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 767984714 164 QDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEF 243
Cdd:cd06619    1 QDIQYQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEF 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 767984714 244 MDGGSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06619   81 MDGGSLDVYRKIPEHVLGRIAVAVVKGLTYLWSLKILHR 119

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 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 767984714 164 QDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEF 243
Cdd:cd06619    1 QDIQYQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEF 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 767984714 244 MDGGSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06619   81 MDGGSLDVYRKIPEHVLGRIAVAVVKGLTYLWSLKILHR 119

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714   170 DTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSL 249
Cdd:smart00220   5 EKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDL 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 767984714   250 ----DVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHRankDL 287
Cdd:smart00220  85 fdllKKRGRLSEDEARFYLRQILSALEYLHSKGIVHR---DL 123

mitogen-activated protein kinase kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714  99 IEPLQifPRACKPPGERNIHGLKVNTRAGPS-----QHSSPAVSDSLP-------SNSLKKSSAELKKILANGQMNEQDi 166
Cdd:PLN00034   1 MKPIQ--PPPGVPLPSTARHTTKSRPRRRPDltlplPQRDPSLAVPLPlpppsssSSSSSSSSASGSAPSAAKSLSELE- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714 167 RYRdTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDG 246
Cdd:PLN00034  78 RVN-RIGSGAGGTVYKVIHRPTGRLYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDG 156

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 767984714 247 GSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:PLN00034 157 GSLEGTHIADEQFLADVARQILSGIAYLHRRHIVHR 192

PB1 domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767984714   19 IRIKIPNSGAVDWTVHSGPQLLFRDVLDVIGQVLPEAT-TTAFEYEDEDGDRITVRSDEEMKAMLSYYYSTVMEQ 92
Cdd:pfam00564   2 VRLKLRYGGGIRRFLSVSRGISFEELRALVEQRFGLDDvDFKLKYPDEDGDLVSLTSDEDLEEALEEARSLGSKS 76

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 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 767984714 164 QDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEF 243
Cdd:cd06619    1 QDIQYQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEF 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 767984714 244 MDGGSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06619   81 MDGGSLDVYRKIPEHVLGRIAVAVVKGLTYLWSLKILHR 119

PB1 domain is essential part of the mitogen-activated protein kinase kinase 5 (Map2k5, alias MEK5) one of the key member of the signaling kinases cascade which involved in angiogenesis and early cardiovascular development. The PB1 domain of Map2k5 interacts with the PB1 domain of another members of kinase cascade MEKK2 (or MEKK3). A canonical PB1-PB1 interaction, involving heterodimerization of two PB1 domain, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. The Map2k5 protein contains a type I PB1 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714  17 LVIRIKIPNSGAVDWTVHSGPQLLFRDVLDVIGQVLPEATTTAFEYEDEDGDRITVRSDEEMKAMLSYYYSTVMEQQVNG 96
Cdd:cd06395    1 LVIRIKIPNGGAVDWTVQSGPQLLFRDVLDVIGQVLPEATTTAFEYEDEDGDRITVRSDEEMKAMLSYYCSTVMEQQVNG 80

                         90
                 ....*....|.
gi 767984714  97 QLIEPLQIFPR 107
Cdd:cd06395   81 QLIEPLQIFPR 91

Catalytic domain of fungal Byr1-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 Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 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 767984714 161 MNEQDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVE-NRISI 239
Cdd:cd06620    2 LKNQDLETLKDLGAGNGGSVSKVLHIPTGTIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAFLNEnNNIII 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767984714 240 CTEFMDGGSLD-VYRK---MPEHVLGRIAVAVVKGLTYLWS-LKILHR 282
Cdd:cd06620   82 CMEYMDCGSLDkILKKkgpFPEEVLGKIAVAVLEGLTYLYNvHRIIHR 129

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK 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 767984714 160 QMNEQDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISI 239
Cdd:cd06650    1 ELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767984714 240 CTEFMDGGSLD-VYRK---MPEHVLGRIAVAVVKGLTYLWSL-KILHR 282
Cdd:cd06650   81 CMEHMDGGSLDqVLKKagrIPEQILGKVSIAVIKGLTYLREKhKIMHR 128

Catalytic domain of fungal PBS2-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 Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714 165 DIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFM 244
Cdd:cd06622    2 EIEVLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYM 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767984714 245 DGGSLD-------VYRKMPEHVLGRIAVAVVKGLTYLW-SLKILHR 282
Cdd:cd06622   82 DAGSLDklyaggvATEGIPEDVLRRITYAVVKGLKFLKeEHNIIHR 127

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 767984714 167 RYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDiTLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDG 246
Cdd:cd05122    3 EILEKIGKGGFGVVYKARHKKTGQIVAIKKINLE-SKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 767984714 247 GSL-DVY----RKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd05122   82 GSLkDLLkntnKTLTEQQIAYVCKEVLKGLEYLHSHGIIHR 122

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 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 767984714 165 DIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEI-LYKCDSSYIIGFYGAFFVENRISICTEF 243
Cdd:cd06617    2 DLEVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICMEV 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 767984714 244 MDgGSLD-VYRK-------MPEHVLGRIAVAVVKGLTYLWS-LKILHR 282
Cdd:cd06617   82 MD-TSLDkFYKKvydkgltIPEDILGKIAVSIVKALEYLHSkLSVIHR 128

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 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 767984714 172 LGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKC-DSSYIIGFYGAFFVENRISICTEFMDgGSLD 250
Cdd:cd06616   14 IGRGAFGTVNKMLHKPSGTIMAVKRIRSTVDEKEQKRLLMDLDVVMRSsDCPYIVKFYGALFREGDCWICMELMD-ISLD 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767984714 251 -----VY----RKMPEHVLGRIAVAVVKGLTYL-WSLKILHR 282
Cdd:cd06616   93 kfykyVYevldSVIPEEILGKIAVATVKALNYLkEELKIIHR 134

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 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 767984714 163 EQDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLElqkQIMSELEILYKCDSSYIIGFYGAFFVENRISICTE 242
Cdd:cd06612    2 EEVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQ---EIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVME 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 767984714 243 FMDGGSLDVYRKMPEHVLG--RIAV---AVVKGLTYLWSLKILHR 282
Cdd:cd06612   79 YCGAGSVSDIMKITNKTLTeeEIAAilyQTLKGLEYLHSNKKIHR 123

mitogen-activated protein kinase kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714  99 IEPLQifPRACKPPGERNIHGLKVNTRAGPS-----QHSSPAVSDSLP-------SNSLKKSSAELKKILANGQMNEQDi 166
Cdd:PLN00034   1 MKPIQ--PPPGVPLPSTARHTTKSRPRRRPDltlplPQRDPSLAVPLPlpppsssSSSSSSSSASGSAPSAAKSLSELE- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714 167 RYRdTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDG 246
Cdd:PLN00034  78 RVN-RIGSGAGGTVYKVIHRPTGRLYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDG 156

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 767984714 247 GSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:PLN00034 157 GSLEGTHIADEQFLADVARQILSGIAYLHRRHIVHR 192

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 767984714 165 DIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLD-ITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEF 243
Cdd:cd06606    1 RWKKGELLGKGSFGSVYLALNLDTGELMAVKEVELSgDSEEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767984714 244 MDGGSL-DV---YRKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06606   81 VPGGSLaSLlkkFGKLPEPVVRKYTRQILEGLEYLHSNGIVHR 123

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase 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 mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) 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. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714 172 LGHGNGGTVYKAYHVpsGKILAVKVILL-DITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSL- 249
Cdd:cd13999    1 IGSGSFGEVYKGKWR--GTDVAIKKLKVeDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLy 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767984714 250 ----DVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHRankDL 287
Cdd:cd13999   79 dllhKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHR---DL 117

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-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 767984714 172 LGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQkQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSLDV 251
Cdd:cd06611   13 LGDGAFGKVYKAQHKETGLFAAAKIIQIESEEELE-DFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALDS 91

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767984714 252 YRKMPEHVL--GRIAVA---VVKGLTYLWSLKILHR 282
Cdd:cd06611   92 IMLELERGLtePQIRYVcrqMLEALNFLHSHKVIHR 127

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984714 172 LGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQkQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSLDV 251
Cdd:cd06644   20 LGDGAFGKVYKAKNKETGALAAAKVIETKSEEELE-DYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGGAVDA 98

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767984714 252 Y-----RKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06644   99 ImleldRGLTEPQIQVICRQMLEALQYLHSMKIIHR 134

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-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 767984714 170 DTLGHGNGGTVYKAYHVPSGKILAVKVI-LLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGS 248
Cdd:cd06627    6 DLIGRGAFGSVYKGLNLNTGEFVAIKQIsLEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGS 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767984714 249 L-DVYRK---MPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06627   86 LaSIIKKfgkFPESLVAVYIYQVLEGLAYLHEQGVIHR 123

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. 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 767984714 170 DTLGHGNGGTVYKAYHVPSGKILAVKVIllDITLELQKQI---MSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDG 246
Cdd:cd08530    6 KKLGKGSYGSVYKVKRLSDNQVYALKEV--NLGSLSQKERedsVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPF 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767984714 247 GSLDVY--------RKMPEHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd08530   84 GDLSKLiskrkkkrRLFPEDDIWRIFIQMLRGLKALHDQKILHR 127

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. 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 767984714 171 TLGHGNGGTVYKAYHVPSGKILAVKVI-LLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSL 249
Cdd:cd08529    7 KLGKGSFGVVYKVVRKVDGRVYALKQIdISRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAENGDL 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767984714 250 DVY------RKMPEHVLGRIAVAVVKGLTYLWSLKILHRANKDL 287
Cdd:cd08529   87 HSLiksqrgRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSM 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 767984714 170 DTLGHGNGGTVYKA-YHVPSGKIL--AVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDG 246
Cdd:cd00192    1 KKLGEGAFGEVYKGkLKGGDGKTVdvAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767984714 247 GSLDVY-----RKMPEHVLG--------RIAVAVVKGLTYLWSLKILHRankDLCT 289
Cdd:cd00192   81 GDLLDFlrksrPVFPSPEPStlslkdllSFAIQIAKGMEYLASKKFVHR---DLAA 133

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK 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 767984714 172 LGHGNGGTVYKAYHVPSGKILAVKVILLD-ITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSLD 250
Cdd:cd14009    1 IGRGSFATVWKGRHKQTGEVVAIKEISRKkLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 767984714 251 VY----RKMPE----HVLGRIAvavvKGLTYLWSLKILHR 282
Cdd:cd14009   81 QYirkrGRLPEavarHFMQQLA----SGLKFLRSKNIIHR 116

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 767984714 171 TLGHGNGGTVYKAYHVPSGKILAVKVI-LLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSL 249
Cdd:cd14003    7 TLGEGSFGKVKLARHKLTGEKVAIKIIdKSKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASGGEL 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767984714 250 DVY----RKMPEHVLGRIAVAVVKGLTYLWSLKILHRankDL 287
Cdd:cd14003   87 FDYivnnGRLSEDEARRFFQQLISAVDYCHSNGIVHR---DL 125

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 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 767984714 170 DTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGS- 248
Cdd:cd06642   10 ERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGSa 89

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767984714 249 LDVYRKMP--EHVLGRIAVAVVKGLTYLWSLKILHR 282
Cdd:cd06642   90 LDLLKPGPleETYIATILREILKGLDYLHSERKIHR 125

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 767984714 172 LGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQkQIMSELEILYKCDSSYIIGFYGAFFVENRISICTEFMDGGSLDV 251
Cdd:cd06643   13 LGDGAFGKVYKAQNKETGILAAAKVIDTKSEEELE-DYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAVDA 91

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767984714 252 YRKMPEHVLGRIAVAVV-----KGLTYLWSLKILHR 282
Cdd:cd06643   92 VMLELERPLTEPQIRVVckqtlEALVYLHENKIIHR 127