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 688575995  68 VKIGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDPSREKVVQLLD 147
Cdd:cd14218    2 VKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLID 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 148 DFKISGVNGTHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHTKCKIIHTDIKPENILMDVNEAYVK 227
Cdd:cd14218   82 DFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEGYVR 161

                        170       180
                 ....*....|....*....|....*..
gi 688575995 228 RLAAEATEWQKSGAPPPSGSAVSTAPA 254
Cdd:cd14218  162 RLAAEATIWQQAGAPPPSGSSVSFGAS 188

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 688575995  68 VKIGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDPSREKVVQLLD 147
Cdd:cd14218    2 VKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLID 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 148 DFKISGVNGTHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHTKCKIIHTDIKPENILMDVNEAYVK 227
Cdd:cd14218   82 DFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEGYVR 161

                        170       180
                 ....*....|....*....|....*..
gi 688575995 228 RLAAEATEWQKSGAPPPSGSAVSTAPA 254
Cdd:cd14218  162 RLAAEATIWQQAGAPPPSGSSVSFGAS 188

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995    78 YHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVK--SAEHYTETALDEIKLLKAVRNtdqndpsrEKVVQLLDDFkisgVN 155
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKH--------PNIVRLYDVF----ED 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 688575995   156 GTHVCMVFEVLGHHLLKWIIKSNyQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILMDVN 222
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLH-SKGIVHRDLKPENILLDED 133

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995  57 PNDYCKGGYHHVKIG---DLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTD 133
Cdd:PTZ00284 107 PNQSREEGHFYVVLGediDVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQAD 186

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 134 QNDpsREKVVQLLDDFKisgvNGT-HVCMVFEVLGHHLLKWIIKS---NYQGLplpcvKSIIRQVLQGLDYLHTKCKIIH 209
Cdd:PTZ00284 187 PAD--RFPLMKIQRYFQ----NETgHMCIVMPKYGPCLLDWIMKHgpfSHRHL-----AQIIFQTGVALDYFHTELHLMH 255

                        170
                 ....*....|....*..
gi 688575995 210 TDIKPENILMDVNEAYV 226
Cdd:PTZ00284 256 TDLKPENILMETSDTVV 272

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995  70 IGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKsaehyTETALDEIKLLK------AVrnTDQNDPSrekVV 143
Cdd:NF033483   1 IGKLLGGRYEIGERIGRGGMAEVYLAKDTRLDRDVAVKVLR-----PDLARDPEFVARfrreaqSA--ASLSHPN---IV 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 144 QLLDdfkiSGVNGTHVCMVFE-VLGHhLLKWIIKSNYqglPLPcVK---SIIRQVLQGLDYLHtKCKIIHTDIKPENILM 219
Cdd:NF033483  71 SVYD----VGEDGGIPYIVMEyVDGR-TLKDYIREHG---PLS-PEeavEIMIQILSALEHAH-RNGIVHRDIKPQNILI 140

                 .
gi 688575995 220 D 220
Cdd:NF033483 141 T 141

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995   78 YHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVK---SAEHYTETALDEIKLLKAVRNtdqndpsrEKVVQLLDDFkisgV 154
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKkekIKKKKDKNILREIKILKKLNH--------PNIVRLYDAF----E 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 688575995  155 NGTHVCMVFE-VLGHHLLKWIikSNYQGLPLPCVKSIIRQVLQGLD 199
Cdd:pfam00069  69 DKDNLYLVLEyVEGGSLFDLL--SEKGAFSEREAKFIMKQILEGLE 112

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 478 QVKIADLGNAcwvhKHFTDDIQTR--------QYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFEPHSGED--YSR 547
Cdd:COG0515  145 RVKLIDFGIA----RALGGATLTQtgtvvgtpGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAEllRAH 220

                         90
                 ....*....|....*....
gi 688575995 548 DEDHIALIIELLGKIPRKL 566
Cdd:COG0515  221 LREPPPPPSELRPDLPPAL 239

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 688575995  68 VKIGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDPSREKVVQLLD 147
Cdd:cd14218    2 VKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLID 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 148 DFKISGVNGTHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHTKCKIIHTDIKPENILMDVNEAYVK 227
Cdd:cd14218   82 DFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEGYVR 161

                        170       180
                 ....*....|....*....|....*..
gi 688575995 228 RLAAEATEWQKSGAPPPSGSAVSTAPA 254
Cdd:cd14218  162 RLAAEATIWQQAGAPPPSGSSVSFGAS 188

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 688575995 463 NLLVNPLEPLNAEKIQVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFEPHSG 542
Cdd:cd14216  173 NFLVNPLEPKNAEKLKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSG 252

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 543 EDYSRDEDHIALIIELLGKIPRKLVMNGKYSKEFFTKKGDLRHITKLKPWGLQDVLVEKYEWHREEAQNFSDFLLPMLDL 622
Cdd:cd14216  253 EDYSRDEDHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWSQEEAAGFTDFLLPMLEL 332

                        170
                 ....*....|....*..
gi 688575995 623 IPEKRATAAECLRHSWI 639
Cdd:cd14216  333 IPEKRATAAECLRHPWL 349

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 688575995 472 LNAEKIQVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFEPHSGEDYSRDEDH 551
Cdd:cd14136  153 LCISKIEVKIADLGNACWTDKHFTEDIQTRQYRSPEVILGAGYGTPADIWSTACMAFELATGDYLFDPHSGEDYSRDEDH 232

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 552 IALIIELLGKIPRKLVMNGKYSKEFFTKKGDLRHITKLKPWGLQDVLVEKYEWHREEAQNFSDFLLPMLDLIPEKRATAA 631
Cdd:cd14136  233 LALIIELLGRIPRSIILSGKYSREFFNRKGELRHISKLKPWPLEDVLVEKYKWSKEEAKEFASFLLPMLEYDPEKRATAA 312

                 ....*...
gi 688575995 632 ECLRHSWI 639
Cdd:cd14136  313 QCLQHPWL 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 688575995 460 AAGNLLVNPLEPLNAEKIQVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFEP 539
Cdd:cd14218  186 GASDFLVNPLEPQNADKIRVKIADLGNACWVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAFELATGDYLFEP 265

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 540 HSGEDYSRDEDHIALIIELLGKIPRKLVMNGKYSKEFFTKKGDLRHITKLKPWGLQDVLVEKYEWHREEAQNFSDFLLPM 619
Cdd:cd14218  266 HSGEDYTRDEDHIAHIVELLGDIPPHFALSGRYSREYFNRRGELRHIKNLKHWGLYEVLVEKYEWPLEQAAQFTDFLLPM 345

                        170       180
                 ....*....|....*....|
gi 688575995 620 LDLIPEKRATAAECLRHSWI 639
Cdd:cd14218  346 MEFLPEKRATAAQCLQHPWL 365

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 688575995  68 VKIGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDPSRekVVQLLD 147
Cdd:cd14134    4 YKPGDLLTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKDPNGKSH--CVQLRD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 148 DFKISGvngtHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILMdVNEAYVK 227
Cdd:cd14134   82 WFDYRG----HMCIVFELLGPSLYDFLKKNNYGPFPLEHVQHIAKQLLEAVAFLH-DLKLTHTDLKPENILL-VDSDYVK 155

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 688575995  64 GYHHVKIGDLFNGRYHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRntdQNDPSREK-V 142
Cdd:cd14210    1 GDYKVVLGDHIAYRYEVLSVLGKGSFGQVVKCLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLN---DNDPDDKHnI 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 688575995 143 VQLLDDFKISGvngtHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILM 219
Cdd:cd14210   78 VRYKDSFIFRG----HLCIVFELLSINLYELLKSNNFQGLSLSLIRKFAKQILQALQFLH-KLNIIHCDLKPENILL 149

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 688575995  78 YHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDpsREKVVQLLDDFkisgVNGT 157
Cdd:cd14133    1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNKKDKAD--KYHIVRLKDVF----YFKN 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 688575995 158 HVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHTkCKIIHTDIKPENILM 219
Cdd:cd14133   75 HLCIVFELLSQNLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHS-LGLIHCDLKPENILL 135

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 688575995 478 QVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIALIIE 557
Cdd:cd14134  172 DIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMMER 245

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 558 LLGKIPRKLVMNGKY-SKEFFTKKGDL-------------RHITKLKPWgLQDVLVEKYEwhreeaqnFSDFLLPMLDLI 623
Cdd:cd14134  246 ILGPLPKRMIRRAKKgAKYFYFYHGRLdwpegsssgrsikRVCKPLKRL-MLLVDPEHRL--------LFDLIRKMLEYD 316

                        170
                 ....*....|....*
gi 688575995 624 PEKRATAAECLRHSW 638
Cdd:cd14134  317 PSKRITAKEALKHPF 331

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 688575995  78 YHVIRKLGWGHFSTVWLAWDTQGKRFVAMKVVKSAEHYTETALDEIKLLKAVrNTDQNDPSREKVVQLLDDFKISGvngt 157
Cdd:cd14212    1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLL-NTKYDPEDKHHIVRLLDHFMHHG---- 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 688575995 158 HVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILM-DVNEAYVK 227
Cdd:cd14212   76 HLCIVFELLGVNLYELLKQNQFRGLSLQLIRKFLQQLLDALSVLK-DARIIHCDLKPENILLvNLDSPEIK 145

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 688575995 464 LLVNPleplnaEKIQVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFephSGe 543
Cdd:cd14226  150 LLCNP------KRSAIKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLF---SG- 219

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 544 dySRDEDHIALIIELLGKIPRKLVMNGKYSKEFFTKKGD-----LRHITKLKPWG-----LQDVL-VE----------KY 602
Cdd:cd14226  220 --ANEVDQMNKIVEVLGMPPVHMLDQAPKARKFFEKLPDgtyylKKTKDGKKYKPpgsrkLHEILgVEtggpggrragEP 297

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 688575995 603 EWHREEAQNFSDFLLPMLDLIPEKRATAAECLRHSWINS 641
Cdd:cd14226  298 GHTVEDYLKFKDLILRMLDYDPKTRITPAEALQHSFFKR 336

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 688575995 464 LLVNPleplnaEKIQVKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFePHSGE 543
Cdd:cd14133  134 LLASY------SRCQIKIIDFGSSCFLTQRLYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLF-PGASE 206

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 544 dysrdEDHIALIIELLGKIPRKLVMNGKYSKEFFTkkgdlrhitklkpwglqdvlvekyewhreeaqnfsDFLLPMLDLI 623
Cdd:cd14133  207 -----VDQLARIIGTIGIPPAHMLDQGKADDELFV-----------------------------------DFLKKLLEID 246

                        170
                 ....*....|....*.
gi 688575995 624 PEKRATAAECLRHSWI 639
Cdd:cd14133  247 PKERPTASQALSHPWL 262

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 688575995  77 RYHVIRKLGWGHFSTVWLAWDTQ-GKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDpsREKVVQLLDDFKISGvn 155
Cdd:cd14135    1 RYRVYGYLGKGVFSNVVRARDLArGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDD--KKHCIRLLRHFEHKN-- 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 688575995 156 gtHVCMVFEVLgHHLLKWIIK--SNYQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILmdVNEA 224
Cdd:cd14135   77 --HLCLVFESL-SMNLREVLKkyGKNVGLNIKAVRSYAQQLFLALKHLK-KCNILHADIKPDNIL--VNEK 141

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 688575995 479 VKIADLGNACWVHKHFTDDIQTRQYRSLEVLIGTGYGTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIALIIEL 558
Cdd:cd14224  209 IKVIDFGSSCYEHQRIYTYIQSRFYRAPEVILGARYGMPIDMWSFGCILAELLTGYPLF---PGED---EGDQLACMIEL 282

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 559 LGKIPRKLVMNGKYSKEFFTKKGDLRHITKLKPWGLQDVLV-------------EKYEWHRE----EAQNFSDFLLPMLD 621
Cdd:cd14224  283 LGMPPQKLLETSKRAKNFISSKGYPRYCTVTTLPDGSVVLNggrsrrgkmrgppGSKDWVTAlkgcDDPLFLDFLKRCLE 362

                        170
                 ....*....|....*...
gi 688575995 622 LIPEKRATAAECLRHSWI 639
Cdd:cd14224  363 WDPAARMTPSQALRHPWL 380

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995  84 LGWGHFSTVWLAWDTQGKRFVAMKVVK--SAEHYTETALDEIKLLKAVRNtdQNdpsrekVVQLLDDFKisgvNGTHVCM 161
Cdd:cd00180    1 LGKGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLNH--PN------IVKLYDVFE----TENFLYL 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 688575995 162 VFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHtKCKIIHTDIKPENILMD 220
Cdd:cd00180   69 VMEYCEGGSLKDLLKENKGPLSEEEALSILRQLLSALEYLH-SNGIIHRDLKPENILLD 126

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 688575995  64 GYHHVKIGDLFNGRYHVIRKLGWGHFSTVWLAWD-TQGKRFVAMKVVKSAEHYTETALDEIKLLKAVRNTDQNDpsREKV 142
Cdd:cd14214    1 GHLVCRIGDWLQERYEIVGDLGEGTFGKVVECLDhARGKSQVALKIIRNVGKYREAARLEINVLKKIKEKDKEN--KFLC 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688575995 143 VQLLDDFKISGvngtHVCMVFEVLGHHLLKWIIKSNYQGLPLPCVKSIIRQVLQGLDYLHTKcKIIHTDIKPENILMdVN 222
Cdd:cd14214   79 VLMSDWFNFHG----HMCIAFELLGKNTFEFLKENNFQPYPLPHIRHMAYQLCHALKFLHEN-QLTHTDLKPENILF-VN 152

                 ...
gi 688575995 223 EAY 225
Cdd:cd14214  153 SEF 155