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 1036542137 520 KKNHYKYVCLKVMKKGKNYFDQGLFELTILNMLseesiNQTSTGNNKssditdsttltnkNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14133    20 DLLTGEEVALKIIKNNKDYLDQSLDEIRLLELL-----NKKDKADKY-------------HIVRLKDVFYFKNHLCIVFE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1036542137 600 YMESDLYDyFIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14133    82 LLSQNLYE-FLKQNKFQylSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILL 135

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 1036542137 520 KKNHYKYVCLKVMKKGKNYFDQGLFELTILNMLseesiNQTSTGNNKssditdsttltnkNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14133    20 DLLTGEEVALKIIKNNKDYLDQSLDEIRLLELL-----NKKDKADKY-------------HIVRLKDVFYFKNHLCIVFE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1036542137 600 YMESDLYDyFIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14133    82 LLSQNLYE-FLKQNKFQylSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILL 135

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137  519 IKKNHYKYVCLKVMKKGKNYFDQGLF--ELTILNMLSeesinqtstgnnkssditdsttltNKNIIQLYDYFYLKGHLII 596
Cdd:smart00220  19 RDKKTGKLVAIKVIKKKKIKKDRERIlrEIKILKKLK------------------------HPNIVRLYDVFEDEDKLYL 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1036542137  597 VTEYME-SDLYDYFIKKGKLgTLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:smart00220  75 VMEYCEgGDLFDLLKKRGRL-SEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLD 131

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 1036542137 576 LTNKNIIQLYDYFYLKGHLIIVTEYMES-DLYDYFIK-KGKLGTLGQLQIlTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:pfam07714  58 LDHPNIVKLLGVCTQGEPLYIVTEYMPGgDLLDFLRKhKRKLTLKDLLSM-ALQIAKGMEYLESKNFVHRDLAARNCLVS 136

Myb-like DNA-binding domain; This family contains the DNA binding domains from Myb proteins, as well as the SANT domain family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1036542137  17 KTEWSKEEEEKLLHLAKLFPTQWRTIAPVV-GRTAQQCLEHYEYLL 61
Cdd:pfam00249   1 RGPWTPEEDELLLEAVEKLGNRWKKIAKLLpGRTDNQCKNRWQNYL 46

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 573 STTLTNKNIIQLYD------YFYlkghliIVTEYME-SDLYDYFIKKGKLGTLGQLQIlTKNLLQGLVYIHSKKLIHCDL 645
Cdd:NF033483   61 AASLSHPNIVSVYDvgedggIPY------IVMEYVDgRTLKDYIREHGPLSPEEAVEI-MIQILSALEHAHRNGIVHRDI 133

                  ....*...
gi 1036542137 646 KPENIMIN 653
Cdd:NF033483  134 KPQNILIT 141

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 520 KKNHYKYVCLKVMKKGKNYFDQGLFELTILNMLseesiNQTSTGNNKssditdsttltnkNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14133    20 DLLTGEEVALKIIKNNKDYLDQSLDEIRLLELL-----NKKDKADKY-------------HIVRLKDVFYFKNHLCIVFE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1036542137 600 YMESDLYDyFIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14133    82 LLSQNLYE-FLKQNKFQylSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILL 135

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137  519 IKKNHYKYVCLKVMKKGKNYFDQGLF--ELTILNMLSeesinqtstgnnkssditdsttltNKNIIQLYDYFYLKGHLII 596
Cdd:smart00220  19 RDKKTGKLVAIKVIKKKKIKKDRERIlrEIKILKKLK------------------------HPNIVRLYDVFEDEDKLYL 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1036542137  597 VTEYME-SDLYDYFIKKGKLgTLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:smart00220  75 VMEYCEgGDLFDLLKKRGRL-SEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLD 131

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 1036542137 521 KNHYKYVCLKVMKKGKNYFDQGLFELTILNMLSEesinqtstgnnkssditdstTLTNKNIIQLYDYFYLKG--HLIIVT 598
Cdd:cd05118    21 KVTGEKVAIKKIKNDFRHPKAALREIKLLKHLND--------------------VEGHPNIVKLLDVFEHRGgnHLCLVF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1036542137 599 EYMESDLYDyFIKKGKLG-TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:cd05118    81 ELMGMNLYE-LIKDYPRGlPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILIN 135

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 1036542137 525 KYVCLKVMKKGKNYFDQGLFELTILNMLseesinqtstgnNKSSDITDsttltNKNIIQLYDYFYLKGHLIIVTEYMESD 604
Cdd:cd14212    25 KLVAVKVLKNKPAYFRQAMLEIAILTLL------------NTKYDPED-----KHHIVRLLDHFMHHGHLCIVFELLGVN 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1036542137 605 LYDYfIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:cd14212    88 LYEL-LKQNQFRglSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILLV 137

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE 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 1036542137 575 TLTNKNIIQLYDYFYLKGHLIIVTEYMES-DLYDYFIKKGKLGTLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:cd05122    53 KCKHPNIVKYYGSYLKKDELWIVMEFCSGgSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLT 132

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 1036542137 525 KYVCLKVMKKGKNYFDQGLFELTILNMLSEesinqtSTGNNKSsditdsttltnkNIIQLYDYFYLKGHLIIVTEYMESD 604
Cdd:cd14134    38 RYVAVKIIRNVEKYREAAKIEIDVLETLAE------KDPNGKS------------HCVQLRDWFDYRGHMCIVFELLGPS 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 605 LYDyFIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMinikkkkkkkkstqhLRENNNDEISNVQISH 682
Cdd:cd14134   100 LYD-FLKKNNYGpfPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENIL---------------LVDSDYVKVYNPKKKR 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1036542137 683 DSNE-KNTcfsnnsdfdknhenifssdqfrEIKIIDFNSSIF 723
Cdd:cd14134   164 QIRVpKST----------------------DIKLIDFGSATF 183

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 1036542137 525 KYVCLKVMKKGKNYFDQGLFELTILNmlseesinQTSTGNNKSSDitdsttltNKNIIQLYDYFYLKG----HLIIVTEY 600
Cdd:cd14136    36 RFVALKVVKSAQHYTEAALDEIKLLK--------CVREADPKDPG--------REHVVQLLDDFKHTGpngtHVCMVFEV 99

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1036542137 601 MESDL------YDY------FIKKgklgtlgqlqiLTKNLLQGLVYIHSK-KLIHCDLKPENIMINI 654
Cdd:cd14136   100 LGPNLlklikrYNYrgiplpLVKK-----------IARQVLQGLDYLHTKcGIIHTDIKPENVLLCI 155

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 1036542137 576 LTNKNIIQLYDYFYLKG------HLIIVTEYMESDLYDY---FIKKGKLGTLGQLQILTKNLLQGLVYIHSKKLIHCDLK 646
Cdd:cd14137    54 LKHPNIVKLKYFFYSSGekkdevYLNLVMEYMPETLYRVirhYSKNKQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIK 133

                  ....*..
gi 1036542137 647 PENIMIN 653
Cdd:cd14137   134 PQNLLVD 140

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 576 LTNKNIIQLYDYFYLKGHLIIVTEYME-SDLYDYFIKKGKLgTLGQ-LQILTKnLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:COG0515    64 LNHPNIVRVYDVGEEDGRPYLVMEYVEgESLADLLRRRGPL-PPAEaLRILAQ-LAEALAAAHAAGIVHRDIKPANILLT 141

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 1036542137 525 KYVCLKVMKKGKNYFDQGLFELTILNMLseesinqtstgNNKSSDitdsttlTNKNIIQLYDYFYLKGHLIIVTEYMESD 604
Cdd:cd14226    39 EWVAIKIIKNKKAFLNQAQIEVRLLELM-----------NKHDTE-------NKYYIVRLKRHFMFRNHLCLVFELLSYN 100

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1036542137 605 LYDYFIKKGKLG-TLGQLQILTKNLLQGLVYIHSKKL--IHCDLKPENIMI 652
Cdd:cd14226   101 LYDLLRNTNFRGvSLNLTRKFAQQLCTALLFLSTPELsiIHCDLKPENILL 151

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. 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 Pho85 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 1036542137 534 KGKNYFDQGLFELTILNMLSEESINQTSTgnnksSDITDSTTLTNKNIIQLYDYFYLKGHLIIVTEYMESDLYDYFIKKG 613
Cdd:cd07836    18 KGRNRTTGEIVALKEIHLDAEEGTPSTAI-----REISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKDLKKYMDTHG 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1036542137 614 KLGTLGQLQI--LTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:cd07836    93 VRGALDPNTVksFTYQLLKGIAFCHENRVLHRDLKPQNLLIN 134

Catalytic domain of Fungal Halotolerance protein 4-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 HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 573 STTLTNKNIIQLYDYFY-LKGHLIIVTEYM-ESDLYdYFIKKGKLGTLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENI 650
Cdd:cd13994    51 SSKLHHPNIVKVLDLCQdLHGKWCLVMEYCpGGDLF-TLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENI 129

                  ...
gi 1036542137 651 MIN 653
Cdd:cd13994   130 LLD 132

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1036542137 580 NIIQLYDYFYLKGHLIIVTEYMESDLYDYFIKKGKLGTLGQLQILTKNLLQGLVYIHSK-KLIHCDLKPENIMIN 653
Cdd:cd06623    60 YVVKCYGAFYKEGEISIVLEYMDGGSLADLLKKVGKIPEPVLAYIARQILKGLDYLHTKrHIIHRDIKPSNLLIN 134

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 1036542137 575 TLTNKNIIQLYDYFYLKGHLIIVTEYME----SDLydyfIKK-GKLgTLGQLQILTKNLLQGLVYIHSKKLIHCDLKPEN 649
Cdd:cd06606    55 SLKHPNIVRYLGTERTENTLNIFLEYVPggslASL----LKKfGKL-PEPVVRKYTRQILEGLEYLHSNGIVHRDIKGAN 129

                  ....
gi 1036542137 650 IMIN 653
Cdd:cd06606   130 ILVD 133

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek 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 1036542137 575 TLTNKNIIQLYDYFYLKGHLIIVTEYMES-DLYDYFIKKGKLGTLGQ----LQILTkNLLQGLVYIHSKKLIHCDLKPEN 649
Cdd:cd08215    55 KLKHPNIVKYYESFEENGKLCIVMEYADGgDLAQKIKKQKKKGQPFPeeqiLDWFV-QICLALKYLHSRKILHRDLKTQN 133

                  ....
gi 1036542137 650 IMIN 653
Cdd:cd08215   134 IFLT 137

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 1036542137 525 KYVCLKVMKKGKNYFDQGLFELTILNMLseesinqtstgnnKSSDITDSTtltNKNIIQLYDYFYLKG----HLIIVTEY 600
Cdd:cd14218    36 RFVALKVVKSAVHYTETAVDEIKLLKCV-------------RDSDPSDPK---RETIVQLIDDFKISGvngvHVCMVLEV 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1036542137 601 MESDLYDYFIKKGKLGT-LGQLQILTKNLLQGLVYIHSK-KLIHCDLKPENIMINI 654
Cdd:cd14218   100 LGHQLLKWIIKSNYQGLpLPCVKSILRQVLQGLDYLHTKcKIIHTDIKPENILMCV 155

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 1036542137 520 KKNHYKYVCLKVMKKGKNYFDQGLFELTILNMLSEESINQTstgnnkssditdsttltnkNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14229    21 KRGTNEIVAVKILKNHPSYARQGQIEVGILARLSNENADEF-------------------NFVRAYECFQHRNHTCLVFE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1036542137 600 YMESDLYDyFIKKGKLGTLgQLQILTKNLLQ---GLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14229    82 MLEQNLYD-FLKQNKFSPL-PLKVIRPILQQvatALKKLKSLGLIHADLKPENIML 135

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK 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 1036542137 520 KKNHYKYVCLKVMKKGKNYFDQGLFELTILNMLSEESINQTstgnnkssditdsttltnkNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14211    20 KRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQENADEF-------------------NFVRAYECFQHKNHTCLVFE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1036542137 600 YMESDLYDyFIKKGKLG--TLGQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14211    81 MLEQNLYD-FLKQNKFSplPLKYIRPILQQVLTALLKLKSLGLIHADLKPENIML 134

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 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 1036542137 534 KGKNYFDQGLFELTILNMLSEESINQTStgnnkssdITDSTTLT---NKNIIQLYDYFYLKGHLIIVTEYMESDLYDYFI 610
Cdd:cd07870    18 KGISRINGQLVALKVISMKTEEGVPFTA--------IREASLLKglkHANIVLLHDIIHTKETLTFVFEYMHTDLAQYMI 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1036542137 611 KK-GKLGTLgQLQILTKNLLQGLVYIHSKKLIHCDLKPENIMIN 653
Cdd:cd07870    90 QHpGGLHPY-NVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLIS 132

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 520 KKNHYKYVcLKVMKKGKnyfdqgLFELTILNMLSEESINQTStgnnkssditdsttLTNKNIIQLYDYFYLKGHLIIVTE 599
Cdd:cd14007    22 KKSGFIVA-LKVISKSQ------LQKSGLEHQLRREIEIQSH--------------LRHPNILRLYGYFEDKKRIYLILE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 600 YMES-DLYDYFIKKGKLGT------LGQLqiltknlLQGLVYIHSKKLIHCDLKPENIMI 652
Cdd:cd14007    81 YAPNgELYKELKKQKRFDEkeaakyIYQL-------ALALDYLHSKNIIHRDIKPENILL 133

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036542137 569 DITDSttLTNKNIIQLYDYFYLKGHLIIVTEYMES-DLYDYFIKKGKLGTLGQLQIlTKNLLQGLVYIHSKKLIHCDLKP 647
Cdd:cd14098    53 NILKS--LEHPGIVRLIDWYEDDQHIYLVMEYVEGgDLMDFIMAWGAIPEQHAREL-TKQILEAMAYTHSMGITHRDLKP 129

                  ....*
gi 1036542137 648 ENIMI 652
Cdd:cd14098   130 ENILI 134

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 1036542137 521 KNHyKYVCLKVMKKGKNYFDQGLFELTILNMLseesinqtstgnnKSSDITDsttltNKNIIQLYDYFYLKGHLIIVTEY 600
Cdd:cd14224    88 KTH-QHVALKMVRNEKRFHRQAAEEIRILEHL-------------KKQDKDN-----TMNVIHMLESFTFRNHICMTFEL 148