Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site Cys residue is not present in this CD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 708 LCELTVTGHFKTPSKKtksskpkLLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGH 787
Cdd:cd01525     1 ISVYDVIRLLDNSPAK-------LAAVDIRSSPDFRRGHIEGSINIPFSSVFLKEGELEQLPTVPRLENYKGKIIVIVSH 73

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1677530150 788 VAKHTAEFAAHLVKMKYPRICILDGGINKIKP 819
Cdd:cd01525    74 SHKHAALFAAFLVKCGVPRVCILDGGINALKP 105

Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site Cys residue is not present in this CD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 708 LCELTVTGHFKTPSKKtksskpkLLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGH 787
Cdd:cd01525     1 ISVYDVIRLLDNSPAK-------LAAVDIRSSPDFRRGHIEGSINIPFSSVFLKEGELEQLPTVPRLENYKGKIIVIVSH 73

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1677530150 788 VAKHTAEFAAHLVKMKYPRICILDGGINKIKP 819
Cdd:cd01525    74 SHKHAALFAAFLVKCGVPRVCILDGGINALKP 105

GTPase-activating protein [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 235 DLTLPEDI--SQLCKDINNDYLAERSIEEVYYLWCLAGG----DLEKELVNKEIIRSKPPICTLPNFLFEDGESFGQGRD 308
Cdd:COG5210    28 EFSSPTSSgsAADISISVNESSEEKSVSLLSSPNEEPGSflnnDLDKSSFNEELPTLLETADRSSSPGNESLSAVVSNFG 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 309 RSSLLDDTTVTLSlcQLRNRLKDvggeaFYPLLEDDQSNLP---HSNSNNE-LSAAATLPLIIREKDT--------EYQL 376
Cdd:COG5210   108 LNNKSLKSQSTSP--ELPKRLKD-----SLPTHLPEASSTEkdfSSFKGSSsLNSNPELNKEINELSLkeepqklrYYEL 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 377 NRIILFDRLLK-----AYPYKKNQIWKEARVDIPPLMRGLTWAALLGVEG---AIHAKYDAI---DKDTPIPT---DRQI 442
Cdd:COG5210   181 AADKLWISYLDpnplsFLPVQLSKLRELIRKGIPNELRGDVWEFLLGIGFdldKNPGLYERLlnlHREAKIPTqeiISQI 260

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 443 EVDIPRCHQYDELLSSPEGH--AKFRRVLKAWVVSHPDLVYWQGLDSLCAPFLYlNFNNEALAYACMSAFI-PKYLYNFF 519
Cdd:COG5210   261 EKDLSRTFPDNSLFQTEISIraENLRRVLKAYSLYNPEVGYVQGMNFLAAPLLL-VLESEEQAFWCLVKLLkNYGLPGYF 339

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 520 LKdNSHVIQEYLTVFSQMIAFHDPELSNHLNEIGFIPDLYAIPWFLTMFTHVFPLHKIFHLWDTLLLGNSSFPFCIGVAI 599
Cdd:COG5210   340 LK-NLSGLHRDLKVLDDLVEELDPELYEHLLREGVVLLMFAFRWFLTLFVREFPLEYALRIWDCLFLEGSSMLFQLALAI 418

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|
gi 1677530150 600 LQQLRDRLL-ANGFNECILLFSDLPEIDIERCVRESINLF 638
Cdd:COG5210   419 LKLLRDKLLkLDSDELLDLLLKQLFLHSGKEAWSSILKFR 458

Rhodanese-like domain; Rhodanese has an internal duplication. This Pfam represents a single copy of this duplicated domain. The domain is found as a single copy in other proteins, including phosphatases and ubiquitin C-terminal hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 731 LLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPyTAMLQNFKGKVIVIVGHVAKHTAEFAAHLVKMKYPRICIL 810
Cdd:pfam00581   6 VVLIDVRPPEEYAKGHIPGAVNVPLSSLSLPPLPLLELL-EKLLELLKDKPIVVYCNSGNRAAAAAALLKALGYKNVYVL 84

                  ....*...
gi 1677530150 811 DGGINKIK 818
Cdd:pfam00581  85 DGGFEAWK 92

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 1677530150  91 PSYLAPEVIAQGifkttdhmpskkplPSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDdtlivlaeeh 170
Cdd:cd05122   161 PYWMAPEVIQGK--------------PYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPG---------- 216

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1677530150 171 gcLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKDK 208
Cdd:cd05122   217 --LRNPKKWSKEFKDFLKKCLQKDPEKRPTAEQLLKHP 252

Rhodanese-related sulfurtransferase [Inorganic ion transport and metabolism]; Rhodanese-related sulfurtransferase is part of the Pathway/BioSystem: Urea cycle

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 732 LVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTqgpytamlqnfKGKVIVIVGHVAKHTAEFAAHLVKMKYPRICILD 811
Cdd:COG0607    21 VLLDVREPEEFAAGHIPGAINIPLGELAERLDELP-----------KDKPIVVYCASGGRSAQAAALLRRAGYTNVYNLA 89

                          90
                  ....*....|....*.
gi 1677530150 812 GGINKIKPTGLLTIPS 827
Cdd:COG0607    90 GGIEAWKAAGLPVEKG 105

NIMA-related protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  91 PSYLAPEVIAQGIFkttdhmpSKKplpsgpkSDVWSLGIILFELCVGRKLFQSLDISERLKFLLtldcvddtlivlaeeH 170
Cdd:PTZ00267  235 PYYLAPELWERKRY-------SKK-------ADMWSLGVILYELLTLHRPFKGPSQREIMQQVL---------------Y 285

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 171 GCLDIIK-ELPETVIDLLNKCLTFHPSKRPTPDQLmkdkvfsevspLYTPFTK-PASLFSSSLRCADLTLPEDISQLCKD 248
Cdd:PTZ00267  286 GKYDPFPcPVSSGMKALLDPLLSKNPALRPTTQQL-----------LHTEFLKyVANLFQDIVRHSETISPHDREEILRQ 354

                  .
gi 1677530150 249 I 249
Cdd:PTZ00267  355 L 355

Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site Cys residue is not present in this CD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 708 LCELTVTGHFKTPSKKtksskpkLLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGH 787
Cdd:cd01525     1 ISVYDVIRLLDNSPAK-------LAAVDIRSSPDFRRGHIEGSINIPFSSVFLKEGELEQLPTVPRLENYKGKIIVIVSH 73

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1677530150 788 VAKHTAEFAAHLVKMKYPRICILDGGINKIKP 819
Cdd:cd01525    74 SHKHAALFAAFLVKCGVPRVCILDGGINALKP 105

GTPase-activating protein [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 235 DLTLPEDI--SQLCKDINNDYLAERSIEEVYYLWCLAGG----DLEKELVNKEIIRSKPPICTLPNFLFEDGESFGQGRD 308
Cdd:COG5210    28 EFSSPTSSgsAADISISVNESSEEKSVSLLSSPNEEPGSflnnDLDKSSFNEELPTLLETADRSSSPGNESLSAVVSNFG 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 309 RSSLLDDTTVTLSlcQLRNRLKDvggeaFYPLLEDDQSNLP---HSNSNNE-LSAAATLPLIIREKDT--------EYQL 376
Cdd:COG5210   108 LNNKSLKSQSTSP--ELPKRLKD-----SLPTHLPEASSTEkdfSSFKGSSsLNSNPELNKEINELSLkeepqklrYYEL 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 377 NRIILFDRLLK-----AYPYKKNQIWKEARVDIPPLMRGLTWAALLGVEG---AIHAKYDAI---DKDTPIPT---DRQI 442
Cdd:COG5210   181 AADKLWISYLDpnplsFLPVQLSKLRELIRKGIPNELRGDVWEFLLGIGFdldKNPGLYERLlnlHREAKIPTqeiISQI 260

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 443 EVDIPRCHQYDELLSSPEGH--AKFRRVLKAWVVSHPDLVYWQGLDSLCAPFLYlNFNNEALAYACMSAFI-PKYLYNFF 519
Cdd:COG5210   261 EKDLSRTFPDNSLFQTEISIraENLRRVLKAYSLYNPEVGYVQGMNFLAAPLLL-VLESEEQAFWCLVKLLkNYGLPGYF 339

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 520 LKdNSHVIQEYLTVFSQMIAFHDPELSNHLNEIGFIPDLYAIPWFLTMFTHVFPLHKIFHLWDTLLLGNSSFPFCIGVAI 599
Cdd:COG5210   340 LK-NLSGLHRDLKVLDDLVEELDPELYEHLLREGVVLLMFAFRWFLTLFVREFPLEYALRIWDCLFLEGSSMLFQLALAI 418

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|
gi 1677530150 600 LQQLRDRLL-ANGFNECILLFSDLPEIDIERCVRESINLF 638
Cdd:COG5210   419 LKLLRDKLLkLDSDELLDLLLKQLFLHSGKEAWSSILKFR 458

Rhodanese-like domain; Rhodanese has an internal duplication. This Pfam represents a single copy of this duplicated domain. The domain is found as a single copy in other proteins, including phosphatases and ubiquitin C-terminal hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 731 LLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPyTAMLQNFKGKVIVIVGHVAKHTAEFAAHLVKMKYPRICIL 810
Cdd:pfam00581   6 VVLIDVRPPEEYAKGHIPGAVNVPLSSLSLPPLPLLELL-EKLLELLKDKPIVVYCNSGNRAAAAAALLKALGYKNVYVL 84

                  ....*...
gi 1677530150 811 DGGINKIK 818
Cdd:pfam00581  85 DGGFEAWK 92

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 1677530150  91 PSYLAPEVIAQGifkttdhmpskkplPSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDdtlivlaeeh 170
Cdd:cd05122   161 PYWMAPEVIQGK--------------PYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPG---------- 216

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1677530150 171 gcLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKDK 208
Cdd:cd05122   217 --LRNPKKWSKEFKDFLKKCLQKDPEKRPTAEQLLKHP 252

Rhodanese Homology Domain; An alpha beta fold found duplicated in the Rhodanese protein. The the Cysteine containing enzymatically active version of the domain is also found in the CDC25 class of protein phosphatases and a variety of proteins such as sulfide dehydrogenases and stress proteins such as Senesence specific protein 1 in plants, PspE and GlpE in bacteria and cyanide and arsenate resistance proteins. Inactive versions with a loss of the cysteine are also seen in Dual specificity phosphatases, ubiquitin hydrolases from yeast and in sulfuryltransferases. These are likely to play a role in protein interactions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  731 LLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPYTAMLQN---FKGKVIVIVGHVAKHTAEFAAHLVKMKYPRI 807
Cdd:smart00450   5 VVLLDVRSPEEYEGGHIPGAVNIPLSELLDRRGELDILEFEELLKRlglDKDKPVVVYCRSGNRSAKAAWLLRELGFKNV 84

                   ....*....
gi 1677530150  808 CILDGGINK 816
Cdd:smart00450  85 YLLDGGYKE 93

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 1677530150  91 PSYLAPEVIAQGifkttdhmpskkplPSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDtlivlaeeh 170
Cdd:cd14014   165 PAYMAPEQARGG--------------PVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPPP--------- 221

                          90       100       110
                  ....*....|....*....|....*....|
gi 1677530150 171 gcLDIIKELPETVIDLLNKCLTFHPSKRPT 200
Cdd:cd14014   222 --SPLNPDVPPALDAIILRALAKDPEERPQ 249

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  91 PSYLAPEVIaQGIfkttdhmpskkplPSGPKSDVWSLGIILFELCVGRKLFQSldiserlkflltldcvdDTLIVLaeeh 170
Cdd:cd08215   167 PYYLSPELC-ENK-------------PYNYKSDIWALGCVLYELCTLKHPFEA-----------------NNLPAL---- 211

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1677530150 171 gCLDIIKE----LPET----VIDLLNKCLTFHPSKRPTPDQLMK 206
Cdd:cd08215   212 -VYKIVKGqyppIPSQysseLRDLVNSMLQKDPEKRPSANEILS 254

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  91 PSYLAPEVIaqgiFKTTDHmpskkplpsGPKSDVWSLGIILFELCVGRKLFQSLDISErlkfllTLDCVDDTLIVLAEEh 170
Cdd:cd14099   165 PNYIAPEVL----EKKKGH---------SFEVDIWSLGVILYTLLVGKPPFETSDVKE------TYKRIKKNEYSFPSH- 224

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1677530150 171 gcldiiKELPETVIDLLNKCLTFHPSKRPTPDQLMKDKVF 210
Cdd:cd14099   225 ------LSISDEAKDLIRSMLQPDPTKRPSLDEILSHPFF 258

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 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 1677530150  91 PSYLAPEVIAQgifkTTDHMPSKKPLPSGPKSDVWSLGIILFELCVGRKLFQSL-DISERLKFLltldcVDDTLIVLAEE 169
Cdd:cd14131   168 LNYMSPEAIKD----TSASGEGKPKSKIGRPSDVWSLGCILYQMVYGKTPFQHItNPIAKLQAI-----IDPNHEIEFPD 238

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1677530150 170 HGcldiikelPETVIDLLNKCLTFHPSKRPTPDQLM 205
Cdd:cd14131   239 IP--------NPDLIDVMKRCLQRDPKKRPSIPELL 266

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  92 SYLAPEVIaqgifkttdhmpskKPLPSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDC-VDDTLIVLAEEh 170
Cdd:cd06605   163 SYMAPERI--------------SGGKYTVKSDIWSLGLSLVELATGRFPYPPPNAKPSMMIFELLSYiVDEPPPLLPSG- 227

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1677530150 171 gcldiikELPETVIDLLNKCLTFHPSKRPTPDQLMK 206
Cdd:cd06605   228 -------KFSPDFQDFVSQCLQKDPTERPSYKELME 256

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 1677530150  87 PVRYpsyLAPEVIAQGIFkTTdhmpskkplpsgpKSDVWSLGIILFELCV-GRKLFQSLDISERLKFLltldcvddtliv 165
Cdd:cd00192   170 PIRW---MAPESLKDGIF-TS-------------KSDVWSFGVLLWEIFTlGATPYPGLSNEEVLEYL------------ 220

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1677530150 166 laEEHGCLDIIKELPETVIDLLNKCLTFHPSKRPTPDQL 204
Cdd:cd00192   221 --RKGYRLPKPENCPDELYELMLSCWQLDPEDRPTFSEL 257

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  91 PSYLAPEVIaqgifkttdhmpSKKPLpSGPKSDVWSLGIILFELCVGRklfqsldiserlkflLTLDcvDDTLIVLAEE- 169
Cdd:cd14081   164 PHYACPEVI------------KGEKY-DGRKADIWSCGVILYALLVGA---------------LPFD--DDNLRQLLEKv 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1677530150 170 -HGCLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKDKVF 210
Cdd:cd14081   214 kRGVFHIPHFISPDAQDLLRRMLEVNPEKRITIEEIKKHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  91 PSYLAPEVIAQGIFkttdhmpskkplpsGPKSDVWSLGIILFELCVGRKLFQSLDiserlkflltlDCVDDTL-IVLAEE 169
Cdd:cd06606   165 PYWMAPEVIRGEGY--------------GRAADIWSLGCTVIEMATGKPPWSELG-----------NPVAALFkIGSSGE 219

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1677530150 170 HgcLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKD 207
Cdd:cd06606   220 P--PPIPEHLSEEAKDFLRKCLQRDPKKRPTADELLQH 255

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  42 FQILKTITHPRLCQYVDISRgKHERLVVVAEHCER-SLEDLLRERKPVRYPSY------------------------LAP 96
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFE-TENFLYLVMEYCEGgSLKDLLKENKGPLSEEEalsilrqllsaleylhsngiihrdLKP 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  97 E---VIAQGIFKTTD-----HMPSKKPLPS---------------------GPKSDVWSLGIILFELcvgrklfqsldis 147
Cdd:cd00180   121 EnilLDSDGTVKLADfglakDLDSDDSLLKttggttppyyappellggryyGPKVDIWSLGVILYEL------------- 187

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150 148 erlkflltldcvddtlivlaeehgcldiikelpETVIDLLNKCLTFHPSKRPTPDQLMKD 207
Cdd:cd00180   188 ---------------------------------EELKDLIRRMLQYDPKKRPSAKELLEH 214

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530150  89 RYpsYLAPEVIaqgiFKTTDHmpskkplpsGPKSDVWSLGIILFELCVGRKLFQSLDISERL----KFLLTlDCVDDtli 164
Cdd:cd14137   170 RY--YRAPELI----FGATDY---------TTAIDIWSAGCVLAELLLGQPLFPGESSVDQLveiiKVLGT-PTREQ--- 230

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1677530150 165 VLAEEHGC----LDIIKELPETV----------IDLLNKCLTFHPSKRPTPDQLMKDKVFSEV 213
Cdd:cd14137   231 IKAMNPNYtefkFPQIKPHPWEKvfpkrtppdaIDLLSKILVYNPSKRLTALEALAHPFFDEL 293

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC 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 1677530150  91 PSYLAPEVIAQGifkttDHmpskkplpsGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDcvddtlivlaeeh 170
Cdd:cd05123   157 PEYLAPEVLLGK-----GY---------GKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSP------------- 209

                          90       100
                  ....*....|....*....|....*...
gi 1677530150 171 gcLDIIKELPETVIDLLNKCLTFHPSKR 198
Cdd:cd05123   210 --LKFPEYVSPEAKSLISGLLQKDPTKR 235