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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452    34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARAdcIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 113
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKDRERI--LREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEY 78

                           90
                   ....*....|.
gi 767908452   114 ADAGDLSRMIK 124
Cdd:smart00220  79 CEGGDLFDLLK 89

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  26 MGYNTLANFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDN 105
Cdd:COG0515    1 MSALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARERFRREARALARLNHPNIVRVYDVGEEDG 80

                         90       100
                 ....*....|....*....|..
gi 767908452 106 ELNIVLELADAGDLSRMIKLRQ 127
Cdd:COG0515   81 RPYLVMEYVEGESLADLLRRRG 102

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  35 RIEKKIGRGQFSEVYRAACLLDGVPVALKkVQIFDLMD-----------AKARAdcikeidllkQLNHPNVIKYYASFiE 103
Cdd:NF033483  10 EIGERIGRGGMAEVYLAKDTRLDRDVAVK-VLRPDLARdpefvarfrreAQSAA----------SLSHPNIVSVYDVG-E 77

                         90       100
                 ....*....|....*....|..
gi 767908452 104 DNELN-IVLELADAGDLSRMIK 124
Cdd:NF033483  78 DGGIPyIVMEYVDGRTLKDYIR 99

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd08224    1 NYEIEKKIGKGQFSVVYRARCLLDGRLVALKKVQIFEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLE 80

                         90
                 ....*....|....*
gi 767908452 113 LADAGDLSRMIKLRQ 127
Cdd:cd08224   81 LADAGDLSRLIKHFK 95

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd08215    1 KYEKIRVIGKGSFGSAYLVRRKSDGKLYVLKEIDLSN-MSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVME 79

                         90
                 ....*....|....*
gi 767908452 113 LADAGDLSRMIKLRQ 127
Cdd:cd08215   80 YADGGDLAQKIKKQK 94

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAkARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd06627    1 NYQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLEKIPKS-DLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILE 79

                         90
                 ....*....|..
gi 767908452 113 LADAGDLSRMIK 124
Cdd:cd06627   80 YVENGSLASIIK 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd08529    1 DFEILNKLGKGSFGVVYKVVRKVDGRVYALKQIDISR-MSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVME 79

                         90
                 ....*....|..
gi 767908452 113 LADAGDLSRMIK 124
Cdd:cd08529   80 YAENGDLHSLIK 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd14014    1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPELAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVME 80

                         90
                 ....*....|..
gi 767908452 113 LADAGDLSRMIK 124
Cdd:cd14014   81 YVEGGSLADLLR 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  40 IGRGQFSEVYRAACLLDGVPVALKKVQIfdLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGDL 119
Cdd:cd00180    1 LGKGSFGKVYKARDKETGKKVAVKVIPK--EKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSL 78

                 ....*
gi 767908452 120 SRMIK 124
Cdd:cd00180   79 KDLLK 83

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  26 MGYNTLANFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDN 105
Cdd:COG0515    1 MSALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARERFRREARALARLNHPNIVRVYDVGEEDG 80

                         90       100
                 ....*....|....*....|..
gi 767908452 106 ELNIVLELADAGDLSRMIKLRQ 127
Cdd:COG0515   81 RPYLVMEYVEGESLADLLRRRG 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIfDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd05117    1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIDK-KKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVME 79

                         90
                 ....*....|...
gi 767908452 113 LADAGDL-SRMIK 124
Cdd:cd05117   80 LCTGGELfDRIVK 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  38 KKIGRGQFSEVYRAACLLDG---VPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELA 114
Cdd:cd00192    1 KKLGEGAFGEVYKGKLKGGDgktVDVAVKTLK--EDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYM 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 767908452 115 DAGDLSRMIKLRQLVNMCINPDPEKRPD-VTYVYDVAKRM 153
Cdd:cd00192   79 EGGDLLDFLRKSRPVFPSPEPSTLSLKDlLSFAIQIAKGM 118

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVqifDLMDAKARADCI-KEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd06609    3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVI---DLEEAEDEIEDIqQEIQFLSQCDSPYITKYYGSFLKGSKLWIIME 79

                         90
                 ....*....|....*...
gi 767908452 113 LADAG---DLSRMIKLRQ 127
Cdd:cd06609   80 YCGGGsvlDLLKPGPLDE 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452    35 RIEKKIGRGQFSEVYRAacLLDG------VPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELN 108
Cdd:smart00219   2 TLGKKLGEGAFGEVYKG--KLKGkggkkkVEVAVKTLK--EDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLY 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 767908452   109 IVLELADAGDL-------SRMIKLRQLVNMCI 133
Cdd:smart00219  78 IVMEYMEGGDLlsylrknRPKLSLSDLLSFAL 109

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452   34 FRIEKKIGRGQFSEVYRAACLLDG----VPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNI 109
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGEGentkIKVAVKTLK--EGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYI 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767908452  110 VLELADAGDL-------SRMIKLRQLVNMCI 133
Cdd:pfam07714  79 VTEYMPGGDLldflrkhKRKLTLKDLLSMAL 109

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd14007    1 DFEIGKPLGKGKFGNVYLAREKKSGFIVALKVISKSQLQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767908452 113 LADAGDLSRMIKlRQlvnmciNPDPEKRPdVTYVYDVAKRMHAC 156
Cdd:cd14007   81 YAPNGELYKELK-KQ------KRFDEKEA-AKYIYQLALALDYL 116

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  38 KKIGRGQFSEVYRAACLLDGVPVALKKVQIfdlmDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAG 117
Cdd:cd06614    6 EKIGEGASGEVYKATDRATGKEVAIKKMRL----RKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGG 81

                 ....*.
gi 767908452 118 DLSRMI 123
Cdd:cd06614   82 SLTDII 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  32 ANFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDlmDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVL 111
Cdd:cd06623    1 SDLERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHVDG--DEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVL 78

                         90
                 ....*....|...
gi 767908452 112 ELADAGDLSRMIK 124
Cdd:cd06623   79 EYMDGGSLADLLK 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKV---QIFDLMDAKARaDCIKEIDLLKQLNHPNVIKYYASFIEDNELNI 109
Cdd:cd07841    1 RYEKGKKLGEGTYAVVYKARDKETGRIVAIKKIklgERKEAKDGINF-TALREIKLLQELKHPNIIGLLDVFGHKSNINL 79

                         90       100
                 ....*....|....*....|
gi 767908452 110 VLELADaGDLSRMIKLRQLV 129
Cdd:cd07841   80 VFEFME-TDLEKVIKDKSIV 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIfdlmdAKARADCI----KEIDLLKQLNHPNVIKYYASFIEDNELNI 109
Cdd:cd14069    3 WDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDM-----KRAPGDCPenikKEVCIQKMLSHKNVVRFYGHRREGEFQYL 77

                         90
                 ....*....|
gi 767908452 110 VLELADAGDL 119
Cdd:cd14069   78 FLEYASGGEL 87

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767908452  27 GYNTLANFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIF---DLMDAKAradcIKEIDLLKQLNHPNVIK 96
Cdd:cd07866    3 GCSKLRDYEILGKLGEGTFGEVYKARQIKTGRVVALKKILMHnekDGFPITA----LREIKILKKLKHPNVVP 71

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARAdcIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 112
Cdd:cd13996    7 DFEEIELLGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKSSASEKV--LREVKALAKLNHPNIVRYYTAWVEEPPLYIQME 84

                         90
                 ....*....|....
gi 767908452 113 LADAGDLSRMIKLR 126
Cdd:cd13996   85 LCEGGTLRDWIDRR 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLmDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVL-- 111
Cdd:cd13983    3 LKFNEVLGRGSFKTVYRAFDTEEGIEVAWNEIKLRKL-PKAERQRFKQEIEILKSLKHPNIIKFYDSWESKSKKEVIFit 81

                         90       100
                 ....*....|....*....|
gi 767908452 112 ELADAGDLSRMIKLRQLVNM 131
Cdd:cd13983   82 ELMTSGTLKQYLKRFKRLKL 101

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVqifdLMDAKARAdciKEIDLLKQLNHPNVIKYYASFI------EDNEL 107
Cdd:cd14137    6 YTIEKVIGSGSFGVVYQAKLLETGEVVAIKKV----LQDKRYKN---RELQIMRRLKHPNIVKLKYFFYssgekkDEVYL 78

                         90
                 ....*....|....*...
gi 767908452 108 NIVLE-LADagDLSRMIK 124
Cdd:cd14137   79 NLVMEyMPE--TLYRVIR 94

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 113
Cdd:cd14099    3 YRRGKFLGKGGFAKCYEVTDMSTGKVYAGKVVPKSSLTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLEL 82

                         90
                 ....*....|....
gi 767908452 114 ADAGDLSRMIKLRQ 127
Cdd:cd14099   83 CSNGSLMELLKRRK 96

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKkvqIFDL-MDAKARADCIKEIDLLKQLNH---PNVIKYYASFIEDNELNI 109
Cdd:cd06917    3 YRRLELVGRGSYGAVYRGYHVKTGRVVALK---VLNLdTDDDDVSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWI 79

                         90       100
                 ....*....|....*....|....
gi 767908452 110 VLELADAGDLSRMIKLRQLVNMCI 133
Cdd:cd06917   80 IMDYCEGGSIRTLMRAGPIAERYI 103

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIfDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 113
Cdd:cd08218    2 YVRIKKIGEGSFGKALLVKSKEDGKQYVIKEINI-SKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDY 80

                         90
                 ....*....|....*..
gi 767908452 114 ADAGDLSRMIKLRQLVN 130
Cdd:cd08218   81 CDGGDLYKRINAQRGVL 97

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767908452  33 NFRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIfDLMDAKARADCIKEIDLLKQL-NHPNVIKYYASFIEDNELNIVL 111
Cdd:cd13997    1 HFHELEQIGSGSFSEVFKVRSKVDGCLYAVKKSKK-PFRGPKERARALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQM 79

                         90
                 ....*....|....
gi 767908452 112 ELADAGDLSRMIKL 125
Cdd:cd13997   80 ELCENGSLQDALEE 93

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767908452  34 FRIEKKIGRGQFSEVYRAACLLDGVPVALKKVQIFDLMDAKARAdCIKEIDLLKQLNHPNVIK 96
Cdd:cd07840    1 YEKIAQIGEGTYGQVYKARNKKTGELVALKKIRMENEKEGFPIT-AIREIKLLQKLDHPNVVR 62