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 37722951   1 ASRQSFWAELNVARLDHNHVVRIVAASTCAPGNqdSLGTIIMEYVGNSTLYHVIYGTGcmaakredDKLSIAQCLGYSCD 80
Cdd:cd13979  42 ASRQSFWAELNAARLRHENIVRVLAAETGTDFA--SLGLIIMEYCGNGTLQQLIYEGS--------EPLPLAHRILISLD 111

                        90       100       110
                ....*....|....*....|....*....|.
gi 37722951  81 IVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd13979 112 IARALRFCHSHGIVHLDVKPANILISEQGVC 142

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951   1 ASRQSFWAELNVARLDHNHVVRIVAASTCAPGNqdSLGTIIMEYVGNSTLYHVIYGTGcmaakredDKLSIAQCLGYSCD 80
Cdd:cd13979  42 ASRQSFWAELNAARLRHENIVRVLAAETGTDFA--SLGLIIMEYCGNGTLQQLIYEGS--------EPLPLAHRILISLD 111

                        90       100       110
                ....*....|....*....|....*....|.
gi 37722951  81 IVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd13979 112 IARALRFCHSHGIVHLDVKPANILISEQGVC 142

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951      3 RQSFWAELNV-ARLDHNHVVRIVAASTcapgNQDSLgTIIMEYVGNSTLYHVIygtgcmaakREDDKLSIAQCLGYSCDI 81
Cdd:smart00220  41 RERILREIKIlKKLKHPNIVRLYDVFE----DEDKL-YLVMEYCEGGDLFDLL---------KKRGRLSEDEARFYLRQI 106

                           90       100
                   ....*....|....*....|....*....
gi 37722951     82 VAGLVFLHSQLIVHLDLKPANIFITEQNV 110
Cdd:smart00220 107 LSALEYLHSKGIVHRDLKPENILLDEDGH 135

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951     2 SRQSFWAELNV-ARLDHNHVVRIVAASTCAPGNQdslgtIIMEYVGNSTLYHVIygtgcmaaKREDDKLSIAQCLGYSCD 80
Cdd:pfam07714  44 EREDFLEEASImKKLDHPNIVKLLGVCTQGEPLY-----IVTEYMPGGDLLDFL--------RKHKRKLTLKDLLSMALQ 110

                          90       100       110
                  ....*....|....*....|....*....|.
gi 37722951    81 IVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:pfam07714 111 IAKGMEYLESKNFVHRDLAARNCLVSENLVV 141

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951    38 GTIIMEYVG--------NSTLYHVIYGTGCMAAKreddklsiaqclgyscdivaglvfLHSQLIVHLDLKPANIFITEQN 109
Cdd:TIGR03724  72 KTIVMEYIEgkplkdviEENGDELAREIGRLVGK------------------------LHKAGIVHGDLTTSNIIVRDDK 127

                  ..
gi 37722951   110 VC 111
Cdd:TIGR03724 128 VY 129

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951   1 ASRQSFWAELNVARLDHNHVVRIVAASTCAPGNqdSLGTIIMEYVGNSTLYHVIYGTGcmaakredDKLSIAQCLGYSCD 80
Cdd:cd13979  42 ASRQSFWAELNAARLRHENIVRVLAAETGTDFA--SLGLIIMEYCGNGTLQQLIYEGS--------EPLPLAHRILISLD 111

                        90       100       110
                ....*....|....*....|....*....|.
gi 37722951  81 IVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd13979 112 IARALRFCHSHGIVHLDVKPANILISEQGVC 142

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951   3 RQSFWAELNV-ARLDHNHVVRIVAAstcapGNQDSLGTIIMEYVGNSTLYHVIygtgcmaakREDDKLSIAQCLGYSCDI 81
Cdd:COG0515  51 RERFRREARAlARLNHPNIVRVYDV-----GEEDGRPYLVMEYVEGESLADLL---------RRRGPLPPAEALRILAQL 116

                        90       100
                ....*....|....*....|....*....
gi 37722951  82 VAGLVFLHSQLIVHLDLKPANIFITEQNV 110
Cdd:COG0515 117 AEALAAAHAAGIVHRDIKPANILLTPDGR 145

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951  11 NVARLDHNHVVRIVAAstcapGNQDSLGTIIMEYVGNSTLYHVIygtgcmaakREDDKLSIAQCLGYSCDIVAGLVFLHS 90
Cdd:cd14014  53 ALARLSHPNIVRVYDV-----GEDDGRPYIVMEYVEGGSLADLL---------RERGPLPPREALRILAQIADALAAAHR 118

                        90
                ....*....|....*....
gi 37722951  91 QLIVHLDLKPANIFITEQN 109
Cdd:cd14014 119 AGIVHRDIKPANILLTEDG 137

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK 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 37722951  14 RLDHNHVVRIVAA--StcaPgNQDSLgTIIMEYVGNSTLYHVIYGTgcmaakrEDDKLSIAQCLGYSCDIVAGLVFLHSQ 91
Cdd:cd14008  60 KLDHPNIVRLYEVidD---P-ESDKL-YLVLEYCEGGPVMELDSGD-------RVPPLPEETARKYFRDLVLGLEYLHEN 127

                        90       100
                ....*....|....*....|
gi 37722951  92 LIVHLDLKPANIFITEQNVC 111
Cdd:cd14008 128 GIVHRDIKPENLLLTADGTV 147

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like 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 37722951  17 HNHVVRIVAAstcapGNQDSLGTIIMEYVGNSTLYHVIygtgcmAAKREDDKLSIAQCLGYSCDIVAGLVFLHSQLIVHL 96
Cdd:cd13997  59 HPNIVRYYSS-----WEEGGHLYIQMELCENGSLQDAL------EELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHL 127

                        90
                ....*....|....*
gi 37722951  97 DLKPANIFITEQNVC 111
Cdd:cd13997 128 DIKPDNIFISNKGTC 142

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951     2 SRQSFWAELNV-ARLDHNHVVRIVAASTCAPGNQdslgtIIMEYVGNSTLYHVIygtgcmaaKREDDKLSIAQCLGYSCD 80
Cdd:pfam07714  44 EREDFLEEASImKKLDHPNIVKLLGVCTQGEPLY-----IVTEYMPGGDLLDFL--------RKHKRKLTLKDLLSMALQ 110

                          90       100       110
                  ....*....|....*....|....*....|.
gi 37722951    81 IVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:pfam07714 111 IAKGMEYLESKNFVHRDLAARNCLVSENLVV 141

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 37722951  14 RLDHNHVVRIVAASTcapgNQDSLgTIIMEYVGNSTLYHVIYGTGcmaakreddKLSIAQCLGYSCDIVAGLVFLHSQLI 93
Cdd:cd06606  55 SLKHPNIVRYLGTER----TENTL-NIFLEYVPGGSLASLLKKFG---------KLPEPVVRKYTRQILEGLEYLHSNGI 120

                        90
                ....*....|....*...
gi 37722951  94 VHLDLKPANIFITEQNVC 111
Cdd:cd06606 121 VHRDIKGANILVDSDGVV 138

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 37722951  13 ARLDHNHVVRIVAASTcapgNQDSLgTIIMEYVGNSTLYHVIygtgcMAAKREDDKLSIAQCLGYSCDIVAGLVFLHSQL 92
Cdd:cd08215  54 SKLKHPNIVKYYESFE----ENGKL-CIVMEYADGGDLAQKI-----KKQKKKGQPFPEEQILDWFVQICLALKYLHSRK 123

                        90
                ....*....|....*...
gi 37722951  93 IVHLDLKPANIFITEQNV 110
Cdd:cd08215 124 ILHRDLKTQNIFLTKDGV 141

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK 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 37722951  16 DHNHVVRIVAAStcapgNQDSLGTIIMEYVGnSTLYHVIygtgcmaaKREDDKLSIAQCLGYSCDIVAGLVFLHSQLIVH 95
Cdd:cd07832  58 GHPYVVKLRDVF-----PHGTGFVLVFEYML-SSLSEVL--------RDEERPLTEAQVKRYMRMLLKGVAYMHANRIMH 123

                        90
                ....*....|..
gi 37722951  96 LDLKPANIFITE 107
Cdd:cd07832 124 RDLKPANLLISS 135

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 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 37722951  14 RLDHNHVVRIVAASTcapgNQDSLGT-IIMEYVGNSTLYhviygtgcMAAKREDDKLSIAQCLGYSCDIVAGLVFLHSQL 92
Cdd:cd14119  50 RLNHRNVIKLVDVLY----NEEKQKLyMVMEYCVGGLQE--------MLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQG 117

                        90
                ....*....|....
gi 37722951  93 IVHLDLKPANIFIT 106
Cdd:cd14119 118 IIHKDIKPGNLLLT 131

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
                ....*....|....*....|....*....|....*....|....*..
gi 37722951  65 EDDKLSIAQCLGYSCDIVAGLVFLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd14050  93 ETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVC 139

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK 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 37722951   1 ASRQSFWAEL-NVARLDHNHVVRIVAasTCApgnQDSLGTIIMEYVGNSTLYHVIYGTGCMAAKREDDKLSIAQclgysc 79
Cdd:cd14066  32 ASKKEFLTELeMLGRLRHPNLVRLLG--YCL---ESDEKLLVYEYMPNGSLEDRLHCHKGSPPLPWPQRLKIAK------ 100

                        90       100       110
                ....*....|....*....|....*....|.
gi 37722951  80 DIVAGLVFLHSQL---IVHLDLKPANIFITE 107
Cdd:cd14066 101 GIARGLEYLHEECpppIIHGDIKSSNILLDE 131

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951  13 ARLDHNHVVRIVAASTcapgnQDSLGTIIMEYVGNSTLYHVIyGTGCMAAKREDDklsiaQCLGYSCDIVAGLVFLHSQL 92
Cdd:cd13996  59 AKLNHPNIVRYYTAWV-----EEPPLYIQMELCEGGTLRDWI-DRRNSSSKNDRK-----LALELFKQILKGVSYIHSKG 127

                        90
                ....*....|....*
gi 37722951  93 IVHLDLKPANIFITE 107
Cdd:cd13996 128 IVHRDLKPSNIFLDN 142

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951   8 AELNV-ARLDHNHVVRIVAASTCApgnqDSLgTIIMEYVGNSTLYHVIYGTGCMaakrEDD--KLSIAQclgyscdIVAG 84
Cdd:cd05579  42 AERNIlSQAQNPFVVKLYYSFQGK----KNL-YLVMEYLPGGDLYSLLENVGAL----DEDvaRIYIAE-------IVLA 105

                        90       100
                ....*....|....*....|....
gi 37722951  85 LVFLHSQLIVHLDLKPANIFITEQ 108
Cdd:cd05579 106 LEYLHSHGIIHRDLKPDNILIDAN 129

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 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 37722951  14 RLDHNHVVRIVAASTCAPGNQDslgTIIMEYVGNSTLYHVI------YGtgcmaakreddkLSIAQCLGYSCDIVAGLVF 87
Cdd:cd13988  47 KLNHKNIVKLFAIEEELTTRHK---VLVMELCPCGSLYTVLeepsnaYG------------LPESEFLIVLRDVVAGMNH 111

                        90
                ....*....|....*.
gi 37722951  88 LHSQLIVHLDLKPANI 103
Cdd:cd13988 112 LRENGIVHRDIKPGNI 127

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 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 37722951  14 RLDHNHVVRIVAASTCAPgnqdsLGTIIMEYVGNSTLYHVIygtgcmaakREDDKLSIAQCLGYSCDIVAGLVFLHSQLI 93
Cdd:cd14059  37 KLNHPNIIKFKGVCTQAP-----CYCILMEYCPYGQLYEVL---------RAGREITPSLLVDWSKQIASGMNYLHLHKI 102

                        90
                ....*....|....*..
gi 37722951  94 VHLDLKPANIFITEQNV 110
Cdd:cd14059 103 IHRDLKSPNVLVTYNDV 119

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 37722951  13 ARLDHNHVVRIVAASTcapgnQDSLGTIIMEYVGNSTLYHVIygtgcmaaKREDDK-LSIAQCLGYSCDIVAGLVFLHSQ 91
Cdd:cd08529  54 SKLNSPYVIKYYDSFV-----DKGKLNIVMEYAENGDLHSLI--------KSQRGRpLPEDQIWKFFIQTLLGLSHLHSK 120

                        90
                ....*....|....*.
gi 37722951  92 LIVHLDLKPANIFITE 107
Cdd:cd08529 121 KILHRDIKSMNIFLDK 136

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951   2 SRQSFWAELNV-ARLDHNHVVRIVAAStcapgnQDSLGT-IIMEYVGNSTLYHVIygtgcmaaKREDdKLSIAQCLGYSC 79
Cdd:cd14099  44 QREKLKSEIKIhRSLKHPNIVKFHDCF------EDEENVyILLELCSNGSLMELL--------KRRK-ALTEPEVRYFMR 108

                        90       100
                ....*....|....*....|....*...
gi 37722951  80 DIVAGLVFLHSQLIVHLDLKPANIFITE 107
Cdd:cd14099 109 QILSGVKYLHSNRIIHRDLKLGNLFLDE 136

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 37722951  40 IIMEYVGNSTLYHVIYGTgcmaaKREDDKLSIAqclgYSC-DIVAGLVFLHSQLIVHLDLKPANIFITE 107
Cdd:cd05122  74 IVMEFCSGGSLKDLLKNT-----NKTLTEQQIA----YVCkEVLKGLEYLHSHGIIHRDIKAANILLTS 133

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 37722951  41 IMEYVGNSTLYHVIYGTGCmaakreddkLSIAQCLGYSCDIVAGLVFLHSQLIVHLDLKPANIFITEQ 108
Cdd:cd05123  71 VLDYVPGGELFSHLSKEGR---------FPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSD 129

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 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 37722951   2 SRQSFWAELNVAR-LDHNHVVRIVAASTcapgnQDSLGTIIMEYVGNSTLYHVIygtgcmaaKREDDKLSIAQCLGYSCD 80
Cdd:cd14221  33 TQRTFLKEVKVMRcLEHPNVLKFIGVLY-----KDKRLNFITEYIKGGTLRGII--------KSMDSHYPWSQRVSFAKD 99

                        90       100
                ....*....|....*....|....*..
gi 37722951  81 IVAGLVFLHSQLIVHLDLKPANIFITE 107
Cdd:cd14221 100 IASGMAYLHSMNIIHRDLNSHNCLVRE 126

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK 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 37722951   9 ELNVAR-LDHNHVVRIVaasTCAPGNQDSLGTIiMEYVGNSTLYHVIYGTGCMAAKreDDKLSIAQclgyscdIVAGLVF 87
Cdd:cd13990  54 EYEIHKsLDHPRIVKLY---DVFEIDTDSFCTV-LEYCDGNDLDFYLKQHKSIPER--EARSIIMQ-------VVSALKY 120

                        90       100
                ....*....|....*....|....*.
gi 37722951  88 L--HSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd13990 121 LneIKPPIIHYDLKPGNILLHSGNVS 146

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37722951  14 RLDHNHVVRIVAASTCapgnQDSLgTIIMEYVgNSTLYHVIygtgcmaaKREDDKLSIAQCLGYSCDIVAGLVFLHSQLI 93
Cdd:cd07829  54 ELKHPNIVKLLDVIHT----ENKL-YLVFEYC-DQDLKKYL--------DKRPGPLPPNLIKSIMYQLLRGLAYCHSHRI 119

                        90
                ....*....|....*..
gi 37722951  94 VHLDLKPANIFITEQNV 110
Cdd:cd07829 120 LHRDLKPQNLLINRDGV 136

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG 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 37722951  40 IIMEYVGNSTLYHVIYGTGCMAakrEDDklsiaqCLGYSCDIVAGLVFLHSQLIVHLDLKPANIFITEQNV 110
Cdd:cd14111  76 LIAEFCSGKELLHSLIDRFRYS---EDD------VVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNA 137

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR 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 37722951  12 VARLDHNHVVR-----------IVAASTCAPGNQDSLGTIIMEYVGNSTLYHVIygtgcmaAKREDDKLSIAQCLGYSCD 80
Cdd:cd14047  53 LAKLDHPNIVRyngcwdgfdydPETSSSNSSRSKTKCLFIQMEFCEKGTLESWI-------EKRNGEKLDKVLALEIFEQ 125

                        90       100
                ....*....|....*....|....*..
gi 37722951  81 IVAGLVFLHSQLIVHLDLKPANIFITE 107
Cdd:cd14047 126 ITKGVEYIHSKKLIHRDLKPSNIFLVD 152

Catalytic domain of Cyclin-Dependent protein Kinase 9-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 CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. 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 CDK9-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 37722951  15 LDHNHVVRIVAASTcAPGNQDSLGTIIM--EYVGNSTlyhviygTGCMAakREDDKLSIAQCLGYSCDIVAGLVFLHSQL 92
Cdd:cd07840  55 LDHPNVVRLKEIVT-SKGSAKYKGSIYMvfEYMDHDL-------TGLLD--NPEVKFTESQIKCYMKQLLEGLQYLHSNG 124

                        90
                ....*....|....*...
gi 37722951  93 IVHLDLKPANIFITEQNV 110
Cdd:cd07840 125 ILHRDIKGSNILINNDGV 142

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 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 37722951  13 ARLDHNHVVRIVaastcapgnqDSLGT-----IIMEYVgNSTLYHVIygtgcmaakrEDDK-LSIAQCLGYSCDIVAGLV 86
Cdd:cd14002  55 RKLNHPNIIEML----------DSFETkkefvVVTEYA-QGELFQIL----------EDDGtLPEEEVRSIAKQLVSALH 113

                        90       100
                ....*....|....*....|....*
gi 37722951  87 FLHSQLIVHLDLKPANIFITEQNVC 111
Cdd:cd14002 114 YLHSNRIIHRDMKPQNILIGKGGVV 138

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK 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 37722951  14 RLDHNHVVRIVaaSTCAPGNQDSLgTIIMEYVGNSTLYHVIygtgcmaakrEDDKLSIAQCLGYSCDIVAGLVFLHSQLI 93
Cdd:cd14118  70 KLDHPNVVKLV--EVLDDPNEDNL-YMVFELVDKGAVMEVP----------TDNPLSEETARSYFRDIVLGIEYLHYQKI 136