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 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06617    1 DDLEVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEQKRLLMDLDISMRSVDCPYTVTFYGALFREGDVWICME 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148706742 151 LMDTSLDKFYRKVLEKNMKIPEDILGEIAVS 181
Cdd:cd06617   81 VMDTSLDKFYKKVYDKGLTIPEDILGKIAVS 111

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 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06617    1 DDLEVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEQKRLLMDLDISMRSVDCPYTVTFYGALFREGDVWICME 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148706742 151 LMDTSLDKFYRKVLEKNMKIPEDILGEIAVS 181
Cdd:cd06617   81 VMDTSLDKFYKKVYDKGLTIPEDILGKIAVS 111

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742   73 LVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNT-QEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMEL 151
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKkKKDKNILREIKI-LKKLNHPNIVRLYDAFEDKDNLYLVLEY 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 148706742  152 MD-TSLDKFyrkvLEKNMKIPEDILGEIAVSM 182
Cdd:pfam00069  80 VEgGSLFDL----LSEKGAFSEREAKFIMKQI 107

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQ--KRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMELMD 153
Cdd:COG0515   12 LRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEarERFRREARA-LARLNHPNIVRVYDVGEEDGRPYLVMEYVE 90

                         90       100       110
                 ....*....|....*....|....*....|
gi 148706742 154 -TSLdkfyRKVLEKNMKIPEDILGEIAVSM 182
Cdd:COG0515   91 gESL----ADLLRRRGPLPPAEALRILAQL 116

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 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06617    1 DDLEVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEQKRLLMDLDISMRSVDCPYTVTFYGALFREGDVWICME 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148706742 151 LMDTSLDKFYRKVLEKNMKIPEDILGEIAVS 181
Cdd:cd06617   81 VMDTSLDKFYKKVYDKGLTIPEDILGKIAVS 111

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 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTvDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06605    1 DDLEYLGELGEGNGGVVSKVRHRPSGQIMAVKVIRLEIDEALQKQILRELDVLHKC-NSPYIVGFYGAFYSEGDISICME 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 148706742 151 LMD-TSLDKFYRKVleknMKIPEDILGEIAVSM 182
Cdd:cd06605   80 YMDgGSLDKILKEV----GRIPERILGKIAVAV 108

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTvDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06623    1 SDLERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHVDGDEEFRKQLLRELKTLRSC-ESPYVVKCYGAFYKEGEISIVLE 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 148706742 151 LMDT-SLDkfyrKVLEKNMKIPEDILGEIA 179
Cdd:cd06623   80 YMDGgSLA----DLLKKVGKIPEPVLAYIA 105

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 148706742  71 DDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCfYTVTFYGALFREGDVWICME 150
Cdd:cd06622    1 DEIEVLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLELDESKFNQIIMELDILHKAVSP-YIVDFYGAFFIEGAVYMCME 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 148706742 151 LMDT-SLDKFYRKVLEKNmKIPEDILGEIA 179
Cdd:cd06622   80 YMDAgSLDKLYAGGVATE-GIPEDVLRRIT 108

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 148706742  67 KVEADDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVW 146
Cdd:cd06650    1 ELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQV-LHECNSPYIVGFYGAFYSDGEIS 79

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 148706742 147 ICMELMD-TSLDkfyrKVLEKNMKIPEDILGEIAVSM 182
Cdd:cd06650   80 ICMEHMDgGSLD----QVLKKAGRIPEQILGKVSIAV 112

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 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 MEK2, 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 MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742  67 KVEADDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVW 146
Cdd:cd06649    1 ELKDDDFERISELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPAIRNQIIRELQV-LHECNSPYIVGFYGAFYSDGEIS 79

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 148706742 147 ICMELMD-TSLDkfyrKVLEKNMKIPEDILGEIAVSM 182
Cdd:cd06649   80 ICMEHMDgGSLD----QVLKEAKRIPEEILGKVSIAV 112

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 148706742  72 DLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRtVDCFYTVTFYGALFREGDVWICMEL 151
Cdd:cd06619    2 DIQYQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDITVELQKQIMSELEILYK-CDSPYIIGFYGAFFVENRISICTEF 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 148706742 152 MD-TSLDkFYRkvleknmKIPEDILGEIAVSM 182
Cdd:cd06619   81 MDgGSLD-VYR-------KIPEHVLGRIAVAV 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 148706742  79 LGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEqkrLLMDLDInMRTVDCFYTVTFYGALFREGDVWICME 150
Cdd:cd06612   11 LGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQE---IIKEISI-LKQCDSPYIVKYYGSYFKNTDLWIVME 78

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRatVNTQE-----QKRLLMdldinMRtvDCFY--TVTFYGALFREGDVWIC 148
Cdd:cd06613    5 IQRIGSGTYGDVYKARNIATGELAAVKVIK--LEPGDdfeiiQQEISM-----LK--ECRHpnIVAYFGSYLRRDKLWIV 75

                 ..
gi 148706742 149 ME 150
Cdd:cd06613   76 ME 77

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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRatVNTQEQ-KRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMELMD- 153
Cdd:cd06611   10 IGELGDGAFGKVYKAQHKETGLFAAAKIIQ--IESEEElEDFMVEIDI-LSECKHPNIVGLYEAYFYENKLWILIEFCDg 86

                         90
                 ....*....|....*....
gi 148706742 154 TSLDKFYRKvLEKNMKIPE 172
Cdd:cd06611   87 GALDSIMLE-LERGLTEPQ 104

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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIR-ATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMELMD- 153
Cdd:cd08215    5 IRVIGKGSFGSAYLVRRKSDGKLYVLKEIDlSNMSEKEREEALNEVKL-LSKLKHPNIVKYYESFEENGKLCIVMEYADg 83

                         90       100
                 ....*....|....*....|
gi 148706742 154 TSLDKFYRKVLEKNMKIPED 173
Cdd:cd08215   84 GDLAQKIKKQKKKGQPFPEE 103

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742    73 LVTISELGRGAYGVVEK--VRHAQSGTIM--AVKRIRATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWIC 148
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKgtLKGKGDGKEVevAVKTLKEDASEQQIEEFLREARI-MRKLDHPNIVKLLGVCTEEEPLMIV 79

                           90
                   ....*....|....*
gi 148706742   149 MELMDT-SLDKFYRK 162
Cdd:smart00221  80 MEYMPGgDLLDYLRK 94

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRATV-NTQEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICMELMDT 154
Cdd:cd14050    6 LSKLGEGSFGEVFKVRSREDGKLYAVKRSRSRFrGEKDRKRKLEEVERHEKLGEHPNCVRFIKAWEEKGILYIQTELCDT 85

                         90       100
                 ....*....|....*....|....*...
gi 148706742 155 SLDKFyrkvLEKNMKIPEDILGEIAVSM 182
Cdd:cd14050   86 SLQQY----CEETHSLPESEVWNILLDL 109

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 148706742  78 ELGRGAYGVVEKVRHAQSGTIMAVKRIRAT-VNTQEQKRLLMDLDInMRTVDCFYTVTFYGAlFREGD-VWICMELMDT- 154
Cdd:cd06627    7 LIGRGAFGSVYKGLNLNTGEFVAIKQISLEkIPKSDLKSVMGEIDL-LKKLNHPNIVKYIGS-VKTKDsLYIILEYVENg 84

                         90
                 ....*....|....*...
gi 148706742 155 SLdkfyRKVLEKNMKIPE 172
Cdd:cd06627   85 SL----ASIIKKFGKFPE 98

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 148706742  79 LGRGAYGVVEKVRHAQSGTIMAVKRIRAT--VNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMELMDTSl 156
Cdd:cd05123    1 LGKGSFGKVLLVRKKDTGKLYAMKVLRKKeiIKRKEVEHTLNERNI-LERVNHPFIVKLHYAFQTEEKLYLVLDYVPGG- 78

                         90
                 ....*....|....*..
gi 148706742 157 DKFYRkvLEKNMKIPED 173
Cdd:cd05123   79 ELFSH--LSKEGRFPEE 93

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK 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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRI-RATVNTQEQKRLLMDLDInMRTVDC-----FYTVTFYGALFREGDVWICM 149
Cdd:cd07834    5 LKPIGSGAYGVVCSAYDKRTGRKVAIKKIsNVFDDLIDAKRILREIKI-LRHLKHeniigLLDILRPPSPEEFNDVYIVT 83

                 ....*....
gi 148706742 150 ELMDTSLDK 158
Cdd:cd07834   84 ELMETDLHK 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLdINMRTVDCFYTVTFYGALFREGDVWICMEL 151
Cdd:cd13996   11 IELLGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKSSASEKVLREV-KALAKLNHPNIVRYYTAWVEEPPLYIQMEL 85

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily 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 148706742  71 DDLVTISELGRGAYGVVEK-----VRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDV 145
Cdd:cd05032    6 EKITLIRELGQGSFGMVYEglakgVVKGEPETRVAIKTVNENASMRERIEFLNEASV-MKEFNCHHVVRLLGVVSTGQPT 84

                 ....*...
gi 148706742 146 WICMELMD 153
Cdd:cd05032   85 LVVMELMA 92

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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIRaTVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMEL---- 151
Cdd:cd06643   10 VGELGDGAFGKVYKAQNKETGILAAAKVID-TKSEEELEDYMVEIDI-LASCDHPNIVKLLDAFYYENNLWILIEFcagg 87

                         90       100
                 ....*....|....*....|
gi 148706742 152 -MDTSLDKFYRKVLEKNMKI 170
Cdd:cd06643   88 aVDAVMLELERPLTEPQIRV 107

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 148706742  79 LGRGAYGVVEKVRHAQSGTIMAVKRI-RATVNTQEQKRLLMDLDInMRTVDCFYTVTFYGALFREGDVWICMELMDT-SL 156
Cdd:cd14009    1 IGRGSFATVWKGRHKQTGEVVAIKEIsRKKLNKKLQENLESEIAI-LKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGgDL 79

                         90
                 ....*....|....*...
gi 148706742 157 DKFYRkvleKNMKIPEDI 174
Cdd:cd14009   80 SQYIR----KRGRLPEAV 93

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148706742  57 PSSLSETETSKVEADDLVTISELGRGAYG-VVEK----VRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCFY 131
Cdd:cd05107   23 PMQLPYDSAWEMPRDNLVLGRTLGSGAFGrVVEAtahgLSHSQSTMKVAVKMLKSTARSSEKQALMSELKIMSHLGPHLN 102

                         90
                 ....*....|....*....
gi 148706742 132 TVTFYGALFREGDVWICME 150
Cdd:cd05107  103 IVNLLGACTKGGPIYIITE 121

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 148706742  79 LGRGAYGVVEKVR-HAQSGTIMAVKRIRAT-----VNTQEQKRLLMDL--DINMRTVDCFY-TVTFYGALFREGD-VWIC 148
Cdd:cd08528    8 LGSGAFGCVYKVRkKSNGQTLLALKEINMTnpafgRTEQERDKSVGDIisEVNIIKEQLRHpNIVRYYKTFLENDrLYIV 87

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 148706742 149 MELMD-TSLDKFYRKVLEKNMKIPEDILGEIAVSM 182
Cdd:cd08528   88 MELIEgAPLGEHFSSLKEKNEHFTEDRIWNIFVQM 122

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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
                 ....*....|....*....|....*...
gi 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKR 103
Cdd:cd07847    6 LSKIGEGSYGVVFKCRNRETGQIVAIKK 33

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. 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 CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148706742  79 LGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICMELMDTSL 156
Cdd:cd07848    9 VGEGAYGVVLKCRHKETKEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNM 86

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 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 148706742  79 LGRGAYGVVEKVRHAQSGTIMAVKRIRATVNTQEQkrllMDLDINMRTVDCFY--TVTFYGALFREG------DVWICME 150
Cdd:cd06636   24 VGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEE----IKLEINMLKKYSHHrnIATYYGAFIKKSppghddQLWLVME 99

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. 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 CDK1 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 148706742  76 ISELGRGAYGVVEKVRHAQSGTIMAVKRIR 105
Cdd:cd07835    4 LEKIGEGTYGVVYKARDKLTGEIVALKKIR 33

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-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 148706742  78 ELGRGAYGVVEKVRHAQSGTIMAVKRIratvNTQEQKRLLMDL--DINM-RTVDCFYTVTFYGALFREGDVWICMELMD- 153
Cdd:cd06609    8 RIGKGSFGEVYKGIDKRTNQVVAIKVI----DLEEAEDEIEDIqqEIQFlSQCDSPYITKYYGSFLKGSKLWIIMEYCGg 83

                         90       100
                 ....*....|....*....|....*.
gi 148706742 154 -TSLDkfyrkvLEKNMKIPEDILGEI 178
Cdd:cd06609   84 gSVLD------LLKPGPLDETYIAFI 103

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 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.