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 1720401100   1 MEEIEDsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGL 80
Cdd:TIGR03724  76 MEYIEG-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDE 141

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720401100  81 PEDKGVDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 135
Cdd:TIGR03724 142 IEDKAVDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100   1 MEEIEDsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGL 80
Cdd:TIGR03724  76 MEYIEG-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDE 141

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720401100  81 PEDKGVDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 135
Cdd:TIGR03724 142 IEDKAVDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100   1 MEEIEDsVTVRDYIQSTMETEkdpqcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGL 80
Cdd:COG3642    35 MEYIEG-ETLADLLEEGELPP-------ELLRELGRLLARLHRAGIVHGDLTTSNILVDDG----GVYLIDFGLARYSDP 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720401100  81 PEDKGVDLYVLEKAFLSTHP-HTETAFEAFLKSYgASSKKSSPVLKKLDEVRLRGR 135
Cdd:COG3642   103 LEDKAVDLAVLKRSLESTHPdPAEELWEAFLEGY-REVGPAEEVLRRLREIELRGR 157

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100   1 MEEIEDSVTVRDYIQSTME-TEKDPQCLLdlaRRMGQVLAGMHDQDLIHGDLTTSNMLLRRP-LAQLHIVLIDFglsfvs 78
Cdd:pfam06293  95 TERLEGAQSLADWLADWAVpSGELRRAIW---EAVGRLIRQMHRAGVQHGDLYAHHILLQQEgDEGFEAWLIDL------ 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1720401100  79 glpeDKGV-----------DLYVLEKAFLsTHPHTETAFEAFLKSY 113
Cdd:pfam06293 166 ----DKGRlrlparrwrnkDLARLLRSFL-NIGFTEADWERLLRAY 206

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 1720401100   1 MEEIEDsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGL 80
Cdd:TIGR03724  76 MEYIEG-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDE 141

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720401100  81 PEDKGVDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 135
Cdd:TIGR03724 142 IEDKAVDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100   1 MEEIEDsVTVRDYIQSTmetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGL 80
Cdd:PRK09605  415 MEYIGG-KDLKDVLEGN----------PELVRKVGEIVAKLHKAGIVHGDLTTSNFIVRDD----RLYLIDFGLGKYSDL 479

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720401100  81 PEDKGVDLYVLEKAFLSTHPHTETAFEAFLKSYGAsSKKSSPVLKKLDEVRLRGR 135
Cdd:PRK09605  480 IEDKAVDLHVLKQSLESTHYDFEELWEAFLEGYRE-TEGAEDVLERLKEIEKRGR 533

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720401100   1 MEEIEdSVTVRDYIQSTMETEKDPQcLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 75
Cdd:cd00180    70 MEYCE-GGSLKDLLKENKGPLSEEE-ALSILRQLLSALEYLHSNGIIHRDLKPENILLDS---DGTVKLADFGLA 139

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720401100   1 MEEIEdSVTVRDYIQstMETEKDPQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 75
Cdd:cd14014    79 MEYVE-GGSLADLLR--ERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTE---DGRVKLTDFGIA 147

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720401100  27 LLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLSF 76
Cdd:cd14015   129 VLQLALRILDVLEYIHENGYVHADIKASNLLLGFGKNKDQVYLVDYGLAS 178

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100  20 TEKDPQCLldlarrMGQVLAG---MHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLSFVsglpEDKGV 86
Cdd:cd14083    99 TEKDASHL------IRQVLEAvdyLHSLGIVHRDLKPENLLYYSPDEDSKIMISDFGLSKM----EDSGV 158

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720401100   1 MEEIEDSVTvrDYIQSTMETEKDP---QCLLDLARRMGQVLAGMH-DQDLIHGDLTTSNMLLRRPLAQlhIVLIDFGLSf 76
Cdd:cd14001    85 MEYGGKSLN--DLIEERYEAGLGPfpaATILKVALSIARALEYLHnEKKILHGDIKSGNVLIKGDFES--VKLCDFGVS- 159

                          90
                  ....*....|....*..
gi 1720401100  77 vsgLPEDKgvDLYVLEK 93
Cdd:cd14001   160 ---LPLTE--NLEVDSD 171

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720401100  14 IQSTMETEKDPQCLLdlaRRMGQVLAGMHDQDLIHGDLTTSNMLLRR-PLAQLHIVLIDFGLSFV 77
Cdd:cd14095    90 TSSTKFTERDASRMV---TDLAQALKYLHSLSIVHRDIKPENLLVVEhEDGSKSLKLADFGLATE 151

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1720401100  31 ARRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGL 74
Cdd:cd05575   102 AAEIASALGYLHSLNIIYRDLKPENILLD---SQGHVVLTDFGL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720401100  41 MHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLSFVsGLpEDKGVDLYVLEKAFLSTHPHTETAF 106
Cdd:cd05579   109 LHSHGIIHRDLKPDNILID---ANGHLKLTDFGLSKV-GL-VRRQIKLSIQKKSNGAPEKEDRRIV 169

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 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 1720401100   1 MEEIEDSvTVRDYIQSTMETEKDPqcLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 75
Cdd:cd14046    83 MEYCEKS-TLRDLIDSGLFQDTDR--LWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLD---SNGNVKIGDFGLA 151

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1720401100   29 DLARR-MGQVLAG---MHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 75
Cdd:smart00220  97 DEARFyLRQILSAleyLHSKGIVHRDLKPENILLDE---DGHVKLADFGLA 144

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-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 ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720401100  37 VLA--GMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLSfvSGLPeDKGVDLYVLEKAFLSTHPHTETAFEAFLKSY 113
Cdd:cd05573   111 VLAldSLHKLGFIHRDIKPDNILLDA---DGHIKLADFGLC--TKMN-KSGDRESYLNDSVNTLFQDNVLARRRPHKQR 183

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
                  ....*....|....*....|....*....|....*....|..
gi 1720401100  34 MGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 75
Cdd:cd05123   102 IVLALEYLHSLGIIYRDLKPENILLD---SDGHIKLTDFGLA 140

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720401100  29 DLARR-MGQVLAG---MHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 75
Cdd:cd14003    99 DEARRfFQQLISAvdyCHSNGIVHRDLKLENILLD---KNGNLKIIDFGLS 146

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-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
                  ....*....|....*....|....*....|....*....|....*...
gi 1720401100  28 LDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 75
Cdd:cd14065    92 VSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRNAVVADFGLA 139

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 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.

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gi 1720401100  31 ARRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGL 74
Cdd:cd05604   103 AAEIASALGYLHSINIVYRDLKPENILLD---SQGHIVLTDFGL 143

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. 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 CDK10 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.

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gi 1720401100  20 TEKDPQCLldlarrMGQVLAG---MHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLSFVSGLP 81
Cdd:cd07845   106 SESQVKCL------MLQLLRGlqyLHENFIIHRDLKVSNLLLTD---KGCLKIADFGLARTYGLP 161

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 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.

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gi 1720401100  32 RRMGQVLAG---MHDQDLIHGDLTTSNMLLRRPLAQlHIVLIDFGLSFVSGLP 81
Cdd:cd13987    95 RCAAQLASAldfMHSKNLVHRDIKPENVLLFDKDCR-RVKLCDFGLTRRVGST 146

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK 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.

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gi 1720401100  28 LDLARRMgqvlAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 75
Cdd:cd14155    95 LDIARGL----SYLHSKGIFHRDLTSKNCLIKRDENGYTAVVGDFGLA 138

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

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gi 1720401100   1 MEEIEDSVTVRDYIQSTMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFG 73
Cdd:cd13968    70 LMELVKGGTLIAYTQEEELDEKDVE---SIMYQLAECMRLLHSFHLIHRDLNNDNILLSE---DGNVKLIDFG 136

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 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.

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gi 1720401100  28 LDLARRMG----QVLAGMHDQDLIHGDLTTSNMLLrRPLAQLHIVLIDFGLS 75
Cdd:cd14225   145 LSLIRRFAisllQCLRLLYRERIIHCDLKPENILL-RQRGQSSIKVIDFGSS 195