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 568981641 686 RYNVYGYTGQGVFSNVVRARDNARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHFYHKQHLCL 765
Cdd:cd14135    1 RYRVYGYLGKGVFSNVVRARDLARGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDDKKHCIRLLRHFEHKNHLCL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 766 VFEPLSMNLREVLKKYGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTILKLCDFGSASHVADND 845
Cdd:cd14135   81 VFESLSMNLREVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKKNTLKLCDFGSASDIGENE 160

                        170
                 ....*....|....*
gi 568981641 846 ITPYLVSRFYRAPEI 860
Cdd:cd14135  161 ITPYLVSRFYRAPEI 175

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 568981641 686 RYNVYGYTGQGVFSNVVRARDNARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHFYHKQHLCL 765
Cdd:cd14135    1 RYRVYGYLGKGVFSNVVRARDLARGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDDKKHCIRLLRHFEHKNHLCL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 766 VFEPLSMNLREVLKKYGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTILKLCDFGSASHVADND 845
Cdd:cd14135   81 VFESLSMNLREVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKKNTLKLCDFGSASDIGENE 160

                        170
                 ....*....|....*
gi 568981641 846 ITPYLVSRFYRAPEI 860
Cdd:cd14135  161 ITPYLVSRFYRAPEI 175

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 681 EVLDKRYNVYGYTGQGVFSNVVRARDnARANQEVAVKIIRNNELMQKTGLK----ELEFLKKLNDAdpddkfHCLRLFRH 756
Cdd:COG0515    3 ALLLGRYRILRLLGRGGMGVVYLARD-LRLGRPVALKVLRPELAADPEARErfrrEARALARLNHP------NIVRVYDV 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 757 FYHKQHLCLVFEPLS-MNLREVLKKYGKdvgLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTIlKLCDF 835
Cdd:COG0515   76 GEEDGRPYLVMEYVEgESLADLLRRRGP---LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRV-KLIDF 151

                        170       180       190
                 ....*....|....*....|....*....|..
gi 568981641 836 GSASHVADNDITP---YLVSRFYRAPEITAAR 864
Cdd:COG0515  152 GIARALGGATLTQtgtVVGTPGYMAPEQARGE 183

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641  694 GQGVFSNVVRAR---DNARANQEVAVKIIRNNelmqKTGLKELEFLKKlndadpddkfhcLRLFRHFYHKqHL------C 764
Cdd:pfam07714   8 GEGAFGEVYKGTlkgEGENTKIKVAVKTLKEG----ADEEEREDFLEE------------ASIMKKLDHP-NIvkllgvC 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641  765 LVFEPLSM--------NLREVLKKYGKDVGLHIKAvrSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTIlKLCDFG 836
Cdd:pfam07714  71 TQGEPLYIvteympggDLLDFLRKHKRKLTLKDLL--SMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVV-KISDFG 147

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 171 KLEITDNKNSAKKRSKSRSKERTRHRSDKRKS------------KGAGEMLREKANRSKSKERrkskspskrsksqDQAR 238
Cdd:PTZ00449 478 KIQFTQEIKKLIKKSKKKLAPIEEEDSDKHDEppegpeasglppKAPGDKEGEEGEHEDSKES-------------DEPK 544

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 239 KSKSPplRRRSQEKVGKARSPAEEKMKSeekgKIKDRKKSPivnersrDRSKKSKSPVDLRDKSKDRRSRSKERKSKRse 318
Cdd:PTZ00449 545 EGGKP--GETKEGEVGKKPGPAKEHKPS----KIPTLSKKP-------EFPKDPKHPKDPEEPKKPKRPRSAQRPTRP-- 609

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568981641 319 idkekkpiKSPSKDASSgKENRSPSRRPGRSPKRRSLSPKLRDKSRRSRSPLLnDRRSKQSKSPSRTLSPGRRAK 393
Cdd:PTZ00449 610 --------KSPKLPELL-DIPKSPKRPESPKSPKRPPPPQRPSSPERPEGPKI-IKSPKPPKSPKPPFDPKFKEK 674

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 568981641 686 RYNVYGYTGQGVFSNVVRARDNARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHFYHKQHLCL 765
Cdd:cd14135    1 RYRVYGYLGKGVFSNVVRARDLARGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDDKKHCIRLLRHFEHKNHLCL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 766 VFEPLSMNLREVLKKYGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTILKLCDFGSASHVADND 845
Cdd:cd14135   81 VFESLSMNLREVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKKNTLKLCDFGSASDIGENE 160

                        170
                 ....*....|....*
gi 568981641 846 ITPYLVSRFYRAPEI 860
Cdd:cd14135  161 ITPYLVSRFYRAPEI 175

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 568981641 673 GYYRVNIGEVLDKRYNVYGYTGQGVFSNVVRARDNaRANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLR 752
Cdd:cd14210    1 GDYKVVLGDHIAYRYEVLSVLGKGSFGQVVKCLDH-KTGQLVAIKIIRNKKRFHQQALVEVKILKHLNDNDPDDKHNIVR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 753 LFRHFYHKQHLCLVFEPLSMNLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNI-LVNESKTILK 831
Cdd:cd14210   80 YKDSFIFRGHLCIVFELLSINLYELLKS-NNFQGLSLSLIRKFAKQILQALQFLHKLNIIHCDLKPENIlLKQPSKSSIK 158

                        170       180
                 ....*....|....*....|....*....
gi 568981641 832 LCDFGSASHVaDNDITPYLVSRFYRAPEI 860
Cdd:cd14210  159 VIDFGSSCFE-GEKVYTYIQSRFYRAPEV 186

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 568981641 694 GQGVFSNVVRARDnARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDA-DPDDKFHCLRLFRHFYHKQHLCLVFEPLSM 772
Cdd:cd14212    8 GQGTFGQVVKCQD-LKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLNTKyDPEDKHHIVRLLDHFMHHGHLCIVFELLGV 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 773 NLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNIL-VNESKTILKLCDFGSASHvADNDITPYLV 851
Cdd:cd14212   87 NLYELLKQ-NQFRGLSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILlVNLDSPEIKLIDFGSACF-ENYTLYTYIQ 164

                 ....*....
gi 568981641 852 SRFYRAPEI 860
Cdd:cd14212  165 SRFYRSPEV 173

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 568981641 674 YYRVNIGEVLDKRYNVYGYTGQGVFSNVVRARDNARaNQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRL 753
Cdd:cd14134    1 HLIYKPGDLLTNRYKILRLLGEGTFGKVLECWDRKR-KRYVAVKIIRNVEKYREAAKIEIDVLETLAEKDPNGKSHCVQL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 754 FRHFYHKQHLCLVFEPLSMNLREVLKKYGKdVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNIL----------V 823
Cdd:cd14134   80 RDWFDYRGHMCIVFELLGPSLYDFLKKNNY-GPFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILlvdsdyvkvyN 158

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568981641 824 NESK--------TILKLCDFGSASHvaDNDITPYLVS-RFYRAPEItaarvselILLLRWHEgSCD 880
Cdd:cd14134  159 PKKKrqirvpksTDIKLIDFGSATF--DDEYHSSIVStRHYRAPEV--------ILGLGWSY-PCD 213

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 568981641 677 VNIGEVLDKRYNVYGYTGQGVFSNVVRARDNaRANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKF--HCLRLF 754
Cdd:cd14136    2 VKIGEVYNGRYHVVRKLGWGHFSTVWLCWDL-QNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGreHVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 755 RHFYHK----QHLCLVFEPLSMNLREVLKKYGKDvGLHIKAVRSYSQQLFLALKLL-KRCNILHADIKPDNILVNESKTI 829
Cdd:cd14136   81 DDFKHTgpngTHVCMVFEVLGPNLLKLIKRYNYR-GIPLPLVKKIARQVLQGLDYLhTKCGIIHTDIKPENVLLCISKIE 159

                        170       180       190
                 ....*....|....*....|....*....|.
gi 568981641 830 LKLCDFGSASHVaDNDITPYLVSRFYRAPEI 860
Cdd:cd14136  160 VKIADLGNACWT-DKHFTEDIQTRQYRSPEV 189

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 684 DKRYNVYGYTGQGVFSNVVRARDNARaNQEVAVKIIrnnelMQKTGLK--ELEFLKKLNdadpddkfH--CLRLFRHFYH 759
Cdd:cd14137    3 EISYTIEKVIGSGSFGVVYQAKLLET-GEVVAIKKV-----LQDKRYKnrELQIMRRLK--------HpnIVKLKYFFYS 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 760 KQ------HLCLVFEPLSMNLREVLKKYgKDVGLHIKA--VRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTILK 831
Cdd:cd14137   69 SGekkdevYLNLVMEYMPETLYRVIRHY-SKNKQTIPIiyVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVDPETGVLK 147

                        170       180
                 ....*....|....*....|....*....
gi 568981641 832 LCDFGSASHVADNDI-TPYLVSRFYRAPE 859
Cdd:cd14137  148 LCDFGSAKRLVPGEPnVSYICSRYYRAPE 176

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 687 YNVYGYTGQGVFSNVVRARDNArANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDkFHCLRLFRHFYHKQHLCLV 766
Cdd:cd14229    2 YEVLDFLGRGTFGQVVKCWKRG-TNEIVAVKILKNHPSYARQGQIEVGILARLSNENADE-FNFVRAYECFQHRNHTCLV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 767 FEPLSMNLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNI-LVNESKTI--LKLCDFGSASHVAD 843
Cdd:cd14229   80 FEMLEQNLYDFLKQ-NKFSPLPLKVIRPILQQVATALKKLKSLGLIHADLKPENImLVDPVRQPyrVKVIDFGSASHVSK 158

                        170
                 ....*....|....*..
gi 568981641 844 NDITPYLVSRFYRAPEI 860
Cdd:cd14229  159 TVCSTYLQSRYYRAPEI 175

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 568981641 686 RYNVYGYTGQGVFSNVVRARDNaRANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHFYHKQHLCL 765
Cdd:cd14224   66 RYEVLKVIGKGSFGQVVKAYDH-KTHQHVALKMVRNEKRFHRQAAEEIRILEHLKKQDKDNTMNVIHMLESFTFRNHICM 144

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 766 VFEPLSMNLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNES-KTILKLCDFGSaSHVADN 844
Cdd:cd14224  145 TFELLSMNLYELIKK-NKFQGFSLQLVRKFAHSILQCLDALHRNKIIHCDLKPENILLKQQgRSGIKVIDFGS-SCYEHQ 222

                        170
                 ....*....|....*.
gi 568981641 845 DITPYLVSRFYRAPEI 860
Cdd:cd14224  223 RIYTYIQSRFYRAPEV 238

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 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 568981641 687 YNVYGYTGQGVFSNVVRARDNArANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDkFHCLRLFRHFYHKQHLCLV 766
Cdd:cd14227   17 YEVLEFLGRGTFGQVVKCWKRG-TNEIVAIKILKNHPSYARQGQIEVSILARLSTESADD-YNFVRAYECFQHKNHTCLV 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 767 FEPLSMNLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNI-LVNESKTI--LKLCDFGSASHVAD 843
Cdd:cd14227   95 FEMLEQNLYDFLKQ-NKFSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENImLVDPSRQPyrVKVIDFGSASHVSK 173

                        170
                 ....*....|....*..
gi 568981641 844 NDITPYLVSRFYRAPEI 860
Cdd:cd14227  174 AVCSTYLQSRYYRAPEI 190

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 686 RYNVYGYTGQGVFSNVVRARDNARaNQEVAVKIIRNNEL------MQKTGLKELEFLKKLNDAdpddkfHCLRLFRHFYH 759
Cdd:cd07841    1 RYEKGKKLGEGTYAVVYKARDKET-GRIVAIKKIKLGERkeakdgINFTALREIKLLQELKHP------NIIGLLDVFGH 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 760 KQHLCLVFEPLSMNLREVLKKygKDVGL---HIKavrSYSQQLFLALKLLKRCNILHADIKPDNILVNeSKTILKLCDFG 836
Cdd:cd07841   74 KSNINLVFEFMETDLEKVIKD--KSIVLtpaDIK---SYMLMTLRGLEYLHSNWILHRDLKPNNLLIA-SDGVLKLADFG 147

                        170       180
                 ....*....|....*....|....*
gi 568981641 837 SA-SHVADNDI-TPYLVSRFYRAPE 859
Cdd:cd07841  148 LArSFGSPNRKmTHQVVTRWYRAPE 172

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-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 568981641 687 YNVYGYTGQGVFSNVVRARDNArANQEVAVKIIRN-----NELMQktgLKELEFLKKLNDADpddkfHCLRLFRHFYHKQ 761
Cdd:cd07830    1 YKVIKQLGDGTFGSVYLARNKE-TGELVAIKKMKKkfyswEECMN---LREVKSLRKLNEHP-----NIVKLKEVFREND 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 762 HLCLVFEPLSMNLREVLKKYGKDVgLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNeSKTILKLCDFGSASHV 841
Cdd:cd07830   72 ELYFVFEYMEGNLYQLMKDRKGKP-FSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVS-GPEVVKIADFGLAREI 149

                        170       180
                 ....*....|....*....|
gi 568981641 842 ADND-ITPYLVSRFYRAPEI 860
Cdd:cd07830  150 RSRPpYTDYVSTRWYRAPEI 169

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 678 NIGEVLDKRYNVYGYTGQGVFSNVVRARDNARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHF 757
Cdd:cd14215    5 RSGDWLQERYEIVSTLGEGTFGRVVQCIDHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPENKNLCVQMFDWF 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 758 YHKQHLCLVFEPLSMNLREVLKKyGKDVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNES----------- 826
Cdd:cd14215   85 DYHGHMCISFELLGLSTFDFLKE-NNYLPYPIHQVRHMAFQVCQAVKFLHDNKLTHTDLKPENILFVNSdyeltynlekk 163

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568981641 827 -------KTILKLCDFGSASHvaDNDITPYLVS-RFYRAPEItaarvselILLLRWHEgSCD 880
Cdd:cd14215  164 rdersvkSTAIRVVDFGSATF--DHEHHSTIVStRHYRAPEV--------ILELGWSQ-PCD 214

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 568981641 680 GEVLDKRYNVYGYTGQGVFSNVVRARDNARANQEVAVKIIRNNELMQKTGLKELEFLKKLNDADPDDKFHCLRLFRHFYH 759
Cdd:cd14213    7 GDVLRARYEIVDTLGEGAFGKVVECIDHKMGGMHVAVKIVKNVDRYREAARSEIQVLEHLNTTDPNSTFRCVQMLEWFDH 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568981641 760 KQHLCLVFEPLSMNLREVLKKYGKdVGLHIKAVRSYSQQLFLALKLLKRCNILHADIKPDNILVNESKTI---------- 829
Cdd:cd14213   87 HGHVCIVFELLGLSTYDFIKENSF-LPFPIDHIRNMAYQICKSVNFLHHNKLTHTDLKPENILFVQSDYVvkynpkmkrd 165

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568981641 830 --------LKLCDFGSASHvADNDITPYLVSRFYRAPEItaarvselILLLRWHEgSCD 880
Cdd:cd14213  166 ertlknpdIKVVDFGSATY-DDEHHSTLVSTRHYRAPEV--------ILALGWSQ-PCD 214