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 66771527     5 ILKQGAEGRLYLGDFKGEACLIKERFVKKYRHPELNTQITRQRMKAEAKASGRCLAAGILAPKILHSDLNTHKLYMEYFD 84
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527    85 aAKTAKQFIQETvstqtedeakkcLLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINpkggDYDVILIDFGLSHYNQATE 164
Cdd:TIGR03724  81 -GKPLKDVIEEN------------GDELAREIGRLVGKLHKAGIVHGDLTTSNIIVR----DDKVYLIDFGLGKYSDEIE 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527   165 DKGVDLYVLERALLSTHSEQP-YIFEHVLAAYRTACGKDEqAVLTKFEEVRARGR 218
Cdd:TIGR03724 144 DKAVDLHVLKRSLESTHPDKAeELFEAFLEGYREVFGEAK-DVLERVKEIELRGR 197

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527     5 ILKQGAEGRLYLGDFKGEACLIKERFVKKYRHPELNTQITRQRMKAEAKASGRCLAAGILAPKILHSDLNTHKLYMEYFD 84
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527    85 aAKTAKQFIQETvstqtedeakkcLLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINpkggDYDVILIDFGLSHYNQATE 164
Cdd:TIGR03724  81 -GKPLKDVIEEN------------GDELAREIGRLVGKLHKAGIVHGDLTTSNIIVR----DDKVYLIDFGLGKYSDEIE 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527   165 DKGVDLYVLERALLSTHSEQP-YIFEHVLAAYRTACGKDEqAVLTKFEEVRARGR 218
Cdd:TIGR03724 144 DKAVDLHVLKRSLESTHPDKAeELFEAFLEGYREVFGEAK-DVLERVKEIELRGR 197

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527  46 QRMKAEAKASGRCLAAGILAPKILHSDLNTHKLYMEYFDAaKTAKQFIQETVSTQtedeakkcllEFCTRIGEIIGKMHS 125
Cdd:COG3642   1 ERTRREARLLRELREAGVPVPKVLDVDPDDADLVMEYIEG-ETLADLLEEGELPP----------ELLRELGRLLARLHR 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527 126 NHIIHGDLTTSNILINPKGgdydVILIDFGLSHYNQATEDKGVDLYVLERALLSTHSE-QPYIFEHVLAAYRTACGKDEq 204
Cdd:COG3642  70 AGIVHGDLTTSNILVDDGG----VYLIDFGLARYSDPLEDKAVDLAVLKRSLESTHPDpAEELWEAFLEGYREVGPAEE- 144

                       170
                ....*....|....
gi 66771527 205 aVLTKFEEVRARGR 218
Cdd:COG3642 145 -VLRRLREIELRGR 157

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 66771527    101 TEDEAKKCLLEfctrIGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLS 157
Cdd:smart00220  95 SEDEARFYLRQ----ILSALEYLHSKGIVHRDLKPENILLDEDG---HVKLADFGLA 144

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527     5 ILKQGAEGRLYLGDFKGEACLIKERFVKKYRHPELNTQITRQRMKAEAKASGRCLAAGILAPKILHSDLNTHKLYMEYFD 84
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527    85 aAKTAKQFIQETvstqtedeakkcLLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINpkggDYDVILIDFGLSHYNQATE 164
Cdd:TIGR03724  81 -GKPLKDVIEEN------------GDELAREIGRLVGKLHKAGIVHGDLTTSNIIVR----DDKVYLIDFGLGKYSDEIE 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527   165 DKGVDLYVLERALLSTHSEQP-YIFEHVLAAYRTACGKDEqAVLTKFEEVRARGR 218
Cdd:TIGR03724 144 DKAVDLHVLKRSLESTHPDKAeELFEAFLEGYREVFGEAK-DVLERVKEIELRGR 197

bifunctional N(6)-L-threonylcarbamoyladenine synthase/serine/threonine protein kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527    4 EILKQGAEGRLYLGDFKGEACLIKERFVKKYRHPELNTQITRQRMKAEAKASGRCLAAGILAPKILHSDLNTHKLYMEYF 83
Cdd:PRK09605 339 HLIGKGAEADIKKGEYLGRDAVIKERVPKGYRHPELDERLRTERTRAEARLLSEARRAGVPTPVIYDVDPEEKTIVMEYI 418

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527   84 DaAKTAKQFIQETvstqtedeakkclLEFCTRIGEIIGKMHSNHIIHGDLTTSNILInpkgGDYDVILIDFGLSHYNQAT 163
Cdd:PRK09605 419 G-GKDLKDVLEGN-------------PELVRKVGEIVAKLHKAGIVHGDLTTSNFIV----RDDRLYLIDFGLGKYSDLI 480

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527  164 EDKGVDLYVLERALLSTHSEQPYIFEHVLAAYRTACGKDEqaVLTKFEEVRARGR 218
Cdd:PRK09605 481 EDKAVDLHVLKQSLESTHYDFEELWEAFLEGYRETEGAED--VLERLKEIEKRGR 533

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527   3 LEILKQGAEGRLYLG--DFKGEACLIKErfvkkYRHPELNTQITRQRMKAEAKASGRCLAAGIlaPKILHSDLNTHKLY- 79
Cdd:COG0515  12 LRLLGRGGMGVVYLArdLRLGRPVALKV-----LRPELAADPEARERFRREARALARLNHPNI--VRVYDVGEEDGRPYl 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 66771527  80 -MEYFDAaKTAKQFIQETvSTQTEDEAkkclLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLS 157
Cdd:COG0515  85 vMEYVEG-ESLADLLRRR-GPLPPAEA----LRILAQLAEALAAAHAAGIVHRDIKPANILLTPDG---RVKLIDFGIA 154

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 66771527   3 LEILKQGAEGRLYLG-DFKGEaclikeRFV--KKYRHPELNTQITRQRMKAEAKASGRCLAAGIlaPKILHSDLNTHKLY 79
Cdd:cd14014   5 VRLLGRGGMGEVYRArDTLLG------RPVaiKVLRPELAEDEEFRERFLREARALARLSHPNI--VRVYDVGEDDGRPY 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527  80 --MEYFDAaKTAKQFIQEtVSTQTEDEAkkclLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINPKGGdydVILIDFGLS 157
Cdd:cd14014  77 ivMEYVEG-GSLADLLRE-RGPLPPREA----LRILAQIADALAAAHRAGIVHRDIKPANILLTEDGR---VKLTDFGIA 147

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527   6 LKQGAEGRLYLGDFKGEAcliKERFVKKYRhpeLNTQITRQRMKAEAKASGRCLAAGILAPKILHSDLNT--HKLYMEYF 83
Cdd:cd13968   1 MGEGASAKVFWAEGECTT---IGVAVKIGD---DVNNEEGEDLESEMDILRRLKGLELNIPKVLVTEDVDgpNILLMELV 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 66771527  84 DAAkTAKQFIQETVSTQTEDEAkkclleFCTRIGEIIGKMHSNHIIHGDLTTSNILINPkggDYDVILIDFG 155
Cdd:cd13968  75 KGG-TLIAYTQEEELDEKDVES------IMYQLAECMRLLHSFHLIHRDLNNDNILLSE---DGNVKLIDFG 136

RIO-like serine/threonine protein kinase fused to N-terminal HTH domain [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527  29 RFVKKYR-----HPELNTqiTRQRMKAEAKASGRCLAAGILAPKILhsDLNTHKLYMEYFDAaktakqfiqetvstqteD 103
Cdd:COG0478  24 RKVRRERadkehYSWLYA--ARTRAEREFRALERLYPAGLPVPRPI--AANRHAIVMERIEG-----------------V 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527 104 EAKKCLLE----FCTRIGEIIGKMHSNHIIHGDLTTSNILINPKGGdydVILIDF 154
Cdd:COG0478  83 ELARLKLEdpeeVLDKILEEIRRAHDAGIVHADLSEYNILVDDDGG---VWIIDW 134

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 66771527  80 MEYFDAAkTAKQFIQETVSTQTEDEAK---KCLLEFCTRIgeiigkmHSNHIIHGDLTTSNILINPKGgdyDVILIDFGL 156
Cdd:cd05122  76 MEFCSGG-SLKDLLKNTNKTLTEQQIAyvcKEVLKGLEYL-------HSHGIIHRDIKAANILLTSDG---EVKLIDFGL 144

                .
gi 66771527 157 S 157
Cdd:cd05122 145 S 145

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK 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 66771527   3 LEILKQGAEGRLYLGDFKGEACLIKerfVKKYRHPELNTQITRQRMkaEAKAsgrclAAGILAPKILH-----SDLNTHK 77
Cdd:cd13996  11 IELLGSGGFGSVYKVRNKVDGVTYA---IKKIRLTEKSSASEKVLR--EVKA-----LAKLNHPNIVRyytawVEEPPLY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527  78 LYMEYFDAaKTAKQFIQEtvSTQTEDEAKKCLLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINPkggDYDVILI-DFGL 156
Cdd:cd13996  81 IQMELCEG-GTLRDWIDR--RNSSSKNDRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLDN---DDLQVKIgDFGL 154

                .
gi 66771527 157 S 157
Cdd:cd13996 155 A 155

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 66771527 101 TEDEAKKclleFCTRIGEIIGKMHSNHIIHGDLTTSNILINpkgGDYDVILIDFGLS 157
Cdd:cd14003  97 SEDEARR----FFQQLISAVDYCHSNGIVHRDLKLENILLD---KNGNLKIIDFGLS 146

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
                ....*....|....*....|....*....|....*
gi 66771527 123 MHSNHIIHGDLTTSNILINPKGGdyDVILIDFGLS 157
Cdd:cd05118 117 LHSNGIIHRDLKPENILINLELG--QLKLADFGLA 149

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 66771527 112 FCTRIGEIIGKMHSNHIIHGDLTTSNILI-------NPKGGDYD-----VILIDFGLS 157
Cdd:cd13981 111 FTIELLKVVEALHEVGIIHGDIKPDNFLLrleicadWPGEGENGwlskgLKLIDFGRS 168

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like 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 66771527  49 KAEAKASGRCLAAGILAPK------ILH--SDLNT--HKLYMEYFDAAKTAKQ--FIQETVSTQ------------TEDE 104
Cdd:cd14006  11 RCIEKATGREFAAKFIPKRdkkkeaVLReiSILNQlqHPRIIQLHEAYESPTElvLILELCSGGelldrlaergslSEEE 90

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 66771527 105 AKkcllEFCTRIGEIIGKMHSNHIIHGDLTTSNILINPKgGDYDVILIDFGLSH 158
Cdd:cd14006  91 VR----TYMRQLLEGLQYLHNHHILHLDLKPENILLADR-PSPQIKIIDFGLAR 139

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK 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
                ....*....|....*....|....*....|....*....|.
gi 66771527 116 IGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVILIDFGL 156
Cdd:cd05575 105 IASALGYLHSLNIIYRDLKPENILLDSQG---HVVLTDFGL 142

ZnF_C4 abd HLH domain containing kinases domain; subfamily of choline kinases

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 66771527    109 LLEFCTRIGEIIGKMHsNHIIHGDLTTSNIL--INPKGGDYDVILIDFGLSHYNQATED 165
Cdd:smart00587 104 LEDLKKEDKEPDEGEF-NVLNHGDLWANNIMfkYDDEGKPEDVALIDFQLSHYGSPAED 161

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-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
                ....*....|....*....|....*....|....*
gi 66771527 123 MHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLS 157
Cdd:cd07829 114 CHSHRILHRDLKPQNLLINRDG---VLKLADFGLA 145

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 66771527  93 IQETVSTQTEDEAKKCLLEFCTRIGEIIGKMHSNHIIHGDLTTSNILINPKGGDyDVILIDFGLSH 158
Cdd:cd14122 113 LQKIYEANAKRFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSYKNPD-QVYLVDYGLAY 177

Euykaryotic Choline Kinase and similar proteins; This group is composed of eukaryotic choline kinase, ethanolamine kinase, and similar proteins. ChoK catalyzes the transfer of the gamma-phosphoryl group from ATP (or CTP) to its substrate, choline, producing phosphorylcholine (PCho), a precursor to the biosynthesis of two major membrane phospholipids, phosphatidylcholine (PC), and sphingomyelin (SM). Although choline is the preferred substrate, ChoK also shows substantial activity towards ethanolamine and its N-methylated derivatives. ETNK catalyzes the transfer of the gamma-phosphoryl group from CTP to ethanolamine (Etn), the first step in the CDP-Etn pathway for the formation of the major phospholipid, phosphatidylethanolamine (PtdEtn). Unlike ChoK, ETNK shows specific activity for its substrate and displays negligible activity towards N-methylated derivatives of Etn. ChoK plays an important role in cell signaling pathways and the regulation of cell growth. The ChoK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases, such as the typical serine/threonine/tyrosine protein kinases (PKs), RIO kinases, actin-fragmin kinase (AFK), and phosphoinositide 3-kinase (PI3K).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527 110 LEFCTRIGEIIGKMHSNHII-----HGDLTTSNILINPKggDYDVILIDFGLSHYNQAtedkGVDL--YVLERALLSTHS 182
Cdd:cd14021  91 PSVLTSIAKLLAKFHKIKTPpvvfcHNDLQENNILLTND--QDGLRLIDFEYSGFNYR----GYDIanFFNESMIDYDHP 164

                ....*..
gi 66771527 183 EQPYIFE 189
Cdd:cd14021 165 EPPYFKI 171

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 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 66771527  66 PKI--LHSDLNTHK---LYMEY------FDAAKTAKQFiqetvstqTEDEAKKCLLEFCtrigEIIGKMHSNHIIHGDLT 134
Cdd:cd14185  58 PNIvkLFEVYETEKeiyLILEYvrggdlFDAIIESVKF--------TEHDAALMIIDLC----EALVYIHSKHIVHRDLK 125

                        90       100
                ....*....|....*....|....*..
gi 66771527 135 TSNILI--NPKGGDyDVILIDFGLSHY 159
Cdd:cd14185 126 PENLLVqhNPDKST-TLKLADFGLAKY 151

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). 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 CDC2L1 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
                ....*....|....*....|....*....|....
gi 66771527 123 MHSNHIIHGDLTTSNILINPKGgdyDVILIDFGL 156
Cdd:cd07843 122 LHDNWILHRDLKTSNLLLNNRG---ILKICDFGL 152

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; 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 the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. 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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66771527 115 RIGE-IIGK-----------MHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLS 157
Cdd:cd06621 101 RIGEkVLGKiaesvlkglsyLHSRKIIHRDIKPSNILLTRKG---QVKLCDFGVS 152

Lipopolysaccharide kinase (Kdo/WaaP) family; These lipopolysaccharide kinases are related to protein kinases pfam00069. This family includes waaP (rfaP) gene product is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region. It has previously been shown that WaaP is necessary for resistance to hydrophobic and polycationic antimicrobials in E. coli and that it is required for virulence in invasive strains of S. enterica.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527    34 YRHPELNTqitrqRMKAEAKASGRCLAAGILAPKIL-----------HSDLNTHKLymeyfDAAKTAKQFIQEtvSTQTE 102
Cdd:pfam06293  48 YRYPLGRT-----RAFREFRLIRRLREAGLPVPKPVaagevkvgggyRADLLTERL-----EGAQSLADWLAD--WAVPS 115

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 66771527   103 DEAKKCLLEfctRIGEIIGKMHSNHIIHGDLTTSNILINPKGGD-YDVILIDFGLS-HYNQATEDKGVDLYVLERALLS 179
Cdd:pfam06293 116 GELRRAIWE---AVGRLIRQMHRAGVQHGDLYAHHILLQQEGDEgFEAWLIDLDKGrLRLPARRWRNKDLARLLRSFLN 191

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 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 66771527  69 LHSDLNTHKLYMEYFDAAKTAKQF--IQETVsTQTEDEAKKCLLEFCtrigEIIGKMHSNHIIHGDLTTSNILINpkgGD 146
Cdd:cd14182  75 LKDTYETNTFFFLVFDLMKKGELFdyLTEKV-TLSEKETRKIMRALL----EVICALHKLNIVHRDLKPENILLD---DD 146

                        90
                ....*....|.
gi 66771527 147 YDVILIDFGLS 157
Cdd:cd14182 147 MNIKLTDFGFS 157

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 66771527 101 TEDEAKKCLLEfctrIGEIIGKMHSNHIIHGDLTTSNILINPKGGDYDVILIDFGLSHYNQATED 165
Cdd:cd14106 106 TEADVRRLMRQ----ILEGVQYLHERNIVHLDLKPQNILLTSEFPLGDIKLCDFGISRVIGEGEE 166

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK 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 66771527  49 KAEAKASGRCLAAGILapKILHSD--------------LNTHKLYMEYfDAAKTAKQF--IQETVS-------------T 99
Cdd:cd14103  11 RCVEKATGKELAAKFI--KCRKAKdredvrneieimnqLRHPRLLQLY-DAFETPREMvlVMEYVAggelfervvdddfE 87

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 66771527 100 QTEdeaKKCLLeFCTRIGEIIGKMHSNHIIHGDLTTSNIL-INPKGgdYDVILIDFGLS-HYN 160
Cdd:cd14103  88 LTE---RDCIL-FMRQICEGVQYMHKQGILHLDLKPENILcVSRTG--NQIKIIDFGLArKYD 144

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK 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 66771527 113 CTRIGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLSHYNQATEDK-----GVDLYVL-ERALLSTHSEQPY 186
Cdd:cd06643 109 CKQTLEALVYLHENKIIHRDLKAGNILFTLDG---DIKLADFGVSAKNTRTLQRrdsfiGTPYWMApEVVMCETSKDRPY 185

                ...
gi 66771527 187 IFE 189
Cdd:cd06643 186 DYK 188

C-terminal catalytic domain of the atypical protein serine kinase, RIO2 kinase; RIO2 is present in archaea and eukaryotes. It contains an N-terminal winged helix (wHTH) domain and a C-terminal RIO kinase catalytic domain. The wHTH domain is primarily seen in DNA-binding proteins, although some wHTH domains may be involved in RNA recognition. RIO2 is essential for survival and is necessary for rRNA cleavage during 40S ribosomal subunit maturation. RIO kinases are atypical protein serine kinases containing a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. The RIO2 kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66771527  72 DLNTHKLYMEYFDAAKTAKqfiqetvSTQTEDEAKkcLLEfctRIGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVIL 151
Cdd:cd05144  87 DWNRHAVVMELIDGYPLYQ-------VRLLEDPEE--VLD---EILELIVKLAKHGLIHGDFSEFNILVDEDE---KITV 151

                        90
                ....*....|...
gi 66771527 152 IDF----GLSHYN 160
Cdd:cd05144 152 IDFpqmvSTSHPN 164

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. 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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 66771527 115 RIGE-IIGKM-----------HSNH-IIHGDLTTSNILINPKGgdyDVILIDFGLS 157
Cdd:cd06605  95 RIPErILGKIavavvkgliylHEKHkIIHRDVKPSNILVNSRG---QVKLCDFGVS 147

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 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
                ....*....|....*....|....*....|....*....|....*....|....
gi 66771527 113 CTRIGEIIGKMHSNHIIHGDLTTSNILINPKGgdyDVILIDFGLSHYNQATEDK 166
Cdd:cd06644 116 CRQMLEALQYLHSMKIIHRDLKAGNVLLTLDG---DIKLADFGVSAKNVKTLQR 166

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase 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
                ....*....|....*....|....*....|....*....|....
gi 66771527 123 MHSNHIIHGDLTTSNILINPKGGDYdvILIDFGLShynQATEDK 166
Cdd:cd14019 117 VHSFGIIHRDVKPGNFLYNRETGKG--VLVDFGLA---QREEDR 155