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 1387212752 650 KPKLGQELGRGQYGVVYLCDSWGGHFPCALKSVVPPDEKHWNDLALEFHYMRSLPKHERLVDLHGSVIDYSYGGGSSIAV 729
Cdd:cd13975     1 KPKLGRELGRGQYGVVYACDSWGGHFPCALKSVVPPDDKHWNDLALEFHYTRSLPKHERIVSLHGSVIDYSYGGGSSIAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1387212752 730 LLIMERLHRDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13975    81 LLIMERLHRDLYTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVL 134

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty 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 1387212752 650 KPKLGQELGRGQYGVVYLCDSWGGHFPCALKSVVPPDEKHWNDLALEFHYMRSLPKHERLVDLHGSVIDYSYGGGSSIAV 729
Cdd:cd13975     1 KPKLGRELGRGQYGVVYACDSWGGHFPCALKSVVPPDDKHWNDLALEFHYTRSLPKHERIVSLHGSVIDYSYGGGSSIAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1387212752 730 LLIMERLHRDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13975    81 LLIMERLHRDLYTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVL 134

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 1387212752 652 KLGQELGRGQYGVVYLC----DSWGGHFPCALKSVVPP-DEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggss 726
Cdd:pfam07714   2 TLGEKLGEGAFGEVYKGtlkgEGENTKIKVAVKTLKEGaDEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQGEP----- 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1387212752 727 iaVLLIMERL-HRDLYTGL---KAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:pfam07714  76 --LYIVTEYMpGGDLLDFLrkhKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCL 134

serine/threonine kinase US3; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 657 LGRGQYGVVYLCDSWG--GHFPCALKSVVPPdekhwNDLALEFHYMRSLPkherlvdlHGSVID--YSYGGGSSiaVLLI 732
Cdd:PHA03207  100 LTPGSEGEVFVCTKHGdeQRKKVIVKAVTGG-----KTPGREIDILKTIS--------HRAIINliHAYRWKST--VCMV 164

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1387212752 733 MERLHRDLYTGL--KAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNV 782
Cdd:PHA03207  165 MPKYKCDLFTYVdrSGPLPLEQAITIQRRLLEALAYLHGRGIIHRDVKTENI 216

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty 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 1387212752 650 KPKLGQELGRGQYGVVYLCDSWGGHFPCALKSVVPPDEKHWNDLALEFHYMRSLPKHERLVDLHGSVIDYSYGGGSSIAV 729
Cdd:cd13975     1 KPKLGRELGRGQYGVVYACDSWGGHFPCALKSVVPPDDKHWNDLALEFHYTRSLPKHERIVSLHGSVIDYSYGGGSSIAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1387212752 730 LLIMERLHRDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13975    81 LLIMERLHRDLYTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVL 134

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752  652 KLGQELGRGQYGVVYLCDSWGGHFPCALKSV-VPPDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggssiaVL 730
Cdd:smart00220   2 EILEKLGEGSFGKVYLARDKKTGKLVAIKVIkKKKIKKDRERILREIKILKKL-KHPNIVRLYDVFEDEDK-------LY 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1387212752  731 LIMERL-HRDLYTGLKA--GLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:smart00220  74 LVMEYCeGGDLFDLLKKrgRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENIL 129

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 1387212752 652 KLGQELGRGQYGVVYLC----DSWGGHFPCALKSVVPP-DEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggss 726
Cdd:pfam07714   2 TLGEKLGEGAFGEVYKGtlkgEGENTKIKVAVKTLKEGaDEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQGEP----- 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1387212752 727 iaVLLIMERL-HRDLYTGL---KAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:pfam07714  76 --LYIVTEYMpGGDLLDFLrkhKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCL 134

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 1387212752 652 KLGQELGRGQYGVVYLCDSWGGHfpCALKSVvppdEKHWNDLAL------EFHYMRSlpKHERLVdlhgSVIDYSYGGGS 725
Cdd:cd13979     6 RLQEPLGSGGFGSVYKATYKGET--VAVKIV----RRRRKNRASrqsfwaELNAARL--RHENIV----RVLAAETGTDF 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1387212752 726 SIAVLLIMER-----LHRDLYTGLKAgLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13979    74 ASLGLIIMEYcgngtLQQLIYEGSEP-LPLAHRILISLDIARALRFCHSHGIVHLDVKPANIL 135

Catalytic domain of Numb-Associated Kinase (NAK)-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 Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-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 1387212752 657 LGRGQYGVVYLCDSWGGHFPCALKSVVPPDEKHWNDLALEFHYMRSLPKHERLVDLHGSVIDYSygGGSSIAVLLIME-- 734
Cdd:cd14037    11 LAEGGFAHVYLVKTSNGGNRAALKRVYVNDEHDLNVCKREIEIMKRLSGHKNIVGYIDSSANRS--GNGVYEVLLLMEyc 88

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1387212752 735 -----------RLHrdlyTGLKAGLAletrLQIALDVVEGIRFLHS--QGLVHRDVKLKNVLGSM 786
Cdd:cd14037    89 kgggvidlmnqRLQ----TGLTESEI----LKIFCDVCEAVAAMHYlkPPLIHRDLKVENVLISD 145

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB 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 1387212752 652 KLGQELGRGQYGVVYLCDSWGGHFPCALKsVVPP----DEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDysyGGGssi 727
Cdd:cd14014     3 RLVRLLGRGGMGEVYRARDTLLGRPVAIK-VLRPelaeDEEFRERFLREARALARL-SHPNIVRVYDVGED---DGR--- 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1387212752 728 aVLLIMERLH-RDLYTGLKAG--LALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd14014    75 -PYIVMEYVEgGSLADLLRERgpLPPREALRILAQIADALAAAHRAGIVHRDIKPANIL 132

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 1387212752 652 KLGQELGRGQYGVVY--LCDSWGghFPCALKSVVPPDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggssiaV 729
Cdd:cd05122     3 EILEKIGKGGFGVVYkaRHKKTG--QIVAIKKINLESKEKKESILNEIAILKKC-KHPNIVKYYGSYLKKDE-------L 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1387212752 730 LLIMERLH----RDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05122    73 WIVMEFCSggslKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANIL 130

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 656 ELGRGQYGVVYLC---DSWGGHFPCALKSVVP-PDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggssiaVLL 731
Cdd:cd00192     2 KLGEGAFGEVYKGklkGGDGKTVDVAVKTLKEdASESERKDFLKEARVMKKL-GHPNVVRLLGVCTEEEP-------LYL 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1387212752 732 IME-----------RLHRD-LYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd00192    74 VMEymeggdlldflRKSRPvFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCL 137

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 1387212752 652 KLGQELGRGQYGVVYLCDSWGGHFPCALKSV--VPPDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYgggssiaV 729
Cdd:cd05117     3 ELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkKKLKSEDEEMLRREIEILKRL-DHPNIVKLYEVFEDDKN-------L 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1387212752 730 LLIMERLH-RDLYTGLKAGLAL---ETRlQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05117    75 YLVMELCTgGELFDRIVKKGSFserEAA-KIMKQILSAVAYLHSQGIVHRDLKPENIL 131

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-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 1387212752 652 KLGQELGRGQYGVVYLcdswGGHFP----CALKsVVP---PDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDYSYggg 724
Cdd:cd14003     3 ELGKTLGEGSFGKVKL----ARHKLtgekVAIK-IIDkskLKEEIEEKIKREIEIMKLL-NHPNIIKLYEVIETENK--- 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1387212752 725 ssiaVLLIMERLHR-DLYTGLKAGLAL---ETRL---QIaldvVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd14003    74 ----IYLVMEYASGgELFDYIVNNGRLsedEARRffqQL----ISAVDYCHSNGIVHRDLKLENIL 131

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 655 QELGRGQYGVVYLC------DSWGGHfpCALKSVVPPD-EKHWNDLALEFHYMRSLpKHERLVDLHGSVIDysyGGGSSI 727
Cdd:cd05079    10 RDLGEGHFGKVELCrydpegDNTGEQ--VAVKSLKPESgGNHIADLKKEIEILRNL-YHENIVKYKGICTE---DGGNGI 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 728 AvlLIMERLH----RDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05079    84 K--LIMEFLPsgslKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVL 141

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 653 LGQELGRGQYGVVYLcDSWGGHFPCALKSVVPPDEKHWNDLALEFHYMRSLpKHERLVDLHGSVidysyGGGSSIAVLL- 731
Cdd:cd05148    10 LERKLGSGYFGEVWE-GLWKNRVRVAIKILKSDDLLKQQDFQKEVQALKRL-RHKHLISLFAVC-----SVGEPVYIITe 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1387212752 732 IMER--LHRDLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05148    83 LMEKgsLLAFLRSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNIL 136

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 1387212752 657 LGRGQYGVVYLCDSW--GGHFPCALKSVVPPDEKHWND-----LALEFHYMRSLpKHERLVDlhgsVIDYSYGGGSSIav 729
Cdd:cd13994     1 IGKGATSVVRIVTKKnpRSGVLYAVKEYRRRDDESKRKdyvkrLTSEYIISSKL-HHPNIVK----VLDLCQDLHGKW-- 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1387212752 730 LLIMERL-HRDLYTGLKAGLAL--ETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13994    74 CLVMEYCpGGDLFTLIEKADSLslEEKDCFFKQILRGVAYLHSHGIAHRDLKPENIL 130

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 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 1387212752 650 KPKLGQELGRGQYGVVYLC-DSWGGHFpCALKsVVPPDEKHwNDLALEFHYMRSLPKHE---RLVDlHGSVIDYSYgggs 725
Cdd:cd14016     1 RYKLVKKIGSGSFGEVYLGiDLKTGEE-VAIK-IEKKDSKH-PQLEYEAKVYKLLQGGPgipRLYW-FGQEGDYNV---- 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1387212752 726 siavlLIMERLHRDL-----YTGLKagLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd14016    73 -----MVMDLLGPSLedlfnKCGRK--FSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFL 128

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 653 LGQELGRGQYGVVYLcDSWGGHFPCALKSVvppDEKHWN--DLALEFHYMRSLpKHERLVDLHGSVIDYSygggssiAVL 730
Cdd:cd05059     8 FLKELGSGQFGVVHL-GKWRGKIDVAIKMI---KEGSMSedDFIEEAKVMMKL-SHPKLVQLYGVCTKQR-------PIF 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1387212752 731 LIMERL-HRDLYTGLKAG---LALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05059    76 IVTEYMaNGCLLNYLRERrgkFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCL 132

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 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 1387212752 652 KLGQELGRGQYGVVYLCDSWGGHFPCALKSV-----VPPDEKHWNDLALEFHYMRSLpKHERLVDLHGSVIDysyggGSS 726
Cdd:cd06652     5 RLGKLLGQGAFGRVYLCYDADTGRELAVKQVqfdpeSPETSKEVNALECEIQLLKNL-LHERIVQYYGCLRD-----PQE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 727 IAVLLIMERLHR-DLYTGLKAGLALETRL--QIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd06652    79 RTLSIFMEYMPGgSIKDQLKSYGALTENVtrKYTRQILEGVHYLHSNMIVHRDIKGANIL 138

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. 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 CDK4 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 1387212752 656 ELGRGQYGVVYLC-DSWGGHFpCALKSV-VPPDEkhwNDLAL----EFHYMRSL-----PKHERLVDLHGSVidysyGGG 724
Cdd:cd07863     7 EIGVGAYGTVYKArDPHSGHF-VALKSVrVQTNE---DGLPLstvrEVALLKRLeafdhPNIVRLMDVCATS-----RTD 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1387212752 725 SSIAVLLIMERLHRDLYTGLKA----GLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd07863    78 RETKVTLVFEHVDQDLRTYLDKvpppGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENIL 140

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 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 1387212752 657 LGRGQYGVVYLCDSWGGHFPCALKsVVPPDEKHWNDLALEFHYMRSLPKHERLVDLHGSVIDysygggSSIAVLLIMER- 735
Cdd:cd13987     1 LGEGTYGKVLLAVHKGSGTKMALK-FVPKPSTKLKDFLREYNISLELSVHPHIIKTYDVAFE------TEDYYVFAQEYa 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1387212752 736 LHRDLYTGLK--AGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd13987    74 PYGDLFSIIPpqVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVL 123

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1387212752 657 LGRGQYGVVYLcDSWGGHFPCALKSVVP----PDekhwnDLALEFHYMRSLpKHERLVDL------------------HG 714
Cdd:cd05034     3 LGAGQFGEVWM-GVWNGTTKVAVKTLKPgtmsPE-----AFLQEAQIMKKL-RHDKLVQLyavcsdeepiyivtelmsKG 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1387212752 715 SVIDYsygggssiavllimerlhrdLYTGLKAGLALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd05034    76 SLLDY--------------------LRTGEGRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNIL 124

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 1387212752 652 KLGQELGRGQYGVVYLCDSwggHFP---CALKSVVPPdEKHWND-LAL-EFHYMRSLPKHERLVDLHGSVIDYSYgggss 726
Cdd:cd07830     2 KVIKQLGDGTFGSVYLARN---KETgelVAIKKMKKK-FYSWEEcMNLrEVKSLRKLNEHPNIVKLKEVFRENDE----- 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1387212752 727 iaVLLIMERLHRDLYTGLKAG----LALETRLQIALDVVEGIRFLHSQGLVHRDVKLKNVL 783
Cdd:cd07830    73 --LYFVFEYMEGNLYQLMKDRkgkpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLL 131