NCBI Conserved Domain Search

NewSearch

CDD Home

Conserved domains on [gi\|119962857\|ref\|YP_945859.1\|]
putative serine/threonine protein kinase [Arthrobacter aurescens TC1]

Graphical summary show options »	Show site features Horizontal zoom: ×	?



List of domain hits		?

References:

Marchler-Bauer A et al. (2009), "CDD: specific functional annotation with the Conserved Domain Database.", Nucleic Acids Res.37(D)205-10.

Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.

Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH

of the residues that compose this conserved feature have been mapped to the query sequence.

Click on the triangle to view details about the feature, including a multiple sequence alignment of your query sequence and the protein sequences used to curate the domain model, where hash marks (#) above the aligned sequences show the location of the conserved feature residues.

The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions. Click on the triangle for interactive 3D structure viewing options.

This image shows a graphical summary of conserved domains identified on the query sequence. The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits (labeled illustration) or all hits (labeled illustration).
Domains are color coded according to superfamilies to which they have been assigned. Hits with scores that pass a domain-specific threshold (specific hits) are drawn in bright colors. Others (non-specific hits) and superfamily placeholders are drawn in pastel colors.
if a domain or superfamily has been annotated with functional sites (conserved features), they are mapped to the query sequence and indicated through sets of triangles with the same color and shade of the domain or superfamily that provides the annotation.
Mouse over the colored bars or triangles to see descriptions of the domains and features. click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.

The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores. Click on the PssmId to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.

To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page, or click on the triangles, if present, that represent functional sites (conserved features) mapped to the query sequence.

Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence. (labeled illustration)
Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance. (labeled illustration)
Four types of hits can be shown, as available, for each region on the query sequence:

specific hits meet or exceed a domain-specific e-value threshold (illustrated example) and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits meet or exceed the RPS-BLAST threshold for statistical significance (default E-value cutoff of 0.01, or an E-value selected by user via the advanced search options)
the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains

The CD-Search help document provides more detail about the tool and its features.

Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool (CDART).

Modify your query to search against a different database and/or use advanced search options

29142

cd00180

S_TKc

Serine/Threonine protein kinases, catalytic domain. Phosphotransferases of the serine or threonine-specific kinase subfamily. The enzymatic activity of these protein kinases is controlled by phosphorylation of specific residues in the activation segment of the catalytic domain, sometimes combined with reversible conformational changes in the C-terminal autoregulatory tail.

Serine/Threonine protein kinases, catalytic domain. Phosphotransferases of the serine...

true

256

5e-54

207.75

93.36

7,25,0,44,70,44,25,104,69,34,138,104,31,170,135,23,196,158,49,246,207,32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQaRFKREAQAVAALNHPSIVAIFDTGEysvpggpgeD 105
cd00180        1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQVE-RILREIKILKRLNHPNIVKLYDVFE---------D 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPYIVMEYVAGRTLRDMIKANELGVEDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAM 184
cd00180       71 EDKLYLVMEYMSGGDLFDLLKKRGRLSEDEARFyFRQILSGLEYLHSKGIIHRDLKPENILLDED-GHVKIADFGLAKQL 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 185 ADSAATMTQtqaVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVaYQHVRETPDLASAHNPEV 264
cd00180      150 DSGGRKLTT---FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDL-LEKILKGKGTPDELPPNI 225

                        250
                 ....*....|....
gi 119962857 265 SEALDSVLVKALQK 278
cd00180      226 SPEAKDLIKKLLVK 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132937

cd06606

STKc_MAPKKK

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. 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.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

259

2e-45

179.28

77.99

7,25,0,45,71,45,24,103,69,26,130,95,6,136,103,33,170,136,20,191,156,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQArFKREAQAVAALNHPSIVAIFDTGEysvpggpgED 105
cd06606        1 EWTRGKLLGRGSFGSVYLALSKDTGELVAVKSVELSSDSEEELES-LEREIRILSKLQHPNIVRYYGCEV--------TE 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPYIVMEYVAGRTLRDMIKANElGVEDSV--GFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARA 183
cd06606       72 ENTLNIFMEYVSGGSLASLLKKFG-KLPEPVirRYTRQILEGLAYLHSNGIVHRDIKGANILLDSD-GVVKLADFGCAKR 149

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 119962857 184 MADSAATmTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06606      150 LASIAYS-GGLKSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPW 202

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

Protein Kinases (PKs), STE family, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The STE family is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). 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), MAPK kinase kinases (MAPKKKs), or MAPK kinase kinase 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.

Protein Kinases (PKs), STE family, catalytic (c) domain. PKs catalyze the transfer of...

false

true

false

253

4e-41

164.63

84.19

7,26,1,39,68,40,23,93,63,9,109,72,29,138,102,31,170,133,11,184,144,70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDpqfQARFKREAQAVAALNHPSIVAIFdtGEYSVPGGPgedv 106
cd05122        2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEE---QEQILNEIQILKKCKHPNIVKYY--GSYLKKDEL---- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 rvpYIVMEYVAGRTLRDMIKANELGVEDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramA 185
cd05122       73 ---WIVMEYCDGGSLDDLLKSTGPLPESQIAYiCREVLQGLEYLHSNGIIHRDIKPANILLTSD-GEVKLADFGVS---A 145

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETP 254
cd05122      146 QLSDTKAKRNTFVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALFKIATNPP 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132958

cd06627

STKc_Cdc7_like

Serine/threonine kinases (STKs), cell division control protein 7 (Cdc7)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Cdc7-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. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane.

Serine/threonine kinases (STKs), cell division control protein 7 (Cdc7)-like subfamily,...

false

true

false

254

1e-38

156.64

93.31

11,25,0,31,58,31,9,67,41,25,92,69,5,109,74,28,137,103,32,170,135,18,191,153,60,251,214,5,261,219,2,263,222,15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQ-FQARFKREAQAVAALNHPSIVAIFD---TGEYSvpgg 101
cd06627        1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIK--QISLEKIKEeALKSIMQEIDLLKNLNHPNIVKYIGsvkTSDSL---- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 pgedvrvpYIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGI 180
cd06627       75 --------YIILEYAENGSLRQIIKKFGKFPESLVAvYVYQVLQGLAYLHEQGVIHRDIKAANILTTKD-GVVKLADFGV 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 181 ARAMADSAatmTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVR-ETPDLasa 259
cd06627      146 ATKLSDVS---KDDESVVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQdDHPPL--- 219

                        250       260
                 ....*....|....*....|
gi 119962857 260 hnPE-VSEALDSVLVKALQK 278
cd06627      220 --PEgISPELKDFLMQCFQK 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

STKc_AGC: Serine/Threonine Kinases (STKs), AGC (Protein Kinases A, G and C) family, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AGC 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 (PI3K). 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. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases.

STKc_AGC: Serine/Threonine Kinases (STKs), AGC (Protein Kinases A, G and C) family,...

false

true

false

250

5e-34

141.00

92.00

6,32,0,59,95,59,3,103,62,38,141,101,28,170,129,16,189,145,85

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFdtgeYSVpggpgEDVRVPYIV 112
cd05123        1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLH----YAF-----QTKEKLYLV 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAMADsaaTM 191
cd05123       72 MEYVNGGDLFTHLSKEGRFDEERARFYAAeIVLALEYLHSLGIIYRDLKPENILLDAD-GHIKLTDFGLAKEGID---DG 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 192 TQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETPDLASAHNPEVSEALDSV 271
cd05123      148 VRTTTFCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRFPEFLSEEAKDLIKKL 227


                 ...
gi 119962857 272 LVK 274
cd05123      228 LTK 230

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

STKc_PDK1: Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PDK1 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 (PI3K). PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. PDK1 is essential for normal embryo development and is important in regulating cell volume.

STKc_PDK1: Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1)...

false

true

false

279

5e-33

137.62

80.29

6,26,2,57,83,60,12,104,72,24,128,97,41,170,138,26,196,181,45

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALN-HPSIVAIFDTGEysvpggpgeD 105
cd05581        3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLDKRHLIKEKKVKYVKREKEVLTRLNgHPGIVKLYYTFQ---------D 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPYIVMEYVAGRTLRDMIKAN-ELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAM 184
cd05581       74 EENLYFVLEYAENGELLEYIKKFgSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKD-GHIKITDFGTAKVL 152

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119962857 185 ADSAATMTQTQA-----------------VVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDS 241
cd05581      153 DPNSSPESNKGKatnidsqieknrrrrasFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSN 226

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

STKc_cGK_PKG: Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or PKG) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cGK 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. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm.

STKc_cGK_PKG: Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or...

false

true

false

262

1e-30

130.31

74.43

6,32,0,61,95,61,2,104,63,37,141,101,25,167,126,25,196,151,44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFDTgeYSvpggpgeDVRVPYIV 112
cd05572        1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRT--FK-------DKKYIYFL 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADSAATM 191
cd05572       72 MEYCLGGELWTILRDRGLLDEYTARFYTAcVVEAFEYLHNRGIIYRDLKPENLLL-DSNGYVKLVDFGFAKKLKSGQKTY 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 119962857 192 TqtqaVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGD 240
cd05572      151 T----FCGTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGED 195

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132954

cd06623

PKc_MAPKK_plant_like

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

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs...

false

true

false

264

2e-30

129.63

75.00

8,27,3,34,63,37,25,88,66,9,110,75,28,138,104,13,151,118,18,170,136,16,189,152,49

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  28 ELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADlaRDPQFQARFKREAQAVAALNHPSIV----AIFDTGEYSvpggpg 103
cd06623        4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHVD--GDEEFRKQLLRELKTLRSCESPYVVkcygAFYKEGEIS------ 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 edvrvpyIVMEYVAGRTLRDMIKANELGVEDSVGF-TLGVLGALEYSHR-AGIVHRDIKPANVMVCADtGDVKVMDFGIA 181
cd06623       76 -------IVLEYMDGGSLADLLKKVGKIPEPVLAYiARQILKGLDYLHTkRHIIHRDIKPSNLLINSK-GEVKIADFGIS 147

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 182 RAMADsaaTMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFI 238
cd06623      148 KVLEN---TLDQCNTFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFL 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132940

cd06609

STKc_MST3_like

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

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 3 (MST3)-like...

false

true

false

274

2e-30

129.27

75.18

9,24,0,45,71,45,20,93,65,4,103,69,5,109,74,22,132,96,8,140,105,26,167,131,19,189,150,56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQarFKREAQAVAALNHPSIVAIFdtGEYSvpggpgE 104
cd06609        1 ELFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIDLEEAEDEIED--IQQEIQFLSQCRSPYITKYY--GSFL------K 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 105 DVRVpYIVMEYVAGRTLRDMIKANELGvEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARA 183
cd06609       71 GSKL-WIIMEYCGGGSCLDLLKPGKLD-ETYIAFILrEVLLGLEYLHEEGKIHRDIKAANILL-SEEGDVKLADFGVSGQ 147

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119962857 184 MADsaaTMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSV 245
cd06609      148 LTS---TMSKRNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRV 206

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

STKc_MAST_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. The MAST kinase subfamily includes MAST kinases, MAST-like (MASTL) kinases, 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 also contains an insert relative to MAST kinases like MASTL. 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. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively.

STKc_MAST_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/...

false

true

false

265

4e-29

124.92

90.19

10,32,0,26,58,27,11,70,38,21,95,59,3,103,62,38,141,101,28,170,129,13,183,147,62,246,209,5,252,214,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVL-RADLARDPQFQaRFKREAQAVAALNHPSIVAIFdtgeYSVpggpgEDVRVPYI 111
cd05579        1 ISKGAYGRVFLAKKKSTGDIYAIKVIkKADMIRKNQVD-QVLTERNILSQAQNPFVVKLY----YSF-----QGKKNLYL 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 112 VMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARA-----MA 185
cd05579       71 VMEYLPGGDLASLLENVGSLDEDMARIYIAeIVLALEYLHSNGIIHRDLKPDNILIDSN-GHLKLTDFGLSKVglvrrQI 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVaYQHVReTPDLASAHNPEVS 265
cd05579      150 NLNDDEKEDKRIVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEI-FQNIL-NGKIEWPEDVEVS 227

                        250
                 ....*....|..
gi 119962857 266 EALDSVLVKALQ 277
cd05579      228 DEAKDLISKLLV 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132957

cd06626

STKc_MEKK4

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK4 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. MEKK4 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates 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. MEKK4 activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (...

false

true

false

264

2e-28

122.83

87.88

10,25,0,45,71,45,20,99,65,9,109,74,28,137,103,29,167,132,24,191,157,26,217,186,22,239,209,9,255,218,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQArFKREAQAVAALNHPSIVAIFdtgeysvpGGPGED 105
cd06626        1 RWQRGNKIGGGTFGKVYTAVNLDTGELMAVKEIRIQDNDPKTIKE-IADEMKVLELLKHPNLVKYY--------GVEVHR 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVpYIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAM 184
cd06626       72 EKV-YIFMEYCSGGTLEELLEHGRILDEHVIRvYTLQLLEGLAYLHSHGIVHRDIKPANIFL-DHNGVIKLGDFGCAVKL 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 185 ADSAATM-TQTQAVVGTAQYLSPEQARGETVDAR---SDLYSAGCLLFELLTSRPPFIG-DSPVSVAYQhvretpdLASA 259
cd06626      150 KNNTTTMgEEVQSLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMFH-------VGAG 222

                        250
                 ....*....|
gi 119962857 260 HNPEVSEALD 269
cd06626      223 HKPPIPDSLQ 232

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88474

cd05573

STKc_ROCK_NDR_like

STKc_ROCK_NDR_like: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) and Nuclear Dbf2-Related (NDR)-like kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK- and NDR-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. 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.

STKc_ROCK_NDR_like: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil...

false

true

false

354

5e-28

121.50

76.27

10,24,0,35,59,36,8,68,44,23,95,67,3,103,70,38,141,109,28,170,137,25,195,190,70,265,261,4,271,265,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLR-ADLARDPQfQARFKREAQAVAALNHPSIVAIFdtgeYSVpggpg 103
cd05573        1 EDFEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRkSDMLKRNQ-VAHVRAERDILADADSPWIVKLY----YSF----- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 EDVRVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAR 182
cd05573       71 QDEEYLYLVMEYMPGGDLMTLLIKYDVFPEETARFYIAeLVLAIDSVHKLGFIHRDIKPDNILIDAD-GHIKLADFGLCK 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 183 AMADSAATMTQTQ----------------------------AVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSR 234
cd05573      150 KMKKAGDSEYYLNdshnlldsdrdnvlkrrrpkkqrrvraySTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGY 229

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 119962857 235 PPFIGDSPVSVAYQHVRETPDLASAHNPEVS-EALDsvLVKAL 276
cd05573      230 PPFYSDTLQETYNKIMNWKESLYFPADVKVSpEAID--LIRRL 270

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, 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 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. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. 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). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, catalytic (c)...

false

true

false

287

1e-27

119.63

82.58

12,26,20,33,61,53,8,70,61,23,95,84,5,107,89,24,131,114,10,141,125,28,170,153,11,188,164,8,196,176,56,252,233,9,261,244,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRadLARDPQFQaRFKREAQAVAALNHPSIVAIFDTgeYSVPGgpgedv 106
cd06614       21 YDNLEKIGEGASGEVYTATDRATGKEVAIKKMR--LRKQPKKE-LIINEILIMKECKHPNIVNYYDS--YLVGD------ 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 rVPYIVMEYVAGRTLRDMIKANELG-VEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAram 184
cd06614       90 -ELWVVMEYMDGGSLTDIITQTFVRmNESQIAYVCReVLQGLEYLHSQNVIHRDIKSDNILLSKD-GSVKLADFGFA--- 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 185 adsaATMTQTQA----VVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE-TPDLASA 259
cd06614      165 ----AQLTKEKSkrnsMVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLITTKgIPPLKNP 240

                        250
                 ....*....|....*..
gi 119962857 260 HN--PEVSEALDSVLVK 274
cd06614      241 EKwsPEFKDFLNKCLVK 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132956

cd06625

STKc_MEKK3_like

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3-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. This subfamily is composed of MEKK3, MEKK2, and related proteins, all containing an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks), proteins that 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. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily,...

false

true

false

263

3e-27

118.76

93.92

7,26,3,30,58,33,13,71,50,20,100,70,37,137,108,29,167,137,85,252,224,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQFQAR----FKREAQAVAALNHPSIVAIFdtgeysvpgGP 102
cd06625        4 WRRGKLLGQGAFGRVYLCYDVDTGRELAVK--QVPFDPDSPETKKevnaLECEIQLLKNLQHERIVQYY---------GC 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 GEDVRVPYIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIA 181
cd06625       73 LRDDETLSIFMEYMPGGSVKDQLKAYGALTETVTRkYTRQILEGVEYLHSNMIVHRDIKGANILR-DSAGNVKLGDFGAS 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 RAMADSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE--TPDLASA 259
cd06625      152 KRLQTICSSGTGMKSVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQptNPQLPSH 231

                        250
                 ....*....|....*....
gi 119962857 260 HNPEVSEALDSVLVKALQK 278
cd06625      232 VSPDARNFLRRTFVENAKK 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132941

cd06610

STKc_OSR1_SPAK

Serine/threonine kinases (STKs), oxidative stress response kinase (OSR1) and Ste20-related proline alanine-rich kinase (SPAK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The OSR1 and SPAK 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. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates.

Serine/threonine kinases (STKs), oxidative stress response kinase (OSR1) and Ste20-...

false

true

false

266

9e-27

117.03

77.44

10,24,0,34,60,34,30,90,67,5,107,72,19,126,92,6,132,100,8,140,109,29,170,138,37,207,178,4,213,182,24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLraDLARDPQFQARFKREAQAVAALNHPSIVAI---FDTGEysvpgg 101
cd06610        1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIKRI--DLEKCQTSMDELRKEIQAMSLCHHPNVVKYytsFVVGD------ 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 pgedvrVPYIVMEYVAGRTLRDMIK-ANELGV--EDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMD 177
cd06610       73 ------ELWVVMPLMSGGSCLDIMKySYPQGGldEAIIATILkEVLKGLEYLHKNGQIHRDIKAGNILLDSD-GSVKLAD 145

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119962857 178 FGIARAMADSAATMTQTQAVVGTAQYLSPE---QARGetVDARSDLYSAGCLLFELLTSRPPF 237
cd06610      146 FGVSASLADGGDRTKVRKTFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPY 206

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin-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. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6). MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAPK signaling cascades are important in mediating cellular responses to extracellular signals.

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain....

false

true

false

275

9e-26

113.91

83.27

10,25,6,40,69,46,13,82,60,9,93,69,15,109,84,18,127,106,13,140,120,26,167,146,14,184,160,23,207,188,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDpqfqARFKREAQAVAAL-NHPSIVAIFdtGEYSVPGGPGE 104
cd06608        7 IFELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDIIEDEE----EEIEEEYNILRKYsNHPNIATFY--GAFIKKGPPGS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 105 DVRVpYIVMEYVAGRTLRDMIKA----NELGVEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFG 179
cd06608       81 DDQL-WLVMELCGGGSVTDLVKGlrkkGKRLKEEWIAYILrETLRGLAYLHENKVIHRDIKGQNILL-TKEGEVKLVDFG 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 180 IAramADSAATMTQTQAVVGTAQYLSPE-----QARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETP 254
cd06608      159 VS---AQLDSTNGRRNTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPLCDMHPMRALFKIPRNPP 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

STKc_PKA: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA) subfamily, catalytic (c) subunit. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKA 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 (PI3K). This subfamily is composed of the cAMP-dependent proteins kinases, PKA and PRKX. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic (C) subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active C subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis.

STKc_PKA: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA)...

false

true

false

290

1e-25

112.92

69.31

7,26,2,32,58,35,11,70,46,25,104,71,21,125,93,44,170,137,16,192,153,50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVL-RADLARDPQFQaRFKREAQAVAALNHPSIVAIFDTGEysvpggpgeD 105
cd05580        3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILsKAKIVKLKQVE-HVLNEKRILQAVRHPFLVNLLGSFK---------D 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPYIVMEYVAGRTLRDMI-KANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAM 184
cd05580       73 NSNLYMVMEFVPGGELFSLLrRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSD-GYIKITDFGFAKRV 151

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 185 ADsaatmtQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSP 242
cd05580      152 KG------RTYTLCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNP 203

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

Serine/threonine kinases (STKs), Nak1 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nak1 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. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also known as N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner.

Serine/threonine kinases (STKs), Nak1 subfamily, catalytic (c) domain. STKs catalyze...

false

true

false

277

2e-25

112.53

76.53

10,24,0,43,69,43,15,84,61,7,93,68,5,100,73,2,106,75,2,109,77,59,169,136,12,184,148,26,210,175,37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQfqARFKREAQAVAALNH---PSIVAIFdtGEYSVpgG 101
cd06917        1 SLYQRLELIGRGAYGAVYRGKHVPTGRVVALKIINLDTPDDDV--SDIQREVALLSQLRQsqpPNITKYY--GSYLK--G 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 PgedvRVpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCAdTGDVKVMDFGIA 181
cd06917       75 P----RL-WIIMEYAEGGSVRTLMKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTN-TGNVKLCDFGVA 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 182 ramADSAATMTQTQAVVGTAQYLSPEQAR-GETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAY 247
cd06917      149 ---ALLNQNSSKRSTFVGTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMM 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

STKc_Sid2p_Dbf2p: Serine/Threonine Kinases (STKs), ROCK- and NDR-like subfamily, fungal Sid2p- and Dbf2p-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Sid2p- and Dbf2p-like group 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. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis.

STKc_Sid2p_Dbf2p: Serine/Threonine Kinases (STKs), ROCK- and NDR-like subfamily, fungal...

false

true

false

333

3e-25

111.93

58.56

8,32,8,10,42,20,5,49,25,42,95,67,3,103,70,38,141,109,27,169,136,11,186,147,56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVY--RGTDTllGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFdtgeYSVpggpgEDVRVPY 110
cd05600        9 VGQGGYGQVFlaKKKDT--GEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLL----YAF-----QDDEYLY 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCAdTGDVKVMDFGIaramadSAA 189
cd05600       78 LAMEYVPGGDFRTLLNNLGVLSEDHARFYMAeMFEAVDALHELGYIHRDLKPENFLIDA-SGHIKLTDFGL------SKG 150

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 119962857 190 TMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSP 242
cd05600      151 IVTYANSVVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTP 203

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK or MAP3K). MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs.

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs...

false

true

false

265

6e-25

111.25

89.81

12,28,5,4,33,9,29,64,38,24,88,66,9,110,75,22,132,98,6,138,105,14,152,120,16,169,136,20,194,156,45,239,206,22,261,230,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  29 LGELiGRGGMADVYRGTDTLLGRTIAVKVLRADLarDPQFQARFKREAQAVAALNHPSIV----AIFDTGEYSvpggpge 104
cd06605        6 LGEL-GAGNSGVVSKVRHRPTGKIMAVKTIRLEI--NEAIQKQILRELDILHKCNSPYIVgfygAFYNNGDIS------- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 105 dvrvpyIVMEYVAGRTLRDMIKANELGV-EDSVGF-TLGVLGALEYSHRA-GIVHRDIKPANVMVCAdTGDVKVMDFGIA 181
cd06605       76 ------ICMEYMDGGSLDKILKEVQGRIpERILGKiAVAVLKGLTYLHEKhKIIHRDVKPSNILVNS-RGEIKLCDFGVS 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 RAMADSAAtmtqtQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIG-----DSPVSVAYQHVRETPDL 256
cd06605      149 GQLVNSLA-----KTFVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPendppDGIFELLQYIVNEPPPR 223

                        250       260
                 ....*....|....*....|
gi 119962857 257 ASAHN--PEVSEALDSVLVK 274
cd06605      224 LPSGRfsPDFQDFVNLCLIK 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 1 (MST1) and MST2 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST1/2 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. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 (a MAPK kinase) and MEKK1 (a MAPK kinase kinase) by acting as a MAPK kinase kinase kinase (MAPKKKK). Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress.

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 1 (MST1) and MST2...

false

true

false

256

1e-24

110.05

79.30

10,26,4,35,65,39,5,71,44,20,93,64,5,102,69,4,109,73,18,127,92,13,140,106,26,167,132,19,189,151,56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADlardPQFQArFKREAQAVAALNHPSIVAIFdtGEYSVpggpGEDV 106
cd06612        5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVE----EDLQE-IIKEISILKQCDSPYIVKYY--GSYFK----NTDL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 rvpYIVMEYVAGRTLRDMIKA-NELGVEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAM 184
cd06612       74 ---WIVMEYCGAGSVSDIMKItNKTLTEEEIAAILyQTLKGLEYLHSNKKIHRDIKAGNILL-NEEGQAKLADFGVSGQL 149

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119962857 185 ADsaaTMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSV 245
cd06612      150 TD---TMAKRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRA 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88513

cd05612

STKc_PRKX_like

STKc_PRKX_like: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA) subfamily, PRKX-like kinases, catalytic (c) subunit. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKA 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. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney.

STKc_PRKX_like: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA)...

false

true

false

291

4e-24

108.41

72.16

10,24,0,35,59,36,10,70,46,25,104,71,21,125,93,44,170,137,21,197,158,10,207,170,5,214,175,31,246,206,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLR-ADLARDPQFQaRFKREAQAVAALNHPSIVAIFDTGEysvpggpg 103
cd05612        1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAiPEVIRLKQVE-HVHNEKSILSEISHPFIVNMYWTFH-------- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 eDVRVPYIVMEYVAGRTLRDMI-KANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAR 182
cd05612       72 -DDKFLYMLMEYVPGGELFSYLrKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKE-GHIKITDFGFAK 149

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 183 AMADSAATMtqtqavVGTAQYLSPE--QARGEtvDARSDLYSAGCLLFELLTSRPPFIGDSPVSVaYQHV 250
cd05612      150 KVRDRTWTL------CGTPEYLAPEiiQSKGH--GKAVDWWALGILIYEMLVGYPPFFDDNPFGI-YEKI 210

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

STKc_Yank1: Serine/Threonine Kinases (STKs), Yank1 or STK32A subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Yank1 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. This subfamily contains uncharacterized STKs with similarity to the human protein designated Yank1 or STK32A.

STKc_Yank1: Serine/Threonine Kinases (STKs), Yank1 or STK32A subfamily, catalytic (c)...

false

true

false

258

3e-23

105.32

93.80

8,26,1,65,95,66,3,103,69,41,144,111,22,167,133,20,191,153,55,246,209,7,253,218,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFdtgeYSVpggpgEDV 106
cd05578        2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLW----YSF-----QDE 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 RVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLG-ALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMA 185
cd05578       73 EDMYLVVDLLLGGDLRYHLQQKVKFSEEQVKFYVCEIVlALEYLHSKGIIHRDIKPDNILL-DEQGHAHLTDFNIATKLT 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 DSaatmTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVA-YQHVRET--PDLASAHNP 262
cd05578      152 PD----TLATSTSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGHSRTPREeILAKFETadVLYPAGWSS 227

                        250
                 ....*....|....*.
gi 119962857 263 EVSEALDSVLVKALQK 278
cd05578      228 EAIDAINKLLERDPQK 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88512

cd05611

STKc_Rim15_like

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, fungal Rim15-like kinases, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase.

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/...

false

true

false

260

6e-23

104.24

76.15

9,32,3,27,59,31,31,90,65,7,109,72,18,129,90,3,132,95,4,136,100,30,167,130,20,194,150,51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLR-ADLARDPQFQARFKREAQAVAALNHPSIVAI---FDTGEYSvpggpgedvrv 108
cd05611        4 ISKGAFGSVYLAKKRSTGDYFAIKVLKkSDMIAKNQVTNVKAERAIMMIQGESPYVAKLyysFQSKDYL----------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 109 pYIVMEYVAGRTLRDMIKAneLGV--EDSV-GFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMA 185
cd05611       73 -YLVMEYLNGGDCASLIKT--LGGlpEDWAkQYIAEVVLGVEDLHQRGIIHRDIKPENLLI-DQTGHLKLTDFGLSRNGL 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 DSaatmtqtQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSV 245
cd05611      149 EN-------KKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAV 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132979

cd06648

STKc_PAK_II

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group II, 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. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group II,...

false

true

false

285

2e-22

102.52

80.35

11,32,26,24,58,50,15,74,65,19,95,84,3,102,87,4,109,91,60,170,151,11,184,162,60,245,222,6,251,230,10,261,242,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQFQARFKrEAQAVAALNHPSIVAIFDTgeYSVpggpGEDVrvpYIV 112
cd06648       27 IGEGSTGIVCIATDKSTGRQVAVK--KMDLRKQQRRELLFN-EVVIMRDYQHPNIVEMYSS--YLV----GDEL---WVV 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramADSAATMT 192
cd06648       95 MEFLEGGALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSD-GRVKLSDFGFC---AQVSKEVP 170

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 193 QTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSvAYQHVR--ETPDLASAHN--PEVSEAL 268
cd06648      171 RRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQ-AMKRIRdnLPPKLKNLHKvsPRLRSFL 249


                 ....*.
gi 119962857 269 DSVLVK 274
cd06648      250 DRMLVR 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132944

cd06613

STKc_MAP4K3_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3-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. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK).

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

261

3e-22

101.98

81.23

9,24,2,44,71,46,20,93,66,4,102,70,5,109,75,29,138,105,28,167,133,14,184,147,30,214,180,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFqarFKREAQAVAALNHPSIVAIFdtGEYSvpggpGE 104
cd06613        3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLEPGDDFEI---IQQEISMLKECRHPNIVAYF--GSYL-----RR 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 105 DVRvpYIVMEYVAGRTLRDMIKANELGVEDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIAra 183
cd06613       73 DKL--WIVMEYCGGGSLQDIYQVTGPLSELQIAYvCRETLKGLAYLHSQGKIHRDIKGANILL-TEDGDVKLADFGVS-- 147

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 184 mADSAATMTQTQAVVGTAQYLSPEQARGETV---DARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQ 248
cd06613      148 -AQLTATIAKRKSFIGTPYWMAPEVAAVERKggyDGKCDIWALGITAIELAELQPPMFDLHPMRALFL 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

Serine/threonine kinases (STKs), plant MAP/ERK kinase kinase 1 (MEKK1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant MEKK1 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. This subfamily is composed of plant mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks) including Arabidopsis thaliana MEKK1 and MAPKKK3. MEKK1 is a MAPKKK that phosphorylates and activates 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. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death.

Serine/threonine kinases (STKs), plant MAP/ERK kinase kinase 1 (MEKK1)-like subfamily,...

false

true

false

258

3e-22

102.11

87.98

12,25,0,31,56,32,15,71,48,24,103,72,5,109,77,28,137,106,32,170,138,9,183,147,24,207,174,9,218,183,29,248,212,8,261,220,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVK-VLRADLARDPQFQAR-FKREAQAVAALNHPSIVAIFDTGEysvpggpg 103
cd06632        1 RWRKGELLGSGSFGSVYEGLNLDDGDFFAVKeVSLADDGQTGQEAVKqLEQEIALLSKLQHPNIVQYLGTER-------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 EDVRVpYIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGiar 182
cd06632       73 EEDNL-YIFLELVPGGSLAKLLKKYGSFPEPVIRlYTRQILLGLEYLHDRNTVHRDIKGANILVDTN-GVVKLADFG--- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 183 aMADSAATMTQTQAVVGTAQYLSPE---QARGETVDArsDLYSAGCLLFELLTSRPPFIGDSPVSVAYqHVRETPDLasa 259
cd06632      148 -MAKQVVEFSFAKSFKGSPYWMAPEviaQQGGYGLAA--DIWSLGCTVLEMATGKPPWSQLEGVAAVF-KIGRSKEL--- 220


                 ....*....
gi 119962857 260 hnPEVSEAL 268
cd06632      221 --PPIPDHL 227

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

STKc_phototropin_like: Serine/Threonine Kinases (STKs), Phototropin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The phototropin-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. Included in this subfamily are plant phototropins and predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. N. crassa nrc-2 plays a role in growth and development by controlling entry into the conidiation program.

STKc_phototropin_like: Serine/Threonine Kinases (STKs), Phototropin-like subfamily,...

false

true

false

315

5e-22

101.48

85.71

8,24,0,64,88,67,9,109,76,23,132,101,9,141,111,28,170,139,21,191,185,67,260,252,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIV---AIFDTGEYSvpgg 101
cd05574        1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPtlyASFQTETYL---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 pgedvrvpYIVMEYVAGRTLRDMIKANELGV--EDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDF 178
cd05574       77 --------CLVMDYCPGGELFRLLQRQPGKCfpEEVARFYAAeVLLALEYLHLLGIVYRDLKPENILLHED-GHIMLSDF 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 179 GIARAMADSAATM-------------------------TQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTS 233
cd05574      148 DLSKQSDVEPTPVskalrkgsrgsvnkittetfseepsFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYG 227

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 119962857 234 RPPFIGDSPVSVAYQHVRETPDLASahNPEVSEALDSVLVKALQK 278
cd05574      228 TTPFKGKNRDETFSNILKKEVTFPG--SPPVSSSARDLIRKLLVK 270

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Byr2-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

267

8e-22

100.68

77.90

9,29,4,32,62,36,9,71,52,20,100,72,25,127,97,4,131,102,5,136,109,30,167,139,19,186,161,51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELIGRGGMADVYRGTDTLLGRTIAVKVLRADlARDPQFQAR-------FKREAQAVAALNHPSIVAIFdtgeysvpgGP 102
cd06628        5 GALIGSGSFGSVYLGMNAHSGELMAVKQVEIP-SNSIGVQDRkrkmldaLQREINLLKELHHENIVQYL---------GS 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 GEDVRVPYIVMEYVAGRTLRDMIkaNELG-VEDSV--GFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFG 179
cd06628       75 SQDAGHLNIFLEYVPGGSVAALL--NNYGaFEESLvrNFVRQILKGLNYLHNRGIIHRDIKGANILV-DNKGGIKISDFG 151

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119962857 180 IARAMAD---SAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06628      152 ISKKLEAnslSTKTNGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPF 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132983

cd06652

STKc_MEKK2

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 2 (MEKK2) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK2 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. MEKK2 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 2 (MEKK2) subfamily, catalytic (...

false

true

false

265

1e-21

100.11

78.49

7,24,1,37,62,38,9,71,50,19,95,69,9,106,78,28,134,107,32,167,139,70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADlARDPQFQAR---FKREAQAVAALNHPSIVAIfdtgeYSVPGG 101
cd06652        2 TNWRLGKLLGQGAFGRVYLCYDADTGRELAVKQVQFD-PESPETSKEvnaLECEIQLLKNLLHERIVQY-----YGCLRD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 PGEdvRVPYIVMEYVAGRTLRDMIKANELGVED-SVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGI 180
cd06652       76 PME--RTLSIFMEHMPGGSIKDQLKSYGALTENvTRKYTRQILEGVSYLHSNMIVHRDIKGANILR-DSVGNVKLGDFGA 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 181 ARAMADSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06652      153 SKRLQTICLSGTGMKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPW 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

STKc_p70S6K: Serine/Threonine Kinases (STKs), 70 kDa ribosomal protein S6 kinase (p70S6K) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The p70S6K 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. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta).

STKc_p70S6K: Serine/Threonine Kinases (STKs), 70 kDa ribosomal protein S6 kinase (...

false

true

false

323

1e-21

100.04

62.85

12,30,1,13,43,19,4,49,23,10,59,34,31,90,68,4,102,72,2,108,74,33,141,108,28,170,136,12,185,148,22,207,174,7,218,181,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYR-----GTDTllGRTIAVKVLR-ADLARDPQFQARFKREAQAVAALNHPSIVAI---FDTGeysvpgg 101
cd05584        2 KVLGKGGYGKVFQvrkvtGADT--GKIFAMKVLKkATIVRNQKDTAHTKAERNILEAVKHPFIVDLiyaFQTG------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 pGEdvrvPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGI 180
cd05584       73 -GK----LYLILEYLSGGELFMHLEREGIFMEDTACFYLSeISLALEHLHQQGIIYRDLKPENILLDAQ-GHVKLTDFGL 146

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 181 ARamaDSAATMTQTQAVVGTAQYLSPE----QARGETVdarsDLYSAGCLLFELLTSRPPFIGDS 241
cd05584      147 CK---ESIHEGTVTHTFCGTIEYMAPEilmrSGHGKAV----DWWSLGALMYDMLTGAPPFTAEN 204

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132984

cd06653

STKc_MEKK3_like_1

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily, catalytic (c) domain, functionally uncharacterized subgroup 1. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3-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. The MEKK3-like subfamily is composed of MEKK3, MEKK2, and related proteins, all containing an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks), proteins that 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. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily,...

false

true

false

264

4e-21

98.17

78.03

7,26,3,30,60,33,14,74,53,16,95,69,9,106,78,28,134,107,32,167,139,70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKvlraDLARDPQFQARFKR------EAQAVAALNHPSIVAIfdtgeYSVPG 100
cd06653        4 WRLGKLLGRGAFGEVYLCYDADTGRELAVK----QVPFDPDSQETSKEvnalecEIQLLKNLRHDRIVQY-----YGCLR 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 101 GPGEdvRVPYIVMEYVAGRTLRDMIKANELGVED-SVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFG 179
cd06653       75 DPEE--KKLSIFVEYMPGGSIKDQLKAYGALTENvTRRYTRQILQGVSYLHSNMIVHRDIKGANILR-DSAGNVKLGDFG 151

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 180 IARAMADSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06653      152 ASKRIQTICMSGTGIKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPW 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132982

cd06651

STKc_MEKK3

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3 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. MEKK3 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3) subfamily, catalytic (...

false

true

false

266

1e-20

96.68

92.48

8,29,6,32,62,38,7,69,48,22,91,74,4,106,78,28,134,107,32,167,139,85,252,226,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELIGRGGMADVYRGTDTLLGRTIAVKVLRADlARDPQFQ---ARFKREAQAVAALNHPSIVAIF----DTGEysvpggp 102
cd06651        7 GKLLGQGAFGRVYLCYDVDTGRELAAKQVQFD-PESPETSkevSALECEIQLLKNLQHERIVQYYgclrDRAE------- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 gedvRVPYIVMEYVAGRTLRDMIKANELGVED-SVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIA 181
cd06651       79 ----KTLTIFMEYMPGGSVKDQLKAYGALTESvTRKYTRQILEGMSYLHSNMIVHRDIKGANILR-DSAGNVKLGDFGAS 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 RAMADSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE--TPDLASA 259
cd06651      154 KRLQTICMSGTGIRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQptNPQLPSH 233

                        250
                 ....*....|....*....
gi 119962857 260 HNPEVSEALDSVLVKALQK 278
cd06651      234 ISEHARDFLGCIFVEARHR 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

3e-20

95.66

77.01

11,30,0,15,45,16,8,53,26,8,62,34,8,71,42,20,93,62,1,95,63,7,108,70,20,128,99,41,170,140,31,202,171,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGT-DTLLGRTI--AVKVLRADlARDPQFQArFKREAQAVAALNHPSIVAIFdtGeYSVPGGPgedvr 107
cd00192        1 KKLGEGAFGEVYKGElKGKGGKKTpvAVKTLKED-ASDSERED-FLKEAKIMKKLGHPNIVRLL--G-VCTEEEP----- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 vPYIVMEYVAGRTLRDMIKAN---------ELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDF 178
cd00192       71 -LYLVLEYMEGGDLLDFLRKSrpvfspessTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGED-LVVKIADF 148

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 119962857 179 GIARAMADSAATMTQTQAVVGTAqYLSPEQARGETVDARSDLYSAGCLLFELLT 232
cd00192      149 GLSRDIYDDDYYRKKGGGKLPIR-WMAPESLKDGKFTTKSDVWSFGVLLWEIFT 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

STKc_ROCK: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK 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. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development.

STKc_ROCK: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing...

false

true

false

370

3e-20

95.39

68.11

6,16,34,75,95,109,3,103,112,60,164,172,20,186,192,30,216,226,60

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  17 VSSQRILNSRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFdtgeY 96
cd05596       35 ITKLRMKAEDFDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLSKFEMIKRSDSAFFWEERDIMAHANSEWIVQLH----Y 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  97 SVpggpgEDVRVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANvMVCADTGDVKVM 176
cd05596      111 AF-----QDDKYLYMVMEYMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDN-MLLDKSGHLKLA 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 177 DFGIARAMadSAATMTQTQAVVGTAQYLSPEQARGETVDA----RSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE 252
cd05596      185 DFGTCMKM--DANGMVRCDTAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMDH 262

                        250       260
                 ....*....|....*....|....
gi 119962857 253 TPDLASAHNPEVSEALDSVLVKAL 276
cd05596      263 KNSLTFPDDIEISKQAKDLICAFL 286

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132986

cd06655

STKc_PAK2

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 2, 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. PAK2 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). 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.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 2, catalytic (c) domain....

false

true

false

296

5e-20

94.79

74.32

10,25,19,31,58,50,9,68,59,25,95,84,3,102,87,4,109,91,60,170,151,11,184,162,64,248,227,8,259,235,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQfQARFKREAQAVAALNHPSIVAIFDTgeYSVpggpGED 105
cd06655       20 KYTRYEKIGQGASGTVFTAIDVATGQEVAIK--QINLQKQPK-KELIINEILVMKELKNPNIVNFLDS--FLV----GDE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VrvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramA 185
cd06655       91 L---FVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMD-GSVKLTDFGFC---A 163

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQ-HVRETPDLasaHNPE 263
cd06655      164 QITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLiATNGTPEL---QNPE 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132973

cd06642

STKc_STK25_YSK1

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

Serine/threonine kinases (STKs), STK25 subfamily, catalytic (c) domain. STKs catalyze...

false

true

false

277

5e-20

94.73

83.03

8,30,9,37,69,46,22,93,68,4,101,72,5,109,77,57,167,134,19,189,153,64,253,218,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQfqARFKREAQAVAALNHPSIVAIFdtGEYSvpggPGEDVrvpY 110
cd06642       10 ERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEI--EDIQQEITVLSQCDSPYITRYY--GSYL----KGTKL---W 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADsaaT 190
cd06642       79 IIMEYLGGGSALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLL-SEQGDVKLADFGVAGQLTD---T 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 191 MTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRET-PDLASAHNPEVSEALD 269
cd06642      155 QIKRNTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSpPTLEGQYSKPFKEFVE 234


                 ....*
gi 119962857 270 SVLVK 274
cd06642      235 ACLNK 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 1 (MEKK1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK1 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. MEKK1 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates 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. MEKK1 activates the extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 1 (MEKK1) subfamily, catalytic (...

false

true

false

268

5e-20

94.54

76.12

8,29,4,29,58,36,30,88,70,9,110,79,16,126,98,6,134,104,52,186,158,9,196,167,41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELIGRGGMADVYRGTDTLLGRTIAVKVL---RADLARDPQFQARFKREAQAVAALNHPSIV----AIFDTGEYSvpggp 102
cd06630        5 GQQLGTGAFSSCYQARDVKTGTLMAVKQVtyvRNTSSEQEEVVEALRKEIRLMARLNHPHIIrmlgATCEDSHFN----- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 gedvrvpyIVMEYVAGRTLRDMIK---ANELGVedSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADTGDVKVMDFG 179
cd06630       80 --------LFVEWMAGGSVSHLLSkygAFKEAV--IINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQRLRIADFG 149

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 180 IARAMAD--SAATMTQTQaVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06630      150 AAARLAAkgTGAGEFQGQ-LLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPW 208

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132962

cd06631

STKc_YSK4

Serine/threonine kinases (STKs), yeast Sps1/Ste20-related kinase 4 (YSK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The YSK4 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. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs (MKKKs or MAP3Ks) 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.

Serine/threonine kinases (STKs), yeast Sps1/Ste20-related kinase 4 (YSK4) subfamily,...

false

true

false

265

8e-20

93.82

80.75

9,29,4,16,46,20,15,61,39,8,70,47,25,103,72,6,110,78,26,136,105,32,169,137,25,194,165,53

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELIGRGGMADVYRGTdTLLGRTIAVKVLRAD----LARDPQFQaRFKREAQAVAALNHPSIVAIFDTGEysvpggpgED 105
cd06631        5 GEVLGKGAYGTVYCGL-TNQGQLIAVKQVELDtsnvLAAEKEYE-KLQEEVDLLKSLKHVNIVQYLGTCL--------DD 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPyIVMEYVAGRTLRDMIKANELGVEDSV-GFTLGVLGALEYSHRAGIVHRDIKPANVMVCAdTGDVKVMDFGIARAM 184
cd06631       75 NTIS-IFMEFVPGGSISSILNRFGPLPEPVFcKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMP-NGIIKLIDFGCARRL 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119962857 185 ADSAATMTQT---QAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAY 247
cd06631      153 AWVGLHGTHSnmlKSMHGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASMDRLAAMF 218

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 3 (MST3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST3 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. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation.

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 3 (MST3) subfamily,..

false

true

false

277

1e-19

93.60

83.03

8,30,9,37,69,46,22,93,68,4,103,72,5,109,77,57,167,134,19,189,153,64,253,218,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQfqARFKREAQAVAALNHPSIVAIFdtGEYSvpggpgEDVRVpY 110
cd06641       10 EKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDEI--EDIQQEITVLSQCDSPYVTKYY--GSYL------KDTKL-W 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADsaaT 190
cd06641       79 IIMEYLGGGSALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLL-SEHGEVKLADFGVAGQLTD---T 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 191 MTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRET-PDLASAHNPEVSEALD 269
cd06641      155 QIKRNTFVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLFLIPKNNpPTLEGNYSKPLKEFVE 234


                 ....*
gi 119962857 270 SVLVK 274
cd06641      235 ACLNK 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88502

cd05601

STKc_CRIK

STKc_CRIK: Serine/Threonine Kinases (STKs), Citron Rho-interacting kinase (CRIK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CRIK 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. CRIK is also called citron kinase. It contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. CRIK, an effector of the small GTPase Rho, plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension.

STKc_CRIK: Serine/Threonine Kinases (STKs), Citron Rho-interacting kinase (CRIK)...

false

true

false

330

1e-19

93.45

66.36

10,26,2,64,94,66,4,103,70,29,132,100,9,141,110,25,167,135,12,186,147,11,197,163,21,218,190,23,242,213,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIfdtgEYSVpggpgEDV 106
cd05601        3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQL----QYAF-----QDK 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 RVPYIVMEYVAGRTLRDMIKANELGV-EDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGiaram 184
cd05601       74 DNLYLVMEYHPGGDLLSLLNRYEDQFdESMAQFYLAeLVLAIHSLHQMGYVHRDIKPENILI-DRTGHIKLADFG----- 147

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 185 adSAATMTQTQAV-----VGTAQYLSPEQARGETVDARS------DLYSAGCLLFELLTSRPPFIGDSpVSVAYQHV 250
cd05601      148 --SAAKLNANKMVnsklpVGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGT-SAVTYSNI 221

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Bck1-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

272

2e-19

92.94

76.10

9,29,5,27,56,35,13,69,52,21,90,75,9,110,84,27,137,112,32,170,144,20,191,164,16,207,182,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELIGRGGMADVYRGTDTLLGRTIAVK---VLRADLARDPQFQ----ARFKREAQAVAALNHPSIVAI--FDTGEYSVPg 100
cd06629        6 GELIGKGTYGRVYLALNVTTGEMMAVKqveLPATIAGRHDSRQkdmvKALRSEIETLKDLDHLNIVQYlgFETTEEYLS- 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 101 gpgedvrvpyIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFG 179
cd06629       85 ----------IFLEYVPGGSIGSCLRTYGRFEEQLVRfFTEQVLEGLAYLHSKGILHRDLKADNLLVDAD-GICKISDFG 153

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 180 IARAMADSAATmTQTQAVVGTAQYLSPE--QARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06629      154 ISKKSDDIYDN-DQNMSMQGSVFWMAPEviHSYSQGYSAKVDIWSLGCVVLEMFAGRRPW 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88523

cd05622

STKc_ROCK1

STKc_ROCK1: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK 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. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring.

STKc_ROCK1: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta)...

false

true

false

371

2e-19

92.81

60.92

6,9,27,82,95,109,3,103,112,60,164,172,24,190,196,26,216,226,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  10 HREESTPVSSQRILNSRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVA 89
cd05622       28 YKDTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQ 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  90 IFdtgeYSVpggpgEDVRVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANvMVCAD 169
cd05622      108 LF----YAF-----QDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDN-MLLDK 177

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 170 TGDVKVMDFGIARAMADSAatMTQTQAVVGTAQYLSPEQARGETVDA----RSDLYSAGCLLFELLTSRPPFIGDSPV 243
cd05622      178 SGHLKLADFGTCMKMNKEG--MVRCDTAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSLV 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group I, 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 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. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. 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.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group I,...

false

true

false

293

3e-19

91.89

80.89

11,23,17,33,58,50,9,68,59,25,95,84,3,102,87,4,109,91,60,170,151,11,184,162,64,248,227,9,260,236,3,263,240,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  24 NSRYELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQfQARFKREAQAVAALNHPSIVAIFDTgeYSVpggpG 103
cd06647       18 KKKYTRFEKIGQGASGTVYTAIDVATGQEVAIK--QMNLQQQPK-KELIINEILVMRENKHPNIVNYLDS--YLV----G 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 EDVrvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAra 183
cd06647       89 DEL---WVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMD-GSVKLTDFGFC-- 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 184 mADSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQ-HVRETPDLAsahNP 262
cd06647      163 -AQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLiATNGTPELQ---NP 238

                        250
                 ....*....|....*.
gi 119962857 263 E-VSEALDSVLVKALQ 277
cd06647      239 EkLSAIFRDFLNRCLE 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132952

cd06621

PKc_MAPKK_Pek1_like

Protein kinases (PKs), MAP kinase kinase(MAPKK) subfamily, fungal Pek1-like proteins, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates the MAPK Pmk1/Spm1 and is regulated by the MAPKKK Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKKK Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis.

Protein kinases (PKs), MAP kinase kinase(MAPKK) subfamily, fungal Pek1-like proteins,...

false

true

false

287

3e-19

91.72

71.08

11,28,8,3,33,11,14,49,25,20,71,45,17,88,66,10,109,76,12,121,92,16,137,109,32,170,141,17,187,159,5,198,164,48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  29 LGEliGRGGMADVYRGTDTllGRTIAVKVLRADLARDPQFQarFKREAQAVAALNHPSIV----AIFDTGEYSVpggpge 104
cd06621        9 LGE--GAGGSVTKCRLKNT--GMIFALKTITTDPNPDLQKQ--ILRELEINKSCKSPYIVkyygAFLDESSSSI------ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 105 dvrvpYIVMEYVAGRTL----RDMIKANELGVEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFG 179
cd06621       77 -----GIAMEYCEGGSLdsiyKKVKKRGGRIGEKVLGkIAESVLKGLSYLHSRKIIHRDIKPSNILLTRK-GQVKLCDFG 150

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 180 IARAMADS-AATMTqtqavvGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVA 246
cd06621      151 VSGELVNSlAGTFT------GTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPPLG 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 4 (MST4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST4 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. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration.

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 4 (MST4) subfamily,..

false

true

false

277

8e-19

90.50

83.03

8,30,9,37,69,46,22,93,68,4,101,72,5,109,77,57,167,134,19,189,153,62,251,216,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQfqARFKREAQAVAALNHPSIVAIFdtGEYSvpggPGEDVrvpY 110
cd06640       10 ERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEI--EDIQQEITVLSQCDSPYVTKYY--GSYL----KGTKL---W 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADsaaT 190
cd06640       79 IIMEYLGGGSALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLL-SEQGDVKLADFGVAGQLTD---T 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 191 MTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVR-ETPDLASAHNPEVSEALD 269
cd06640      155 QIKRNTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLIPKnNPPTLTGEFSKPFKEFID 234


                 ....*
gi 119962857 270 SVLVK 274
cd06640      235 ACLNK 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88500

cd05599

STKc_NDR_like

STKc_NDR_like: Serine/Threonine Kinases (STKs), Nuclear Dbf2-Related (NDR) kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The NDR 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. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases.

STKc_NDR_like: Serine/Threonine Kinases (STKs), Nuclear Dbf2-Related (NDR) kinase...

false

true

false

364

1e-18

90.34

67.03

9,26,2,33,59,36,9,69,45,22,95,67,3,103,70,38,141,109,28,170,137,14,184,172,11,195,197,49

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLR-ADLARDPQFqARFKREAQAVAALNHPSIVAIFdtgeYSVpggpgED 105
cd05599        3 FESIKVIGRGAFGEVRLVQKKDTGHIYAMKKLRkSEMLEKEQV-AHVRAERDILAEADNPWVVKLY----YSF-----QD 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VRVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAM 184
cd05599       73 ENYLYLIMEYLPGGDMMTLLMKKDTFTEEETRFYIAeTILAIDSIHKLGYIHRDIKPDNLLLDAK-GHIKLSDFGLCTGL 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 185 ---------------------ADSAATMTQTQ--------------AVVGTAQYLSPEQARGETVDARSDLYSAGCLLFE 229
cd05599      152 kkshrtefyrilshalpsnflDFISKPMSSKRkaetwkrnrralaySTVGTPDYIAPEVFLQTGYNKECDWWSLGVIMYE 231

                        250
                 ....*....|....*
gi 119962857 230 LLTSRPPFIGDSPVS 244
cd05599      232 MLVGYPPFCSDNPQE 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132990

cd06659

STKc_PAK6

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 6, 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. PAK6 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 6, catalytic (c) domain....

false

true

false

297

1e-18

89.70

78.45

11,32,28,26,60,54,13,74,67,19,95,86,3,102,89,4,109,93,60,170,153,11,184,164,60,245,224,8,253,234,7,260,243,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLraDLARDPQFQARFKrEAQAVAALNHPSIVAIFDTgeYSVpggpGEDVrvpYIV 112
cd06659       29 IGEGSTGIVCIAREKHSGRQVAVKMM--DLRKQQRRELLFN-EVVIMRDYQHQNVVEMYKS--YLV----GEEL---WVL 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramADSAATMT 192
cd06659       97 MEFLQGGALTDIVSQTRLNEEQIATVCESVLQALCYLHSQGVIHRDIKSDSILLTLD-GRVKLSDFGFC---AQISKDVP 172

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 193 QTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSvAYQHVRET--PDLASAH--NPEVSEAL 268
cd06659      173 KRKSLVGTPYWMAPEVISRTPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQ-AMKRLRDSppPKLKNAHkiSPVLRDFL 251

                        250
                 ....*....|
gi 119962857 269 DSVLVKALQK 278
cd06659      252 ERMLTREPQE 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132955

cd06624

STKc_ASK

Serine/threonine kinases (STKs), apoptosis signal-regulating kinase (ASK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ASK 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. Subfamily members are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks) and include ASK1, ASK2, and MAPKKK15. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species (ROS)-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown.

Serine/threonine kinases (STKs), apoptosis signal-regulating kinase (ASK) subfamily,...

false

true

false

268

2e-18

89.09

77.61

11,26,4,5,31,14,29,63,43,28,93,71,7,107,78,21,128,102,10,138,113,47,186,160,8,196,168,11,207,183,4,213,187,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGE-----LIGRGGMADVYRGTDTLLGRTIAVKVLRAdlaRDPQFQARFKREAQAVAALNHPSIVAIFdtGEYSVPGg 101
cd06624        5 YEYDEngervVLGKGTYGVVYAGRDLSTQVRIAIKEIPE---RDSRYSQPLHEEIALHSRLKHKNIVQYL--GSDSENG- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 102 pgedvrVPYIVMEYVAGRTLRDMIKAN---ELGVEDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVCADTGDVKVMD 177
cd06624       79 ------YFKIFMEQVPGGSLSALLRSKwgpLKDNESTIIFyTKQILEGLKYLHDNQIVHRDIKGDNVLVNTYSGVLKISD 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 178 FGIARAMAdSAATMTQTqaVVGTAQYLSPE----QARGetVDARSDLYSAGCLLFELLTSRPPFI 238
cd06624      153 FGTSKRLA-GINPCTET--FTGTLQYMAPEiidkGPRG--YGAPADIWSLGCTIIEMATGKPPFH 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132977

cd06646

STKc_MAP4K5

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 5 (MAPKKKK5 or MAP4K5) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K5 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

267

2e-18

89.32

78.28

9,26,10,42,71,52,20,93,72,6,103,78,3,109,81,31,140,113,26,167,139,14,184,153,29,213,185,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFqarFKREAQAVAALNHPSIVAIFdtGEYSVPggpgEDV 106
cd06646       11 YELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSL---IQQEIFMVKECKHCNIVAYF--GSYLSR----EKL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 rvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIAramA 185
cd06646       82 ---WICMEYCGGGSLQDIYHVTGPLSELQIAYVCrETLQGLAYLHSKGKMHRDIKGANILL-TDNGDVKLADFGVA---A 154

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGET---VDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAY 247
cd06646      155 KITATIAKRKSFIGTPYWMAPEVAAVEKnggYNQLCDIWAVGITAIELAELQPPMFDLHPMRALF 219

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

STKc_ROCK2: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK2 (or ROK-alpha) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK 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. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction.

STKc_ROCK2: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK2 (or ROK-alpha)...

false

true

false

370

3e-18

88.57

62.70

5,26,44,65,100,109,63,164,172,24,190,196,26,216,226,50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAIFdtgeysvpgGPGEDV 106
cd05621       45 YDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLF---------CAFQDD 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 RVPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANvMVCADTGDVKVMDFGIARAMAD 186
cd05621      116 KYLYMVMEYMPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDN-MLLDKHGHLKLADFGTCMKMDE 194

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 187 SAatMTQTQAVVGTAQYLSPEQARGETVDA----RSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETPDLASAHNP 262
cd05621      195 TG--MVRCDTAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIMDHKNSLNFPEDV 272


                 ....
gi 119962857 263 EVSE 266
cd05621      273 EISK 276

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133173

cd05041

PTKc_Fes_like

Catalytic Domain of Fes-like Protein Tyrosine Kinases

false

true

false

251

4e-18

88.29

77.69

10,30,0,14,46,14,6,52,21,11,65,32,34,108,66,17,125,85,41,167,126,26,198,152,4,202,160,30,237,190,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGtdTLLGRT-IAVKVLRADLArdPQFQARFKREAQAVAALNHPSIVAIFDTGEYSVPggpgedvrvP 109
cd05041        1 EKIGKGNFGDVYKG--VLKGKTeVAVKTCRSTLP--PDLKRKFLQEAEILKQYDHPNIVKLIGVCVQKQP---------I 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 110 YIVMEYVAGRTLRDMI--KANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADS 187
cd05041       68 YIVMELVPGGSLLTFLrkKKNRLTVKKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLV-GENNVLKISDFGMSREEEGG 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119962857 188 AATMTQtqavvGTAQ----YLSPEQARGETVDARSDLYSAGCLLFELLTsrppfIGDSP 242
cd05041      147 IYTVSD-----GLKQipikWTAPEALNYGRYTSESDVWSYGILLWETFS-----LGDTP 195

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133171

cd05039

PTKc_Csk_like

Catalytic Domain of C-terminal Src kinase-like Protein Tyrosine Kinases

false

true

false

256

4e-18

88.61

75.00

11,27,8,18,47,26,23,74,49,19,96,68,6,108,74,21,129,98,37,167,135,15,187,150,9,196,162,5,205,167,27,232,195,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  28 ELGELIGRGGMADVYRGTdtLLGRTIAVKVLRADLARDPQFQArfkrEAQAVAALNHPSIVAIFDTgeySVPGGPgedvr 107
cd05039        9 KLGATIGKGEFGDVMLGD--YRGQKVAVKCLKDDSTAAQAFLA----EASVMTTLRHPNLVQLLGV---VLQGNP----- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 vPYIVMEYVAGRTLRDMIKANE---LGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARam 184
cd05039       75 -LYIVTEYMAKGSLVDYLRSRGravITLAQQLGFALDVCEGMEYLEEKNFVHRDLAARNVLV-SEDLVAKVSDFGLAK-- 150

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 185 adsAATMTQTQA---VVGTAqylsPEQARGETVDARSDLYSAGCLLFELLT-SRPPF 237
cd05039      151 ---EASQGQDSGklpVKWTA----PEALREKKFSTKSDVWSFGILLWEIYSfGRVPY 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132985

cd06654

STKc_PAK1

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 1, 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. PAK1 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). 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.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 1, catalytic (c) domain....

false

true

false

296

4e-18

88.24

76.01

10,25,20,31,58,51,9,68,60,25,95,85,3,102,88,4,109,92,60,170,152,11,184,163,64,248,228,8,259,236,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQfQARFKREAQAVAALNHPSIVAIFDTgeYSVpggpGED 105
cd06654       21 KYTRFEKIGQGASGTVYTAMDVATGQEVAIR--QMNLQQQPK-KELIINEILVMRENKNPNIVNYLDS--YLV----GDE 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VrvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramA 185
cd06654       92 L---WVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMD-GSVKLTDFGFC---A 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQ-HVRETPDLasaHNPEV 264
cd06654      165 QITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLiATNGTPEL---QNPEK 241


                 ....
gi 119962857 265 SEAL 268
cd06654      242 LSAI 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88483

cd05582

STKc_RSK_N

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The RSK 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. 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. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks.

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK)...

false

true

false

318

6e-18

87.71

62.58

14,30,1,12,42,18,5,49,23,10,59,34,3,62,38,3,68,41,22,90,66,3,101,69,3,108,72,36,144,109,25,170,134,18,191,152,16,207,170,9,218,179,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVY-----RGTDTllGRTIAVKVLR-ADL-ARDpqfQARFKREAQAVAALNHPSIVAI---FDTgeysvpg 100
cd05582        2 KVLGQGSFGKVFlvrkiTGPDA--GQLYAMKVLKkATLkVRD---RVRTKMERDILAEVNHPFIVKLhyaFQT------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 101 gPGEdvrvPYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLG-ALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFG 179
cd05582       70 -EGK----LYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELAlALDHLHSLGIIYRDLKPENILLDEE-GHIKLTDFG 143

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119962857 180 IARAMADSAatmTQTQAVVGTAQYLSPE--QARGETVDArsDLYSAGCLLFELLTSRPPFIG 239
cd05582      144 LSKESIDHE---KKAYSFCGTVEYMAPEvvNRRGHTQSA--DWWSFGVLMFEMLTGSLPFQG 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132976

cd06645

STKc_MAP4K3

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

267

1e-17

87.03

81.27

8,18,2,47,68,49,23,102,72,7,109,81,29,138,111,28,167,139,14,184,153,25,209,181,38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  19 SQRILNSRYELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDpqfQARFKREAQAVAALNHPSIVAIFdtgeysv 98
cd06645        3 SRRNPQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPGED---FAVVQQEIIMMKDCKHSNIVAYF------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  99 pggpGEDVRVP--YIVMEYVAGRTLRDMIKANELGVEDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKV 175
cd06645       73 ----GSYLRRDklWICMEFCGGGSLQDIYHVTGPLSESQIAYvSRETLQGLYYLHSKGKMHRDIKGANILL-TDNGHVKL 147

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 176 MDFGIAramADSAATMTQTQAVVGTAQYLSPEQA---RGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAY 247
cd06645      148 ADFGVS---AQITATIAKRKSFIGTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALF 219

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132987

cd06656

STKc_PAK3

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.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain....

false

true

false

297

1e-17

87.08

74.07

10,25,19,31,58,50,9,68,59,25,95,84,3,102,87,4,109,91,60,170,151,11,184,162,64,248,227,8,259,235,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  26 RYELGELIGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQfQARFKREAQAVAALNHPSIVAIFDTgeYSVpggpGED 105
cd06656       20 KYTRFEKIGQGASGTVYTAIDIATGQEVAIK--QMNLQQQPK-KELIINEILVMRENKNPNIVNYLDS--YLV----GDE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 VrvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramA 185
cd06656       91 L---WVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMD-GSVKLTDFGFC---A 163

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119962857 186 DSAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQ-HVRETPDLasaHNPE 263
cd06656      164 QITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLiATNGTPEL---QNPE 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132968

cd06637

STKc_TNIK

Serine/threonine kinases (STKs),Traf2- and Nck-interacting kinase (TNIK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TNIK 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to mitogen-activated protein kinase (MAPK), kinase kinase kinase 4 (MAP4K4), and MAP4K6. MAP4Ks participate in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton.

Serine/threonine kinases (STKs),Traf2- and Nck-interacting kinase (TNIK) subfamily,...

false

true

false

272

1e-17

86.69

91.18

11,26,7,32,60,39,6,68,45,23,92,68,16,109,84,16,125,103,41,167,144,14,184,158,23,207,186,45,252,232,8,260,241,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLraDLARDPqfQARFKREAQAVAALNHPSIVAIFdTGEYSVPGGPGEDV 106
cd06637        8 FELVELVGNGTYGQVYKGRHVKTGQLAAIKVM--DVTGDE--EEEIKQEINMLKKYSHHRNIATY-YGAFIKKNPPGMDD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 RVpYIVMEYVAGRTLRDMI---KANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIAra 183
cd06637       83 QL-WLVMEFCGAGSVTDLIkntKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLL-TENAEVKLVDFGVS-- 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 184 mADSAATMTQTQAVVGTAQYLSPE-----QARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE-TPDLA 257
cd06637      159 -AQLDRTVGRRNTFIGTPYWMAPEviacdENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNpAPRLK 237

                        250
                 ....*....|....*...
gi 119962857 258 SAH-NPEVSEALDSVLVK 274
cd06637      238 SKKwSKKFQSFIESCLVK 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

Catalytic (Repeat 2) Domain of the Protein Tyrosine Kinases, Janus kinases

false

true

false

279

2e-17

85.86

70.25

7,32,11,17,49,32,12,63,44,27,92,71,11,108,82,18,126,102,40,167,142,65

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLL----GRTIAVKVLRADlaRDPQFQARFKREAQAVAALNHPSIVAIfdTGEYSVPGGPGedvrv 108
cd05038       12 LGEGHFGTVYLGTYDPPddntGEIVAVKKLNTS--GVEAHRQDFEREIEIMRTLDHENIVKY--KGVSEEPGGRS----- 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 109 PYIVMEYVAGRTLRDMIK--ANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMAD 186
cd05038       83 LSLIMEYLPSGSLRDYLRrhRDQLNLKRLLLFALQIAKGMDYLGSKRLIHRDLAARNILV-DSEDLVKISDFGLAKVLPE 161

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 119962857 187 SAATMTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLT 232
cd05038      162 DKDYYYVKEPRESPIFWYAPECLRTGKFSSASDVWSYGVTLYEMFT 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

STKc_PKC: Serine/Threonine Kinases (STKs), Protein Kinase C (PKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC 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. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs.

STKc_PKC: Serine/Threonine Kinases (STKs), Protein Kinase C (PKC) subfamily, catalytic (..

false

true

false

318

2e-17

85.67

62.26

11,31,1,10,41,15,8,53,23,27,80,51,10,90,64,5,106,69,2,109,71,13,122,85,47,170,132,12,182,145,10,196,155,44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADV----YRGTDTLLgrtiAVKVLRADLARDPQFQARFKREAQAVA-ALNHPSIVAI---FDTGEysvpggpg 103
cd05570        2 VLGKGSFGKVllaeLKGTDELY----AIKVLKKDVVLQDDDVECTMTEKRVLAlAGKHPFLTQLhscFQTKD-------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 edvRVpYIVMEYVAGRTLR-DMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAR 182
cd05570       70 ---RL-FFVMEYVNGGDLMyHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAE-GHIKIADFGMCK 144

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119962857 183 -AMADSAATMTqtqaVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGD 240
cd05570      145 eGILGGVTTST----FCGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGD 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132947

cd06616

PKc_MKK4

Protein kinases (PKs), MAP kinase kinase 4 (MKK4) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic.

Protein kinases (PKs), MAP kinase kinase 4 (MKK4) subfamily, catalytic (c) domain. PKs...

false

true

false

288

3e-17

85.49

81.94

15,27,7,4,32,11,30,64,41,15,79,57,9,88,70,6,107,76,7,114,94,6,121,100,10,136,110,16,152,127,14,167,141,22,192,163,4,197,167,11,208,181,42,250,225,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  28 ELGElIGRGGMADVYRGTDTLLGRTIAVKVLRADLarDPQFQARFKREAQAV-AALNHPSIV----AIFDTGeysvpggp 102
cd06616        8 DLGE-IGRGAFGTVNKMLHKPSGTIMAVKRIRSTV--DEKEQKRLLMDLDVVmRSSDCPYIVkfygALFREG-------- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 gedvrVPYIVME-----------YVAGRTlRDMIKANELGvedsvGFTLGVLGALEYSHRA-GIVHRDIKPANVMVcADT 170
cd06616       77 -----DCWICMElmdisldkfykYVYEVL-KSVIPEEILG-----KIAVATVKALNYLKEElKIIHRDVKPSNILL-DRN 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 171 GDVKVMDFGIARAMADSAAtmtQTQAvVGTAQYLSPEQ---ARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAY 247
cd06616      145 GNIKLCDFGISGQLVDSIA---KTRD-AGCRPYMAPERidpSARDGYDVRSDVWSLGITLYEVATGKFPYPKWNSVFDQL 220

                        250       260
                 ....*....|....*....|...
gi 119962857 248 QHV--RETPDLASAHNPEVSEAL 268
cd06616      221 TQVvkGDPPILSNSEEREFSPSF 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132989

cd06658

STKc_PAK5

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 5, 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. PAK5 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 5, catalytic (c) domain....

false

true

false

292

3e-17

85.47

76.37

11,32,29,24,58,53,15,74,68,19,95,87,3,102,90,4,109,94,60,170,154,11,184,165,60,245,225,8,253,235,7,262,242,10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQFQARFKrEAQAVAALNHPSIVAIFDTgeYSVpggpGEDVrvpYIV 112
cd06658       30 IGEGSTGIVCIATEKHTGKQVAVK--KMDLRKQQRRELLFN-EVVIMRDYHHENVVDMYNS--YLV----GDEL---WVV 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramADSAATMT 192
cd06658       98 MEFLEGGALTDIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSD-GRIKLSDFGFC---AQVSKEVP 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 193 QTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSvAYQHVRET--PDLASAHnpEVSEALDS 270
cd06658      174 KRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQ-AMRRIRDNlpPRVKDSH--KVSSVLRG 250


                 ..
gi 119962857 271 VL 272
cd06658      251 FL 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132967

cd06636

STKc_MAP4K4_6

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K4/MAP4K6 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4Ks (or MAPKKKKs) are involved in MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

282

5e-17

84.67

80.14

11,26,17,32,60,49,6,68,55,23,92,78,16,109,94,16,125,113,6,132,119,8,140,128,26,167,154,14,184,168,23,207,196,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLraDLARDPqfQARFKREAQAVAALNHPSIVAIFdTGEYSVPGGPGEDV 106
cd06636       18 FELVEVVGNGTYGQVYKGRHVKTGQLAAIKVM--DVTEDE--EEEIKLEINMLKKYSHHRNIATY-YGAFIKKSPPGHDD 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 RVpYIVMEYVAGRTLRDMI---KANELGvEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIAr 182
cd06636       93 QL-WLVMEFCGAGSVTDLVkntKGNALK-EDWIAYICrEILRGLAHLHAHKVIHRDIKGQNVLL-TENAEVKLVDFGVS- 168

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119962857 183 amADSAATMTQTQAVVGTAQYLSPE-----QARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETP 254
cd06636      169 --AQLDRTVGRRNTFIGTPYWMAPEviacdENPDATYDYRSDIWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPP 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88507

cd05606

STKc_beta_ARK

STKc_beta_ARK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, beta-adrenergic receptor kinase (beta-ARK) group, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK 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. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism.

STKc_beta_ARK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

278

8e-17

83.92

70.50

12,31,0,11,42,13,5,49,18,10,68,28,27,107,55,13,120,74,10,130,91,2,132,95,9,141,105,25,167,130,20,192,150,15,207,166,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADVY--RGTDTllGRTIAVKVLRadlardpqfQARFKREAQAVAALNHPSIVAIFDTGEysvpggpgedvrVP 109
cd05606        1 IIGRGGFGEVYgcRKADT--GKMYAMKCLD---------KKRIKMKQGETLALNERIMLSLVSTGD------------CP 57

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 110 YIVMEYVAGRT------LRDMIKANEL-------GV--EDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVcADTGDV 173
cd05606       58 FIVCMTYAFHTpdklcfILDLMNGGDLhyhlsqhGVfsEAEMRFYAAeIILGLEHMHNRFVVYRDLKPANILL-DEHGHV 136

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 174 KVMDFGIARAMADSaatmtQTQAVVGTAQYLSPE-QARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd05606      137 RISDLGLACDFSKK-----KPHASVGTHGYMAPEvLQKGVAYDSSADWFSLGCMLFKLLRGHSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132946

cd06615

PKc_MEK

MEK1/2 (MAPK kinase 1/2, MAPKK1/2 or MKK1/2): Protein kinases (PKs), MAP/ERK kinase (MEK) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MEK1 and MEK2 are dual-specificity PKs that phosphorylate and activate the downstream targets, extracellular signal-regulated kinase (ERK) 1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients.

MEK1/2 (MAPK kinase 1/2, MAPKK1/2 or MKK1/2): Protein kinases (PKs), MAP/ERK kinase (...

false

true

false

308

2e-16

82.48

71.43

9,27,4,5,33,9,26,61,35,27,88,66,9,110,75,27,137,103,11,148,115,21,170,136,19,194,155,69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  28 ELGELiGRGGMADVYRGTDTLLGRTIAVKVLRadLARDPQFQARFKREAQAVAALNHPSIV----AIFDTGEYSvpggpg 103
cd06615        5 KLGEL-GAGNGGVVTKVLHRPSGLIMARKLIH--LEIKPAIRNQIIRELKVLHECNSPYIVgfygAFYSDGEIS------ 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 104 edvrvpyIVMEYVAGRTLRDMIKANELGVEDSVG-FTLGVLGALEY-SHRAGIVHRDIKPANVMVCADtGDVKVMDFGIA 181
cd06615       76 -------ICMEHMDGGSLDQVLKKAGRIPENILGkISIAVLRGLTYlREKHKIMHRDVKPSNILVNSR-GEIKLCDFGVS 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 RAMADSAAtmtqtQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRETPDLASAHN 261
cd06615      148 GQLIDSMA-----NSFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKELEAMFGRPVSEGEAKES 222


                 ..
gi 119962857 262 PE 263
cd06615      223 HR 224

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

STKc_MAST: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. 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. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also referred to as syntrophin-associated STK (SAST), while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3.

STKc_MAST: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (...

false

true

false

305

2e-16

82.67

83.28

11,24,0,18,42,20,6,49,26,24,74,50,17,100,67,26,126,94,42,169,136,23,192,171,15,207,190,7,218,197,33,251,233,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  25 SRYELGELIGRGGMADVY--RGTDTLlGRTIAVKVLRADLARDPQFQARFKrEAQAVAALNHPSIVAIFdtgeysvpgGP 102
cd05609        1 EDFETIKLISNGAYGAVYlvRHKETR-QRFAMKKINKQNLILRNQIQQVFV-ERDILTFAENPFVVSMF---------CS 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 GEDVRVPYIVMEYVAGRTLRDMIK-ANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCAdTGDVKVMDFGIA 181
cd05609       70 FETRRHLCMVMEYVEGGDCATLLKnIGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITS-MGHIKLTDFGLS 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 RAMADSAATMT------------QTQAVVGTAQYLSPE----QARGETVdarsDLYSAGCLLFELLTSRPPFIGDSPVSV 245
cd05609      149 KIGLMSLTTNLyeghiekdtrefLDKQVCGTPEYIAPEvilrQGYGKPV----DWWAMGIILYEFLVGCVPFFGDTPEEL 224

                        250       260       270
                 ....*....|....*....|....*....|
gi 119962857 246 AYQHVR---ETPDLASAHNPEVSEALDSVL 272
cd05609      225 FGQVISddiEWPEGDEALPADAQDLISRLL 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

STKc_PKN: Serine/Threonine Kinases (STKs), Protein Kinase N (PKN) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKN 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. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis.

STKc_PKN: Serine/Threonine Kinases (STKs), Protein Kinase N (PKN) subfamily, catalytic (..

false

true

false

324

3e-16

82.24

61.42

8,31,5,30,61,37,11,72,49,16,88,68,9,109,77,60,170,137,12,182,150,10,196,160,44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADVYRGTDTLLGRTIAVKVLRAD--LARDPQFQARF-KREAQAVAALNHPSIV---AIFDTGEYSvpggpged 105
cd05589        6 VLGRGHFGKVLLAEYKKTGELYAIKALKKGdiIARDEVESLMCeKRIFETANSERHPFLVnlfACFQTEDHV-------- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 106 vrvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAR-AM 184
cd05589       78 ----CFVMEYAAGGDLMMHIHTDVFSEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTE-GYVKIADFGLCKeGM 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 119962857 185 ADSAATMTqtqaVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGD 240
cd05589      153 GFGDRTST----FCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGD 204

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88489

cd05588

STKc_aPKC

STKc_aPKC: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC 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. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes.

STKc_aPKC: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily,...

false

true

false

329

3e-16

82.33

61.40

9,31,1,48,79,50,11,90,64,3,104,67,4,109,71,13,122,85,47,170,132,20,193,152,44,237,198,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAV-AALNHPSIVAI---FDTgeysvpggpgeDVR 107
cd05588        2 VIGRGSYAKVLLVELKKTRRIYAMKVIKKELVNDDEDIDWVQTEKHVFeTASNHPFLVGLhscFQT-----------ESR 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 VpYIVMEYVAGRTLR-DMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAMAD 186
cd05588       71 L-FFVIEFVSGGDLMfHMQRQRKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAE-GHIKLTDYGMCKEGIR 148

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 119962857 187 SAATmtqTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF--IGDSP 242
cd05588      149 PGDT---TSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFdiVGMSD 203

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132988

cd06657

STKc_PAK4

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 4, 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. PAK4 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 4, catalytic (c) domain....

false

true

false

292

3e-16

82.38

78.42

11,32,27,24,58,51,15,74,66,19,95,85,3,102,88,4,109,92,60,170,152,11,184,163,60,245,223,8,253,233,7,260,242,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKvlRADLARDPQFQARFKrEAQAVAALNHPSIVAIFDTgeYSVpggpGEDVrvpYIV 112
cd06657       28 IGEGSTGIVCIATVKSSGKLVAVK--KMDLRKQQRRELLFN-EVVIMRDYQHENVVEMYNS--YLV----GDEL---WVV 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 113 MEYVAGRTLRDMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramADSAATMT 192
cd06657       96 MEFLEGGALTDIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHD-GRVKLSDFGFC---AQVSKEVP 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 193 QTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSvAYQHVRET--PDLASAH--NPEVSEAL 268
cd06657      172 RRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLK-AMKMIRDNlpPKLKNLHkvSPSLKGFL 250


                 ....*.
gi 119962857 269 DSVLVK 274
cd06657      251 DRLLVR 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88515

cd05614

STKc_MSK2_N

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK2, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis.

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

332

3e-16

82.39

75.60

12,26,1,16,42,22,5,49,27,10,59,38,19,81,57,18,103,75,5,109,80,32,141,113,28,170,141,19,191,160,27,218,188,20,238,212,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVY-----RGTDTllGRTIAVKVLR-ADLARDPQFQARFKREAQAvaaLNHPSIVAIFDTGEYSVPg 100
cd05614        2 FELLKVLGTGAYGKVFlvrkvTGHDT--GKLYAMKVLQkAALVQKAKTVEHTRTERNV---LEHVRQSPFLVTLHYAFQ- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 101 gpgEDVRVpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFG 179
cd05614       76 ---TEAKL-HLILDYVSGGEMFTHLYQRDNFSEDEVRFYSGeIILALEHLHKLGIVYRDIKLENILLDSE-GHVVLTDFG 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 180 IARAMADSAAtmTQTQAVVGTAQYLSPEQARGETVDARS-DLYSAGCLLFELLTSRPPFI----GDSPVSVAYQHVRETP 254
cd05614      151 LSKEFLSEEK--ERTYSFCGTIEYMAPEIIRGKGGHGKAvDWWSLGILIFELLTGASPFTlegeRNTQSEVSRRILKCDP 228

                        250       260
                 ....*....|....*....|....
gi 119962857 255 DLASAHNPEVSEALDSVLVKALQK 278
cd05614      229 PFPSFIGPEAQDLLHKLLRKDPKK 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88499

cd05598

STKc_LATS

STKc_LATS: Serine/Threonine Kinases (STKs), Large Tumor Suppressor (LATS) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The LATS 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. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation.

STKc_LATS: Serine/Threonine Kinases (STKs), Large Tumor Suppressor (LATS) subfamily,...

false

true

false

376

3e-16

82.32

71.81

11,32,10,15,49,25,10,59,36,8,68,44,23,95,67,3,103,70,41,144,112,25,170,137,11,181,175,11,192,199,73,265,273,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTllGRTIAVKVLR-ADLARDPQfQARFKREAQAVAALNHPSIVAIFdtgeYSVpggpgEDVRVPYI 111
cd05598       11 IGAFGEVCLVRKVDT--NALYAMKTLRkADVLMRNQ-AAHVKAERDILAEADNEWVVKLY----YSF-----QDKDNLYF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 112 VMEYVAGRTLRDMIKANELGVEDSVGFTLGVLG-ALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIA--------- 181
cd05598       79 VMDYIPGGDMMSLLIRLGIFEEDLARFYIAELTcAIESVHKMGFIHRDIKPDNILIDRD-GHIKLTDFGLCtgfrwthds 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 182 ------------------RAMADSAATMT-------------QTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFEL 230
cd05598      158 kyyqkgdhhrqdsmepseEWSEIDRCRLKplerrrvrqhqrcLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEM 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 119962857 231 LTSRPPFIGDSPVSVAYQHVRETPDLASAHNPEVS-EALDSVL 272
cd05598      238 LVGQPPFLADTPAETQLKVINWENTLHIPPQAKLSrEASDLIL 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132938

cd06607

STKc_TAO

Serine/threonine kinases (STKs), thousand-and-one amino acids (TAO) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TAO 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. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MAP3K or MKKK) activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3.

Serine/threonine kinases (STKs), thousand-and-one amino acids (TAO) subfamily,...

false

true

false

307

4e-16

81.78

75.24

16,32,22,26,61,48,12,73,63,15,94,78,3,102,81,5,107,88,11,119,99,13,132,113,5,137,119,29,167,148,12,186,160,21,207,183,5,212,189,35,248,224,2,250,228,10,263,238,15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLradLARDPQFQARFK---REAQAVAALNHPSIVaifdtgEYSvpggpGEDVR-- 107
cd06607       23 IGHGSFGAVYFARDVRTNEVVAIKKM---SYSGKQSNEKWQdiiKEVRFLQQLRHPNTI------EYK-----GCYLReh 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 VPYIVMEYVAGrTLRDMIKANELGV-EDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGiarama 185
cd06607       89 TAWLVMEYCLG-SASDILEVHKKPLqEVEIAaICHGALQGLAYLHSHERIHRDIKAGNILL-TEPGTVKLADFG------ 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 dSAATMTQTQAVVGTAQYLSPE--QARGE-TVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYqHV--RETPDLASAH 260
cd06607      161 -SASLVSPANSFVGTPYWMAPEviLAMDEgQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALY-HIaqNDSPTLSSND 238

                        250
                 ....*....|....*...
gi 119962857 261 npeVSEALDSVLVKALQK 278
cd06607      239 ---WSDYFRNFVDSCLQK 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

STKc_MSK_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2.

STKc_MSK_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

288

5e-16

81.52

87.50

13,26,1,16,42,22,5,49,27,10,59,38,25,84,64,7,95,71,4,103,75,5,109,80,32,141,113,28,170,141,15,187,156,27,214,185,26,240,215,38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVY-----RGTDTllGRTIAVKVLR-ADLARDPQFQARFKREAQAVAALNH-PSIVAIFdtgeYSVP 99
cd05583        2 FELLRVLGTGAYGKVFlvrkvGGHDA--GKLYAMKVLKkATIVQKAKTAEHTRTERQVLEAVRRcPFLVTLH----YAFQ 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 100 ggpgEDVRVpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDF 178
cd05583       76 ----TDTKL-HLILDYVNGGELFTHLYQREHFTESEVRVYIAeIVLALDHLHQLGIIYRDIKLENILLDSE-GHVVLTDF 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 179 GIARAMAdsAATMTQTQAVVGTAQYLSPEQARGETV--DARSDLYSAGCLLFELLTSRPPFIGD----SPVSVAYQHVRE 252
cd05583      150 GLSKEFL--AEEEERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDgeqnSQSEISRRILKS 227

                        250       260
                 ....*....|....*....|....*.
gi 119962857 253 TPDLASAHNPEVSEALDSVLVKALQK 278
cd05583      228 KPPFPKTMSAEARDFIQKLLEKDPKK 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132951

cd06620

PKc_MAPKK_Byr1_like

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, fungal Byr1-like proteins, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKKK Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis.

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, fungal Byr1-like proteins,...

false

true

false

284

7e-16

81.00

84.86

16,27,11,4,33,15,14,49,29,12,63,41,28,102,69,10,112,81,9,122,90,3,125,95,23,148,121,3,153,124,15,169,139,20,194,159,43,237,210,8,245,220,5,250,227,18,268,246,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  28 ELGEliGRGGMADVYRGTDTllGRTIAVKVLRADlaRDPQFQARFKREAQAVAALNHPSIVAIFdtgeysvpggpGEDVR 107
cd06620       12 DLGA--GNGGSVSKVKHIPT--GTVMAKKVVHIG--AKSSVRKQILRELQIMHECRSPYIVSFY-----------GAFLN 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 VPYIV--MEYVAGRTLrDMI--KANELGVEDSVGFTLGVLGALEY---SHRagIVHRDIKPANVMVCAdTGDVKVMDFGI 180
cd06620       75 ENNICmcMEFMDCGSL-DRIykKGGPIPVEILGKIAVAVVEGLTYlynVHR--IMHRDIKPSNILVNS-RGQIKLCDFGV 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 181 ARAMADSAAtmtqtQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF--------IGDSPVSV--AYQHV 250
cd06620      151 SGELINSIA-----DTFVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFafsnidddGQDDPMGIldLLQQI 225

                        250       260
                 ....*....|....*....|....*..
gi 119962857 251 --RETPDLASAHNPEVSEAL-DSVLVK 274
cd06620      226 vqEPPPRLPSSDFPEDLRDFvDACLLK 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132970

cd06639

STKc_myosinIIIB

Serine/threonine kinases (STKs), class IIIB myosin subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin 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. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities.

Serine/threonine kinases (STKs), class IIIB myosin subfamily, catalytic (c) domain....

false

true

false

291

7e-16

80.82

80.41

11,26,23,44,74,67,8,82,76,6,88,85,14,109,99,18,127,121,13,140,135,29,170,164,11,184,175,23,207,203,47,256,250,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  27 YELGELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQArfkrEAQAVAAL-NHPSIV---AIFDTGEYSVPGGP 102
cd06639       24 WEIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEA----EYNILQSLpNHPNVVkfyGMFYKADKLVGGQL 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 103 gedvrvpYIVMEYVAGRTLRDMIKA----NELGVEDSVGFTL-GVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMD 177
cd06639      100 -------WLVLELCNGGSVTELVKGllicGQRLDEAMISYILyGALLGLQHLHNNRIIHRDVKGNNILLTTE-GGVKLVD 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 178 FGIAramADSAATMTQTQAVVGTAQYLSPE-----QARGETVDARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVRE 252
cd06639      172 FGVS---AQLTSTRLRRNTSVGTPFWMAPEviaceQQYDYSYDARCDVWSLGITAIELGDGDPPLFDMHPVKTLFKIPRN 248

                        250
                 ....*....|.
gi 119962857 253 TPdlASAHNPE 263
cd06639      249 PP--PTLLHPE 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133166

cd05034

PTKc_Src_like

Catalytic Domain of Src kinase-like Protein Tyrosine Kinases

false

true

false

261

1e-15

80.43

80.08

14,28,9,17,47,26,5,52,32,9,62,41,4,69,45,21,95,66,6,102,72,4,109,76,20,129,99,37,167,136,23,195,159,6,201,168,31,232,200,7,258,207,11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  29 LGELIGRGGMADVYRGTdtLLGRT-IAVKVLRADlARDPqfqARFKREAQAVAALNHPSIVAIfdtgeYSVPGGpGEDVr 107
cd05034       10 LERKLGAGQFGEVWMGT--WNGTTkVAVKTLKPG-TMSP---EAFLEEAQIMKKLRHDKLVQL-----YAVCSE-EEPI- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 108 vpYIVMEYVAGRTLRDMIKANE---LGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAM 184
cd05034       77 --YIVTEYMSKGSLLDFLKSGEgkkLRLPQLVDMAAQIAEGMAYLESRNYIHRDLAARNVLV-GENLVCKVADFGLARLI 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 185 ADSAATmtqtqAVVGTA---QYLSPEQARGETVDARSDLYSAGCLLFELLT-SRPPFIGdspvsvayqhvretpdlasAH 260
cd05034      154 EDDEYT-----AREGAKfpiKWTAPEAALYGRFTIKSDVWSFGILLTEIVTyGRVPYPG-------------------MT 209


                 ....*....
gi 119962857 261 NPEVSEALD 269
cd05034      210 NREVLEQVE 218

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132950

cd06619

PKc_MKK5

Protein kinases (PKs), MAP kinase kinase 5 (MKK5) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK5, also referred to as MEK5, is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer.

Protein kinases (PKs), MAP kinase kinase 5 (MKK5) subfamily, catalytic (c) domain. PKs...

false

true

false

279

1e-15

79.92

67.03

10,30,6,33,65,39,26,93,65,5,104,70,5,110,75,11,122,86,7,132,93,5,137,99,29,167,128,23,195,151,42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGTDTLLGRTIAVKVLRADLArdPQFQARFKREAQAVAALNHPSIVAIFdtGEYSVpggpgeDVRVPy 110
cd06619        7 EILGHGNGGTVYKAYHLLTRRILAVKVIPLDIT--VELQKQIMSELEILYKCDSPYIIGFY--GAFFV------ENRIS- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLrDMIKANElgvEDSVG-FTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMADSAA 189
cd06619       76 ICTEFMDGGSL-DVYRKIP---EHVLGrIAVAVVKGLTYLWSLKILHRDVKPSNMLV-NTRGQVKLCDFGVSTQLVNSIA 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 119962857 190 TmtqtqAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd06619      151 K-----TYVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

STKc_GRK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK 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. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7. They are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 shows a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems.

STKc_GRK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

277

2e-15

79.94

70.04

7,32,0,58,90,61,8,110,69,15,125,85,10,135,97,31,167,128,20,191,148,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  33 IGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAVAALNHPSIVAI---FDTGEYSVpggpgedvrvp 109
cd05577        1 LGKGGFGEVCACQVRATGKMYACKKLDKKRIKKRKGETMALNEKIILEKVSSPFIVSLayaFETKDALC----------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 110 yIVMEYVAGRTLRDMI-KANELGVEDS--VGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMAD 186
cd05577       70 -LVLTLMNGGDLKFHIyNVGNPGFDEAraRFYAAEIICGLEHLHRRRIVYRDLKPENILL-DDHGHIRISDLGLAVEFPE 147

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 119962857 187 SaatmTQTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd05577      148 G----KKIHGRVGTVGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHSPF 194

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88534

cd05633

STKc_GRK3

STKc_GRK3: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK3 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK 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. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK3 (also known as beta-adrenergic receptor kinase 2) is widely expressed in many tissues. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 is involved in modulating the cholinergic response of airway smooth muscles. It also plays a role in dopamine receptor regulation. GRK3 promoter polymorphisms may be associated with bipolar disorder.

STKc_GRK3: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

279

2e-15

79.68

70.25

11,31,0,11,42,13,5,49,18,10,68,28,27,107,55,13,120,74,10,130,91,2,132,96,34,167,130,20,192,150,15,207,166,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADVY--RGTDTllGRTIAVKVLRadlardpqfQARFKREAQAVAALNHPSIVAIFDTGEysvpggpgedvrVP 109
cd05633        1 IIGRGGFGEVYgcRKADT--GKMYAMKCLD---------KKRIKMKQGETLALNERIMLSLVSTGD------------CP 57

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 110 YIVMEYVAGRT------LRDMIKANEL-------GV---EDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVcADTGDV 173
cd05633       58 FIVCMTYAFHTpdklcfILDLMNGGDLhyhlsqhGVfseKEMRFYATEIILGLEHMHNRFVVYRDLKPANILL-DEHGHV 136

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119962857 174 KVMDFGIARAMADSaatmtQTQAVVGTAQYLSPE-QARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd05633      137 RISDLGLACDFSKK-----KPHASVGTHGYMAPEvLQKGTAYDSSADWFSLGCMLFKLLRGHSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132942

cd06611

STKc_SLK_like

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

Serine/threonine kinases (STKs), Ste20-like kinase (SLK)-like subfamily, catalytic (c)...

false

true

false

280

2e-15

79.40

85.00

13,29,10,3,33,13,24,59,37,10,70,47,23,95,70,7,109,77,23,132,101,6,138,108,31,170,139,11,184,150,30,214,185,37,251,223,9,262,232,16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  30 GELiGRGGMADVYRGTDTLLGRTIAVKVlrADLARDPQFQaRFKREAQAVAALNHPSIVAIFDTgeYSVPGGPgedvrvp 109
cd06611       11 GEL-GDGAFGKVYKAQHKETGLFAAAKI--IQIESEEELE-DFMVEIDILSECKHPNIVGLYEA--YFYENKL------- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 110 YIVMEYVAGRTLRDMIKANELGV-EDSVGF-TLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIAramADS 187
cd06611       78 WILIEFCDGGALDSIMLELERGLtEPQIRYvCRQMLEALNFLHSHKVIHRDLKAGNILLTLD-GDVKLADFGVS---AKN 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 188 AATMTQTQAVVGTAQYLSPEQARGETV-----DARSDLYSAGCLLFELLTSRPPFIGDSPVSVAYQHVR-ETPDLASAHn 261
cd06611      154 KSTLQKRDTFIGTPYWMAPEVVACETFkdnpyDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKsEPPTLDQPS- 232

                        250
                 ....*....|....*..
gi 119962857 262 pEVSEALDSVLVKALQK 278
cd06611      233 -KWSSSFNDFLKSCLVK 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88519

cd05618

STKc_aPKC_iota

STKc_aPKC_iota: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, iota isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC 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. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. There are two aPKC isoforms, zeta and iota. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions.

STKc_aPKC_iota: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC)...

false

true

false

329

3e-15

78.95

59.27

7,31,1,48,79,50,16,103,66,5,109,71,13,122,85,47,170,132,20,193,152,44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  32 LIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQAV-AALNHPSIVAIFDTGEysvpggpgEDVRVpY 110
cd05618        2 VIGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEDIDWVQTEKHVFeQASNHPFLVGLHSCFQ--------TESRL-F 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 111 IVMEYVAGRTLR-DMIKANELGVEDSVGFTLGVLGALEYSHRAGIVHRDIKPANVMVCADtGDVKVMDFGIARAMADSAA 189
cd05618       73 FVIEYVNGGDLMfHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSE-GHIKLTDYGMCKEGLRPGD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 119962857 190 TmtqTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPF 237
cd05618      152 T---TSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88476

cd05575

STKc_SGK

STKc_SGK: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SGK 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. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). 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.

STKc_SGK: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (...

false

true

false

323

4e-15

78.46

73.37

9,30,0,48,78,49,12,90,64,7,109,71,32,141,104,25,167,129,23,193,152,48,242,200,12,254,213,24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857  31 ELIGRGGMADVYRGTDTLLGRTIAVKVLRADLARDPQFQARFKREAQA-VAALNHPSIVAI---FDTGEYSvpggpgedv 106
cd05575        1 KVIGKGSFGKVLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVlLKNVKHPFLVGLhysFQTKEKL--------- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 107 rvpYIVMEYVAGRTLRDMIKANELGVEDSVGFTLG-VLGALEYSHRAGIVHRDIKPANVMVcADTGDVKVMDFGIARAMA 185
cd05575       72 ---YFVLDYVNGGELFFHLQRERSFPEPRARFYAAeIASALGYLHSLNIIYRDLKPENILL-DSKGHVVLTDFGLCKEGI 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119962857 186 DSAATmtqTQAVVGTAQYLSPEQARGETVDARSDLYSAGCLLFELLTSRPPFIGDSpVSVAYQHVRETP-DLASAHNPEV 264
cd05575      148 AGSKT---T</