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 2527961604  72 HPQVPRLGALIPAEAGLWQVREWVNGRTYRELLRSRQERQLvfgaGEVLLLLRQLLPALAALHGQDLIHGDLTPANLLrR 151
Cdd:cd14014    59 HPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLLRERGPLPP----REALRILAQIADALAAAHRAGIVHRDIKPANIL-L 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 152 DNDGLPVLIDFGLQGAPGEEPLLSA-----TPGYAPVAQAK-QPPAPWMDLHSMAVTAMVLLSGEEP-----AGLLDPQT 220
Cdd:cd14014   134 TEDGRVKLTDFGIARALGDSGLTQTgsvlgTPAYMAPEQARgGPVDPRSDIYSLGVVLYELLTGRPPfdgdsPAAVLAKH 213

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2527961604 221 MEWRWPDGLELDP----LFRLLLERMLSVDPERRFASAAQLLE 259
Cdd:cd14014   214 LQEAPPPPSPLNPdvppALDAIILRALAKDPEERPQSAAELLA 256

Kae1-associated kinase Bud32;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 2527961604 134 HGQDLIHGDLTPANLLRRDNDglPVLIDFGL 164
Cdd:PRK14879  112 HSAGIIHGDLTTSNMILSGGK--IYLIDFGL 140

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 2527961604  72 HPQVPRLGALIPAEAGLWQVREWVNGRTYRELLRSRQERQLvfgaGEVLLLLRQLLPALAALHGQDLIHGDLTPANLLrR 151
Cdd:cd14014    59 HPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLLRERGPLPP----REALRILAQIADALAAAHRAGIVHRDIKPANIL-L 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 152 DNDGLPVLIDFGLQGAPGEEPLLSA-----TPGYAPVAQAK-QPPAPWMDLHSMAVTAMVLLSGEEP-----AGLLDPQT 220
Cdd:cd14014   134 TEDGRVKLTDFGIARALGDSGLTQTgsvlgTPAYMAPEQARgGPVDPRSDIYSLGVVLYELLTGRPPfdgdsPAAVLAKH 213

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2527961604 221 MEWRWPDGLELDP----LFRLLLERMLSVDPERRFASAAQLLE 259
Cdd:cd14014   214 LQEAPPPPSPLNPdvppALDAIILRALAKDPEERPQSAAELLA 256

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 134 HGQDLIHGDLTPANLLrRDNDGLPVLIDFGL------QGAPGEEPLLSATPGYAPVAQAKQPPA-PWMDLHSMAVTAMVL 206
Cdd:cd00180   109 HSNGIIHRDLKPENIL-LDSDGTVKLADFGLakdldsDDSLLKTTGGTTPPYYAPPELLGGRYYgPKVDIWSLGVILYEL 187

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2527961604 207 lsgeepaglldpqtmewrwpdgleldPLFRLLLERMLSVDPERRFaSAAQLLE 259
Cdd:cd00180   188 --------------------------EELKDLIRRMLQYDPKKRP-SAKELLE 213

The catalytic domain of CAMK family Serine/Threonine Kinases; 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. 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. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 2527961604 134 HGQDLIHGDLTPANLL--RRDNDGLPVLIDFGLQGAPGEEPLLSA---TPGYApvaqakqppAPWM----------DLHS 198
Cdd:cd05117   116 HSQGIVHRDLKPENILlaSKDPDSPIKIIDFGLAKIFEEGEKLKTvcgTPYYV---------APEVlkgkgygkkcDIWS 186

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2527961604 199 MAVTAMVLLSGEEP--------------AGLLDPQTMEWRwpdglELDPLFRLLLERMLSVDPERRFaSAAQLLE 259
Cdd:cd05117   187 LGVILYILLCGYPPfygeteqelfekilKGKYSFDSPEWK-----NVSEEAKDLIKRLLVVDPKKRL-TAAEALN 255

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 134 HGQDLIHGDLTPANLL--RRDNDGLPVLIDFGLQGAPGEEPLLSA--TPGY-APVAQAKQPPAPWMDLHSMAVTAMVLLS 208
Cdd:cd14083   118 HSLGIVHRDLKPENLLyySPDEDSKIMISDFGLSKMEDSGVMSTAcgTPGYvAPEVLAQKPYGKAVDCWSIGVISYILLC 197

                  ....
gi 2527961604 209 GEEP 212
Cdd:cd14083   198 GYPP 201

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 2527961604 134 HGQDLIHGDLTPANLLRRDNDGLPVlIDFGL-QGAPGEEPLLSATPG----YAPVA---QAKQPPAPWMDLHSMAVTAMV 205
Cdd:cd14118   132 HYQKIIHRDIKPSNLLLGDDGHVKI-ADFGVsNEFEGDDALLSSTAGtpafMAPEAlseSRKKFSGKALDIWAMGVTLYC 210

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2527961604 206 LLSGEEPagLLDPQTM---------EWRWPDGLELDPLFRLLLERMLSVDPERR 250
Cdd:cd14118   211 FVFGRCP--FEDDHILglhekiktdPVVFPDDPVVSEQLKDLILRMLDKNPSER 262

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 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 2527961604 134 HGQDLIHGDLTPANLLRRD--NDGLPVLIDFGL--QGAPGEEPLLS---ATPGY-APVAQAKQPPAPWMDLHSMAVTAMV 205
Cdd:cd14087   114 HGLGITHRDLKPENLLYYHpgPDSKIMITDFGLasTRKKGPNCLMKttcGTPEYiAPEILLRKPYTQSVDMWAVGVIAYI 193

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2527961604 206 LLSGEEPAGlLDPQTMEWR-------------WPDgleLDPLFRLLLERMLSVDPERRFASAAQLLEP 260
Cdd:cd14087   194 LLSGTMPFD-DDNRTRLYRqilrakysysgepWPS---VSNLAKDFIDRLLTVNPGERLSATQALKHP 257

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). 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-delta 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 2527961604 134 HGQDLIHGDLTPANLLR-RDNDGLPVLI-DFGLQGAPGEEPLLS---ATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLL 207
Cdd:cd14168   125 HRMGIVHRDLKPENLLYfSQDEESKIMIsDFGLSKMEGKGDVMStacGTPGYvAPEVLAQKPYSKAVDCWSIGVIAYILL 204

                  ....*
gi 2527961604 208 SGEEP 212
Cdd:cd14168   205 CGYPP 209

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 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 2527961604  72 HPQVPRLGALIPAEAGLWQVREWVNGRtyrELLrSRQERQLVFGAGEVLLLLRQLLPALAALHGQDLIHGDLTPANLLRR 151
Cdd:cd14176    72 HPNIITLKDVYDDGKYVYVVTELMKGG---ELL-DKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYV 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 152 DNDGLPVLI---DFGLQGAPGEEPLLSATPGY-----APVAQAKQPPAPWMDLHSMAVTAMVLLSGEEP--AGLLD-PQT 220
Cdd:cd14176   148 DESGNPESIricDFGFAKQLRAENGLLMTPCYtanfvAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPfaNGPDDtPEE 227

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 2527961604 221 MEWRWPDGL---------ELDPLFRLLLERMLSVDPERRFASAAQLLEP 260
Cdd:cd14176   228 ILARIGSGKfslsggywnSVSDTAKDLVSKMLHVDPHQRLTAALVLRHP 276

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 134 HGQDLIHGDLTPANLLRRDnDGLPVLIDFGL--QGAPGEEPL-LSATPGY-AP-VAQAKQ--PPA--------------- 191
Cdd:cd05122   115 HSHGIIHRDIKAANILLTS-DGEVKLIDFGLsaQLSDGKTRNtFVGTPYWmAPeVIQGKPygFKAdiwslgitaiemaeg 193

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 192 --PWMDLHSMAvtAMVLLSGEEPAGLLDPqtmeWRWPDgleldpLFRLLLERMLSVDPERRfASAAQLLE 259
Cdd:cd05122   194 kpPYSELPPMK--ALFLIATNGPPGLRNP----KKWSK------EFKDFLKKCLQKDPEKR-PTAEQLLK 250

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 134 HGQDLIHGDLTPANLL-RRDNDGLPV--LIDFGLqGAPGEEPLLS--ATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLL 207
Cdd:cd14095   115 HSLSIVHRDIKPENLLvVEHEDGSKSlkLADFGL-ATEVKEPLFTvcGTPTYvAPEILAETGYGLKVDIWAAGVITYILL 193

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2527961604 208 SGEEPaglldpqtmeWRWPDGLElDPLFRL----------------------LLERMLSVDPERRFaSAAQLLE 259
Cdd:cd14095   194 CGFPP----------FRSPDRDQ-EELFDLilagefeflspywdnisdsakdLISRMLVVDPEKRY-SAGQVLD 255

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, 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. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK 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 2527961604 134 HGQDLIHGDLTPANLLRrDNDGLPVLIDFGL--QGAP--GEEPLLSATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLLS 208
Cdd:cd06647   120 HSNQVIHRDIKSDNILL-GMDGSVKLTDFGFcaQITPeqSKRSTMVGTPYWmAPEVVTRKAYGPKVDIWSLGIMAIEMVE 198

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2527961604 209 GEEPAGLLDP----------QTMEWRWPDglELDPLFRLLLERMLSVDPERRfASAAQLLE 259
Cdd:cd06647   199 GEPPYLNENPlralyliatnGTPELQNPE--KLSAIFRDFLNRCLEMDVEKR-GSAKELLQ 256

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK 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 2527961604  88 LWQVREWVNGRTYRELLRsrqerQLVFGAGEVLLLLRQLLPALAALHGQDLIHGDLTPANLLRrDNDGLPVLIDFGL--Q 165
Cdd:cd06654    92 LWVVMEYLAGGSLTDVVT-----ETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILL-GMDGSVKLTDFGFcaQ 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 166 GAP--GEEPLLSATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLLSGEEPAGLLDP----------QTMEWRWPDglELD 232
Cdd:cd06654   166 ITPeqSKRSTMVGTPYWmAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPlralyliatnGTPELQNPE--KLS 243

                         170       180
                  ....*....|....*....|....*..
gi 2527961604 233 PLFRLLLERMLSVDPERRfASAAQLLE 259
Cdd:cd06654   244 AIFRDFLNRCLEMDVEKR-GSAKELLQ 269

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK 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 2527961604 134 HGQDLIHGDLTPANLLRrDNDGLPVLIDFGL--QGAP--GEEPLLSATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLLS 208
Cdd:cd06655   132 HANQVIHRDIKSDNVLL-GMDGSVKLTDFGFcaQITPeqSKRSTMVGTPYWmAPEVVTRKAYGPKVDIWSLGIMAIEMVE 210

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2527961604 209 GEEPAGLLDP----------QTMEWRWPDglELDPLFRLLLERMLSVDPERRfASAAQLLE 259
Cdd:cd06655   211 GEPPYLNENPlralyliatnGTPELQNPE--KLSPIFRDFLNRCLEMDVEKR-GSAKELLQ 268

Kae1-associated kinase Bud32;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 2527961604 134 HGQDLIHGDLTPANLLRRDNDglPVLIDFGL 164
Cdd:PRK14879  112 HSAGIIHGDLTTSNMILSGGK--IYLIDFGL 140

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like 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 2527961604 134 HGQDLIHGDLTPANLLRRDNDGLPV-LIDFGLQGAPGEEPLLSATPGY----APVAQAKQPPAPWMDLHSMAVTAMVLLS 208
Cdd:cd14114   117 HENNIVHLDIKPENIMCTTKRSNEVkLIDFGLATHLDPKESVKVTTGTaefaAPEIVEREPVGFYTDMWAVGVLSYVLLS 196

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2527961604 209 GEEP-AGLLDPQTM------EWRWPDGL--ELDPLFRLLLERMLSVDPERRFASAAQLLEP 260
Cdd:cd14114   197 GLSPfAGENDDETLrnvkscDWNFDDSAfsGISEEAKDFIRKLLLADPNKRMTIHQALEHP 257

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
                  ....*....|....*....|....*....|.
gi 2527961604 134 HGQDLIHGDLTPANLLRRDNDglPVLIDFGL 164
Cdd:TIGR03724 107 HKAGIVHGDLTTSNIIVRDDK--VYLIDFGL 135

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2527961604  91 VREWVNGRTYRELLRSRQERqlVFGAGEvllllrqllpALAALHGQDLIHGDLTPANLLRRDNDglPVLIDFGL 164
Cdd:PRK09605  414 VMEYIGGKDLKDVLEGNPEL--VRKVGE----------IVAKLHKAGIVHGDLTTSNFIVRDDR--LYLIDFGL 473

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604  88 LWQVREWVNGRTYRELLRsrqerQLVFGAGEVLLLLRQLLPALAALHGQDLIHGDLTPANLLRrDNDGLPVLIDFGL--Q 165
Cdd:cd06656    91 LWVVMEYLAGGSLTDVVT-----ETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILL-GMDGSVKLTDFGFcaQ 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604 166 GAP--GEEPLLSATPGY-APVAQAKQPPAPWMDLHSMAVTAMVLLSGEEPAGLLDP----------QTMEWRWPDglELD 232
Cdd:cd06656   165 ITPeqSKRSTMVGTPYWmAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlralyliatnGTPELQNPE--RLS 242

                         170       180
                  ....*....|....*....|....*..
gi 2527961604 233 PLFRLLLERMLSVDPERRfASAAQLLE 259
Cdd:cd06656   243 AVFRDFLNRCLEMDVDRR-GSAKELLQ 268

Pseudokinase domain of the peptidoglycan biosynthetic protein MviN; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This family is composed of the mycobacterial protein MviN and similar proteins. MviN is an integral membrane protein that is essential for growth and is required for cell wall integrity and peptidogylcan (PG) biosynthesis. It comprises of 14 predicted transmembrane (TM) helices at the N-terminus, followed by an intracellular pseudokinase domain linked through a single TM helix to a carbohydrate binding extracellular domain. Phosphorylation of the MviN pseudokinase domain by the PG-sensitive serine/threonine protein kinase PknB recruits a forkhead associated (FHA) domain protein FhaA, which modulates local PG synthesis at cell poles and the septum. The MviN pseudokinase forms a canonical receptor kinase dimer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2527961604  16 RYRLEQLLSESPGVQLWRGSDTlAGGLAVAIR----GWGDLNEQKLLLLRQRLERLQGVLHPQVPRLGALIPAEAGLWQV 91
Cdd:cd13973     1 RYRLLEDHGGVPGARFWRARDT-VLGRDVALTfvdpGGAAAAARRAAEVLRAARRLARLNDPGLARVLDAVAYRGGVYVV 79