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 301122567 124 VLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTVHAARTQfesteqQEAIK 203
Cdd:cd14136    2 VKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKD------PGREH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 204 VIRLVDSFEHKGPNGVHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDKCQIIHTDLKPENVLLSH 283
Cdd:cd14136   76 VVQLLDDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCI 155

                 ....*...
gi 301122567 284 QIPQLpKI 291
Cdd:cd14136  156 SKIEV-KI 162

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 301122567 124 VLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTVHAARTQfesteqQEAIK 203
Cdd:cd14136    2 VKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKD------PGREH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 204 VIRLVDSFEHKGPNGVHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDKCQIIHTDLKPENVLLSH 283
Cdd:cd14136   76 VVQLLDDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCI 155

                 ....*...
gi 301122567 284 QIPQLpKI 291
Cdd:cd14136  156 SKIEV-KI 162

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567   642 KSEvfNLMkLDA----KICDLGNAC-WTSKHFTND-IQTRQYRCPEVILGKRYDTSADIWSMACFVFELLTGDLLFnpks 715
Cdd:smart00220 124 KPE--NIL-LDEdghvKLADFGLARqLDPGEKLTTfVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPF---- 196

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567   716 grnfnRDEDHLAQMIELLGrmpksytgsqrglreffnrKGDLKRIRSLKFWSlqqvlvekyhfsrqdaECLASFLGPMLR 795
Cdd:smart00220 197 -----PGDDQLLELFKKIG-------------------KPKPPFPPPEWDIS----------------PEAKDLIRKLLV 236

                          170
                   ....*....|....*...
gi 301122567   796 YDPAKRATAQDCLAHPWL 813
Cdd:smart00220 237 KDPEKRLTAEEALQHPFF 254

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 654 KICDLGNACWTSKHFTNDIQTRQYRCPEVILGKRYDTSADIWSMACFVFELLTGDLLFNPKSgrnfnrDEDHLAQMIELL 733
Cdd:PTZ00284 288 RICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELYTGKLLYDTHD------NLEHLHLMEKTL 361

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 734 GRMPKSYT---GSQRGlREFFNRKGDLK---------RIRSLKfwSLQQVLVEKYhfsrqdaecLASFLGPMLRYDPAKR 801
Cdd:PTZ00284 362 GRLPSEWAgrcGTEEA-RLLYNSAGQLRpctdpkhlaRIARAR--PVREVIRDDL---------LCDLIYGLLHYDRQKR 429

                        170
                 ....*....|..
gi 301122567 802 ATAQDCLAHPWL 813
Cdd:PTZ00284 430 LNARQMTTHPYV 441

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567  134 FEVLEKLGWGHFSTVWKCLDRETGALVAMKV--QKSARH-YTEAAKDEIELLECTVHAartqfesteqqeaiKVIRLVDS 210
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKikKEKIKKkKDKNILREIKILKKLNHP--------------NIVRLYDA 66

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 301122567  211 FEhkgpNGVHVCMVFE-MMGDNLLTLIKYynYRGVPMQLVQRLTRDIMEGLA 261
Cdd:pfam00069  67 FE----DKDNLYLVLEyVEGGSLFDLLSE--KGAFSEREAKFIMKQILEGLE 112

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 301122567 674 TRQYRCPEVILGKRYDTSADIWSMACFVFELLTGDLLFNPKS 715
Cdd:COG0515  171 TPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDS 212

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 301122567 124 VLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTVHAARTQfesteqQEAIK 203
Cdd:cd14136    2 VKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKD------PGREH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 204 VIRLVDSFEHKGPNGVHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDKCQIIHTDLKPENVLLSH 283
Cdd:cd14136   76 VVQLLDDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCI 155

                 ....*...
gi 301122567 284 QIPQLpKI 291
Cdd:cd14136  156 SKIEV-KI 162

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell 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 301122567 627 QQRLGRWAARFNKLAKSEVFNLM------KLDAKICDLGNACWTSKHFTNDIQTRQYRCPEVILGKRYDTSADIWSMACF 700
Cdd:cd14216  157 EQYIRRLAAEATEWQRNFLVNPLepknaeKLKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACM 236

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 701 VFELLTGDLLFNPKSGRNFNRDEDHLAQMIELLGRMPKSYTGSQRGLREFFNRKGDLKRIRSLKFWSLQQVLVEKYHFSR 780
Cdd:cd14216  237 AFELATGDYLFEPHSGEDYSRDEDHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWSQ 316

                        170       180       190
                 ....*....|....*....|....*....|...
gi 301122567 781 QDAECLASFLGPMLRYDPAKRATAQDCLAHPWL 813
Cdd:cd14216  317 EEAAGFTDFLLPMLELIPEKRATAAECLRHPWL 349

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 301122567 124 VLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTvhaaRTQFESTEQQEAIk 203
Cdd:cd14218    2 VKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCV----RDSDPSDPKRETI- 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 301122567 204 vIRLVDSFEHKGPNGVHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDKCQIIHTDLKPENVLL 281
Cdd:cd14218   77 -VQLIDDFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILM 153

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 301122567 121 YHRVLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTVHAartqfeSTEQQE 200
Cdd:cd14217    1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRES------DPEDPN 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 201 AIKVIRLVDSFEHKGPNGVHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDKCQIIHTDLKPENVL 280
Cdd:cd14217   75 KDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENIL 154

                 .
gi 301122567 281 L 281
Cdd:cd14217  155 M 155

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 301122567 134 FEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECtvhaartqFESTEQQEAIkvIRLVDSFEH 213
Cdd:cd05118    1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKH--------LNDVEGHPNI--VKLLDVFEH 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 301122567 214 KGpnGVHVCMVFEMMGDNLLTLIKYYNyRGVPMQLVQRLTRDIMEGLAFLHdKCQIIHTDLKPENVLLSHQIPQL 288
Cdd:cd05118   71 RG--GNHLCLVFELMGMNLYELIKDYP-RGLPLDLIKSYLYQLLQALDFLH-SNGIIHRDLKPENILINLELGQL 141

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 134 FEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLEctvhaartQFESTEQQEAIKVIRLVDSFEH 213
Cdd:cd14133    1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLE--------LLNKKDKADKYHIVRLKDVFYF 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 301122567 214 KGpngvHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHDkCQIIHTDLKPENVLL 281
Cdd:cd14133   73 KN----HLCIVFELLSQNLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHS-LGLIHCDLKPENILL 135

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; 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. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and 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. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 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 301122567 124 VLAGEVYNSRFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLECTvhaartqfESTEQQEAIK 203
Cdd:cd14226    5 VKNGEKWMDRYEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELM--------NKHDTENKYY 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 301122567 204 VIRLVDSFEHKGpngvHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFL-HDKCQIIHTDLKPENVLL 281
Cdd:cd14226   77 IVRLKRHFMFRN----HLCLVFELLSYNLYDLLRNTNFRGVSLNLTRKFAQQLCTALLFLsTPELSIIHCDLKPENILL 151

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 301122567 654 KICDLGNACWTSKHFTNDIQTRQYRCPEVILGKRYDTSADIWSMACFVFELLTGDLLFNPKSGRnfnrdeDHLAQMIELL 733
Cdd:cd14134  174 KLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHDNL------EHLAMMERIL 247

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 734 GRMPKSYT-GSQRGLREFFNRKGDL------KRIRSLK--FWSLQQVLVEKYHFSRQDAECLASflgpMLRYDPAKRATA 804
Cdd:cd14134  248 GPLPKRMIrRAKKGAKYFYFYHGRLdwpegsSSGRSIKrvCKPLKRLMLLVDPEHRLLFDLIRK----MLEYDPSKRITA 323

                 ....*....
gi 301122567 805 QDCLAHPWL 813
Cdd:cd14134  324 KEALKHPFF 332

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 654 KICDLGNACWTSKHFTNDIQTRQYRCPEVILGKRYDTSADIWSMACFVFELLTGDLLFNPKSgrnfnrDEDHLAQMIELL 733
Cdd:cd14133  144 KIIDFGSSCFLTQRLYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGAS------EVDQLARIIGTI 217

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 734 GRMPksytgsqrglreffnrkgdlkrirslkFWSLQQvlvekyhfSRQDAECLASFLGPMLRYDPAKRATAQDCLAHPWL 813
Cdd:cd14133  218 GIPP---------------------------AHMLDQ--------GKADDELFVDFLKKLLEIDPKERPTASQALSHPWL 262

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 301122567 646 FNLMKLDAKICDLGNACW-TSKHFTNDIQTRQYRCPEVILG-KRYDTSADIWSMACFVFELLTGDLLFNPKSgrnfnrDE 723
Cdd:cd05118  134 INLELGQLKLADFGLARSfTSPPYTPYVATRWYRAPEVLLGaKPYGSSIDIWSLGCILAELLTGRPLFPGDS------EV 207

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 724 DHLAQMIELLGRMPksytgsqrglreffnrkgdlkrirslkfwslqqvlvekyhfsrqdaecLASFLGPMLRYDPAKRAT 803
Cdd:cd05118  208 DQLAKIVRLLGTPE------------------------------------------------ALDLLSKMLKYDPAKRIT 239

                        170
                 ....*....|
gi 301122567 804 AQDCLAHPWL 813
Cdd:cd05118  240 ASQALAHPYF 249

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 301122567 133 RFEVLEKLGWGHFSTVWKCLDRETGALVAMKVQKSARHYTEAAKDEIELLEctvHAARTQFESTeqqeaIKVIRLVDSFE 212
Cdd:cd14224   66 RYEVLKVIGKGSFGQVVKAYDHKTHQHVALKMVRNEKRFHRQAAEEIRILE---HLKKQDKDNT-----MNVIHMLESFT 137

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 301122567 213 HKGpngvHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHdKCQIIHTDLKPENVLLSHQ 284
Cdd:cd14224  138 FRN----HICMTFELLSMNLYELIKKNKFQGFSLQLVRKFAHSILQCLDALH-RNKIIHCDLKPENILLKQQ 204

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. 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 CLK1/4 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 301122567 126 AGEVYNSRFEVLEKLGWGHFSTVWKCLDRE-TGALVAMKVQKSARHYTEAAKDEIELLEctvhaartQFESTEQQEAIKV 204
Cdd:cd14213    6 SGDVLRARYEIVDTLGEGAFGKVVECIDHKmGGMHVAVKIVKNVDRYREAARSEIQVLE--------HLNTTDPNSTFRC 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 301122567 205 IRLVDSFEHKGpngvHVCMVFEMMGDNLLTLIKYYNYRGVPMQLVQRLTRDIMEGLAFLHdKCQIIHTDLKPENVLLSH 283
Cdd:cd14213   78 VQMLEWFDHHG----HVCIVFELLGLSTYDFIKENSFLPFPIDHIRNMAYQICKSVNFLH-HNKLTHTDLKPENILFVQ 151

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 301122567 654 KICDLGNA-CWTS--KHFTNDIQTRQYRCPEVILG-KRYDTSADIWSMACFVFELLTGDLLFNPKSgrnfnrDEDHLAQM 729
Cdd:cd07829  138 KLADFGLArAFGIplRTYTHEVVTLWYRAPEILLGsKHYSTAVDIWSVGCIFAELITGKPLFPGDS------EIDQLFKI 211

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301122567 730 IELLGrMPKSYTGSqrglrEFFNRKGDLKRIRSLKFWSLQQVlvekyhFSRQDAECLaSFLGPMLRYDPAKRATAQDCLA 809
Cdd:cd07829  212 FQILG-TPTEESWP-----GVTKLPDYKPTFPKWPKNDLEKV------LPRLDPEGI-DLLSKMLQYNPAKRISAKEALK 278

                 ....
gi 301122567 810 HPWL 813
Cdd:cd07829  279 HPYF 282

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 301122567 127 GEVYNSRFEVLEKLGWGHFSTVWKCLDRETG-ALVAMKVQKSARHYTEAAKDEIELLEctvhaartQFESTEQQEAIKVI 205
Cdd:cd14214    8 GDWLQERYEIVGDLGEGTFGKVVECLDHARGkSQVALKIIRNVGKYREAARLEINVLK--------KIKEKDKENKFLCV 79