRAYRELV----LMKLVNHKNIIGLLNVFTPQKSleefq 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 -VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGIsagmKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd07850   79 dVYLVMELMDANLCQVIQMDLDHERMSYLLYQMLCGI----KHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGT 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 760 D----PEAayTTRggkipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07850  155 SfmmtPYV--VTR------YYRAPEVILGMGYKENVDIWSVGCIMGEMI 195
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
650-832 5.47e-13

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 70.46  E-value: 5.47e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 650 RRDFLGEASIMGQFD-HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKndgqftVIQLV-----GMLRGISAGMKYL 723
Cdd:cd14093   52 REATRREIEILRQVSgHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTE------VVTLSekktrRIMRQLFEAVEFL 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 724 SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT--TRGgkipirWTAPEAIAFRKFTSAS------DVWS 795
Cdd:cd14093  126 HSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEKLRELcgTPG------YLAPEVLKCSMYDNAPgygkevDMWA 199
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 974005246 796 YGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14093  200 CGVIMYTLLA-GCPPFWHRKQMVMLRNIMEGkYEFGSP 236
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
286-529 6.58e-13

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 72.73  E-value: 6.58e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 286 TRPPSAPRN-AISNVNETSVFLEWIPPADtggrKDVSYYIACKKCNShagvceecGGHVRYLprqSGLKNTSVMMVDLLA 364
Cdd:COG3401  230 TTPPSAPTGlTATADTPGSVTLSWDPVTE----SDATGYRVYRSNSG--------DGPFTKV---ATVTTTSYTDTGLTN 294
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 365 HTNYTFEIEAVNGVSDLSPGArqyVSVNVTTNQAAPSPVTNVKKGKIAKNSISLSWQEPDrpNGIILEYEIkYFEKDQET 444
Cdd:COG3401  295 GTTYYYRVTAVDAAGNESAPS---NVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASS--DADVTGYNV-YRSTSGGG 368
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 445 SYTIIKS--KETTITAEGLKPASVYVFQIRARTAAGygvfsrRFEFETTPVSVAASSDQSQIPVIAVSVTVGVILLAVVI 522
Cdd:COG3401  369 TYTKIAEtvTTTSYTDTGLTPGTTYYYKVTAVDAAG------NESAPSEEVSATTASAASGESLTASVDAVPLTDVAGAT 442

                 ....*..
gi 974005246 523 GVLLSGS 529
Cdd:COG3401  443 AAASAAS 449
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
612-865 7.17e-13

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 69.60  E-value: 7.17e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpgKRElpVAIKTLKVGYTEKQRRDflgEASIMGQFDHPNIIHLegVVTKSKPVMIVTEYMENG 691
Cdd:cd14068    1 LLGDGGFGSVYRAVYR---GED--VAVKIFNKHTSFRLLRQ---ELVVLSHLHHPSLVAL--LAAGTAPRMLVMELAPKG 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVCKVSDFGLsrvleddpeAAYT 766
Cdd:cd14068   71 SLDALLQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGI---------AQYC 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGkipIR-------WTAPE-AIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSPM---DC 835
Cdd:cd14068  142 CRMG---IKtsegtpgFRAPEvARGNVIYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPVkeyGC 218
                        250       260       270
                 ....*....|....*....|....*....|..
gi 974005246 836 P--AALYQLMLDCWQKERNSRPKFDEIVNMLD 865
Cdd:cd14068  219 ApwPGVEALIKDCLKENPQCRPTSAQVFDILN 250
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
665-811 7.85e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 70.45  E-value: 7.85e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 665 HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---N 741
Cdd:cd14179   61 HPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKKKQ-HFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFtdeS 139
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 742 SNLVCKVSDFGLSRVLEDDPEAAYTTrggKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14179  140 DNSEIKIIDFGFARLKPPDNQPLKTP---CFTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
643-811 8.44e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 70.04  E-value: 8.44e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 643 VGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEYMENGS-LDTFLKKNdgQFTVIQLVGMLRGISAGM 720
Cdd:cd14178   33 VKIIDKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKFVYLVMELMRGGElLDRILRQK--CFSEREASAVLCTITKTV 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 721 KYLSDMGYVHRDLAARNILI----NSNLVCKVSDFGLSRVLEDDP----EAAYTTrggkipiRWTAPEAIAFRKFTSASD 792
Cdd:cd14178  111 EYLHSQGVVHRDLKPSNILYmdesGNPESIRICDFGFAKQLRAENgllmTPCYTA-------NFVAPEVLKRQGYDAACD 183
                        170
                 ....*....|....*....
gi 974005246 793 VWSYGIVMWEVVSyGERPY 811
Cdd:cd14178  184 IWSLGILLYTMLA-GFTPF 201
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
613-803 8.54e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 69.99  E-value: 8.54e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEkqrrDFLGEASI--------MGQFDHPNIIHLEGVVTKSK----- 679
Cdd:cd07863    8 IGVGAYGTVYKARDPHSGHF---VALKSVRVQTNE----DGLPLSTVrevallkrLEAFDHPNIVRLMDVCATSRtdret 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENgSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVle 758
Cdd:cd07863   81 KVTLVFEHVDQ-DLRTYLDKVPPPgLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARI-- 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 759 ddpeaaYTTRGGKIPIRWT----APEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd07863  158 ------YSCQMALTPVVVTlwyrAPEVLLQSTYATPVDMWSVGCIFAEM 200
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
651-826 8.95e-13

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 69.46  E-value: 8.95e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 651 RDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDT--FLKKNDGQFTVIQLVGMLRGISAGMKYLSDMG 727
Cdd:cd14109   40 DPFLmREVDIHNSLDHPNIVQMHDAYDDEKLAVTVIDNLASTIELVrdNLLPGKDYYTERQVAVFVRQLLLALKHMHDLG 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 728 YVHRDLAARNILINSNLVCkVSDFGLSRVLEDDpeaAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyG 807
Cdd:cd14109  120 IAHLDLRPEDILLQDDKLK-LADFGQSRRLLRG---KLTTLIYGSP-EFVSPEIVNSYPVTLATDMWSVGVLTYVLLG-G 193
                        170
                 ....*....|....*....
gi 974005246 808 ERPYWEMTNQDVIKAVEEG 826
Cdd:cd14109  194 ISPFLGDNDRETLTNVRSG 212
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
611-860 9.43e-13

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 70.78  E-value: 9.43e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKrelPVAIKTLK--VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05573    7 KVIGRGAFGEVWLVRDKDTGQ---VYAMKILRksDMLKREQIAHVRAERDILADADSPWIVRLHYAFQDEDHLYLVMEYM 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKND------GQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS-RVLEDDP 761
Cdd:cd05573   84 PGGDLMNLLIKYDvfpeetARFYIAELV-------LALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCtKMNKSGD 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPIR-------------------------WTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTN 816
Cdd:cd05573  157 RESYLNDSVNTLFQdnvlarrrphkqrrvraysavgtpdYIAPEVLRGTGYGPECDWWSLGVILYEML-YGFPPFYSDSL 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 817 QDV---IKAVEEGYRLPSPMDCPAALYQLM--LDCWQKERNSRpkFDEI 860
Cdd:cd05573  236 VETyskIMNWKESLVFPDDPDVSPEAIDLIrrLLCDPEDRLGS--AEEI 282
SAM_EPH-A3 cd09544
SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
898-959 9.55e-13

SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A3 subfamily of receptor tyrosine kinases is a C-terminal putative protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A3 receptors bind SH2/SH3 containing adaptor protein Nck1 and this adaptor is a key factor in EPH-A3 mediated signaling. However SAM domain is not implemented in this interaction. Activation of EPH-A3 receptors inhibits outgrowth and cell migration. Mutations in SAM domain may play a role in development of hepatocellular carcinoma. Expression of EPH-A3 is associated with lymphocytic leukemia and defines the subset of rhabdomyosarcoma tumors. EPH-A3 receptors are attractive targets for drug design.


Pssm-ID: 188943  Cd Length: 63  Bit Score: 63.92  E-value: 9.55e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 898 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQEMK 959
Cdd:cd09544    1 TFHTTGDWLNGARTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIVSSIKTLE 62
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
612-811 1.03e-12

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 70.41  E-value: 1.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRELpVAIKTLK--VGYTEKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKPVMIVTEYM 688
Cdd:cd05615   17 VLGKGSFGKVMLAERK--GSDEL-YAIKILKkdVVIQDDDVECTMVEKRVLALQDKPPFLtQLHSCFQTVDRLYFVMEYV 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPEAAYTTR 768
Cdd:cd05615   94 NGGDLMYHIQQV-GKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCK--EHMVEGVTTRT 170
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 974005246 769 GGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05615  171 FCGTP-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPF 211
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
610-832 1.09e-12

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 70.08  E-value: 1.09e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 610 ERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14168   15 KEVLGTGAFSEVVLAEERATGKL---FAVKCIPKKALKGKESSIENEIAVLRKIKHENIVALEDIYESPNHLYLVMQLVS 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVCKVSDFGLSRvLEDDPEAAY 765
Cdd:cd14168   92 GGELfDRIVEK--GFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYfsqDEESKIMISDFGLSK-MEGKGDVMS 168
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 766 TTRGGKipiRWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAV-EEGYRLPSP 832
Cdd:cd14168  169 TACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDSKLFEQIlKADYEFDSP 232
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
613-805 1.16e-12

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 70.02  E-value: 1.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPgkrELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgS 692
Cdd:cd07872   14 LGEGTYATVFKGRSKLT---ENLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLDK-D 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAYTTrggKI 772
Cdd:cd07872   90 LKQYMDDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA-KSVPTKTYSN---EV 165
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 974005246 773 PIRWTAPEAIAF--RKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07872  166 VTLWYRPPDVLLgsSEYSTQIDMWGVGCIFFEMAS 200
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
664-801 1.21e-12

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 69.24  E-value: 1.21e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 DHPNIIHL----EGVVTKSKPVMIVTEYMENGSL-DTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNI 738
Cdd:cd14089   52 GCPHIVRIidvyENTYQGRKCLLVVMECMEGGELfSRIQERADSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENL 131
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 739 LINS---NLVCKVSDFGLSRvlEDDPEAAYTTrggkiPI---RWTAPEAIAFRKFTSASDVWSYGIVMW 801
Cdd:cd14089  132 LYSSkgpNAILKLTDFGFAK--ETTTKKSLQT-----PCytpYYVAPEVLGPEKYDKSCDMWSLGVIMY 193
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
611-827 1.27e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 69.28  E-value: 1.27e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRD--FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05630    6 RVLGKGGFGEVCACQVRATGKM---YACKKLEKKRIKKRKGEamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLM 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFL-KKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddPEAAyTT 767
Cdd:cd05630   83 NGGDLKFHIyHMGQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHV---PEGQ-TI 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 768 RGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN-------QDVIKAVEEGY 827
Cdd:cd05630  159 KGRVGTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPFQQRKKkikreevERLVKEVPEEY 224
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
901-957 1.33e-12

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886 [Multi-domain]  Cd Length: 56  Bit Score: 63.03  E-value: 1.33e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENgYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQE 957
Cdd:cd09487    1 DVAEWLESLGLEQYADLFRKN-EIDGDALLLLTDEDLKELGITSPGHRKKILRAIQR 56
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
611-804 1.54e-12

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 69.13  E-value: 1.54e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPgkrELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHL---------EGVVTKSKPV 681
Cdd:cd14048   12 QCLGRGGFGVVFEAKNKVD---DCNYAVKRIRLPNNELAREKVLREVRALAKLDHPGIVRYfnawlerppEGWQEKMDEV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 M--IVTEYMENGSLDTFLKKN----DGQFTViqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGL-S 754
Cdd:cd14048   89 YlyIQMQLCRKENLKDWMNRRctmeSRELFV--CLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLvT 166
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 755 RVLEDDPE-------AAYTTRGGKIPIR-WTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd14048  167 AMDQGEPEqtvltpmPAYAKHTGQVGTRlYMSPEQIHGNQYSEKVDIFALGLILFELI 224
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
613-832 1.55e-12

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 69.39  E-value: 1.55e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGR-LKLPGKrelPVAIKTLK------VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14096    9 IGEGAFSNVYKAVpLRNTGK---PVAIKVVRkadlssDNLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYYIVL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSL------DTFLKKNDGQFTVIQLvgmlrgiSAGMKYLSDMGYVHRDLAARNILINS----------------- 742
Cdd:cd14096   86 ELADGGEIfhqivrLTYFSEDLSRHVITQV-------ASAVKYLHEIGVVHRDIKPENLLFEPipfipsivklrkaddde 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 743 -----------------NLVcKVSDFGLSRVLedDPEAAYTTRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd14096  159 tkvdegefipgvggggiGIV-KLADFGLSKQV--WDSNTKTPCG---TVGYTAPEVVKDERYSKKVDMWALGCVLYTLLC 232
                        250       260
                 ....*....|....*....|....*...
gi 974005246 806 yGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14096  233 -GFPPFYDESIETLTEKISRGdYTFLSP 259
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
636-860 1.72e-12

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 68.44  E-value: 1.72e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKTLKvgyTEKQRRDFLGEA------SIMGQFDHPNIIHLEGVVT---KSKpVMIVTEYMENGSLDTFLKKNDGQFTV 706
Cdd:cd14119   21 RAVKILK---KRKLRRIPNGEAnvkreiQILRRLNHRNVIKLVDVLYneeKQK-LYMVMEYCVGGLQEMLDSAPDKRLPI 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 707 IQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE--DDPEAAYTTRGGkiPiRWTAPEaIA- 783
Cdd:cd14119   97 WQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALDlfAEDDTCTTSQGS--P-AFQPPE-IAn 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 784 ----FRKFtsASDVWSYGIVMWEVVSyGERPYwEMTNQ-DVIKAVEEG-YRLPSpmDCPAALYQLMLDCWQKERNSRPKF 857
Cdd:cd14119  173 gqdsFSGF--KVDIWSAGVTLYNMTT-GKYPF-EGDNIyKLFENIGKGeYTIPD--DVDPDLQDLLRGMLEKDPEKRFTI 246

                 ...
gi 974005246 858 DEI 860
Cdd:cd14119  247 EQI 249
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
611-806 1.72e-12

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 69.57  E-value: 1.72e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK---------VGYTeKQRRDFLGEAsimgqfDHPNIIHLEGVVTKSKPV 681
Cdd:cd05599    7 KVIGRGAFGEVRLVRKKDTGHV---YAMKKLRksemlekeqVAHV-RAERDILAEA------DNPWVVKLYYSFQDEENL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKND------GQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR 755
Cdd:cd05599   77 YLIMEFLPGGDMMTLLMKKDtlteeeTRFYIAETV-------LAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCT 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005246 756 VLEDDPeAAYTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWE-VVSY 806
Cdd:cd05599  150 GLKKSH-LAYSTVG--TP-DYIAPEVFLQKGYGKECDWWSLGVIMYEmLIGY 197
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
611-811 1.73e-12

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 69.59  E-value: 1.73e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRELpVAIKTLK--VGYTEKQRRDFLGEASIMG-QFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05620    1 KVLGKGSFGKVLLAELK--GKGEY-FAVKALKkdVVLIDDDVECTMVEKRVLAlAWENPFLTHLYCTFQTKEHLFFVMEF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR--VLEDDPEAAY 765
Cdd:cd05620   78 LNGGDL-MFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKenVFGDNRASTF 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 766 TTRGGKIpirwtAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPY 811
Cdd:cd05620  157 CGTPDYI-----APEILQGLKYTFSVDWWSFGVLLYEML-IGQSPF 196
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
605-832 1.74e-12

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 68.76  E-value: 1.74e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 605 SCITIERVIGAGEFGEV------CSGRLklpgkrelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd14169    3 SVYELKEKLGEGAFSEVvlaqerGSQRL---------VALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESP 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVckVSDFG 752
Cdd:cd14169   74 THLYLAMELVTGGELfDRIIER--GSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYatpfeDSKIM--ISDFG 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 753 LSRVLEDDPEA-AYTTRGgkipirWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAV-EEGYRLP 830
Cdd:cd14169  150 LSKIEAQGMLStACGTPG------YVAPELLEQKPYGKAVDVWAIGVISY-ILLCGYPPFYDENDSELFNQIlKAEYEFD 222

                 ..
gi 974005246 831 SP 832
Cdd:cd14169  223 SP 224
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
613-881 1.83e-12

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 69.37  E-value: 1.83e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrLKLPGKRElpVAIKTLKVGYTEKQRRdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06656   27 IGQGASGTVYTA-IDIATGQE--VAIKQMNLQQQPKKEL-IINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGS 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKK---NDGQftviqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTTRG 769
Cdd:cd06656  103 LTDVVTEtcmDEGQ-----IAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQIT--PEQSKRSTM 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwemTNQDVIKAV-----EEGYRLPSPMDCPAALYQLML 844
Cdd:cd06656  176 VGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY---LNENPLRALyliatNGTPELQNPERLSAVFRDFLN 250
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 845 DCWQKERNSRPKFDEIVNM-LDKLIRNPSSLKTLVNAS 881
Cdd:cd06656  251 RCLEMDVDRRGSAKELLQHpFLKLAKPLSSLTPLIIAA 288
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
665-826 2.01e-12

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 69.13  E-value: 2.01e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 665 HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS-- 742
Cdd:cd14180   60 HPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKKKA-RFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADes 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 743 -NLVCKVSDFGLSRVLeddPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQ---- 817
Cdd:cd14180  139 dGAVLKVIDFGFARLR---PQGSRPLQTPCFTLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPFQSKRGKmfhn 214
                        170
                 ....*....|..
gi 974005246 818 ---DVIKAVEEG 826
Cdd:cd14180  215 haaDIMHKIKEG 226
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
635-811 2.28e-12

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 68.45  E-value: 2.28e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 635 PVAIKTLKVGYTEKQRR--DFLGEASimgqfDHPNIIHLEGVVTKSKPVMIVTEYMeNGSLDTFLKK----NDGQFTVIQ 708
Cdd:cd13982   27 PVAVKRLLPEFFDFADRevQLLRESD-----EHPNVIRYFCTEKDRQFLYIALELC-AASLQDLVESpresKLFLRPGLE 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 709 LVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTAPEAI- 782
Cdd:cd13982  101 PVRLLRQIASGLAHLHSLNIVHRDLKPQNILIstpnaHGNVRAMISDFGLCKKLDVGRSSFSRRSGVAGTSGWIAPEMLs 180
                        170       180       190
                 ....*....|....*....|....*....|.
gi 974005246 783 --AFRKFTSASDVWSYGIVMWEVVSYGERPY 811
Cdd:cd13982  181 gsTKRRQTRAVDIFSLGCVFYYVLSGGSHPF 211
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
613-811 2.45e-12

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 68.02  E-value: 2.45e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLK---VGYTEKQRRDFLgEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd05572    1 LGVGGFGRVELVQLKSKGRT---FALKCVKkrhIVQTRQQEHIFS-EKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLK------KNDGQFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEA 763
Cdd:cd05572   77 GGELWTILRdrglfdEYTARFYTACVV-------LAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSG-RK 148
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 764 AYTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05572  149 TWTFCG--TP-EYVAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPF 192
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
662-855 2.49e-12

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 68.16  E-value: 2.49e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 662 QFDHPNIIHLEGVVTKSKP------VMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAA 735
Cdd:cd14012   54 KLRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELLDSV-GSVPLDTARRWTLQLLEALEYLHRNGVVHKSLHA 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 736 RNILINSNL---VCKVSDFGLSRVLEDdpeaaYTTRGGKI---PIRWTAPEAIAF-RKFTSASDVWSYGIVMWEVvsyge 808
Cdd:cd14012  133 GNVLLDRDAgtgIVKLTDYSLGKTLLD-----MCSRGSLDefkQTYWLPPELAQGsKSPTRKTDVWDLGLLFLQM----- 202
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 809 rpyweMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRP 855
Cdd:cd14012  203 -----LFGLDVLEKYTSPNPVLVSLDLSASLQDFLSKCLSLDPKKRP 244
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
613-805 2.52e-12

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 68.88  E-value: 2.52e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPgkrELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgS 692
Cdd:cd07873   10 LGEGTYATVYKGRSKLT---DNLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLDK-D 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAYTTrggKI 772
Cdd:cd07873   86 LKQYLDDCGNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA-KSIPTKTYSN---EV 161
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 974005246 773 PIRWTAPEAIAF--RKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07873  162 VTLWYRPPDILLgsTDYSTQIDMWGVGCIFYEMST 196
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
613-812 2.93e-12

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 68.55  E-value: 2.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTlkvgYTEKQ-----RRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd07847    9 IGEGSYGVVFKCRNRETGQ---IVAIKK----FVESEddpviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTfLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeDDPEAAYTT 767
Cdd:cd07847   82 CDHTVLNE-LEKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARIL-TGPGDDYTD 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 974005246 768 rggKIPIRW-TAPEAIAF-RKFTSASDVWSYGIVMWEVVSyGErPYW 812
Cdd:cd07847  160 ---YVATRWyRAPELLVGdTQYGPPVDVWAIGCVFAELLT-GQ-PLW 201
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
611-831 3.68e-12

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 68.20  E-value: 3.68e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL---KVGYTeKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd14209    7 KTLGTGSFGRVMLVRHKETGNY---YAMKILdkqKVVKL-KQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDdpeAAYTT 767
Cdd:cd14209   83 VPGGEMFSHLRRI-GRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKG---RTWTL 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 768 RGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWemTNQDVI---KAVEEGYRLPS 831
Cdd:cd14209  159 CG--TP-EYLAPEIILSKGYNKAVDWWALGVLIYEMAA-GYPPFF--ADQPIQiyeKIVSGKVRFPS 219
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
613-801 3.82e-12

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 67.41  E-value: 3.82e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTEKQRRDFLgEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENG 691
Cdd:cd14078   11 IGSGGFAKVKLATHILTGEK---VAIKIMdKKALGDDLPRVKT-EIEALKNLSHQHICRLYHVIETDNKIFMVLEYCPGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SL-DTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGG 770
Cdd:cd14078   87 ELfDYIVAKD--RLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAKPKGGMDHHLETCCG 164
                        170       180       190
                 ....*....|....*....|....*....|..
gi 974005246 771 KiPIrWTAPEAIAFRKFT-SASDVWSYGIVMW 801
Cdd:cd14078  165 S-PA-YAAPELIQGKPYIgSEADVWSMGVLLY 194
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
611-812 3.85e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 68.45  E-value: 3.85e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL--KVGYTEKQRRDFLGEASIM-GQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05604    2 KVIGKGSFGKVLLAKRKRDGKY---YAVKVLqkKVILNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPEAAYTT 767
Cdd:cd05604   79 VNGGELFFHLQR-ERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCK--EGISNSDTTT 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 768 RGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYW 812
Cdd:cd05604  156 TFCGTP-EYLAPEVIRKQPYDNTVDWWCLGSVLYEML-YGLPPFY 198
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
613-823 4.05e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 68.21  E-value: 4.05e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06655   27 IGQGASGTVFTAIDVATGQE---VAIKQINL-QKQPKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAGGS 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTTRGGKI 772
Cdd:cd06655  103 LTDVVTET--CMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQIT--PEQSKRSTMVGT 178
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 974005246 773 PIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwemTNQDVIKAV 823
Cdd:cd06655  179 PY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY---LNENPLRAL 224
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
609-801 4.67e-12

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 67.33  E-value: 4.67e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEV--CSGRlklpgKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd14183   10 VGRTIGDGNFAVVkeCVER-----STGREYALKIINKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDMPTELYLVME 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSL-DTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI----NSNLVCKVSDFGLSRVLeDDP 761
Cdd:cd14183   85 LVKGGDLfDAITSTN--KYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVyehqDGSKSLKLGDFGLATVV-DGP 161
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 974005246 762 eaAYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMW 801
Cdd:cd14183  162 --LYTVCGTPT---YVAPEIIAETGYGLKVDIWAAGVITY 196
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
611-804 4.73e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 68.52  E-value: 4.73e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP------VMI 683
Cdd:cd07876   27 KPIGSGAQGIVCAAFDTVLG---INVAVKKLSRPFqNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKSleefqdVYL 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSLDTFLKKNDGQftviQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpea 763
Cdd:cd07876  104 VMELMDANLCQVIHMELDHE----RMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTN--- 176
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 764 aYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07876  177 -FMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELV 216
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
609-815 5.03e-12

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 68.11  E-value: 5.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLK--VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05601    5 VKNVIGRGHFGEVQVVKEKATGD---IYAMKVLKksETLAQEEVSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKNDGQFT--VIQ--LVGMLRGISAgmkyLSDMGYVHRDLAARNILINSNLVCKVSDFGlsrvleddpE 762
Cdd:cd05601   82 YHPGGDLLSLLSRYDDIFEesMARfyLAELVLAIHS----LHSMGYVHRDIKPENILIDRTGHIKLADFG---------S 148
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 763 AAYTTRGG----KIPIrwTAPEAIAFRKFTSAS-----------DVWSYGIVMWEVVsYGERPYWEMT 815
Cdd:cd05601  149 AAKLSSDKtvtsKMPV--GTPDYIAPEVLTSMNggskgtygvecDWWSLGIVAYEML-YGKTPFTEDT 213
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
607-866 5.73e-12

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 67.36  E-value: 5.73e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRdFLGEASIMGQF-DHPNII-HLEGVVTKSKP---V 681
Cdd:cd13985    2 YQVTKQLGEGGFSYVYLAHDVNTGRR---YALKRMYFNDEEQLRV-AIKEIEIMKRLcGHPNIVqYYDSAILSSEGrkeV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMEnGSLDTFLKKN-DGQFTVIQLVGMLRGISAGMKYLSDMG--YVHRDLAARNILINSNLVCKVSDFGlsrvle 758
Cdd:cd13985   78 LLLMEYCP-GSLVDILEKSpPSPLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFG------ 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 759 ddpeaaYTTRGGKIPIRWT------------------APEAI-AFRKF--TSASDVWSYGIVMWEVVsYGERPYWEMTnq 817
Cdd:cd13985  151 ------SATTEHYPLERAEevniieeeiqknttpmyrAPEMIdLYSKKpiGEKADIWALGCLLYKLC-FFKLPFDESS-- 221
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 818 dVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDK 866
Cdd:cd13985  222 -KLAIVAGKYSIPEQPRYSPELHDLIRHMLTPDPAERPDIFQVINIITK 269
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
613-804 5.92e-12

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 67.09  E-value: 5.92e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIK-------------TLKVGYTEKQRRD-FLGEASIMGQFDHPNIIHLEGVVTKS 678
Cdd:cd14077    9 IGAGSMGKVKLAKHIRTGEK---CAIKiiprasnaglkkeREKRLEKEISRDIrTIREAALSSLLNHPHICRLRDFLRTP 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTF------LKKNDGQftviqlvGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFG 752
Cdd:cd14077   86 NHYYMLFEYVDGGQLLDYiishgkLKEKQAR-------KFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFG 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 753 LSRVLedDPEAAYTTRGGKipIRWTAPEAIAFRKFTSAS-DVWSYGIVMWEVV 804
Cdd:cd14077  159 LSNLY--DPRRLLRTFCGS--LYFAAPELLQAQPYTGPEvDVWSFGVVLYVLV 207
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
613-804 6.15e-12

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 67.80  E-value: 6.15e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgS 692
Cdd:cd07869   13 LGEGSYATVYKGKSKVNGKL---VALKVIRLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEYVHT-D 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAYTTrggKI 772
Cdd:cd07869   89 LCQYMDKHPGGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARA-KSVPSHTYSN---EV 164
                        170       180       190
                 ....*....|....*....|....*....|....
gi 974005246 773 PIRWTAPEAIAF--RKFTSASDVWSYGIVMWEVV 804
Cdd:cd07869  165 VTLWYRPPDVLLgsTEYSTCLDMWGVGCIFVEMI 198
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
611-825 6.47e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 67.33  E-value: 6.47e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRD--FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05631    6 RVLGKGGFGEVCACQVRATGKM---YACKKLEKKRIKKRKGEamALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIM 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLdTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddPEAAyT 766
Cdd:cd05631   83 NGGDL-KFHIYNMGNpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQI---PEGE-T 157
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 767 TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS-------YGERPYWEMTNQDVIKAVEE 825
Cdd:cd05631  158 VRGRVGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQgqspfrkRKERVKREEVDRRVKEDQEE 223
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
611-811 6.61e-12

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 67.65  E-value: 6.61e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL-KVGYTE--KQRRdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05574    7 KLLGKGDVGRVYLVRLKGTGKL---FAMKVLdKEEMIKrnKVKR-VLTEREILATLDHPFLPTLYASFQTSTHLCFVMDY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDG--------QFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS----- 754
Cdd:cd05574   83 CPGGELFRLLQKQPGkrlpeevaRFYAAEVL-------LALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDLSkqssv 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 755 ---RVLEDDPEAAYTTRGGKIPIR------------------WTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPY 811
Cdd:cd05574  156 tppPVRKSLRKGSRRSSVKSIEKEtfvaepsarsnsfvgteeYIAPEVIKGDGHGSAVDWWTLGILLYEML-YGTTPF 232
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
613-881 7.14e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 67.44  E-value: 7.14e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRdFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06654   28 IGQGASGTVYTAMDVATGQE---VAIRQMNLQQQPKKEL-IINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGS 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKK---NDGQftviqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEddPEAAYTTRG 769
Cdd:cd06654  104 LTDVVTEtcmDEGQ-----IAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQIT--PEQSKRSTM 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 GKIPIrWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYwemTNQDVIKAV-----EEGYRLPSPMDCPAALYQLML 844
Cdd:cd06654  177 VGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPY---LNENPLRALyliatNGTPELQNPEKLSAIFRDFLN 251
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 845 DCWQKERNSRPKFDEIV-NMLDKLIRNPSSLKTLVNAS 881
Cdd:cd06654  252 RCLEMDVEKRGSAKELLqHQFLKIAKPLSSLTPLIAAA 289
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
613-811 8.28e-12

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 66.55  E-value: 8.28e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLpgKRELpVAIKTLKVG--YTEKQRRDFLGEASIMgqfdHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd14665    8 IGSGNFGVARLMRDKQ--TKEL-VAVKYIERGekIDENVQREIINHRSLR----HPNIVRFKEVILTPTHLAIVMEYAAG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLkKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV--CKVSDFGLSR--VLEDDPEAAYT 766
Cdd:cd14665   81 GELFERI-CNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKssVLHSQPKSTVG 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 767 TRGgkipirWTAPEAIAFRKFTSA-SDVWSYGIVMWeVVSYGERPY 811
Cdd:cd14665  160 TPA------YIAPEVLLKKEYDGKiADVWSCGVTLY-VMLVGAYPF 198
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
604-814 1.10e-11

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 66.67  E-value: 1.10e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 604 ASCITIERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVgyTEKQRRDFLGEASIMGQFDH-PNIIHLEGVVTKSKP-- 680
Cdd:cd06637    5 AGIFELVELVGNGTYGQVYKGRHVKTGQL---AAIKVMDV--TGDEEEEIKQEINMLKKYSHhRNIATYYGAFIKKNPpg 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 ----VMIVTEYMENGSLDTFLKKNDGQFTVIQLVGML-RGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR 755
Cdd:cd06637   80 mddqLWLVMEFCGAGSVTDLIKNTKGNTLKEEWIAYIcREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSA 159
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 756 VLEDDPEAAYTTRGGKIpirWTAPEAIAFRKFTSA-----SDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd06637  160 QLDRTVGRRNTFIGTPY---WMAPEVIACDENPDAtydfkSDLWSLGITAIEMAE-GAPPLCDM 219
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
613-823 1.30e-11

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 66.18  E-value: 1.30e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEK--QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd14195   13 LGSGQFAIVRKCREKGTGKEYAAKFIKKRRLSSSRRgvSREEIEREVNILREIQHPNIITLHDIFENKTDVVLILELVSG 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI----NSNLVCKVSDFGLSRVLEDDPEaaYT 766
Cdd:cd14195   93 GELFDFLAEKE-SLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLldknVPNPRIKLIDFGIAHKIEAGNE--FK 169
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 767 TRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV 823
Cdd:cd14195  170 NIFGT-P-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGETKQETLTNI 223
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
613-805 1.44e-11

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 66.14  E-value: 1.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVV--TKSKPVMIVTEYME 689
Cdd:cd07831    7 IGEGTFSEVLKAQSRKTGKY---YAIKCMKKHFKSLEQVNNLREIQALRRLsPHPNILRLIEVLfdRKTGRLALVFELMD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 nGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVcKVSDFGLSR-VLEDDPEAAYttr 768
Cdd:cd07831   84 -MNLYELIKGRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDDIL-KLADFGSCRgIYSKPPYTEY--- 158
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 974005246 769 ggkIPIRW-TAPEAIAFRKFTSAS-DVWSYGIVMWEVVS 805
Cdd:cd07831  159 ---ISTRWyRAPECLLTDGYYGPKmDIWAVGCVFFEILS 194
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
611-811 1.52e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 66.53  E-value: 1.52e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRD--FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05632    8 RVLGKGGFGEVCACQVRATGKM---YACKRLEKKRIKKRKGEsmALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLdTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLS-RVLEDDpeaay 765
Cdd:cd05632   85 NGGDL-KFHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAvKIPEGE----- 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05632  159 SIRGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPF 203
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
609-810 1.55e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 66.29  E-value: 1.55e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERvIGAGEFGEVCSGRLKLPGKRelpVAIKTLKV-----GYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd07861    5 IEK-IGEGTYGVVYKGRNKKTGQI---VAMKKIRLeseeeGVPSTAIR----EISLLKELQHPNIVCLEDVLMQENRLYL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMengSLDtfLKKN-----DGQFTVIQLV-GMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVL 757
Cdd:cd07861   77 VFEFL---SMD--LKKYldslpKGKYMDAELVkSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAF 151
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 758 eddpeaayttrggKIPIR----------WTAPEAI-AFRKFTSASDVWSYGIVMWEVVSygERP 810
Cdd:cd07861  152 -------------GIPVRvythevvtlwYRAPEVLlGSPRYSTPVDIWSIGTIFAEMAT--KKP 200
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
613-842 1.57e-11

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 65.79  E-value: 1.57e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVA---IKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHL----EGVVTKSKPVMIVT 685
Cdd:cd14033    9 IGRGSFKTVYRG---LDTETTVEVAwceLQTRKLSKGERQR--FSEEVEMLKGLQHPNIVRFydswKSTVRGHKCIILVT 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKK-NDGQFTVIQLVGmlRGISAGMKYLSDMG--YVHRDLAARNILINS-NLVCKVSDFGLSRVleddP 761
Cdd:cd14033   84 ELMTSGTLKTYLKRfREMKLKLLQRWS--RQILKGLHFLHSRCppILHRDLKCDNIFITGpTGSVKIGDLGLATL----K 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPiRWTAPEAIAfRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRlpspmdcPAALY 840
Cdd:cd14033  158 RASFAKSVIGTP-EFMAPEMYE-EKYDEAVDVYAFGMCILEMAT-SEYPYSECQNaAQIYRKVTSGIK-------PDSFY 227

                 ..
gi 974005246 841 QL 842
Cdd:cd14033  228 KV 229
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
613-827 1.57e-11

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 66.12  E-value: 1.57e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgyteKQRRDFLGEASIM---GQfdHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14091    8 IGKGSYSVCKRCIHKATGKE---YAVKIID-----KSKRDPSEEIEILlryGQ--HPNIITLRDVYDDGNSVYLVTELLR 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNL----VCKVSDFGLSRVLEDD---- 760
Cdd:cd14091   78 GGELlDRILRQ--KFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESgdpeSLRICDFGFAKQLRAEngll 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 761 --PeaAYTTrggkipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW---EMTNQDVIKAVEEGY 827
Cdd:cd14091  156 mtP--CYTA-------NFVAPEVLKKQGYDAACDIWSLGVLLYTMLA-GYTPFAsgpNDTPEVILARIGSGK 217
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
613-826 1.64e-11

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 65.99  E-value: 1.64e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMI-------- 683
Cdd:cd14049   14 LGKGGYGKVYKVRNKLDGQY---YAIKKILIkKVTKRDCMKVLREVKVLAGLQHPNIVGYHTAWMEHVQLMLyiqmqlce 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 ------VTEYMENGSLDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILIN-SNLVCKVSDFGLS-- 754
Cdd:cd14049   91 lslwdwIVERNKRPCEEEFKSAPYTPVDVDVTTKILQQLLEGVTYIHSMGIVHRDLKPRNIFLHgSDIHVRIGDFGLAcp 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 755 RVLED-------DPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsygeRPY-WEMTNQDVIKAVEEG 826
Cdd:cd14049  171 DILQDgndsttmSRLNGLTHTSGVGTCLYAAPEQLEGSHYDFKSDMYSIGVILLELF----QPFgTEMERAEVLTQLRNG 246
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
611-805 1.86e-11

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 66.73  E-value: 1.86e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKtlKVGYTEKQR-RDFLGEASIMGQFDHPNIIHL--------------EGVV 675
Cdd:cd07854   11 RPLGCGSNGLVFSAVDSDCDKR---VAVK--KIVLTDPQSvKHALREIKIIRRLDHDNIVKVyevlgpsgsdltedVGSL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 676 TKSKPVMIVTEYMENgSLDTFLKKNDGQFTVIQLVG--MLRGisagMKYLSDMGYVHRDLAARNILINS-NLVCKVSDFG 752
Cdd:cd07854   86 TELNSVYIVQEYMET-DLANVLEQGPLSEEHARLFMyqLLRG----LKYIHSANVLHRDLKPANVFINTeDLVLKIGDFG 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 753 LSRVLedDPEaaYTTRG----GKIPIRWTAPE-AIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07854  161 LARIV--DPH--YSHKGylseGLVTKWYRSPRlLLSPNNYTKAIDMWAAGCIFAEMLT 214
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
611-862 1.98e-11

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 66.53  E-value: 1.98e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTL--KVGYTEKQRRDFLGEASIM-GQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05603    1 KVIGKGSFGKVLLAKRKCDGKF---YAVKVLqkKTILKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlED-DPEAAYT 766
Cdd:cd05603   78 VNGGELFFHLQR-ERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCK--EGmEPEETTS 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWemtNQDVIKAVEEgyRLPSPMDCPAA-------L 839
Cdd:cd05603  155 TFCGT-P-EYLAPEVLRKEPYDRTVDWWCLGAVLYEML-YGLPPFY---SRDVSQMYDN--ILHKPLHLPGGktvaacdL 226
                        250       260
                 ....*....|....*....|....
gi 974005246 840 YQLMLDCWQKER-NSRPKFDEIVN 862
Cdd:cd05603  227 LQGLLHKDQRRRlGAKADFLEIKN 250
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
612-803 2.14e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 65.79  E-value: 2.14e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRELpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd07848    8 VVGEGAYGVVLKCRHK--ETKEI-VAIKKFKDSEeNEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDG------QFTVIQLVgmlrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAA 764
Cdd:cd07848   85 NMLELLEEMPNGvppekvRSYIYQLI-------KAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSNAN 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 974005246 765 YTTRggkIPIRW-TAPEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd07848  158 YTEY---VATRWyRSPELLLGAPYGKAVDMWSVGCILGEL 194
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
613-871 2.66e-11

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 65.85  E-value: 2.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06650   13 LGAGNGGVVFKVSHKPSG---LVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNdGQFTViQLVGMLR-GISAGMKYLSDMGYV-HRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT-TRG 769
Cdd:cd06650   90 LDQVLKKA-GRIPE-QILGKVSiAVIKGLTYLREKHKImHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVgTRS 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 770 gkipirWTAPEAIAFRKFTSASDVWSYGIVMWEvVSYGERPY--------WEMTNQDVIKAVEEGYRLPSPMDCPAALYQ 841
Cdd:cd06650  168 ------YMSPERLQGTHYSVQSDIWSMGLSLVE-MAVGRYPIpppdakelELMFGCQVEGDAAETPPRPRTPGRPLSSYG 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 974005246 842 LmldcwqkerNSRPKFdEIVNMLDKLIRNP 871
Cdd:cd06650  241 M---------DSRPPM-AIFELLDYIVNEP 260
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
611-812 2.81e-11

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 65.07  E-value: 2.81e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEV--CsgrLKLPGKRELpvAIKTLKVG----YTEKQRRDFLGEASIMGQFDHPNIIHLEGVV--TKSKPVM 682
Cdd:cd06652    8 KLLGQGAFGRVylC---YDADTGREL--AVKQVQFDpespETSKEVNALECEIQLLKNLLHERIVQYYGCLrdPQERTLS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPE 762
Cdd:cd06652   83 IFMEYMPGGSIKDQLKSY-GALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICL 161
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 763 AAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSygERPYW 812
Cdd:cd06652  162 SGTGMKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLT--EKPPW 209
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
609-803 2.91e-11

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 65.07  E-value: 2.91e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERvIGAGEFGEVCSGRLKLPGkrELpVAIKTLKVGYTEkqrrDF---LGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd06645   16 IQR-IGSGTYGDVYKARNVNTG--EL-AAIKVIKLEPGE----DFavvQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICM 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddpEAAY 765
Cdd:cd06645   88 EFCGGGSLQDIYHVT-GPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQI----TATI 162
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 766 TTRGGKIPI-RWTAPEAIAFRK---FTSASDVWSYGIVMWEV 803
Cdd:cd06645  163 AKRKSFIGTpYWMAPEVAAVERkggYNQLCDIWAVGITAIEL 204
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
609-833 2.92e-11

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 66.10  E-value: 2.92e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK---------VGYTEKQRRdFLGEAsimgqFDHPNIIHLEGVVTKSK 679
Cdd:cd05619    9 LHKMLGKGSFGKVFLAELKGTNQF---FAIKALKkdvvlmdddVECTMVEKR-VLSLA-----WEHPFLTHLFCTFQTKE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 PVMIVTEYMENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlED 759
Cdd:cd05619   80 NLFFVMEYLNGGDL-MFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCK--EN 156
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 760 DPEAAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVeegyRLPSPM 833
Cdd:cd05619  157 MLGDAKTSTFCGTP-DYIAPEILLGQKYNTSVDWWSFGVLLYEML-IGQSPFHGQDEEELFQSI----RMDNPF 224
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
611-811 3.02e-11

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 65.89  E-value: 3.02e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRlKLPGKRELPV-AIKTLKVGYTEKQRRDFL---GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05584    2 KVLGKGGYGKVFQVR-KTTGSDKGKIfAMKVLKKASIVRNQKDTAhtkAERNILEAVKHPFIVDLHYAFQTGGKLYLILE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd05584   81 YLSGGELFMHLER-EGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHDGTVTHT 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 767 TRGgkiPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05584  160 FCG---TIEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPF 200
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
609-805 3.21e-11

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 64.98  E-value: 3.21e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEV--CSGRLKlpgkrELPVAIKTLKvgytekQRRDF----LGEASIM------GQFDHPNIIHLEGVVT 676
Cdd:cd14133    3 VLEVLGKGTFGQVvkCYDLLT-----GEEVALKIIK------NNKDYldqsLDEIRLLellnkkDKADKYHIVRLKDVFY 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 677 KSKPVMIVTEYMENgSLDTFLKKNDGQ-FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVC--KVSDFGl 753
Cdd:cd14133   72 FKNHLCIVFELLSQ-NLYEFLKQNKFQyLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCqiKIIDFG- 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005246 754 SRVLEDDPEAAYttrggkIPIR-WTAPEAIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd14133  150 SSCFLTQRLYSY------IQSRyYRAPEVILGLPYDEKIDMWSLGCILAELYT 196
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
613-857 3.76e-11

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 65.88  E-value: 3.76e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP------VMIVT 685
Cdd:cd07874   25 IGSGAQGIVCAAYDAVLDRN---VAIKKLSRPFqNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKSleefqdVYLVM 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLrgisAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVleddPEAAY 765
Cdd:cd07874  102 ELMDANLCQVIQMELDHERMSYLLYQML----CGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLART----AGTSF 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS----YGERPYWEMTNqdviKAVEEgyrLPSPmdCPAALYQ 841
Cdd:cd07874  174 MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRhkilFPGRDYIDQWN----KVIEQ---LGTP--CPEFMKK 244
                        250
                 ....*....|....*.
gi 974005246 842 LMLDCWQKERNsRPKF 857
Cdd:cd07874  245 LQPTVRNYVEN-RPKY 259
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
613-832 4.00e-11

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 65.14  E-value: 4.00e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRDflGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14086    9 LGKGAFSVVRRCVQKSTGQEFAAKIINTKKLSARDHQKLE--REARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGE 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 L------DTFLKKNDGQFTVIQlvgmlrgISAGMKYLSDMGYVHRDLAARNILINS---NLVCKVSDFGLSRVLEDDPEA 763
Cdd:cd14086   87 LfedivaREFYSEADASHCIQQ-------ILESVNHCHQNGIVHRDLKPENLLLASkskGAAVKLADFGLAIEVQGDQQA 159
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 764 AYTTRGGKIpirWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14086  160 WFGFAGTPG---YLSPEVLRKDPYGKPVDIWACGVILY-ILLVGYPPFWDEDQHRLYAQIKAGaYDYPSP 225
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
609-870 4.41e-11

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 64.43  E-value: 4.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEV--CSGRlklpGKRElPVAIKTLkVGYTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVT-------KS 678
Cdd:cd13975    4 LGRELGRGQYGVVyaCDSW----GGHF-PCALKSV-VPPDDKHWNDLALEFHYTRSLpKHERIVSLHGSVIdysygggSS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENgSLDTFLKKNdgqFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvle 758
Cdd:cd13975   78 IAVLLIMERLHR-DLYTGIKAG---LSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK--- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 759 ddPEAAYTtrgGKI---PIRwTAPEAIAfRKFTSASDVWSYGIVMWEVVSYGER---PYWEMTNQDVI-KAVEEGYR--- 828
Cdd:cd13975  151 --PEAMMS---GSIvgtPIH-MAPELFS-GKYDNSVDVYAFGILFWYLCAGHVKlpeAFEQCASKDHLwNNVRKGVRper 223
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 974005246 829 LPSPMDcpaALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRN 870
Cdd:cd13975  224 LPVFDE---ECWNLMEACWSGDPSQRPLLGIVQPKLQGIMDR 262
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
649-805 4.65e-11

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 65.79  E-value: 4.65e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 649 QRRDFLGEASIMGQFDHPNIIHLEGVVTKSK-PVMIVTEYMENgsLDTFL--KKNdgqFTVIQLVGMLRGISAGMKYLSD 725
Cdd:PHA03212 126 QRGGTATEAHILRAINHPSIIQLKGTFTYNKfTCLILPRYKTD--LYCYLaaKRN---IAICDILAIERSVLRAIQYLHE 200
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 726 MGYVHRDLAARNILIN-SNLVCkVSDFGLSRVLEDDPEAAYTTRGGKIPIrwTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:PHA03212 201 NRIIHRDIKAENIFINhPGDVC-LGDFGAACFPVDINANKYYGWAGTIAT--NAPELLARDPYGPAVDIWSAGIVLFEMA 277

                 .
gi 974005246 805 S 805
Cdd:PHA03212 278 T 278
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
613-807 5.18e-11

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 65.45  E-value: 5.18e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVAIKTLKVGY-TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKP------VMIVT 685
Cdd:cd07875   32 IGSGAQGIVCAA---YDAILERNVAIKKLSRPFqNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSleefqdVYIVM 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNDGQFTVIQLVGMLRGIsagmKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVleddPEAAY 765
Cdd:cd07875  109 ELMDANLCQVIQMELDHERMSYLLYQMLCGI----KHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLART----AGTSF 180
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 766 TTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYG 807
Cdd:cd07875  181 MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMIKGG 222
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
611-812 6.67e-11

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 63.89  E-value: 6.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEV--CsgrLKLPGKRELPVAIKTLKVGY--TEKQRRDFLGEASIMGQFDHPNIIHLEGVVT--KSKPVMIV 684
Cdd:cd06653    8 KLLGRGAFGEVylC---YDADTGRELAVKQVPFDPDSqeTSKEVNALECEIQLLKNLRHDRIVQYYGCLRdpEEKKLSIF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAA 764
Cdd:cd06653   85 VEYMPGGSVKDQLKAY-GALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMSG 163
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 974005246 765 YTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSygERPYW 812
Cdd:cd06653  164 TGIKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLT--EKPPW 209
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
642-862 7.27e-11

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 63.97  E-value: 7.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 642 KVGYTEKQRrdFLGEASIMGQFDHPNIIHL----EGVVTKSKPVMIVTEYMENGSLDTFLKKndgqFTVIQ---LVGMLR 714
Cdd:cd14031   47 KLTKAEQQR--FKEEAEMLKGLQHPNIVRFydswESVLKGKKCIVLVTELMTSGTLKTYLKR----FKVMKpkvLRSWCR 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 715 GISAGMKYLSDMG--YVHRDLAARNILINSNL-VCKVSDFGLSRVLeddpEAAYTTRGGKIPiRWTAPEAIAfRKFTSAS 791
Cdd:cd14031  121 QILKGLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLATLM----RTSFAKSVIGTP-EFMAPEMYE-EHYDESV 194
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 792 DVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRlPSPMD--CPAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14031  195 DVYAFGMCMLEMAT-SEYPYSECQNaAQIYRKVTSGIK-PASFNkvTDPEVKEIIEGCIRQNKSERLSIKDLLN 266
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
609-804 7.66e-11

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 63.73  E-value: 7.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKlpgKRELPVAIKTL------KVGYTEKQRRdflgEASIMGQFDHPNIIHLEGVVTKSKPVM 682
Cdd:cd14117   10 IGRPLGKGKFGNVYLAREK---QSKFIVALKVLfksqieKEGVEHQLRR----EIEIQSHLRHPNILRLYNYFHDRKRIY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSrvlEDDPE 762
Cdd:cd14117   83 LILEYAPRGELYKELQKH-GRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWS---VHAPS 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 763 AAYTTRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd14117  159 LRRRTMCGTLD--YLPPEMIEGRTHDEKVDLWCIGVLCYELL 198
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
613-862 7.89e-11

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 64.30  E-value: 7.89e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGrlkLPGKRELPVA---IKTLKVGYTEKQRrdFLGEASIMGQFDHPNIIHL----EGVVTKSKPVMIVT 685
Cdd:cd14030   33 IGRGSFKTVYKG---LDTETTVEVAwceLQDRKLSKSERQR--FKEEAGMLKGLQHPNIVRFydswESTVKGKKCIVLVT 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKndgqFTVIQ---LVGMLRGISAGMKYLSDMG--YVHRDLAARNILINSNL-VCKVSDFGLSRVled 759
Cdd:cd14030  108 ELMTSGTLKTYLKR----FKVMKikvLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLATL--- 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 dPEAAYTTRGGKIPiRWTAPEAIAfRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRlPSPMDCPA- 837
Cdd:cd14030  181 -KRASFAKSVIGTP-EFMAPEMYE-EKYDESVDVYAFGMCMLEMAT-SEYPYSECQNaAQIYRRVTSGVK-PASFDKVAi 255
                        250       260
                 ....*....|....*....|....*.
gi 974005246 838 -ALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14030  256 pEVKEIIEGCIRQNKDERYAIKDLLN 281
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
609-804 8.91e-11

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 63.85  E-value: 8.91e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERvIGAGEFGEVCSGRLKLPGKRelpVAIKTLKV-GYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd07835    4 LEK-IGEGTYGVVYKARDKLTGEI---VALKKIRLeTEDEGVPSTAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 mengsLDTFLKKNDGQFTVIQLVGML-----RGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeDDPE 762
Cdd:cd07835   80 -----LDLDLKKYMDSSPLTGLDPPLiksylYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAF-GVPV 153
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 974005246 763 AAYTTrggKIPIRW-TAPEA-IAFRKFTSASDVWSYGIVMWEVV 804
Cdd:cd07835  154 RTYTH---EVVTLWyRAPEIlLGSKHYSTPVDIWSVGCIFAEMV 194
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
647-832 9.07e-11

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 63.84  E-value: 9.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 647 EKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSD 725
Cdd:cd14181   56 EEVRSSTLKEIHILRQVsGHPSIITLIDSYESSTFIFLVFDLMRRGELFDYLTEKV-TLSEKETRSIMRSLLEAVSYLHA 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 726 MGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT--TRGgkipirWTAPEAI------AFRKFTSASDVWSYG 797
Cdd:cd14181  135 NNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGEKLRELcgTPG------YLAPEILkcsmdeTHPGYGKEVDLWACG 208
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 974005246 798 IVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLPSP 832
Cdd:cd14181  209 VILFTLLA-GSPPFWHRRQMLMLRMIMEGrYQFSSP 243
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
609-811 9.12e-11

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 65.59  E-value: 9.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGR-LKLpgKRElpVAIKTLKVGYTEK---QRRdFLGEASIMGQFDHPNIIHL-----EGVVtksk 679
Cdd:NF033483  11 IGERIGRGGMAEVYLAKdTRL--DRD--VAVKVLRPDLARDpefVAR-FRREAQSAASLSHPNIVSVydvgeDGGI---- 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 pVMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:NF033483  82 -PYIVMEYVDGRTLKDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSS 159
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 760 D----------------PEAAyttRGGKIPIRwtapeaiafrkftsaSDVWSYGIVMWEVVSyGERPY 811
Cdd:NF033483 160 TtmtqtnsvlgtvhylsPEQA---RGGTVDAR---------------SDIYSLGIVLYEMLT-GRPPF 208
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
611-811 9.98e-11

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 63.77  E-value: 9.98e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQ--RRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05607    8 RVLGKGGFGEVCAVQVKNTGQM---YACKKLDKKRLKKKsgEKMALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMSLM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLdTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpeAAYT 766
Cdd:cd05607   85 NGGDL-KYHIYNVGErgIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEG--KPIT 161
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05607  162 QRAGTNG--YMAPEILKEESYSYPVDWFAMGCSIYEMVA-GRTPF 203
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
609-801 1.07e-10

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 63.43  E-value: 1.07e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRlklPGKRELPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14185    4 IGRTIGDGNFAVVKECR---HWNENQEYAMKIIDKSKLKGKEDMIESEILIIKSLSHPNIVKLFEVYETEKEIYLILEYV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSL-DTFLKKNdgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSN----LVCKVSDFGLsrvleddpeA 763
Cdd:cd14185   81 RGGDLfDAIIESV--KFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNpdksTTLKLADFGL---------A 149
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 764 AYTTRggkiPI-------RWTAPEAIAFRKFTSASDVWSYGIVMW 801
Cdd:cd14185  150 KYVTG----PIftvcgtpTYVAPEILSEKGYGLEVDMWAAGVILY 190
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
366-524 1.07e-10

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 65.41  E-value: 1.07e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 366 TNYTFEIEAVN--GVSDLSPgarqyvSVNVTTNQAAPSPVTNVKKGKIAKNSISLSWQEPDRPNgiILEYEIkYFEKDQE 443
Cdd:COG3401  203 TTYYYRVAATDtgGESAPSN------EVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRV-YRSNSGD 273
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 444 TSYTII-KSKETTITAEGLKPASVYVFQIRARTAAGygvfsrrfefettpvsvaASSDQSQIpviaVSVTVGVILLAVVI 522
Cdd:COG3401  274 GPFTKVaTVTTTSYTDTGLTNGTTYYYRVTAVDAAG------------------NESAPSNV----VSVTTDLTPPAAPS 331

                 ..
gi 974005246 523 GV 524
Cdd:COG3401  332 GL 333
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
612-805 1.18e-10

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 63.60  E-value: 1.18e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQ-RRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMEN 690
Cdd:cd07846    8 LVGEGSYGMVMKCRHKETGQ---IVAIKKFLESEDDKMvKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLDTFLKKNDG-QFTVIQ--LVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEdDPEAAYTT 767
Cdd:cd07846   85 TVLDDLEKYPNGlDESRVRkyLFQILRGID----FCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLA-APGEVYTD 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 974005246 768 rggKIPIRW-TAPE-AIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd07846  160 ---YVATRWyRAPElLVGDTKYGKAVDVWAVGCLVTEMLT 196
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
665-854 1.18e-10

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 63.52  E-value: 1.18e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 665 HPNIIHLEGVVTKSKPV----MIVTEYMENGSLDTFLKKNDGQFTVIQLVG--MLRGIS------AGMKYLSDMGYVHRD 732
Cdd:cd14141   48 HENILQFIGAEKRGTNLdvdlWLITAFHEKGSLTDYLKANVVSWNELCHIAqtMARGLAylhediPGLKDGHKPAIAHRD 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 733 LAARNILINSNLVCKVSDFGLSRVLEDDPEAAyTTRGGKIPIRWTAPE----AIAFRKFTSAS-DVWSYGIVMWEVVSYG 807
Cdd:cd14141  128 IKSKNVLLKNNLTACIADFGLALKFEAGKSAG-DTHGQVGTRRYMAPEvlegAINFQRDAFLRiDMYAMGLVLWELASRC 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 808 ER----------PYWEMTNQ-----DVIKAVEEGYRLPSPMDC------PAALYQLMLDCWQKERNSR 854
Cdd:cd14141  207 TAsdgpvdeymlPFEEEVGQhpsleDMQEVVVHKKKRPVLRECwqkhagMAMLCETIEECWDHDAEAR 274
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
611-811 1.20e-10

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 63.25  E-value: 1.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRELpVAIKTLKVGYT--EKQRRDFLGEASImgqfDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd14662    6 KDIGSGNFGVARLMRNK--ETKEL-VAVKYIERGLKidENVQREIINHRSL----RHPNIIRFKEVVLTPTHLAIVMEYA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLdtFLK-KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV--CKVSDFGLSR--VLEDDPEA 763
Cdd:cd14662   79 AGGEL--FERiCNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKssVLHSQPKS 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 764 AYTTRGgkipirWTAPEAIAFRKFT-SASDVWSYGIVMWeVVSYGERPY 811
Cdd:cd14662  157 TVGTPA------YIAPEVLSRKEYDgKVADVWSCGVTLY-VMLVGAYPF 198
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
646-812 1.25e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 63.18  E-value: 1.25e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 646 TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTK--SKPVMIVTEYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYL 723
Cdd:cd06651   49 TSKEVSALECEIQLLKNLQHERIVQYYGCLRDraEKTLTIFMEYMPGGSVKDQLKAY-GALTESVTRKYTRQILEGMSYL 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 724 SDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd06651  128 HSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICMSGTGIRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEM 207

                 ....*....
gi 974005246 804 VSygERPYW 812
Cdd:cd06651  208 LT--EKPPW 214
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
612-811 1.25e-10

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 63.86  E-value: 1.25e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKlpGKRELpVAIKTLK---------VGYTEKQRRDFlgeaSIMGQfdHPNIIHLEGVVTKSKPVM 682
Cdd:cd05616    7 VLGKGSFGKVMLAERK--GTDEL-YAVKILKkdvviqdddVECTMVEKRVL----ALSGK--PPFLTQLHSCFQTMDRLY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPE 762
Cdd:cd05616   78 FVMEYVNGGDL-MYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCK--ENIWD 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 974005246 763 AAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05616  155 GVTTKTFCGTP-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPF 201
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
613-818 1.27e-10

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 63.40  E-value: 1.27e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKvgyteKQRR------DFLGEASIM-GQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd14198   16 LGRGKFAVVRQCISKSTGQE---YAAKFLK-----KRRRgqdcraEILHEIAVLeLAKSNPRVVNLHEVYETTSEIILIL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSL-DTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLV---CKVSDFGLSRVLEDDP 761
Cdd:cd14198   88 EYAAGGEIfNLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSRKIGHAC 167
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 762 EaaytTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQD 818
Cdd:cd14198  168 E----LREIMGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQE 219
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
611-811 1.32e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 63.77  E-value: 1.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRELpVAIKTLK---------VGYTEKQRRDFLGEASimgqfdHPNIIHLEGVVTKSKPV 681
Cdd:cd05570    1 KVLGKGSFGKVMLAERK--KTDEL-YAIKVLKkeviiedddVECTMTEKRVLALANR------HPFLTGLHACFQTEDRL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDP 761
Cdd:cd05570   72 YFVMEYVNGGDL-MFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK--EGIW 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05570  149 GGNTTSTFCGTP-DYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPF 196
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
604-823 1.51e-10

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 63.31  E-value: 1.51e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 604 ASCITIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDflgEASIMGQFDHPNIIHLEGVVTKSKPVMI 683
Cdd:cd14085    2 EDFFEIESELGRGATSVVYRCRQKGTQK---PYAVKKLKKTVDKKIVRT---EIGVLLRLSHPNIIKLKEIFETPTEISL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 684 VTEYMENGSL-DTFLKKndGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS---NLVCKVSDFGLSRVLED 759
Cdd:cd14085   76 VLELVTGGELfDRIVEK--GYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATpapDAPLKIADFGLSKIVDQ 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 760 D--PEAAYTTRGgkipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAV 823
Cdd:cd14085  154 QvtMKTVCGTPG------YCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDERGDQYMFKRI 213
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
612-837 1.55e-10

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 63.36  E-value: 1.55e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGY--TEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd05585    1 VIGKGSFGKVMQVRKKDTSR---IYALKTIRKAHivSRSEVTHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFIN 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRG 769
Cdd:cd05585   78 GGELFHHLQR-EGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCKLNMKDDDKTNTFCG 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 770 GKipiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYW-EMTNQDVIKAVEEGYRLPSPMDCPA 837
Cdd:cd05585  157 TP---EYLAPELLLGHGYTKAVDWWTLGVLLYEMLT-GLPPFYdENTNEMYRKILQEPLRFPDGFDRDA 221
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
609-803 1.93e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 62.74  E-value: 1.93e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERViGAGEFGEVCSGRLKLPGkrELpVAIKTLKVgyteKQRRDF---LGEASIMGQFDHPNIIHLEGVVTKSKPVMIVT 685
Cdd:cd06646   14 IQRV-GSGTYGDVYKARNLHTG--EL-AAVKIIKL----EPGDDFsliQQEIFMVKECKHCNIVAYFGSYLSREKLWICM 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 686 EYMENGSLDTFLKKNdGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLeddpEAAY 765
Cdd:cd06646   86 EYCGGGSLQDIYHVT-GPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKI----TATI 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 766 TTRGGKIPI-RWTAPEAIAFRK---FTSASDVWSYGIVMWEV 803
Cdd:cd06646  161 AKRKSFIGTpYWMAPEVAAVEKnggYNQLCDIWAVGITAIEL 202
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
613-811 2.12e-10

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 62.22  E-value: 2.12e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYtEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd14114   10 LGTGAFGVVHRCTERATGNN---FAAKFIMTPH-ESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSGGE 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI---NSNLVcKVSDFGLSRVLEDDPEAAYTTRG 769
Cdd:cd14114   86 LFERIAAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCttkRSNEV-KLIDFGLATHLDPKESVKVTTGT 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 974005246 770 GKipirWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd14114  165 AE----FAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPF 201
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
611-811 2.30e-10

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 62.71  E-value: 2.30e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVC---------SGRL---KLPGKRELPVAIKTLKVGYTEKQRRDFLGEAsimgqfdhPNIIHLEGVVTKS 678
Cdd:cd05613    6 KVLGTGAYGKVFlvrkvsghdAGKLyamKVLKKATIVQKAKTAEHTRTERQVLEHIRQS--------PFLVTLHYAFQTD 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 679 KPVMIVTEYMENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSR-VL 757
Cdd:cd05613   78 TKLHLILDYINGGELFTHLSQRE-RFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKeFL 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 758 EDDPEAAYTTRGgkiPIRWTAPEAI--AFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd05613  157 LDENERAYSFCG---TIEYMAPEIVrgGDSGHDKAVDWWSLGVLMYELLT-GASPF 208
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
664-811 2.78e-10

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 62.26  E-value: 2.78e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 664 DHPNIIHLEGVVTKSKPVMIVTEYMENGSL-DTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS 742
Cdd:cd14197   67 ANPWVINLHEVYETASEMILVLEYAAGGEIfNQCVADREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTS 146
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005246 743 NLV---CKVSDFGLSRVLEDDPEaaytTRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPY 811
Cdd:cd14197  147 ESPlgdIKIVDFGLSRILKNSEE----LREIMGTPEYVAPEILSYEPISTATDMWSIGVLAY-VMLTGISPF 213
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
613-803 2.79e-10

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 62.76  E-value: 2.79e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGkreLPVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGS 692
Cdd:cd06649   13 LGAGNGGVVTKVQHKPSG---LIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKknDGQFTVIQLVGMLR-GISAGMKYLSDMGYV-HRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT-TRG 769
Cdd:cd06649   90 LDQVLK--EAKRIPEEILGKVSiAVLRGLAYLREKHQImHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVgTRS 167
                        170       180       190
                 ....*....|....*....|....*....|....
gi 974005246 770 gkipirWTAPEAIAFRKFTSASDVWSYGIVMWEV 803
Cdd:cd06649  168 ------YMSPERLQGTHYSVQSDIWSMGLSLVEL 195
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
612-862 3.00e-10

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 61.91  E-value: 3.00e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSGRLKLPGkreLPVAIK-------------------TLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLe 672
Cdd:cd14100    7 LLGSGGFGSVYSGIRVADG---APVAIKhvekdrvsewgelpngtrvPMEIVLLKKVGSGFRGVIRLLDWFERPDSFVL- 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 673 gVVTKSKPVMIVTEYM-ENGSLDTFLKKNdgqftviqlvgMLRGISAGMKYLSDMGYVHRDLAARNILINSNL-VCKVSD 750
Cdd:cd14100   83 -VLERPEPVQDLFDFItERGALPEELARS-----------FFRQVLEAVRHCHNCGVLHRDIKDENILIDLNTgELKLID 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 751 FGLSRVLEDdpeAAYTT-RGGKIpirWTAPEAIAFRKFTSAS-DVWSYGIVMWEVVSyGERPYWEmtNQDVIKAvEEGYR 828
Cdd:cd14100  151 FGSGALLKD---TVYTDfDGTRV---YSPPEWIRFHRYHGRSaAVWSLGILLYDMVC-GDIPFEH--DEEIIRG-QVFFR 220
                        250       260       270
                 ....*....|....*....|....*....|....
gi 974005246 829 LPSPMDCPaalyQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14100  221 QRVSSECQ----HLIKWCLALRPSDRPSFEDIQN 250
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
611-811 3.22e-10

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 62.79  E-value: 3.22e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpGKRELpVAIKTLK---------VGYTEKQRRdFLGEASImgqfdHPNIIHLEGVVTKSKPV 681
Cdd:cd05592    1 KVLGKGSFGKVMLAELK--GTNQY-FAIKALKkdvvledddVECTMIERR-VLALASQ-----HPFLTHLFCTFQTESHL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLdTFLKKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP 761
Cdd:cd05592   72 FFVMEYLNGGDL-MFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKENIYGE 150
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRGgkIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPY 811
Cdd:cd05592  151 NKASTFCG--TP-DYIAPEILKGQKYNQSVDWWSFGVLLYEML-IGQSPF 196
SAM_AIDA1AB-like_repeat2 cd09500
SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of ...
901-957 3.42e-10

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188899  Cd Length: 65  Bit Score: 56.54  E-value: 3.42e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQV-TLEDLRRLGVTLVGHQKKIMNSLQE 957
Cdd:cd09500    7 SVSEWLDSIGLGDYIETFLKHGYTSMERVKRIwEVELTNVLEINKLGHRKRILASLAD 64
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
611-860 3.59e-10

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 61.55  E-value: 3.59e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVcsgRLKLPGKRELPVAIKTL-KVGYTEKQRRDFLG-EASIMGQFDHPNIIHL-EGVVTKSKPVMIVTEY 687
Cdd:cd14163    6 KTIGEGTYSKV---KEAFSKKHQRKVAIKIIdKSGGPEEFIQRFLPrELQIVERLDHKNIIHVyEMLESADGKIYLVMEL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSL-DTFLkkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVcKVSDFGLSRVLEDDPEAAYT 766
Cdd:cd14163   83 AEDGDVfDCVL--HGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFTL-KLTDFGFAKQLPKGGRELSQ 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKIPirWTAPEAIAFRKFTS-ASDVWSYGIVMWeVVSYGERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLD 845
Cdd:cd14163  160 TFCGSTA--YAAPEVLQGVPHDSrKGDIWSMGVVLY-VMLCAQLPFDDTDIPKMLCQQQKGVSLPGHLGVSRTCQDLLKR 236
                        250
                 ....*....|....*
gi 974005246 846 CWQKERNSRPKFDEI 860
Cdd:cd14163  237 LLEPDMVLRPSIEEV 251
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
611-818 3.89e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 62.37  E-value: 3.89e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK---------VGYTekqrrdfLGEASIMGQFDHPNIIHLEGVVTKSKPV 681
Cdd:cd05571    1 KVLGKGTFGKVILCREKATGEL---YAIKILKkeviiakdeVAHT-------LTENRVLQNTRHPFLTSLKYSFQTNDRL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 682 MIVTEYMENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDP 761
Cdd:cd05571   71 CFVMEYVNGGELFFHLSR-ERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCK--EEIS 147
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005246 762 EAAYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWemtNQD 818
Cdd:cd05571  148 YGATTKTFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFY---NRD 199
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
608-800 4.24e-10

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 62.17  E-value: 4.24e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRdflgEASIMGQF-DHPNIIHLEGVVT--KSKPVMIV 684
Cdd:cd14132   21 EIIRKIGRGKYSEVFEGINIGNNE---KVVIKVLKPVKKKKIKR----EIKILQNLrGGPNIVKLLDVVKdpQSKTPSLI 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 685 TEYMENGSLDTFLKK---NDGQFTVIQLvgmLRGISagmkYLSDMGYVHRDLAARNILINSN---LvcKVSDFGLSrvle 758
Cdd:cd14132   94 FEYVNNTDFKTLYPTltdYDIRYYMYEL---LKALD----YCHSKGIMHRDVKPHNIMIDHEkrkL--RLIDWGLA---- 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 974005246 759 dD---PEAAYTTRGGKipIRWTAPEA-IAFRKFTSASDVWSYGIVM 800
Cdd:cd14132  161 -EfyhPGQEYNVRVAS--RYYKGPELlVDYQYYDYSLDMWSLGCML 203
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
613-810 4.52e-10

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 61.76  E-value: 4.52e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYT-EKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYmeng 691
Cdd:PLN00009  10 IGEGTYGVVYKARDRVTNE---TIALKKIRLEQEdEGVPSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEY---- 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 sLDTFLKK---------NDGQFTVIQLVGMLRGISagmkYLSDMGYVHRDLAARNILIN-SNLVCKVSDFGLSRVLeDDP 761
Cdd:PLN00009  83 -LDLDLKKhmdsspdfaKNPRLIKTYLYQILRGIA----YCHSHRVLHRDLKPQNLLIDrRTNALKLADFGLARAF-GIP 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 762 EAAYTTRggKIPIRWTAPEA-IAFRKFTSASDVWSYGIVMWEVVSygERP 810
Cdd:PLN00009 157 VRTFTHE--VVTLWYRAPEIlLGSRHYSTPVDIWSVGCIFAEMVN--QKP 202
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
611-824 4.62e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 62.41  E-value: 4.62e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK--VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05593   21 KLLGKGTFGKVILVREKASGKY---YAMKILKkeVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYV 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPEAAYTTR 768
Cdd:cd05593   98 NGGELFFHLSR-ERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCK--EGITDAATMKT 174
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 769 GGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWemtNQDVIKAVE 824
Cdd:cd05593  175 FCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFY---NQDHEKLFE 225
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
613-813 5.95e-10

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 61.19  E-value: 5.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKlpgKRELPVAIKTLKVGYTeKQRrDFLGEASIMGQF-DHPNIIHLEGVVTKSKPV-MIVTEYMEN 690
Cdd:cd13987    1 LGEGTYGKVLLAVHK---GSGTKMALKFVPKPST-KLK-DFLREYNISLELsVHPHIIKTYDVAFETEDYyVFAQEYAPY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GSLdtflkkndgqFTVIQ-LVGM--------LRGISAGMKYLSDMGYVHRDLAARNILI--NSNLVCKVSDFGLSRvled 759
Cdd:cd13987   76 GDL----------FSIIPpQVGLpeervkrcAAQLASALDFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFGLTR---- 141
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974005246 760 dpeAAYTT---RGGKIPirWTAPE---AIAFRKFT--SASDVWSYGIVM---------WEVVSYGERPYWE 813
Cdd:cd13987  142 ---RVGSTvkrVSGTIP--YTAPEvceAKKNEGFVvdPSIDVWAFGVLLfccltgnfpWEKADSDDQFYEE 207
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
663-814 7.06e-10

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. The STRAD-beta subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 61.81  E-value: 7.06e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 663 FDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQFTVIQLVG-MLRGISAGMKYLSDMGYVHRDLAARNILIN 741
Cdd:cd08226   56 FRHPNIMTHWTVFTEGSWLWVISPFMAYGSARGLLKTYFPEGMNEALIGnILYGAIKALNYLHQNGCIHRSVKASHILIS 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 742 ----------SNLVCKVSDFGLSRVLEDDPEAAYTTrggkipIRWTAPEAIA--FRKFTSASDVWSYGIVMWEVVSyGER 809
Cdd:cd08226  136 gdglvslsglSHLYSMVTNGQRSKVVYDFPQFSTSV------LPWLSPELLRqdLHGYNVKSDIYSVGITACELAR-GQV 208

                 ....*
gi 974005246 810 PYWEM 814
Cdd:cd08226  209 PFQDM 213
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
613-810 7.55e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 60.91  E-value: 7.55e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTLKVGYTEKQRRDF-LGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENg 691
Cdd:cd07839    8 IGEGTYGTVFKAKNRETHE---IVALKRVRLDDDDEGVPSSaLREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCDQ- 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 692 SLDTFLKKNDGQF--TVIQ--LVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvleddpeaAYtt 767
Cdd:cd07839   84 DLKKYFDSCNGDIdpEIVKsfMFQLLKGLA----FCHSHNVLHRDLKPQNLLINKNGELKLADFGLAR--------AF-- 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005246 768 rggKIPIR---------WTAPEAIAF--RKFTSASDVWSYGIVMWEVVSYGeRP 810
Cdd:cd07839  150 ---GIPVRcysaevvtlWYRPPDVLFgaKLYSTSIDMWSAGCIFAELANAG-RP 199
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
653-835 8.35e-10

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 61.16  E-value: 8.35e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 653 FLGEASIMGQFDHPNII-HLEGVVTKSKpVMIVTEYMENGSLDTFLKKN--DGqF--TVIQLVgmLRGISAGMKYLSDMG 727
Cdd:cd08216   46 LQQEILTSRQLQHPNILpYVTSFVVDND-LYVVTPLMAYGSCRDLLKTHfpEG-LpeLAIAFI--LRDVLNALEYIHSKG 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 728 YVHRDLAARNILINSN----------LVCKVSDFGLSRVLEDDPEAAYTTrggkipIRWTAPEAIA--FRKFTSASDVWS 795
Cdd:cd08216  122 YIHRSVKASHILISGDgkvvlsglryAYSMVKHGKRQRVVHDFPKSSEKN------LPWLSPEVLQqnLLGYNEKSDIYS 195
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 796 YGIVMWEVVSyGERPYWEM-TNQDVIKAVeEGYrLPSPMDC 835
Cdd:cd08216  196 VGITACELAN-GVVPFSDMpATQMLLEKV-RGT-TPQLLDC 233
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
613-804 8.37e-10

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 61.13  E-value: 8.37e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENgS 692
Cdd:cd07870    8 LGEGSYATVYKGISRINGQL---VALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYMHT-D 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 693 LDTFLKKNDGQF----TVIQLVGMLRGISagmkYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVlEDDPEAAYTTr 768
Cdd:cd07870   84 LAQYMIQHPGGLhpynVRLFMFQLLRGLA----YIHGQHILHRDLKPQNLLISYLGELKLADFGLARA-KSIPSQTYSS- 157
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 974005246 769 ggKIPIRWTAPEAIAF--RKFTSASDVWSYGIVMWEVV 804
Cdd:cd07870  158 --EVVTLWYRPPDVLLgaTDYSSALDIWGAGCIFIEML 193
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
611-818 9.97e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 61.18  E-value: 9.97e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK--VGYTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYM 688
Cdd:cd05595    1 KLLGKGTFGKVILVREKATGRY---YAMKILRkeVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYA 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 689 ENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDpEAAYTTR 768
Cdd:cd05595   78 NGGELFFHLSR-ERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITD-GATMKTF 155
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 974005246 769 GGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWemtNQD 818
Cdd:cd05595  156 CGT-P-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFY---NQD 199
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
611-818 1.09e-09

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 60.42  E-value: 1.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKreLPVAIKTLKVGyTEKQRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEyMEN 690
Cdd:cd14088    7 QVIKTEEFCEIFRAKDKTTGK--LYTCKKFLKRD-GRKVRKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLE-LAT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 691 GS--LDTFLkkNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILI-----NSNLVckVSDFGLSRVleddpEA 763
Cdd:cd14088   83 GRevFDWIL--DQGYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYynrlkNSKIV--ISDFHLAKL-----EN 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 764 AYTTRGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQD 818
Cdd:cd14088  154 GLIKEPCGTP-EYLAPEVVGRQRYGRPVDCWAIGVIMYILLS-GNPPFYDEAEED 206
fn3 pfam00041
Fibronectin type III domain;
290-378 1.15e-09

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 55.88  E-value: 1.15e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  290 SAPRN-AISNVNETSVFLEWIPPaDTGGRKDVSYYIACKKCNShagvceecGGHVRY--LPRQSglknTSVMMVDLLAHT 366
Cdd:pfam00041   1 SAPSNlTVTDVTSTSLTVSWTPP-PDGNGPITGYEVEYRPKNS--------GEPWNEitVPGTT----TSVTLTGLKPGT 67
                          90
                  ....*....|..
gi 974005246  367 NYTFEIEAVNGV 378
Cdd:pfam00041  68 EYEVRVQAVNGG 79
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
611-879 1.34e-09

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 60.80  E-value: 1.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKlpgKRELPVAIKTL--KVGYTEKQRRDFLGEASIM-GQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05602   13 KVIGKGSFGKVLLARHK---SDEKFYAVKVLqkKAILKKKEEKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLDY 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlED-DPEAAYT 766
Cdd:cd05602   90 INGGELFYHLQR-ERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK--ENiEPNGTTS 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 767 TRGGKiPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAVeegyrLPSPM----DCPAALYQL 842
Cdd:cd05602  167 TFCGT-P-EYLAPEVLHKQPYDRTVDWWCLGAVLYEML-YGLPPFYSRNTAEMYDNI-----LNKPLqlkpNITNSARHL 238
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 974005246 843 MLDCWQKERNSRPKF-DEIVNMLDKLIRNPSSLKTLVN 879
Cdd:cd05602  239 LEGLLQKDRTKRLGAkDDFTEIKNHIFFSPINWDDLIN 276
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
609-831 1.81e-09

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 60.79  E-value: 1.81e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKlpgKRELPVAIKTLKVGYTEKQRRD--FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05624   76 IIKVIGRGAFGEVAVVKMK---NTERIYAMKILNKWEMLKRAETacFREERNVLVNGDCQWITTLHYAFQDENYLYLVMD 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKND-------GQFTVIQLVGMLRGISagmkylsDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLED 759
Cdd:cd05624  153 YYVGGDLLTLLSKFEdklpedmARFYIGEMVLAIHSIH-------QLHYVHRDIKPDNVLLDMNGHIRLADFGSCLKMND 225
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 760 DPEAAYTTRGGKiPiRWTAPEAI-----AFRKFTSASDVWSYGIVMWEVVsYGERPYWEMTNQDVIKAV---EEGYRLPS 831
Cdd:cd05624  226 DGTVQSSVAVGT-P-DYISPEILqamedGMGKYGPECDWWSLGVCMYEML-YGETPFYAESLVETYGKImnhEERFQFPS 302
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
611-823 1.92e-09

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 60.31  E-value: 1.92e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKRelpVAIKTLK--VGYTEKQRRDFLGEASIMG-QFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05590    1 RVLGKGSFGKVMLARLKESGRL---YAVKVLKkdVILQDDDVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKNDgQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRvlEDDPEAAYTT 767
Cdd:cd05590   78 VNGGDLMFHIQKSR-RFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCK--EGIFNGKTTS 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 768 RGGKIPiRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAV 823
Cdd:cd05590  155 TFCGTP-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFEAENEDDLFEAI 208
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
608-806 2.01e-09

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 59.99  E-value: 2.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 608 TIERVIGAGEFGEVCSGRLKlPGKRELPVAIKTLKvgyTEKQRRDFLG-----EASIMGQFDHPNIIHLEGVVTKS--KP 680
Cdd:cd07842    3 EIEGCIGRGTYGRVYKAKRK-NGKDGKEYAIKKFK---GDKEQYTGISqsacrEIALLRELKHENVVSLVEVFLEHadKS 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 681 VMIVTEYME--------------NGSLDTFLKKNdgqftviqlvgMLRGISAGMKYLSDMGYVHRDLAARNILINSNL-- 744
Cdd:cd07842   79 VYLLFDYAEhdlwqiikfhrqakRVSIPPSMVKS-----------LLWQILNGIHYLHSNWVLHRDLKPANILVMGEGpe 147
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 745 --VCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTAPEAI-AFRKFTSASDVWSYGIVMWEVVSY 806
Cdd:cd07842  148 rgVVKIGDLGLARLFNAPLKPLADLDPVVVTIWYRAPELLlGARHYTKAIDIWAIGCIFAELLTL 212
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
656-811 2.06e-09

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 59.58  E-value: 2.06e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 656 EASIMGQFDHPNIIHLEGVVTKSKP--VMIVTEYMENGSLDTFlkKNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDL 733
Cdd:cd14200   73 EIAILKKLDHVNIVKLIEVLDDPAEdnLYMVFDLLRKGPVMEV--PSDKPFSEDQARLYFRDIVLGIEYLHYQKIVHRDI 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 734 AARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIpirWTAPEAIA--FRKFT-SASDVWSYGIVMWEVVsYGERP 810
Cdd:cd14200  151 KPSNLLLGDDGHVKIADFGVSNQFEGNDALLSSTAGTPA---FMAPETLSdsGQSFSgKALDVWAMGVTLYCFV-YGKCP 226

                 .
gi 974005246 811 Y 811
Cdd:cd14200  227 F 227
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
613-805 2.09e-09

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 59.85  E-value: 2.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRlklpgKRELPVAIKTLKVGYTEKQR---RDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYME 689
Cdd:cd14157    1 ISEGTFADIYKGY-----RHGKQYVIKRLKETECESPKsteRFFQTEVQICFRCCHPNILPLLGFCVESDCHCLIYPYMP 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 690 NGSLDTFLKKNDGQ--FTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLsRVLEDDPEAAYT- 766
Cdd:cd14157   76 NGSLQDRLQQQGGShpLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLGHSGL-RLCPVDKKSVYTm 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 974005246 767 --TRGGKIPIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS 805
Cdd:cd14157  155 mkTKVLQISLAYLPEDFVRHGQLTEKVDIFSCGVVLAEILT 195
PHA02988 PHA02988
hypothetical protein; Provisional
635-864 2.13e-09

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 59.76  E-value: 2.13e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 635 PVAIKTLKVGYT--EKQRRDFLGEASIMGQFDHPNIIHLEG----VVTKSKPVMIVTEYMENGSLDTFLKKN-DGQFTVi 707
Cdd:PHA02988  45 EVIIRTFKKFHKghKVLIDITENEIKNLRRIDSNNILKIYGfiidIVDDLPRLSLILEYCTRGYLREVLDKEkDLSFKT- 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 708 QLVGML---RGISAGMKYLSDmgyVHRDLAARNILINSNLVCKVSDFGLSRVLEDDP-----EAAYTTRGGKIPIrwtap 779
Cdd:PHA02988 124 KLDMAIdccKGLYNLYKYTNK---PYKNLTSVSFLVTENYKLKIICHGLEKILSSPPfknvnFMVYFSYKMLNDI----- 195
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 780 eaiaFRKFTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKA-VEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFD 858
Cdd:PHA02988 196 ----FSEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLiINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIK 270

                 ....*.
gi 974005246 859 EIVNML 864
Cdd:PHA02988 271 EILYNL 276
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
604-892 2.29e-09

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 59.68  E-value: 2.29e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 604 ASCITIERVIGAGEFGEVCSGRLKlpGKRelpVAIKTlkvgYTEKQRRDFLGEASIMGQ--FDHPNIIHLEGVVTKSK-- 679
Cdd:cd14219    4 AKQIQMVKQIGKGRYGEVWMGKWR--GEK---VAVKV----FFTTEEASWFRETEIYQTvlMRHENILGFIAADIKGTgs 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 680 --PVMIVTEYMENGSLDTFLKKndgqfTVIQLVGMLRGISAGMKYLSDM-----------GYVHRDLAARNILINSNLVC 746
Cdd:cd14219   75 wtQLYLITDYHENGSLYDYLKS-----TTLDTKAMLKLAYSSVSGLCHLhteifstqgkpAIAHRDLKSKNILVKKNGTC 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 747 KVSDFGLS-RVLEDDPEA--AYTTRGGKipIRWTAPEAI-------AFRKFTSAsDVWSYGIVMWEVvsygerpywemTN 816
Cdd:cd14219  150 CIADLGLAvKFISDTNEVdiPPNTRVGT--KRYMPPEVLdeslnrnHFQSYIMA-DMYSFGLILWEV-----------AR 215
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 817 QDVIKAVEEGYRLPSPMDCPA-ALYQLMLD--CWQKERNSRP---KFDEIVNMLDKLI-----RNPSSLKTlvnaSCRVS 885
Cdd:cd14219  216 RCVSGGIVEEYQLPYHDLVPSdPSYEDMREivCIKRLRPSFPnrwSSDECLRQMGKLMtecwaHNPASRLT----ALRVK 291

                 ....*..
gi 974005246 886 NLLAEHS 892
Cdd:cd14219  292 KTLAKMS 298
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
289-395 2.30e-09

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 55.20  E-value: 2.30e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 289 PSAPRN-AISNVNETSVFLEWIPPADTGGRkDVSYYIACKKCNSHAGvcEECGGHVrylprqsgLKNTSVMMVDLLAHTN 367
Cdd:cd00063    1 PSPPTNlRVTDVTSTSVTLSWTPPEDDGGP-ITGYVVEYREKGSGDW--KEVEVTP--------GSETSYTLTGLKPGTE 69
                         90       100       110
                 ....*....|....*....|....*....|
gi 974005246 368 YTFEIEAVN--GVSDLSPgarqyvSVNVTT 395
Cdd:cd00063   70 YEFRVRAVNggGESPPSE------SVTVTT 93
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
609-832 2.54e-09

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 59.62  E-value: 2.54e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVcsgrLKLPGKRELPVA-IKTLKVgyTEKQRRDFLGEASIMGQF-DHPNIIHLEGVVTKSKPVM---- 682
Cdd:cd06639   26 IIETIGKGTYGKV----YKVTNKKDGSLAaVKILDP--ISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQYVggql 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 -IVTEYMENGSLDTFLK---KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE 758
Cdd:cd06639  100 wLVLELCNGGSVTELVKgllKCGQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLT 179
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005246 759 DDPEAAYTTRGGKIpirWTAPEAIAFRK-----FTSASDVWSYGIVMWEVVSyGERPYWEMtnqDVIKAVEEGYRLPSP 832
Cdd:cd06639  180 SARLRRNTSVGTPF---WMAPEVIACEQqydysYDARCDVWSLGITAIELAD-GDPPLFDM---HPVKALFKIPRNPPP 251
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
652-862 2.57e-09

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 59.15  E-value: 2.57e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 652 DFLGEASIMGQF-DHPNIIHLEG--VVTKSKPVMIVTEYMEnGSLDTFLKKNDGQ-----FTVIQLVGMLRGIsagmKYL 723
Cdd:cd14131   45 SYKNEIELLKKLkGSDRIIQLYDyeVTDEDDYLYMVMECGE-IDLATILKKKRPKpidpnFIRYYWKQMLEAV----HTI 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 724 SDMGYVHRDLAARNILI-NSNLvcKVSDFGLSRVLEDDpeaayTT---RGGKI-PIRWTAPEAIAFRKFTS--------- 789
Cdd:cd14131  120 HEEGIVHSDLKPANFLLvKGRL--KLIDFGIAKAIQND-----TTsivRDSQVgTLNYMSPEAIKDTSASGegkpkskig 192
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 790 -ASDVWSYGIVMWEVVsYGERPYWEMTNQ-DVIKA-VEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14131  193 rPSDVWSLGCILYQMV-YGKTPFQHITNPiAKLQAiIDPNHEIEFPDIPNPDLIDVMKRCLQRDPKKRPSIPELLN 267
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
901-956 2.89e-09

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 53.84  E-value: 2.89e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 901 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSLQ 956
Cdd:cd09490    5 DIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLP 60
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
612-861 2.99e-09

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 58.71  E-value: 2.99e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 612 VIGAGEFGEVCSG-RL--------------------KLPGKRELPVAIKTLKvgytekqrrdflgeaSIMGQFDHPNIIH 670
Cdd:cd14101    7 LLGKGGFGTVYAGhRIsdglqvaikqisrnrvqqwsKLPGVNPVPNEVALLQ---------------SVGGGPGHRGVIR 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 671 L-------EG---VVTKSKPVMIVTEYM-ENGSLDTFLKKndgQFtviqlvgmLRGISAGMKYLSDMGYVHRDLAARNIL 739
Cdd:cd14101   72 LldwfeipEGfllVLERPQHCQDLFDYItERGALDESLAR---RF--------FKQVVEAVQHCHSKGVVHRDIKDENIL 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 740 INSNLVC-KVSDFGLSRVLEDDPeaaYTT-RGGKIpirWTAPEAIAFRKFTS-ASDVWSYGIVMWEVVSyGERPYWEmtN 816
Cdd:cd14101  141 VDLRTGDiKLIDFGSGATLKDSM---YTDfDGTRV---YSPPEWILYHQYHAlPATVWSLGILLYDMVC-GDIPFER--D 211
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 817 QDVIKAvEEGYRLPSPMDCPAalyqLMLDCWQKERNSRPKFDEIV 861
Cdd:cd14101  212 TDILKA-KPSFNKRVSNDCRS----LIRSCLAYNPSDRPSLEQIL 251
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
609-852 3.14e-09

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 59.25  E-value: 3.14e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQrrDFLGEASIMGQF-DHPNIIHLEGV-----VTKSKPVM 682
Cdd:cd06638   22 IIETIGKGTYGKVFKVLNKKNGSK---AAVKILDPIHDIDE--EIEAEYNILKALsDHPNVVKFYGMyykkdVKNGDQLW 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDT----FLKKNDGQFTVIqLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLE 758
Cdd:cd06638   97 LVLELCNGGSVTDlvkgFLKRGERMEEPI-IAYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQLT 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 759 DDPEAAYTTRGGKIpirWTAPEAIAFRK-----FTSASDVWSYGIVMWEvVSYGERPYWEMTNQDVIKAVeegyrlpsPM 833
Cdd:cd06638  176 STRLRRNTSVGTPF---WMAPEVIACEQqldstYDARCDVWSLGITAIE-LGDGDPPLADLHPMRALFKI--------PR 243
                        250
                 ....*....|....*....
gi 974005246 834 DCPAALYQLMLdcWQKERN 852
Cdd:cd06638  244 NPPPTLHQPEL--WSNEFN 260
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
672-862 3.16e-09

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 59.28  E-value: 3.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 672 EGVVTKSKPVMIVTEYMENGSLDTFLK-KNDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINS---NLVCK 747
Cdd:cd14170   65 ENLYAGRKCLLIVMECLDGGELFSRIQdRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSkrpNAILK 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 748 VSDFGLSRVLEDDPEAA---YTTRggkipirWTAPEAIAFRKFTSASDVWSYGIVMWeVVSYGERPYWE----MTNQDVI 820
Cdd:cd14170  145 LTDFGFAKETTSHNSLTtpcYTPY-------YVAPEVLGPEKYDKSCDMWSLGVIMY-ILLCGYPPFYSnhglAISPGMK 216
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 974005246 821 KAVEEG-YRLPSP--MDCPAALYQLMLDCWQKERNSRPKFDEIVN 862
Cdd:cd14170  217 TRIRMGqYEFPNPewSEVSEEVKMLIRNLLKTEPTQRMTITEFMN 261
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
636-814 4.15e-09

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. The STRAD alpha subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 59.19  E-value: 4.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 636 VAIKTLKVGYTEKQRRDFL-GEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKN--DGqFTVIQLVGM 712
Cdd:cd08227   28 VTVRRINLEACTNEMVTFLqGELHVSKLFNHPNIVPYRATFIADNELWVVTSFMAYGSAKDLICTHfmDG-MSELAIAYI 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 713 LRGISAGMKYLSDMGYVHRDLAARNILINSNlvCKVSDFGL------------SRVLEDDPEaaYTTRggkiPIRWTAPE 780
Cdd:cd08227  107 LQGVLKALDYIHHMGYVHRSVKASHILISVD--GKVYLSGLrsnlsminhgqrLRVVHDFPK--YSVK----VLPWLSPE 178
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 974005246 781 AIA--FRKFTSASDVWSYGIVMWEVVSyGERPYWEM 814
Cdd:cd08227  179 VLQqnLQGYDAKSDIYSVGITACELAN-GHVPFKDM 213
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
646-816 4.23e-09

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 58.55  E-value: 4.23e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 646 TEKQRRDFLGEASIMGQFDHPNIIHL----EGVVTKSKPVMIVTEYMENGSLDTFLKKndgqFTVIQ---LVGMLRGISA 718
Cdd:cd14032   40 TKVERQRFKEEAEMLKGLQHPNIVRFydfwESCAKGKRCIVLVTELMTSGTLKTYLKR----FKVMKpkvLRSWCRQILK 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 719 GMKYLSDMG--YVHRDLAARNILINSNL-VCKVSDFGLSRVleddPEAAYTTRGGKIPiRWTAPEAIAfRKFTSASDVWS 795
Cdd:cd14032  116 GLLFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLATL----KRASFAKSVIGTP-EFMAPEMYE-EHYDESVDVYA 189
                        170       180
                 ....*....|....*....|.
gi 974005246 796 YGIVMWEVVSyGERPYWEMTN 816
Cdd:cd14032  190 FGMCMLEMAT-SEYPYSECQN 209
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
585-830 4.32e-09

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 60.52  E-value: 4.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  585 PHTYEDPNQAVHEFAkeieascitIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLkvGYTEKQRRDFLGEASIMGQFD 664
Cdd:PTZ00266    2 PGKYDDGESRLNEYE---------VIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYR--GLKEREKSQLVIEVNVMRELK 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  665 HPNII-HLEGVVTKS-KPVMIVTEYMENGSLDTFLKKNDGQFTVIQ---LVGMLRGISAGMKYLSDMG-------YVHRD 732
Cdd:PTZ00266   71 HKNIVrYIDRFLNKAnQKLYILMEFCDAGDLSRNIQKCYKMFGKIEehaIVDITRQLLHALAYCHNLKdgpngerVLHRD 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246  733 LAARNILINSNL-----------------VCKVSDFGLSRVLEDDpEAAYTTRGgkIPIRWTaPEAIAF--RKFTSASDV 793
Cdd:PTZ00266  151 LKPQNIFLSTGIrhigkitaqannlngrpIAKIGDFGLSKNIGIE-SMAHSCVG--TPYYWS-PELLLHetKSYDDKSDM 226
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 974005246  794 WSYGIVMWEVVSyGERPYWEMTN-QDVIKAVEEGYRLP 830
Cdd:PTZ00266  227 WALGCIIYELCS-GKTPFHKANNfSQLISELKRGPDLP 263
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
649-810 7.79e-09

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 57.80  E-value: 7.79e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 649 QRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKkNDGQFTViqlvGMLRGISA----GMKYLS 724
Cdd:cd05609   43 QIQQVFVERDILTFAENPFVVSMYCSFETKRHLCMVMEYVEGGDCATLLK-NIGPLPV----DMARMYFAetvlALEYLH 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 725 DMGYVHRDLAARNILINSNLVCKVSDFGLSRV-------------LEDDPEAAYTTRGGKIPiRWTAPEAIAFRKFTSAS 791
Cdd:cd05609  118 SYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIglmslttnlyeghIEKDTREFLDKQVCGTP-EYIAPEVILRQGYGKPV 196
                        170       180
                 ....*....|....*....|....
gi 974005246 792 DVWSYGIVMWE-----VVSYGERP 810
Cdd:cd05609  197 DWWAMGIILYEflvgcVPFFGDTP 220
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
613-830 8.59e-09

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 58.35  E-value: 8.59e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 613 IGAGEFGEVCSGRLKLPGKrelPVAIKTL--KVGYTEKQRRDFLGEASIM---GQFDHPNIIHLEGVVTKSKPVMIVTEY 687
Cdd:cd05586    1 IGKGTFGQVYQVRKKDTRR---IYAMKVLskKVIVAKKEVAHTIGERNILvrtALDESPFIVGLKFSFQTPTDLYLVTDY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 688 MENGSLDTFLKKnDGQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTT 767
Cdd:cd05586   78 MSGGELFWHLQK-EGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKADLTDNKTTNTF 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005246 768 RGgkiPIRWTAPEAIAFRK-FTSASDVWSYGIVMWEVVSyGERPYWEMTNQDVIKAVEEG-YRLP 830
Cdd:cd05586  157 CG---TTEYLAPEVLLDEKgYTKMVDFWSLGVLVFEMCC-GWSPFYAEDTQQMYRNIAFGkVRFP 217
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
665-832 1.02e-08

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 57.62  E-value: 1.02e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 665 HPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKndgQFTVIQ--LVGMLRGISAGMKYLSDMGYVHRDLAARNILINS 742
Cdd:cd14182   69 HPNIIQLKDTYETNTFFFLVFDLMKKGELFDYLTE---KVTLSEkeTRKIMRALLEVICALHKLNIVHRDLKPENILLDD 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 743 NLVCKVSDFGLSRVLeddPEAAYTTRGGKIPiRWTAPEAIA------FRKFTSASDVWSYGIVMWEVVSyGERPYWEMTN 816
Cdd:cd14182  146 DMNIKLTDFGFSCQL---DPGEKLREVCGTP-GYLAPEIIEcsmddnHPGYGKEVDMWSTGVIMYTLLA-GSPPFWHRKQ 220
                        170
                 ....*....|....*..
gi 974005246 817 QDVIKAVEEG-YRLPSP 832
Cdd:cd14182  221 MLMLRMIMSGnYQFGSP 237
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
596-812 1.04e-08

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 58.16  E-value: 1.04e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 596 HEFAKEIEASCITIE-----RVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKvgYTEKQRRD----FLGEASIMGQFDHP 666
Cdd:cd05596   12 EKPVNEITKLRMNAEdfdviKVIGRGAFGEVQLVRHKSTKK---VYAMKLLS--KFEMIKRSdsafFWEERDIMAHANSE 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 667 NIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKND-----GQFTVIQLVGMLRGISAgmkylsdMGYVHRDLAARNILIN 741
Cdd:cd05596   87 WIVQLHYAFQDDKYLYMVMDYMPGGDLVNLMSNYDvpekwARFYTAEVVLALDAIHS-------MGFVHRDVKPDNMLLD 159
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005246 742 SNLVCKVSDFGLS-RVLEDDPEAAYTTRGGKIPIrwtAPEAI----AFRKFTSASDVWSYGIVMWEVVsYGERPYW 812
Cdd:cd05596  160 ASGHLKLADFGTCmKMDKDGLVRSDTAVGTPDYI---SPEVLksqgGDGVYGRECDWWSVGVFLYEML-VGDTPFY 231
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
607-811 1.05e-08

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 57.52  E-value: 1.05e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 607 ITIERVIGAGEFGEVCSGRLKLPGkreLPVAIKTLKVgytekqRRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd13991    8 ATHQLRIGRGSFGEVHRMEDKQTG---FQCAVKKVRL------EVFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMD 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLdtflkkndGQftVIQLVGML---RGIS------AGMKYLSDMGYVHRDLAARNILINSN----LVCkvsDFGL 753
Cdd:cd13991   79 LKEGGSL--------GQ--LIKEQGCLpedRALHylgqalEGLEYLHSRKILHGDVKADNVLLSSDgsdaFLC---DFGH 145
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 754 SRVLEDDPEAAYTTRGGKIPIRWT--APEAIAFRKFTSASDVWSYGIVMWEVVSyGERPY 811
Cdd:cd13991  146 AECLDPDGLGKSLFTGDYIPGTEThmAPEVVLGKPCDAKVDVWSSCCMMLHMLN-GCHPW 204
pknD PRK13184
serine/threonine-protein kinase PknD;
609-844 1.14e-08

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 59.40  E-value: 1.14e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 609 IERVIGAGEFGEVCSGRLKLPGKRelpVAIKTLKVGYTEKQ--RRDFLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:PRK13184   6 IIRLIGKGGMGEVYLAYDPVCSRR---VALKKIREDLSENPllKKRFLREAKIAADLIHPGIVPVYSICSDGDPVYYTMP 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLK--------KND--GQFTVIQLVGMLRGISAGMKYLSDMGYVHRDLAARNILIN--SNLVckVSDFG-- 752
Cdd:PRK13184  83 YIEGYTLKSLLKsvwqkeslSKElaEKTSVGAFLSIFHKICATIEYVHSKGVLHRDLKPDNILLGlfGEVV--ILDWGaa 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 753 LSRVLEDDPEAAYT-----------TRGGKI--PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVS----YGERPYWEMT 815
Cdd:PRK13184 161 IFKKLEEEDLLDIDvdernicyssmTIPGKIvgTPDYMAPERLLGVPASESTDIYALGVILYQMLTlsfpYRRKKGRKIS 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 974005246 816 NQDVIKAVEE--GYRlpspmDCPAALYQLML 844
Cdd:PRK13184 241 YRDVILSPIEvaPYR-----EIPPFLSQIAM 266
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
289-378 1.16e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 53.00  E-value: 1.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246   289 PSAPRN-AISNVNETSVFLEWIPPADTGGRKDVSYYIACKKcnshagvceecGGHVRYLPRQSGLKNTSVMMVDLLAHTN 367
Cdd:smart00060   1 PSPPSNlRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYR-----------EEGSEWKEVNVTPSSTSYTLTGLKPGTE 69
                           90
                   ....*....|.
gi 974005246   368 YTFEIEAVNGV 378
Cdd:smart00060  70 YEFRVRAVNGA 80
STKc_NDR_like_fungal cd05629
Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs ...
611-768 1.24e-08

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270778 [Multi-domain]  Cd Length: 377  Bit Score: 58.32  E-value: 1.24e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 611 RVIGAGEFGEVCSGRLKLPGKrelPVAIKTLKvgYTEKQRRDFLG----EASIMGQFDHPNIIHLEGVVTKSKPVMIVTE 686
Cdd:cd05629    7 KVIGKGAFGEVRLVQKKDTGK---IYAMKTLL--KSEMFKKDQLAhvkaERDVLAESDSPWVVSLYYSFQDAQYLYLIME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 687 YMENGSLDTFLKKND------GQFTVIQLVGMLRGISAgmkylsdMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDD 760
Cdd:cd05629   82 FLPGGDLMTMLIKYDtfsedvTRFYMAECVLAIEAVHK-------LGFIHRDIKPDNILIDRGGHIKLSDFGLSTGFHKQ 154

                 ....*...
gi 974005246 761 PEAAYTTR 768
Cdd:cd05629  155 HDSAYYQK 162
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
647-874 1.24e-08

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 58.49  E-value: 1.24e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 647 EKQRRDFLGEASIMGQFDHPNII-HLEGVVTKSKpVMIVTEYMENGSLDTFLKKNDGQFTVIQL--VGML-RGISAGMKY 722
Cdd:PTZ00267 106 ERQAAYARSELHCLAACDHFGIVkHFDDFKSDDK-LLLIMEYGSGGDLNKQIKQRLKEHLPFQEyeVGLLfYQIVLALDE 184
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 723 LSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIrWTAPEAIAFRKFTSASDVWSYGIVMWE 802
Cdd:PTZ00267 185 VHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQYSDSVSLDVASSFCGTPY-YLAPELWERKRYSKKADMWSLGVILYE 263
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 803 VVSYgERPYWEMTNQDVIKAVEEGYRLPSPMDCPAALYQLMLDCWQKERNSRPKFDE---------IVNMLDKLIRNPSS 873
Cdd:PTZ00267 264 LLTL-HRPFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRPTTQQllhteflkyVANLFQDIVRHSET 342

                 .
gi 974005246 874 L 874
Cdd:PTZ00267 343 I 343
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
683-805 1.32e-08

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 57.35  E-value: 1.32e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005246 683 IVTEYMENGSLDTFLKKNdgQFTVIQLVGMLRGISAGMKYLSD-----------MGYVHRDLAARNILINSNLVCKVSDF 751
Cdd:cd14140   70 LITAFHDKGSLTDYLKGN--IVSWNELCHIAETMARGLSYLHEdvprckgeghkPAIAHRDFKSKNVLLKNDLTAVLADF 147
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005246 752 GLSRVLE-----DDPEAAYTTRggkipiRWTAPE----AIAFRKFTSAS-DVWSYGIVMWEVVS 805
Cdd:cd14140  148 GLAVRFEpgkppGDTHGQVGTR------RYMAPEvlegAINFQRDSFLRiDMYAMGLVLWELVS 205
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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