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 442634145 269 PVVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDVKRERIVRLM 348
Cdd:cd14136    1 PVKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 349 NHFTVRGVNGMHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKCSIIHTDIKPENILLVID---- 424
Cdd:cd14136   81 DDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISkiev 160

                        170
                 ....*....|....*....
gi 442634145 425 ------NAAAMNQQIDDEI 437
Cdd:cd14136  161 kiadlgNACWTDKHFTEDI 179

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145  560 SSGDCDEDAESDTLGEQST---LASTMDSPTDLD-PEPELDSKPNTVPEPSEGPIPEPTPNST--NSSCPSHNTATIAKS 633
Cdd:PHA03307  237 SDSSSSESSGCGWGPENECplpRPAPITLPTRIWeASGWNGPSSRPGPASSSSSPRERSPSPSpsSPGSGPAPSSPRASS 316

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 442634145  634 KINSnilSTCTSLTSTNEycftntNTTTASTPSAPPSATPSSAPALASATPPSTCTPS 691
Cdd:PHA03307  317 SSSS---SRESSSSSTSS------SSESSRGAAVSPGPSPSRSPSPSRPPPPADPSSP 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 442634145 269 PVVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDVKRERIVRLM 348
Cdd:cd14136    1 PVKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 349 NHFTVRGVNGMHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKCSIIHTDIKPENILLVID---- 424
Cdd:cd14136   81 DDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISkiev 160

                        170
                 ....*....|....*....
gi 442634145 425 ------NAAAMNQQIDDEI 437
Cdd:cd14136  161 kiadlgNACWTDKHFTEDI 179

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 274 DIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSA----PHYIETAADEIRLLEAIRDadpmdvkrERIVRLMN 349
Cdd:COG0515    3 ALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPElaadPEARERFRREARALARLNH--------PNIVRVYD 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442634145 350 HFTVRGvngmHTCLVFEAL-GCSLYKLIVKNnyQGLAIAQVRNIIRQVLEGLDYLHSKcSIIHTDIKPENILLVIDNAA 427
Cdd:COG0515   75 VGEEDG----RPYLVMEYVeGESLADLLRRR--GPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPDGRV 146

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 266 GYHPVVIG---DIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDvkRE 342
Cdd:PTZ00284 114 GHFYVVLGediDVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQADPAD--RF 191

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 343 RIVRLMNHFtvRGVNGmHTCLVFEALGCSLYKLIVKN---NYQGLAiaqvrNIIRQVLEGLDYLHSKCSIIHTDIKPENI 419
Cdd:PTZ00284 192 PLMKIQRYF--QNETG-HMCIVMPKYGPCLLDWIMKHgpfSHRHLA-----QIIFQTGVALDYFHTELHLMHTDLKPENI 263

                 ..
gi 442634145 420 LL 421
Cdd:PTZ00284 264 LM 265

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145  280 FRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVK---SAPHYIETAADEIRLLEairdadpmDVKRERIVRLMNHFTvrgv 356
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKkekIKKKKDKNILREIKILK--------KLNHPNIVRLYDAFE---- 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 442634145  357 NGMHTCLVFE-ALGCSLYKLIVKNNYqgLAIAQVRNIIRQVLEGLDYLHSKCSIIHT 412
Cdd:pfam00069  69 DKDNLYLVLEyVEGGSLFDLLSEKGA--FSEREAKFIMKQILEGLESGSSLTTFVGT 123

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145  805 TRQYRSIEVLLGAPYNYTADIWSTACLAFELATGDYLFDPHAG-ESYSRDEDHLAHIVELLGSIPQSVIfrgkhglkyft 883
Cdd:pfam00069 123 TPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGnEIYELIIDQPYAFPELPSNLSEEAK----------- 191

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442634145  884 sygslrnitklkpwslmnvlvekydwdpveakkfsDFLLPMLEYNPVIRASAAECLQHPWL 944
Cdd:pfam00069 192 -----------------------------------DLLKKLLKKDPSKRLTATQALQHPWF 217

MSCRAMM family adhesin clumping factor ClfB; Clumping factor B is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 442634145 586 PTDLDPEPELDSKPNTVPEPSEGPIPEPTPNSTNSSCPSHNTATIAKSKINSNILSTCTSLTSTN 650
Cdd:NF033845 551 PVDPEPSPEPEPEPTPDPEPSPDPDPEPSPDPDPDSDSDSDSGSDSDSGSDSDSDSDSDSDSDSD 615

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 442634145 269 PVVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDVKRERIVRLM 348
Cdd:cd14136    1 PVKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 349 NHFTVRGVNGMHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKCSIIHTDIKPENILLVID---- 424
Cdd:cd14136   81 DDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISkiev 160

                        170
                 ....*....|....*....
gi 442634145 425 ------NAAAMNQQIDDEI 437
Cdd:cd14136  161 kiadlgNACWTDKHFTEDI 179

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 442634145 782 VRVKIADLGNACYDYHHFTEDIQTRQYRSIEVLLGAPYNYTADIWSTACLAFELATGDYLFDPHAGESYSRDEDHLAHIV 861
Cdd:cd14216  187 LKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSGEDYSRDEDHIALII 266

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 862 ELLGSIPQSVIFRGKHGLKYFTSYGSLRNITKLKPWSLMNVLVEKYDWDPVEAKKFSDFLLPMLEYNPVIRASAAECLQH 941
Cdd:cd14216  267 ELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWSQEEAAGFTDFLLPMLELIPEKRATAAECLRH 346

                 ...
gi 442634145 942 PWL 944
Cdd:cd14216  347 PWL 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 442634145 269 PVVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDVKRERIVRLM 348
Cdd:cd14218    1 PVKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 442634145 349 NHFTVRGVNGMHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKCSIIHTDIKPENILLVIDNA 426
Cdd:cd14218   81 DDFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEG 158

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 442634145 267 YHPVVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDVKRERIVR 346
Cdd:cd14217    1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 347 LMNHFTVRGVNGMHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKCSIIHTDIKPENILLVIDNA 426
Cdd:cd14217   81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 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 442634145 280 FRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPmdvkRERIVRLMNHFTVRGVNgm 359
Cdd:cd05118    1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLNDVEG----HPNIVKLLDVFEHRGGN-- 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442634145 360 HTCLVFEALGCSLYKLIvKNNYQGLAIAQVRNIIRQVLEGLDYLHSkCSIIHTDIKPENILLVIDN 425
Cdd:cd05118   75 HLCLVFELMGMNLYELI-KDYPRGLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILINLEL 138

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 442634145 280 FRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDvkRERIVRLMNHFTVRGvngm 359
Cdd:cd14133    1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNKKDKAD--KYHIVRLKDVFYFKN---- 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 442634145 360 HTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSkCSIIHTDIKPENILLViDNAAAMNQQID 434
Cdd:cd14133   75 HLCIVFELLSQNLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHS-LGLIHCDLKPENILLA-SYSRCQIKIID 147

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 442634145 781 NVRVKIADLGNACYDYHHFTEDIQTRQYRSIEVLLGAPYNYTADIWSTACLAFELATGDYLFDPHAgesysrDEDHLAHI 860
Cdd:cd14134  170 STDIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMM 243

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 861 VELLGSIPQSVIFRGKHGLKYFTSYGSLRNitklkpWS-----------LMNVLVEKYDWDPVEAKKFSDFLLPMLEYNP 929
Cdd:cd14134  244 ERILGPLPKRMIRRAKKGAKYFYFYHGRLD------WPegsssgrsikrVCKPLKRLMLLVDPEHRLLFDLIRKMLEYDP 317

                        170
                 ....*....|....*
gi 442634145 930 VIRASAAECLQHPWL 944
Cdd:cd14134  318 SKRITAKEALKHPFF 332

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 442634145 270 VVIGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMDvkRERIVRLMN 349
Cdd:cd14226    5 VKNGEKWMDRYEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEN--KYYIVRLKR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 350 HFTVRGvngmHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYL-HSKCSIIHTDIKPENILLVIDNAAA 428
Cdd:cd14226   83 HFMFRN----HLCLVFELLSYNLYDLLRNTNFRGVSLNLTRKFAQQLCTALLFLsTPELSIIHCDLKPENILLCNPKRSA 158

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 442634145 429 mnqqiddeinslrVKGVDFPDS---------YISS 454
Cdd:cd14226  159 -------------IKIIDFGSScqlgqriyqYIQS 180

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 442634145 776 LIDNSNVRVKIADLGNACYDYHHFTEDIQTRQYRSIEVLLGAPYNYTADIWSTACLAFELATGDYLFdPHAGESysrdeD 855
Cdd:cd14133  135 LASYSRCQIKIIDFGSSCFLTQRLYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLF-PGASEV-----D 208

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 856 HLAHIVELLGSIPQSVIFRGKHGlkyftsygslrnitklkpwslmnvlvekydwDPveakKFSDFLLPMLEYNPVIRASA 935
Cdd:cd14133  209 QLARIIGTIGIPPAHMLDQGKAD-------------------------------DE----LFVDFLKKLLEIDPKERPTA 253

                 ....*....
gi 442634145 936 AECLQHPWL 944
Cdd:cd14133  254 SQALSHPWL 262

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 442634145 253 DEEQedasqycrGGYHPVViGDIFDNRFRVVRKLGWGHFSTVWLCRDLKDEKYVALKVVKSAPHYIETAADEIRLLEAIR 332
Cdd:cd14224   49 DDEQ--------GSYIHVP-HDHIAYRYEVLKVIGKGSFGQVVKAYDHKTHQHVALKMVRNEKRFHRQAAEEIRILEHLK 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 333 DADPMDVKRerIVRLMNHFTVRGvngmHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHsKCSIIHT 412
Cdd:cd14224  120 KQDKDNTMN--VIHMLESFTFRN----HICMTFELLSMNLYELIKKNKFQGFSLQLVRKFAHSILQCLDALH-RNKIIHC 192

                 ....*....
gi 442634145 413 DIKPENILL 421
Cdd:cd14224  193 DLKPENILL 201

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 442634145 784 VKIADLGNACYDYHHFTEDIQTRQYRSIEVLLGAPYNYTADIWSTACLAFELATGDYLFDphaGESysrDEDHLAHIVEL 863
Cdd:cd14226  159 IKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLFS---GAN---EVDQMNKIVEV 232

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 864 LGSIPQSVIFRGKHGLKYFT-----SYGSLRNITKLKPW-----SLMNVL-VE----------KYDWDPVEAKKFSDFLL 922
Cdd:cd14226  233 LGMPPVHMLDQAPKARKFFEklpdgTYYLKKTKDGKKYKppgsrKLHEILgVEtggpggrragEPGHTVEDYLKFKDLIL 312

                        170       180
                 ....*....|....*....|....
gi 442634145 923 PMLEYNPVIRASAAECLQHPWLEQ 946
Cdd:cd14226  313 RMLDYDPKTRITPAEALQHSFFKR 336

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 442634145 273 GDIFDNRFRVVRKLGWGHFSTVWLCRDL-KDEKYVALKVVKSAPHYIETAADEIRLLEAIRDADPMdvKRERIVRLMNHF 351
Cdd:cd14213    7 GDVLRARYEIVDTLGEGAFGKVVECIDHkMGGMHVAVKIVKNVDRYREAARSEIQVLEHLNTTDPN--STFRCVQMLEWF 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442634145 352 TVRGvngmHTCLVFEALGCSLYKLIVKNNYQGLAIAQVRNIIRQVLEGLDYLHSKcSIIHTDIKPENILLV-IDNAAAMN 430
Cdd:cd14213   85 DHHG----HVCIVFELLGLSTYDFIKENSFLPFPIDHIRNMAYQICKSVNFLHHN-KLTHTDLKPENILFVqSDYVVKYN 159

                        170       180
                 ....*....|....*....|
gi 442634145 431 QQIDDEINSLR---VKGVDF 447
Cdd:cd14213  160 PKMKRDERTLKnpdIKVVDF 179