Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   1 MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 80
Cdd:cd14217    34 MQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 113

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720412818  81 NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAGAPPPSGSAVSTAP 156
Cdd:cd14217   114 NYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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 1720412818   1 MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 80
Cdd:cd14217    34 MQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 113

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720412818  81 NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAGAPPPSGSAVSTAP 156
Cdd:cd14217   114 NYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   4 KRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ--LIDDfkiSGmngiHVCMVFEVLGHHLLKWIIKsn 81
Cdd:PTZ00284  154 KEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQADPADRFPLMKIQryFQNE---TG----HMCIVMPKYGPCLLDWIMK-- 224

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720412818  82 YQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEAT 137
Cdd:PTZ00284  225 HGPFSHRHLAQIIFQTGVALDYFHTELHLMHTDLKPENILMETSDTVVDPVTNRAL 280

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   5 RFVAMKVVKSAQHYTETALD----EIKLLKCVResdpsDPNkdmVVQLIDDFKISGmngiHVCMVFE-VLGHHLLKWIik 79
Cdd:COG0515    33 RPVALKVLRPELAADPEARErfrrEARALARLN-----HPN---IVRVYDVGEEDG----RPYLVMEyVEGESLADLL-- 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1720412818  80 SNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 125
Cdd:COG0515    99 RRRGPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPD 143

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 443 TRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGedysrDEDHIAHIIELLgsiprhfalsgkysreFFNR 522
Cdd:pfam00069 123 TPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGING-----NEIYELIIDQPY----------------AFPE 181

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 523 RDHIaliiellgkvprkyamlgkYSKEfftrkgelrhitklkpwslfdvlvekygwphedaaqFTDFLIPMLEMVPEKRA 602
Cdd:pfam00069 182 LPSN-------------------LSEE------------------------------------AKDLLKKLLKKDPSKRL 206

                         170
                  ....*....|.
gi 1720412818 603 SAGECLRHPWL 613
Cdd:pfam00069 207 TATQALQHPWF 217

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818  203 EENITSAEASGEQQDGEYQPEVTLKAADLEDTTEEETAKDNGEVEDQEEKEDAEKENAEKDEDDVEQELANLDPTWVESP 282
Cdd:TIGR00927  820 ETQADDTEVKDETGEQELNAENQGEAKQDEKGVDGGGGSDGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWP 899

                   .
gi 1720412818  283 K 283
Cdd:TIGR00927  900 E 900

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 1720412818   7 VAMKVVKsaQHYTETA----LDEIKLLKCVREsdpsdPNkdmVVQLIddfkisG--MNGIHVCMVFEVLGHHLLKWIIKS 80
Cdd:pfam07714  31 VAVKTLK--EGADEEEredfLEEASIMKKLDH-----PN---IVKLL------GvcTQGEPLYIVTEYMPGGDLLDFLRK 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720412818  81 NYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENIL 121
Cdd:pfam07714  95 HKRKLTLKDLLSMALQIAKGMEYLESK-NFVHRDLAARNCL 134

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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 1720412818 404 AADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPH 483
Cdd:cd14218   187 ASDFLVNPLEPQNADKIRVKIADLGNACWVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAFELATGDYLFEPH 266

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 484 SGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellgkvprkyamlgkyskefftrkGELRHITKL 563
Cdd:cd14218   267 SGEDYTRDEDHIAHIVELLGDIPPHFALSGRYSREYFNRR-------------------------------GELRHIKNL 315

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720412818 564 KPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14218   316 KHWGLYEVLVEKYEWPLEQAAQFTDFLLPMMEFLPEKRATAAQCLQHPWL 365

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK 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 1720412818 412 LDPRN----ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 487
Cdd:cd14136   146 IKPENvllcISKIEVKIADLGNACWTDKHFTEDIQTRQYRSPEVILGAGYGTPADIWSTACMAFELATGDYLFDPHSGED 225

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 488 YSRDEDHIAHIiellgsiprhfalsgkysreffnrrdhialiIELLGKVPRKYAMLGKYSKEFFTRKGELRHITKLKPWS 567
Cdd:cd14136   226 YSRDEDHLALI-------------------------------IELLGRIPRSIILSGKYSREFFNRKGELRHISKLKPWP 274

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1720412818 568 LFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14136   275 LEDVLVEKYKWSKEEAKEFASFLLPMLEYDPEKRATAAQCLQHPWL 320

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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 1720412818   1 MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 80
Cdd:cd14218    32 IQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLIDDFKISGVNGVHVCMVLEVLGHQLLKWIIKS 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720412818  81 NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAGAPPPSGSAVS 153
Cdd:cd14218   112 NYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEGYVRRLAAEATIWQQAGAPPPSGSSVS 184

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK 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 1720412818   1 MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS 80
Cdd:cd14136    32 LQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLLDDFKHTGPNGTHVCMVFEVLGPNLLKLIKRY 111

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1720412818  81 NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYV 129
Cdd:cd14136   112 NYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISKIEV 160

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   4 KRFVAMKVVKSAQHYTETALDEIKLLKCVREsdpsDPNKDMVVQLIDDFKISGMNgiHVCMVFEVLGHHLLKwIIKSNYQ 83
Cdd:cd05118    24 GEKVAIKKIKNDFRHPKAALREIKLLKHLND----VEGHPNIVKLLDVFEHRGGN--HLCLVFELMGMNLYE-LIKDYPR 96

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1720412818  84 GLPVRCVKSIIRQVLQGLDYLHSkCKIIHTDIKPENILMC 123
Cdd:cd05118    97 GLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILIN 135

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. 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. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   4 KRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDpnKDMVVQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQ 83
Cdd:cd14210    38 GQLVAIKIIRNKKRFHQQALVEVKILKHLNDNDPDD--KHNIVRYKDSFIFRG----HLCIVFELLSINLYELLKSNNFQ 111

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1720412818  84 GLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMC 123
Cdd:cd14210   112 GLSLSLIRKFAKQILQALQFLHKL-NIIHCDLKPENILLK 150

Catalytic domain of the Dual-specificity protein kinases, CDC-like 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. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK 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 1720412818 421 RVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIAHIIE 500
Cdd:cd14134   172 DIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMMER 245

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 501 LLGSIPRHFALSGKYSREFFNRRDhialiiellGKVPR-KYAMLGKYSKefftrkgelRHITKLKPWSLFDvlvekygwp 579
Cdd:cd14134   246 ILGPLPKRMIRRAKKGAKYFYFYH---------GRLDWpEGSSSGRSIK---------RVCKPLKRLMLLV--------- 298

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1720412818 580 HEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14134   299 DPEHRLLFDLIRKMLEYDPSKRITAKEALKHPFF 332

Catalytic domain of the Dual-specificity protein kinase, YAK1; 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 proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 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 1720412818 407 LLVNPLDPRnadkirVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFePHSGE 486
Cdd:cd14212   135 LLVNLDSPE------IKLIDFGSACFENYTLYTYIQSRFYRSPEVLLGLPYSTAIDMWSLGCIAAELFLGLPLF-PGNSE 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 487 dYsrdeDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellGKVPRKYAMLGKYSKEFftrkgELRHITKLKP- 565
Cdd:cd14212   208 -Y----NQLSRIIEMLGMPPDWMLEKGKNTNKFFKKV----------AKSGGRSTYRLKTPEEF-----EAENNCKLEPg 267

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720412818 566 -----WSLFDVLVEKYGWPHEDAAQ----------FTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14212   268 kryfkYKTLEDIIMNYPMKKSKKEQidkemetrlaFIDFLKGLLEYDPKKRWTPDQALNHPFI 330

Catalytic domain of the Dual-specificity protein kinase, YAK1; 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 proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 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 1720412818   4 KRFVAMKVVKSAQHYTETALDEIKLLKCVRESDpSDPNKDMVVQLIDDFkisgMNGIHVCMVFEVLGHHLLKWIIKSNYQ 83
Cdd:cd14212    24 NKLVAVKVLKNKPAYFRQAMLEIAILTLLNTKY-DPEDKHHIVRLLDHF----MHHGHLCIVFELLGVNLYELLKQNQFR 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1720412818  84 GLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILMCVDDA 127
Cdd:cd14212    99 GLSLQLIRKFLQQLLDALSVLK-DARIIHCDLKPENILLVNLDS 141

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 416 NADKIRVKIADLGNACWVHKHF-TEDIQTRQYRSIEVLIGA-GYSTPADIWSTACMAFELATGDYLFEPHSgedysrDED 493
Cdd:cd05118   135 NLELGQLKLADFGLARSFTSPPyTPYVATRWYRAPEVLLGAkPYGSSIDIWSLGCILAELLTGRPLFPGDS------EVD 208

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 494 HIAHIIELLGsiprhfalsgkysreffnrrdhialiiellgkvprkyamlgkyskefftrkgelrhitklkpwslfdvlv 573
Cdd:cd05118   209 QLAKIVRLLG---------------------------------------------------------------------- 218

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1720412818 574 ekygwphedAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd05118   219 ---------TPEALDLLSKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 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 1720412818 422 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIAHIIEL 501
Cdd:cd14214   175 IRVADFGSATFDHEHHTTIVATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHE------NREHLVMMEKI 248

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 502 LGSIPRHFALSGKYSREFFNRrdhialiiellGKVPRKYAMLGKYSKEfftrkgelrHITKLKPWSLFDVLvekygwphe 581
Cdd:cd14214   249 LGPIPSHMIHRTRKQKYFYKG-----------SLVWDENSSDGRYVSE---------NCKPLMSYMLGDSL--------- 299

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1720412818 582 DAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14214   300 EHTQLFDLLRRMLEFDPALRITLKEALLHPFF 331

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   2 QGKRFVAMKVVKSAQH---YTETALDEIKLLKcvresDPSDPNkdmVVQLIDdfKISGMNGIHvcMVFEVLgHHLLKWII 78
Cdd:cd07829    22 KTGEIVALKKIRLDNEeegIPSTALREISLLK-----ELKHPN---IVKLLD--VIHTENKLY--LVFEYC-DQDLKKYL 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1720412818  79 KSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILM 122
Cdd:cd07829    89 DKRPGPLPPNLIKSIMYQLLRGLAYCHSH-RILHRDLKPQNLLI 131

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 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 1720412818   2 QGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSN 81
Cdd:cd14215    36 RGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPE--NKNLCVQMFDWFDYHG----HMCISFELLGLSTFDFLKENN 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1720412818  82 YQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVDDAYVR 130
Cdd:cd14215   110 YLPYPIHQVRHMAFQVCQAVKFLHDN-KLTHTDLKPENILFVNSDYELT 157

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; 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. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 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 1720412818 422 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIAHIIEL 501
Cdd:cd14225   187 IKVIDFGSSCYEHQRVYTYIQSRFYRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLF---PGEN---EVEQLACIMEV 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 502 LGSIPRHfalsgkysreffnrrdhialiieLLGKVPRKyamlgkysKEFFTRKGELRHIT-----KLKPWS--LFDVLve 574
Cdd:cd14225   261 LGLPPPE-----------------------LIENAQRR--------RLFFDSKGNPRCITnskgkKRRPNSkdLASAL-- 307

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1720412818 575 kygwpHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14225   308 -----KTSDPLFLDFIRRCLEWDPSKRMTPDEALQHEWI 341

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 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 1720412818 416 NADKIRVKIADLGNACWVHKH-FTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephsgedysrdedh 494
Cdd:cd14135   139 NEKKNTLKLCDFGSASDIGENeITPYLVSRFYRAPEIILGLPYDYPIDMWSVGCTLYELYTGKILF-------------- 204

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818 495 iahiiellgsiprhfalSGKysreffNRRDHIALIIELLGKVPRKyaML--GKYSKEFF--------------TRKGELR 558
Cdd:cd14135   205 -----------------PGK------TNNHMLKLMMDLKGKFPKK--MLrkGQFKDQHFdenlnfiyrevdkvTKKEVRR 259

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720412818 559 HITKLKP-WSLFDVLVEKYGWPHEDA---AQFTDFLIPMLEMVPEKRASAGECLRHPWL 613
Cdd:cd14135   260 VMSDIKPtKDLKTLLIGKQRLPDEDRkklLQLKDLLDKCLMLDPEKRITPNEALQHPFI 318

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; 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 DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720412818   7 VAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLP 86
Cdd:cd14224    93 VALKMVRNEKRFHRQAAEEIRILEHLKKQDKD--NTMNVIHMLESFTFRN----HICMTFELLSMNLYELIKKNKFQGFS 166

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720412818  87 VRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILM 122
Cdd:cd14224   167 LQLVRKFAHSILQCLDALH-RNKIIHCDLKPENILL 201