NCBI Conserved Domain Search

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Conserved domains on [gi\|94967801\|ref\|YP_589849.1\|]
TPR repeat-containing serine/threonin protein kinase [Candidatus Koribacter versatilis Ellin345]

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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.

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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

7e-47

184.25

98.83

6,27,0,55,83,55,35,118,91,58,196,149,69,266,218,27,294,245,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  28 HYVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASaLNHPNICTIYDIGEYEGRPFIAME 107
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQVERILREIKILKR-LNHPNIVKLYDVFEDEDKLYLVME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 108 LLEGQTLKHRI-GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTlknavsaaet 186
cd00180      80 YMSGGDLFDLLkKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQL---------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 187 matmpapvvsEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKSa 266
cd00180     150 ----------DSGGRKLTTFVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGKGTP- 218

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967801 267 SEVNHRIPLAFDTLLNKAMEKDRDLRCqSAAELRAD 302
cd00180     219 DELPPNISPEAKDLIKKLLVKDPEKRP-TAEELLQH 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

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

1e-36

150.38

97.63

11,28,1,37,68,38,50,118,89,10,130,99,3,133,104,41,175,145,13,207,158,41,248,201,7,257,208,8,266,216,27,294,243,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDIShdpQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMEL 108
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESD---EEQEQILNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 109 LEGQTLKHRI-GTRPMDITEIldAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvTLKNAVSAAE 185
cd05122      79 CDGGSLDDLLkSTGPLPESQI--AYIcrEVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSA-QLSDTKAKRN 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 186 TMAtmpapvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAA--ATAALMFdgILHSEP 263
cd05122     156 TFV-------------------GTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSElnPMKALFK--IATNPP 214

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967801 264 KSaSEVNHRIPLAFDTLLNKAMEKDRDLRCqSAAEL 299
cd05122     215 PG-LPSPEKWSPEFRDFLKKCLQKDPEKRP-TAEEL 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

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

4e-35

145.00

85.33

6,28,1,35,64,36,39,103,76,17,120,94,55,193,149,55,248,207,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDiSHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPF-IAME 107
cd06606       2 WTRGKLLGRGSFGSVYLALSKDTGELVAVKSVELS-SDSEEELESLEREIRILSKLQHPNIVRYYGCEVTEENTLnIFME 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 108 LLEGQTLKHRIGT-RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtlknavsaaet 186
cd06606      81 YVSGGSLASLLKKfGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKR----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 187 matmpapVVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAA---ATAALMFDGILHSEP 263
cd06606     150 -------LASIAYSGGLKSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSElgnPMALLYKIGSSGEPP 222

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

4e-32

135.41

73.86

7,34,8,27,63,35,60,124,95,9,133,106,13,146,120,30,184,150,8,204,158,45

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPddISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06623       9 LGQGSSGVVYKVRHKPTGKIYALKKIH--VDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGSL 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRIGTRPMdITEILDAGI--QIANGLDAAHTKS-IVHRDIKPANIFLVEPGEAKILDFGLAKVTlknavsaaETMATMP 191
cd06623      87 ADLLKKVGK-IPEPVLAYIarQILKGLDYLHTKRhIIHRDIKPSNLLINSKGEVKIADFGISKVL--------ENTLDQC 157

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94967801 192 ApvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAA 249
cd06623     158 N------------TFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPP 203

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

1e-31

133.76

97.85

7,28,2,32,62,34,22,84,59,31,115,93,16,133,109,130,267,239,25,292,266,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASAL---NHPNICTIYDIGEYEGRPFIA 105
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVL--DKRHLIKEKKVKYVKREKEVLTrlnGHPGIVKLYYTFQDEENLYFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 106 MELLEGQTLK---HRIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVS 182
cd05581      81 LEYAENGELLeyiKKFGSFDEKCTRFYTA--EILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVLDPNSSP 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 183 AAETMATMPAPVVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE 262
cd05581     159 ESNKGKATNIDSQIEKNRRRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLE 238

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967801 263 PksasEVNHRIPLAFDTLLNKAMEKDRDLR--CQSAAELRA 301
cd05581     239 Y----EFPPNFPPDAKDLIEKLLVLDPQDRlgVNGYDELKA 275

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

2e-28

122.89

98.40

7,34,0,84,118,87,13,133,100,50,203,150,67,273,217,5,279,222,13,292,237,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRI---GTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAaetmatmp 191
cd05123      81 FTHLskeGRFDEERARFYAA--EIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAKEGIDDGVRT-------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 192 apvvsedqltspGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKSASEVNh 271
cd05123     151 ------------TTFCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRFPEFLS- 217

                       250       260       270
                ....*....|....*....|....*....|..
gi 94967801 272 riPLAFDtLLNKAMEKDRDLR--CQSAAELRA 301
cd05123     218 --EEAKD-LIKKLLTKDPTKRlgSGGAEEIKA 246

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-26

115.90

79.55

6,34,7,31,66,38,52,118,91,72,206,163,20,226,186,25,251,213,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIShDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06626       8 IGGGTFGKVYTAVNLDTGELMAVKEIRIQDN-DPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCSGGTL 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRI-GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAETMATMpap 193
cd06626      87 EELLeHGRILDEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAVKLKNNTTTMGEEVQSL--- 163

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967801 194 vvsedqltspgssLGTVAYMSPEQARGEELDAR---SDLFSLGVVLYEMATGQLPFAAATA--ALMF 255
cd06626     164 -------------AGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSELDNefQIMF 217

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

5e-26

115.01

87.11

10,26,18,34,62,52,20,83,72,50,133,124,40,174,164,13,206,177,40,246,222,14,260,237,9,276,246,16,293,262,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASaLNHPNICTIYDIGEYEGRPFIAM 106
cd06614      19 ELYDNLEKIGEGASGEVYTATDRATGKEVAIKKM--RLRKQPKKELIINEILIMKE-CKHPNIVNYYDSYLVGDELWVVM 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEGQTLKHRIGTRPMDITEILDAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkVTLKNAVSAA 184
cd06614      96 EYMDGGSLTDIITQTFVRMNESQIAYVcrEVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFA-AQLTKEKSKR 174

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 185 ETMatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPF-----AAATAALMFDGIL 259
cd06614     175 NSM-------------------VGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYlneppLRALFLITTKGIP 235

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967801 260 H-SEPKSASEVnhriplaFDTLLNKAMEKDRDLRcQSAAEL 299
cd06614     236 PlKNPEKWSPE-------FKDFLNKCLVKDPEKR-PSAEEL 268

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-26

114.72

92.83

12,34,8,30,66,38,45,111,87,11,125,98,6,131,105,14,145,120,30,176,150,3,181,153,7,207,160,47,254,212,13,269,225,23,293,248,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIshDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG--- 111
cd06605       9 LGAGNSGVVSKVRHRPTGKIMAVKTIRLEI--NEAIQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICMEYMDGgsl 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 112 -QTLKHRIGTRPmdiTEILDA-GIQIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKVtLKNavSAAETMA 188
cd06605      87 dKILKEVQGRIP---ERILGKiAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGEIKLCDFGVSGQ-LVN--SLAKTFV 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 189 tmpapvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALM-----FDGILHSEP 263
cd06605     161 -------------------GTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPENDPPDgifelLQYIVNEPP 221

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967801 264 KSASevNHRIPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06605     222 PRLP--SGRFSPDFQDFVNLCLIKDPRER-PSYKEL 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-23

105.97

69.34

7,32,6,51,85,57,9,94,68,21,115,92,12,127,106,44,194,150,8,202,159,46

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASAlnHPNICTIYD--IGEYEGRPFIAMELLE 110
cd06621       7 SRLGEGAGGSVTKCRLKNTGMIFALKTITTDPNPDLQKQILRELEINKSCK--SPYIVKYYGafLDESSSSIGIAMEYCE 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTLK---HRIGTRPMDITE--ILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlknavsaae 185
cd06621      85 GGSLDsiyKKVKKRGGRIGEkvLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFG-------------- 150

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94967801 186 tmatmpapvVSEDQLTS-PGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAA 248
cd06621     151 ---------VSGELVNSlAGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPP 205

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

3e-23

105.79

81.89

8,27,0,31,58,32,6,66,38,45,111,86,20,133,106,40,175,146,11,204,157,43,247,202,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  28 HYVVAERLGGGGMGVVYKATDSRLGRSVALK-FLPDDIshDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAM 106
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKqISLEKI--KEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEG---QTLKHRIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvTLKNAVSA 183
cd06627      79 EYAENgslRQIIKKFGKFPESLVAVYVY--QVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVA--TKLSDVSK 154

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967801 184 AETmatmpapvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFA--AATAAL 253
cd06627     155 DDE------------------SVVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYdlNPMPAL 208

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

2e-22

102.62

94.57

5,27,0,94,121,95,53,193,148,12,207,160,47,255,207,37

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  28 HYVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAME 107
cd05578       1 HFEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 108 LLEGQTLKHRIGTR-PMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlknavsaaet 186
cd05578      81 LLLGGDLRYHLQQKvKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIAT------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 187 matmpapVVSEDQLTSPGSslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMfDGILHSEPKSA 266
cd05578     149 -------KLTPDTLATSTS--GTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGHSRTPR-EEILAKFETAD 218

                       250       260
                ....*....|....*....|....*.
gi 94967801 267 SEVNHRIPLAFDTLLNKAMEKDRDLR 292
cd05578     219 VLYPAGWSSEAIDAINKLLERDPQKR 244

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

7e-22

101.03

81.89

5,34,0,77,111,80,20,133,100,46,185,146,15,206,161,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG--- 111
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGgdl 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 112 QTLKHRIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNavsaaeTMATMP 191
cd05579      81 ASLLENVGSLDEDMARIYIA--EIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKVGLVR------RQINLN 152

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 192 APVVSEDQLtspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE 262
cd05579     153 DDEKEDKRI------VGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGK 217

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

2e-21

99.90

83.14

7,32,0,20,52,23,11,65,34,49,114,88,12,126,104,65,209,169,32,241,202,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLG---RSVALKFLPDDisHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELL 109
cd00192       1 KKLGEGAFGEVYKGELKGKGgkkTPVAVKTLKED--ASDSEREDFLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 110 EGQTL-----KHRIGTRPMDIT----EILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNA 180
cd00192      79 EGGDLldflrKSRPVFSPESSTlslkDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRDIYDDD 158

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967801 181 VSAAETMATMPapvvsedqltspgsslgtVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPFAAATAALMFD 256
cd00192     159 YYRKKGGGKLP------------------IRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEVLE 217

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-21

99.61

71.90

8,28,2,32,62,34,28,96,62,4,100,72,28,130,100,3,133,105,41,175,146,13,207,159,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICtiydigEYEG------RP 102
cd06609       3 FTLLECIGKGSFGEVYKAIDKRTNQVVAIKVI--DLEEAEDEIEDIQQEIQFLSQCRSPYIT------KYYGsflkgsKL 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 103 FIAMELLEGQTLKHRIGTRPMDITEIldAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvTLKNA 180
cd06609      75 WIIMEYCGGGSCLDLLKPGKLDETYI--AFIlrEVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGVSG-QLTST 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967801 181 VSAAETMAtmpapvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFA 247
cd06609     152 MSKRNTFV-------------------GTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLS 199

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

2e-20

96.48

90.79

6,26,0,111,137,114,37,174,158,14,188,173,82,272,255,23,295,281,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAM 106
cd05574       1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEGQTLKHRIGTRPMDITEILDAGIQIAN---GLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAK-------VT 176
cd05574      81 DYCPGGELFRLLQRQPGKCFPEEVARFYAAEvllALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSKqsdveptPV 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 177 LKNAVSAAETMA-TMPAPVVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMF 255
cd05574     161 SKALRKGSRGSVnKITTETFSEEPSFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETF 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 94967801 256 DGILHSEPKSASEVNhrIPLAFDTLLNKAMEKDRDLRCQS---AAELR 300
cd05574     241 SNILKKEVTFPGSPP--VSSSARDLIRKLLVKDPSKRLGSkrgAAEIK 286

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

4e-20

95.04

75.64

12,32,11,28,62,39,21,84,60,9,95,69,7,102,84,12,114,101,10,124,114,6,133,120,38,180,158,3,198,161,5,203,170,13,216,188,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASAlNHPNICTIYdiGEYEGRP--------FI 104
cd06608      12 EVIGTGTYGKVYKARHKKTGQLVAIKIM--DIIEDEEEEIEEEYNILRKYS-NHPNIATFY--GAFIKKGppgsddqlWL 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 105 AMELLEGQTL-----KHRIGTRPMD---ITEILDagiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvt 176
cd06608      87 VMELCGGGSVtdlvkGLRKKGKRLKeewIAYILR---ETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFG----- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 177 lknaVSAaetmatmpapvvsedQLTSP----GSSLGTVAYMSPE-----QARGEELDARSDLFSLGVVLYEMATGQLPFA 247
cd06608     159 ----VSA---------------QLDSTngrrNTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPLC 219

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

4e-20

95.05

78.54

13,26,2,35,61,41,16,84,57,9,95,66,3,98,71,17,115,91,2,119,93,53,182,146,8,195,154,4,204,158,14,218,175,27,253,202,3,258,205,2

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLP----DDISHDPQAIERFRREaraasalNHPNICTIYdiGEY--EG 100
cd06613       3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKlepgDDFEIIQQEISMLKEC-------RHPNIVAYF--GSYlrRD 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 101 RPFIAMELLEGQTLK---HRigTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLakvtl 177
cd06613      74 KLWIVMEYCGGGSLQdiyQV--TGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGV----- 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 178 knavsAAETMATMpapvvSEDQltspgSSLGTVAYMSPEQA---RGEELDARSDLFSLGVVLYEMATGQLPfaaataalM 254
cd06613     147 -----SAQLTATI-----AKRK-----SFIGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPP--------M 203


                ....*.
gi 94967801 255 FDgiLH 260
cd06613     204 FD--LH 207

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

7e-20

94.64

75.78

7,30,6,31,63,37,18,84,55,49,133,106,38,180,144,3,183,149,7,203,156,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  31 VAERLGGGGMGVVYKATDSRLGRSVALKFLPddISHDPQAIERFRREARAAsalNHPNICTIYDIGEYEGRPFIAMELLE 110
cd06612       7 ILEKLGEGSYGSVYKAIHKETGQVVAIKVVP--VEEDLQEIIKEISILKQC---DSPYIVKYYGSYFKNTDLWIVMEYCG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTLKHRIGTRPMDITEILDAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlknaVSA--AET 186
cd06612      82 AGSVSDIMKITNKTLTEEEIAAIlyQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFG---------VSGqlTDT 152

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 187 MATMpapvvsedqltspGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFA 247
cd06612     153 MAKR-------------NTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYS 200

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

1e-19

93.84

89.62

7,37,6,24,61,31,50,111,84,20,133,104,47,204,151,69,273,221,5,279,226,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  38 GGMGVVYKATDSRLGRSVALKFLP-DDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG---QT 113
cd05611       7 GAFGSVYLAKKRSTGDYFAIKVLKkSDMIAKNQVTNVKAERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLNGgdcAS 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAvsaaetmatmpap 193
cd05611      87 LIKTLGGLPEDWAKQYIA--EVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLENK------------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 194 vvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKSASEVNHRI 273
cd05611     152 -----------KFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFC 220

                       250       260
                ....*....|....*....|
gi 94967801 274 -PLAFDtLLNKAMEKDRDLR 292
cd05611     221 sPEAVD-LINRLLCMDPAKR 239

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

2e-19

92.99

68.93

4,28,2,83,111,88,25,138,113,66,204,190,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMEL 108
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILADADSPWIVKLYYSFQDEEYLYLVMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 109 LEG---QTLKHRIGTRPMDITEILDAGIQIAngLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAE 185
cd05573      83 MPGgdlMTLLIKYDVFPEETARFYIAELVLA--IDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCKKMKKAGDSEYY 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 186 TMATMPAPVVSEDQLTSPG-----------SSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALM 254
cd05573     161 LNDSHNLLDSDRDNVLKRRrpkkqrrvraySTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQET 240


                ....*.
gi 94967801 255 FDGILH 260
cd05573     241 YNKIMN 246

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

6e-19

91.41

94.30

10,34,9,24,58,36,5,64,41,57,121,99,50,182,149,10,198,159,49,247,210,23,273,233,5,279,238,13,293,251,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALK---FLPDDiSHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG 111
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKqvpFDPDS-PETKKEVNALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPG 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 112 QTLKHRIGTR-PMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlknavsAAETMATM 190
cd06625      89 GSVKDQLKAYgALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFG-----------ASKRLQTI 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 191 PApvvsedQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFA--AATAALMFDGILHSEPKSASE 268
cd06625     158 CS------SGTGMKSVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAefEAMAAIFKIATQPTNPQLPSH 231

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967801 269 VNhriPLAFDtLLNKAMEKDRDLRcQSAAEL 299
cd06625     232 VS---PDARN-FLRRTFVENAKKR-PSAEEL 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88493

cd05592

STKc_nPKC_theta_delta

STKc_nPKC_theta_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), theta and delta-like isoforms, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC 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. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types.

STKc_nPKC_theta_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC),...

false

true

false

316

8e-19

90.76

66.77

5,34,2,29,63,32,55,118,88,59,182,147,7,204,154,59

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDD-ISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05592       3 LGKGSFGKVMLAELKGTNEYYAIKALKKDvVLEDDDVECTMVERRVLILAWEHPFLTHLFCTFQTKEHLFFVMEYLNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRI-GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLknavsAAETMATmpa 192
cd05592      83 LMFHIqSSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENI-----NGEGKAS--- 154

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 193 pvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEP 263
cd05592     155 ------------TFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILNDRP 213

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

1e-18

90.57

91.43

9,25,3,35,63,38,57,120,97,51,174,148,6,195,154,7,204,161,19,223,185,45,269,230,23,293,253,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  26 ISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpddISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIA 105
cd06611       4 NDIWEIIGELGDGAFGKVYKAQHKETGLFAAAKII---QIESEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 106 MELLEGQTLKHRIGT--RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakVTLKNAvsa 183
cd06611      81 IEFCDGGALDSIMLEleRGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFG---VSAKNK--- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 184 aetmatmpapvvSEDQLTSpgSSLGTVAYMSPEQARGEEL-----DARSDLFSLGVVLYEMATGQLPFAAATAALMFDGI 258
cd06611     155 ------------STLQKRD--TFIGTPYWMAPEVVACETFkdnpyDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKI 220

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967801 259 LHSEPKSASEvNHRIPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06611     221 LKSEPPTLDQ-PSKWSSSFNDFLKSCLVKDPDDR-PTAAEL 259

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

3e-18

89.09

74.05

6,34,0,78,112,81,19,133,100,42,176,142,3,180,145,8,207,153,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQ-- 112
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGel 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 -TLKHRIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtLKNaVSAAETMAtmp 191
cd05572      81 wTILRDRGLLDEYTARFYTA--CVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKK-LKS-GQKTYTFC--- 153

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967801 192 apvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAA 248
cd05572     154 ----------------GTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGE 194

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

3e-18

89.03

79.06

10,26,0,34,60,38,23,86,61,7,95,68,7,102,77,22,124,106,7,138,113,35,174,148,14,207,162,12,219,175,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFL----PDDISHDPQAIERFRREARAASAlnhPNICTIYdiGEYEGRP 102
cd06917       1 SLYQRLELIGRGAYGAVYRGKHVPTGRVVALKIInldtPDDDVSDIQREVALLSQLRQSQP---PNITKYY--GSYLKGP 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 103 --FIAMELLEGQTLKHRIGTRPMD-------ITEILDAgiqiangLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLA 173
cd06917      76 rlWIIMEYAEGGSVRTLMKAGPIAekyisviIREVLVA-------LKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 174 kVTLKNAVSAAETMAtmpapvvsedqltspgsslGTVAYMSPEQAR-GEELDARSDLFSLGVVLYEMATGQLPFAAATAA 252
cd06917     149 -ALLNQNSSKRSTFV-------------------GTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDAF 208

                       250
                ....*....|.
gi 94967801 253 LMFDGILHSEP 263
cd06917     209 RAMMLIPKSKP 219

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

1e-17

87.23

95.15

10,27,0,31,58,34,53,111,90,8,121,98,43,164,142,9,187,151,14,203,165,48,251,217,17,270,234,11,282,245,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  28 HYVVAERLGGGGMGVVYKATDSRLGRSVALK---FLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFI 104
cd06630       1 EWLKGQQLGTGAFSSCYQARDVKTGTLMAVKqvtYVRNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 105 AMELLEG---QTLKHRIGtrPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGE-AKILDFGLAkvtlkna 180
cd06630      81 FVEWMAGgsvSHLLSKYG--AFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFGAA------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 181 vsaaetmATMPAPVVSEDQLTspGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATA----ALMFD 256
cd06630     152 -------ARLAAKGTGAGEFQ--GQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHsnhlALIFK 222

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967801 257 GILHSEPKSASEvnHRIPLAFDTLLnKAMEKDRDLR 292
cd06630     223 IASATTAPSIPE--HLSPGLRDVTL-RCLELQPEDR 255

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

1e-17

86.88

75.81

4,34,0,84,118,87,55,194,142,54,259,196,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd05577       1 LGKGGFGEVCACQVRATGKMYACKKLDKKRIKKRKGETMALNEKIILEKVSSPFIVSLAYAFETKDALCLVLTLMNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRI---GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlknavsaaetmatmp 191
cd05577      81 KFHIynvGNPGFDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLA------------------ 142

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 192 apvVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAataalmfdgilHSEPKSASEVNH 271
cd05577     143 ---VEFPEGKKIHGRVGTVGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHSPFRQ-----------RKEKVKKEEVDR 208


                ..
gi 94967801 272 RI 273
cd05577     209 RT 210

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

4e-17

85.13

68.95

4,32,9,28,62,37,111,173,149,3,197,152,48

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQ 112
cd06641      10 EKIGKGSFGEVFKGIDNRTQKVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLA-KVTlknavsaaetmatmp 191
cd06641      88 SALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAgQLT--------------- 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 94967801 192 apvvseDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLP 245
cd06641     153 ------DTQIKRNTFVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPP 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132949

cd06618

PKc_MKK7

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) 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 MKK7 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). MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 (not included in this subfamily) and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade.

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs...

false

true

false

296

5e-17

85.12

81.76

12,34,22,28,63,50,48,111,100,7,118,108,7,130,115,2,132,120,13,145,134,33,181,167,5,204,172,12,216,188,37,253,226,22,276,248,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDdISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG--Q 112
cd06618      23 IGSGTCGQVYKMRFKKTGHVMAVKQMRR-TGNKEENKRILMDLDVVLKSHDCPYIVKCYGYFITDSDVFICMELMSTclD 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TLKHRI-GTRPMDIteildAG---IQIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKnavSAAETm 187
cd06618     102 KLLKRIqGPIPEDI-----LGkmtVAIVKALHYLKEKhGVIHRDVKPSNILLDASGNVKLCDFGISGRLVD---SKAKT- 172

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 188 atmpapvvsedqltspgSSLGTVAYMSPE----QARGEELDARSDLFSLGVVLYEMATGQLPFAAATAAL-MFDGILHSE 262
cd06618     173 -----------------RSAGCAAYMAPEridpPDPNPKYDIRADVWSLGISLVELATGQFPYKNCKTEFeVLTKILQEE 235

                       250       260       270
                ....*....|....*....|....*....|
gi 94967801 263 PKSASEVNHRIPLaFDTLLNKAMEKDRDLR 292
cd06618     236 PPSLPPNEGFSPD-FCSFVDLCLTKDHRKR 264

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

5e-17

84.93

67.03

6,32,6,33,67,39,47,114,93,6,130,99,44,175,143,8,204,151,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLPDDIShdPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQ 112
cd06619       7 EILGHGNGGTVYKAYHLLTRRILAVKVIPLDIT--VELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TL-------KHRIGTrpmditeildAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvTLKNAVSAae 185
cd06619      85 SLdvyrkipEHVLGR----------IAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVST-QLVNSIAK-- 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 186 tmatmpapvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPF 246
cd06619     152 -------------------TYVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

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

8e-17

84.24

45.28

3,83,54,50,133,105,41,194,146,52

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  84 LNHPNICTIYDIGEYEGRPFIAMELLEGQTLKHRIGTRPMDITEILDAGI-QIANGLDAAHTKSIVHRDIKPANIFLVEP 162
cd05582      55 VNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLaELALALDHLHSLGIIYRDLKPENILLDEE 134

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 163 GEAKILDFGLAKvtlknavsaaetmatmpapvVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATG 242
cd05582     135 GHIKLTDFGLSK--------------------ESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTG 194


                ....
gi 94967801 243 QLPF 246
cd05582     195 SLPF 198

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

1e-16

83.75

78.30

6,34,2,26,60,29,60,120,90,64,204,154,59,271,213,8,279,225,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFL-PDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05570       3 LGKGSFGKVLLAELKGTDELYAIKVLkKDVVLQDDDVECTMTEKRVLALAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGT-RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAetmatmpa 192
cd05570      83 LMYHIQQqGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEGILGGVTTS-------- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 193 pvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPksasevnhR 272
cd05570     155 ------------TFCGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILEDNV--------R 214

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967801 273 IPLAFDT----LLNKAMEKDRDLRCQSAAELRADLKR 305
cd05570     215 YPRWLSKeaksILKGFLTKNPEKRLGCGPTGEQDIKG 251

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

1e-16

83.81

63.66

5,26,0,85,111,88,13,124,106,7,138,113,45,206,158,54

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAM 106
cd05600       1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEG---QTLKHRIGTRPMD-----ITEILDAgiqiangLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLK 178
cd05600      81 EYVPGgdfRTLLNNLGVLSEDharfyMAEMFEA-------VDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSKGIVT 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 179 NAVSAaetmatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGI 258
cd05600     154 YANSV-----------------------VGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETWENL 210


                ..
gi 94967801 259 LH 260
cd05600     211 KY 212

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

2e-16

82.86

77.13

6,32,5,29,61,36,53,115,89,18,133,109,50,204,159,13,217,173,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLP--DDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLE 110
cd06632       6 ELLGSGSFGSVYEGLNLDDGDFFAVKEVSlaDDGQTGQEAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTLkHRIGTRPMDITEILDAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAaetma 188
cd06632      86 GGSL-AKLLKKYGSFPEPVIRLYtrQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAKQVVEFSFAK----- 159

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 189 tmpapvvsedqltspgSSLGTVAYMSPEQ-ARGEELDARSDLFSLGVVLYEMATGQLPFAA 248
cd06632     160 ----------------SFKGSPYWMAPEViAQQGGYGLAADIWSLGCTVLEMATGKPPWSQ 204

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

2e-16

82.70

44.58

4,133,103,41,178,144,12,206,156,58,268,214,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 134 QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlkNAVSAAETMATMpapvvsedqltspgssLGTVAYM 213
cd05575     104 EIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCK----EGIAGSKTTSTF----------------CGTPEYL 163

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 214 SPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKsaseVNHRIPLAFDTLLNKAMEKDRDLRC 293
cd05575     164 APEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNKPLR----LRPNISVSARHLLEGLLQKDRTKRL 239


                ....*...
gi 94967801 294 QSAAELRA 301
cd05575     240 GAKNDFLE 247

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

3e-16

82.36

77.82

8,26,0,34,62,34,59,121,94,7,128,102,5,133,109,47,197,156,19,216,178,4,222,182,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAM 106
cd06610       1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIKRI--DLEKCQTSMDELRKEIQAMSLCHHPNVVKYYTSFVVGDELWVVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEGQTLKHRIGTR-PMDITEI-LDAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAvs 182
cd06610      79 PLMSGGSCLDIMKYSyPQGGLDEaIIATIlkEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVSASLADGG-- 156

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967801 183 aaetmatmpapvvseDQLTSPGSSLGTVAYMSPE---QARGeeLDARSDLFSLGVVLYEMATGQLPFA 247
cd06610     157 ---------------DRTKVRKTFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYS 207

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

3e-16

82.49

70.00

6,34,8,27,61,36,21,83,57,33,116,93,15,133,108,51,207,159,52

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLP-DDISHDPQAIERFRREARAASaLNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05580       9 LGTGSFGRVMLVKHKGTGKYYAMKILSkAKIVKLKQVEHVLNEKRILQA-VRHPFLVNLLGSFKDNSNLYMVMEFVPGGE 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKH---RIGTRPMDITEILDAgiQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAetmatm 190
cd05580      88 LFSllrRSGRFPEPVARFYAA--QVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAKRVKGRTYTLC------ 159

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967801 191 papvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGIL 259
cd05580     160 -----------------GTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKIYEKIL 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88520

cd05619

STKc_nPKC_theta

STKc_nPKC_theta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), theta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC 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. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases.

STKc_nPKC_theta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), theta...

false

true

false

316

3e-16

82.35

66.77

5,34,2,31,65,34,55,120,90,54,177,144,9,203,153,60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIS-HDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05619       3 LGKGSFGKVFLAELKGTNQFFAIKALKKDVVlMDDDVECTMVEKRVLSLAWEHPFLTHLYCTFQTKENLFFVMEYLNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGT-RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlKNAVSAAETmatmpa 192
cd05619      83 LMFHIQScHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCK---ENMLGDAKT------ 153

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 193 pvvsedqltspGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEP 263
cd05619     154 -----------CTFCGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEELFQSIRMDNP 213

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

8e-16

80.92

89.90

7,21,13,39,62,52,23,86,75,86,172,162,7,181,169,6,206,175,44,251,219,61

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  22 VGRTISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNhPNICTIYDIGEYEGR 101
cd06656      14 VGDPKKKYTRFEKIGQGASGTVYTAIDIATGQEVAIKQM--NLQQQPKKELIINEILVMRENKN-PNIVNYLDSYLVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 102 PFIAMELLEGQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGL-AKVTLKNa 180
cd06656      91 LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQITPEQ- 169

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 181 vSAAETMatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATaALMFDGILH 260
cd06656     170 -SKRSTM-------------------VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNEN-PLRALYLIA 228

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 94967801 261 SEPKSASEVNHRIPLAFDTLLNKAMEKDRDLRCQSAAELRADLKRLKRDIES 312
cd06656     229 TNGTPELQNPERLSAVFRDFLNRCLEMDVDRRGSAKELLQHPFLKLAKPLSS 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88491

cd05590

STKc_nPKC_eta

STKc_nPKC_eta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), eta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC 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. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM.

STKc_nPKC_eta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), eta...

false

true

false

320

1e-15

80.83

65.62

4,34,2,29,63,32,55,118,88,66,204,154,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDD-ISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05590       3 LGKGSFGKVMLARLKESGRLYAVKVLKKDvILQDDDVECTMTEKRILSLARNHPFLTQLYCCFQTPDRLFFVMEFVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRI-GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAetmatmpa 192
cd05590      83 LMFHIqKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKTTS-------- 154

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 193 pvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE 262
cd05590     155 ------------TFCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDE 212

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

1e-15

80.54

90.20

7,21,13,39,62,52,20,83,72,89,172,162,7,181,169,6,206,175,69,276,244,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  22 VGRTISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASaLNHPNICTIYDIGEYEGR 101
cd06655      14 IGDPKKKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQI--NLQKQPKKELIINEILVMKE-LKNPNIVNFLDSFLVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 102 PFIAMELLEGQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGL-AKVTLKNa 180
cd06655      91 LFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFcAQITPEQ- 169

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 181 vSAAETMatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILH 260
cd06655     170 -SKRSTM-------------------VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIAT 229

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 94967801 261 SEPKSASEVNHRIPLaFDTLLNKAMEKDRDLRCQSAAELRADLKRLKRDIES 312
cd06655     230 NGTPELQNPEKLSPI-FRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSS 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132981

cd06650

PKc_MEK1

MEK1 (MAPKK1 or MKK1): Protein kinases (PKs), MAP/ERK kinase (MEK) 1 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 is a dual-specificity PK that phosphorylates and activates 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, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control.

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

false

true

false

333

1e-15

80.46

63.96

8,34,12,31,67,43,49,116,95,9,127,104,18,145,123,32,184,155,5,204,160,48,252,211,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIShdPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06650      13 LGAGNGGVVFKVSHKPSGLIMARKLIHLEIK--PAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KH---RIGTRPMDIteILDAGIQIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKVTLknavsaaETMATm 190
cd06650      91 DQvlkKAGRIPEQI--LGKVSIAVIKGLTYLREKhKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLI-------DSMAN- 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967801 191 papvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAA---LMFDGILHSEPKSA 266
cd06650     161 --------------SFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAIGRYPIPPPDAKeleLMFGCPVEGDPAES 225

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

1e-15

80.48

87.00

7,32,9,28,62,37,111,173,149,3,197,152,69,267,221,7,276,228,16,293,244,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQ 112
cd06642      10 ERIGKGSFGEVYKGIDNRTKEVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLA-KVTlknavsaaetmatmp 191
cd06642      88 SALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAgQLT--------------- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 192 apvvseDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKSAsEVNH 271
cd06642     153 ------DTQIKRNTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTL-EGQY 225

                       250       260
                ....*....|....*....|....*...
gi 94967801 272 RIPlaFDTLLNKAMEKDRDLRcQSAAEL 299
cd06642     226 SKP--FKEFVEACLNKDPRFR-PTAKEL 250

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

1e-15

80.27

95.13

8,34,7,27,61,35,22,83,62,28,111,93,8,121,101,65,200,166,50,253,216,39,293,255,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLP-DDISHDPQAIERFRREARAASA-----LNHPNICTIYDIGEYEGRPFIAMEL 108
cd06628       8 IGSGSFGSVYLGMNAHSGELMAVKQVEiPSNSIGVQDRKRKMLDALQREInllkeLHHENIVQYLGSSQDAGHLNIFLEY 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 109 LEG---QTLKHRIGtrPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAE 185
cd06628      88 VPGgsvAALLNNYG--AFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKT 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 186 TmatmpapvvsedqlTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATaalMFDGILHSEPKS 265
cd06628     166 N--------------GARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFPDCT---QMQAIFKIGTNA 228

                       250       260       270
                ....*....|....*....|....*....|....
gi 94967801 266 ASEVNHRIPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06628     229 SPEIPSNASSEAKNFLRKTFEIDYNKR-PTAAEL 261

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

1e-15

80.10

68.95

4,32,9,28,62,37,112,175,149,12,206,161,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQ 112
cd06640      10 ERIGKGSFGEVFKGIDNRTQQVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvTLKNAVSAAETMatmpa 192
cd06640      88 SALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAG-QLTDTQIKRNTF----- 161

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 94967801 193 pvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLP 245
cd06640     162 --------------VGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPP 200

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

2e-15

79.56

86.35

10,21,13,39,62,52,20,83,72,89,172,162,7,181,169,6,206,175,40,258,215,8,266,232,6,272,240,20,293,260,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  22 VGRTISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASaLNHPNICTIYDIGEYEGR 101
cd06647      14 VGDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQM--NLQQQPKKELIINEILVMRE-NKHPNIVNYLDSYLVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 102 PFIAMELLEGQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGL-AKVTLKNa 180
cd06647      91 LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQITPEQ- 169

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 181 vSAAETMatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFaaataalmfdgiLH 260
cd06647     170 -SKRSTM-------------------VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPY------------LN 217

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 94967801 261 SEPKSA---------SEVNHR--IPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06647     218 ENPLRAlyliatngtPELQNPekLSAIFRDFLNRCLEMDVEKR-GSAKEL 266

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-15

79.41

66.67

5,33,25,27,62,52,5,68,57,104,182,161,9,201,170,45

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  34 RLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDpQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd06648      26 KIGEGSTGIVCIATDKSTGRQVAVKKM--DLRKQ-QRRELLFNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGA 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLakvtlknavsAAETMATMPap 193
cd06648     103 LTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGF----------CAQVSKEVP-- 170

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 94967801 194 vvsedqltSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPF 246
cd06648     171 --------RRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPY 215

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

3e-15

79.02

68.18

11,34,8,31,67,39,44,111,87,4,116,91,6,126,97,10,136,109,9,145,119,26,180,145,4,184,151,5,204,156,50,256,206,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIShdPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG--- 111
cd06615       9 LGAGNGGVVTKVLHRPSGLIMARKLIHLEIK--PAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGgsl 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 112 -QTLKhRIGTRPmditEILDAGIQIA--NGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGlakvtlknaVSAA--E 185
cd06615      87 dQVLK-KAGRIP----ENILGKISIAvlRGLTYLREKhKIMHRDVKPSNILVNSRGEIKLCDFG---------VSGQliD 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 186 TMATmpapvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMfdGILHSEPKS 265
cd06615     153 SMAN---------------SFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKEL--EAMFGRPVS 215


                ...
gi 94967801 266 ASE 268
cd06615     216 EGE 218

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88505

cd05604

STKc_SGK3

STKc_SGK3: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK3 isoform, 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). SGK3 is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling.

STKc_SGK3: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (...

false

true

false

325

3e-15

78.93

41.54

5,133,103,41,178,144,12,206,156,54,266,210,6,272,218,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 134 QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlkNAVSAAETMATMpapvvsedqltspgssLGTVAYM 213
cd05604     104 EIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCK----EGIAQSDTTTTF----------------CGTPEYL 163

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 214 SPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHsepksaSEVNHR--IPLAFDTLLNKAMEKDRDL 291
cd05604     164 APEVIRKQPYDNTVDWWCLGAVLYEMLYGLPPFYCRDVAEMYDNILH------KPLVLRpgASLTAWSILEELLEKDRQR 237


                .
gi 94967801 292 R 292
cd05604     238 R 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88492

cd05591

STKc_nPKC_epsilon

STKc_nPKC_epsilon: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), epsilon isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC 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. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility.

STKc_nPKC_epsilon: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC),...

false

true

false

321

6e-15

78.10

65.42

6,34,2,29,63,32,56,119,89,55,184,144,4,196,148,6,204,154,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDD-ISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05591       3 LGKGSFGKVMLAELKGTDEVYAIKVLKKDvILQDDDVDCTMTEKRILALAAKHPFLTALHCCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIG-TRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlknavsaaETMAtmpa 192
cd05591      83 LMFQIQrSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCK----------EGIL---- 148

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 193 pvvsEDQLTSpgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE 262
cd05591     149 ----NGVTTT--TFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDD 212

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-15

77.92

90.14

14,23,7,5,34,12,26,62,38,53,115,94,11,126,106,5,134,111,11,145,123,29,175,152,6,183,158,4,206,162,47,255,209,5,262,214,11,273,238,19,293,257,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  24 RTISHyvvaerLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPF 103
cd06620       8 ETISD------LGAGNGGSVSKVKHIPTGTVMAKKVV--HIGAKSSVRKQILRELQIMHECRSPYIVSFYGAFLNENNIC 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 104 IAMELLEGQTLK---HRIGTRPMDIT-EILDAgiqIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKvTLK 178
cd06620      80 MCMEFMDCGSLDriyKKGGPIPVEILgKIAVA---VVEGLTYLYNVhRIMHRDIKPSNILVNSRGQIKLCDFGVSG-ELI 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 179 NAVsaAETMatmpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALmfDGI 258
cd06620     156 NSI--ADTF-------------------VGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFAFSNIDD--DGQ 212

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 94967801 259 LHsePKSASEVNHRI-------------PLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06620     213 DD--PMGILDLLQQIvqeppprlpssdfPEDLRDFVDACLLKDPTER-PTPQQL 263

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

9e-15

77.39

70.61

9,33,10,14,47,28,13,62,41,40,102,83,16,118,100,4,122,105,53,194,158,5,199,167,7,208,174,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  34 RLGGGGMGVVYKAT----DSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRP--FIAME 107
cd05038      11 QLGEGHFGTVYLGTydppDDNTGEIVAVKKL--NTSGVEAHRQDFEREIEIMRTLDHENIVKYKGVSEEPGGRslSLIME 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 108 LLEGQTLKHRI-GTRP-MDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtlknavsaae 185
cd05038      89 YLPSGSLRDYLrRHRDqLNLKRLLLFALQIAKGMDYLGSKRLIHRDLAARNILVDSEDLVKISDFGLAKV---------- 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 186 tmatmpapvVSEDQ----LTSPGSSlgTVAYMSPEQARGEELDARSDLFSLGVVLYEMAT 241
cd05038     159 ---------LPEDKdyyyVKEPRES--PIFWYAPECLRTGKFSSASDVWSYGVTLYEMFT 207

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-14

76.93

78.02

9,34,3,10,44,16,18,62,35,52,114,90,22,138,112,38,194,150,8,204,158,58,265,216,13,279,229,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVY---KATDSRLGRSVALKFLPD-DISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLE 110
cd05584       4 LGKGGYGKVFqvrKVTGADTGKIFAMKVLKKaTIVRNQKDTAHTKAERNILEAVKHPFIVDLIYAFQTGGKLYLILEYLS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTL---KHRIGTRPMDITEILDAGIQIAngLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTlknavsaaetm 187
cd05584      84 GGELfmhLEREGIFMEDTACFYLSEISLA--LEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCKES----------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 188 atmpapvVSEDQLTSpgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEpksAS 267
cd05584     151 -------IHEGTVTH--TFCGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGK---LN 218

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94967801 268 EVNHRIPLAFDtLLNKAMEKDRDLRCQSAAELRADLKR 305
cd05584     219 LPPYLTPEARD-LLKKLLKRNPSSRLGAGPGDAAEVQS 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132974

cd06643

STKc_SLK

Serine/threonine kinases (STKs), Ste20-like kinase (SLK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SLK 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. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase (MAPKKK) by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration.

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

false

true

false

282

1e-14

76.98

85.46

8,34,12,26,61,38,6,69,44,51,120,97,51,180,148,8,199,156,16,215,177,59,275,236,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLpDDISHDpqAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06643      13 LGDGAFGKVYKAQNKETGVLAAAKVI-DTKSEE--ELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAV 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRIGT--RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlknaVSAAETMAtmpa 192
cd06643      90 DAVMLEleRPLTEPQIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGDIKLADFG---------VSAKNTRT---- 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 193 pvvsedqLTSPGSSLGTVAYMSP-----EQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPKSAS 267
cd06643     157 -------IQRRDSFIGTPYWMAPevvmcETSKDRPYDYKADVWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLA 229

                       250       260
                ....*....|....*....|....*
gi 94967801 268 EVNHRIPlAFDTLLNKAMEKDRDLR 292
cd06643     230 QPSRWSS-EFKDFLKKCLEKNVDAR 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132948

cd06617

PKc_MKK3_6

Protein kinases (PKs), MAP kinase kinase 3 (MKK3) and MKK6 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 MKK3 and MKK6 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). MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 plays roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma.

Protein kinases (PKs), MAP kinase kinase 3 (MKK3) and MKK6 subfamily, catalytic (c)...

false

true

false

280

2e-14

76.69

73.21

10,29,3,54,84,57,27,111,91,7,119,98,10,131,108,14,145,123,29,175,152,7,187,159,5,207,164,14,221,182,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  30 VVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASAlNHPNICTIYDIGEYEGRPFIAMELL 109
cd06617       4 EVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEQKRLLMDLDISMRSS-DCPYTVHFYGALFREGDVWICMEVM 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 110 EG-------QTLKHRIgTRPMDITEILdaGIQIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKvTLKNAV 181
cd06617      83 DTsldkfykKVYKKGL-TIPEDILGKI--AVSVVKALEYLHEKlSVIHRDVKPSNILINRNGQVKLCDFGISG-YLVDSL 158

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 182 SaaetmATMPApvvsedqltspgsslGTVAYMSPEQARGE----ELDARSDLFSLGVVLYEMATGQLPFA 247
cd06617     159 A-----KTVDA---------------GCKPYMAPERIDPEgnqkGYDVRSDVWSLGITMIELATGRFPYD 208

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132953

cd06622

PKc_MAPKK_PBS2_like

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, fungal PBS2-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 Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1.

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, fungal PBS2-like proteins,...

false

true

false

286

2e-14

76.43

87.06

11,30,4,30,62,34,52,114,92,11,125,104,18,145,122,33,181,155,5,205,160,21,226,187,29,255,219,9,271,228,8,279,240,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  31 VAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLE 110
cd06622       5 VLDELGKGNYGSVYKVLHRPTGVTMAMKEI--RLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTL------KHRIGTRPMDI-TEILDAGIQIANGLDAAHtkSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKnavSA 183
cd06622      83 AGSLdklyagGVATEGIPEDVlRRITYAVVKGLKFLKEEH--NIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVA---SL 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 184 AETmatmpapvvsedqltspgsSLGTVAYMSPEQARGEELDAR------SDLFSLGVVLYEMATGQLPFAAATAALMF-- 255
cd06622     158 AKT-------------------NIGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYANIFaq 218

                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 94967801 256 -DGILHSEPKsasevnhRIPLAFDT----LLNKAMEKDRDLR 292
cd06622     219 lSAIVDGDPP-------TLPSGYSDdaqdFVAKCLNKIPNRR 253

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

3e-14

75.61

93.28

12,34,15,46,83,61,38,121,101,6,127,109,32,159,142,15,175,157,13,207,170,9,216,183,4,222,187,24,246,214,17,267,231,25,293,256,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAasaLNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06624      16 LGKGTYGVVYAGRDLSTQVRIAIKEIPERDSRYSQPLHEEIALHSR---LKHKNIVQYLGSDSENGYFKIFMEQVPGGSL 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRIGTR--PMDITE--ILDAGIQIANGLDAAHTKSIVHRDIKPANIFL-VEPGEAKILDFGLAKvTLKNAVSAAETMAt 189
cd06624      93 SALLRSKwgPLKDNEstIIFYTKQILEGLKYLHDNQIVHRDIKGDNVLVnTYSGVLKISDFGTSK-RLAGINPCTETFT- 170

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 190 mpapvvsedqltspgsslGTVAYMSPE----QARGeeLDARSDLFSLGVVLYEMATGQLPF---AAATAALMFDGILHSE 262
cd06624     171 ------------------GTLQYMAPEiidkGPRG--YGAPADIWSLGCTIIEMATGKPPFhelGEPQAAMFKVGMFKIH 230

                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 94967801 263 PksasEVNHRIPLAFDTLLNKAMEKDRDLRcQSAAELRAD 302
cd06624     231 P----EIPESLSAEAKAFILRCFEPDPDKR-ASAHDLLQD 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88509

cd05608

STKc_GRK1

STKc_GRK1: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK1 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. GRK1, also called rhodopsin kinase, belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease.

STKc_GRK1: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

280

3e-14

75.81

54.29

6,133,104,40,174,144,14,207,158,41,259,199,14,273,216,4,277,232,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 134 QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkVTLKNAVSAAETMAtmpapvvsedqltspgsslGTVAYM 213
cd05608     105 QIILGLEHLHQHRIVYRDLKPENVLLDNDGNVRISDLGLA-VELKDGQSKTKGYA-------------------GTPGFM 164

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 214 SPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAataalmfdgilHSEPKSASEVNHRI---PLAF------------D 278
cd05608     165 APELLQGEEYDYSVDYFTLGVTLYEMIAAKGPFRR-----------RGEKVENKEVKRRIlndSVTYsekfsaasksicE 233

                       170       180
                ....*....|....*....|...
gi 94967801 279 TLLNKAMEKDRDLRCQSAAELRA 301
cd05608     234 GLLAKDPQKRLGFRDGNCDMLRA 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133172

cd05040

PTKc_Ack_like

Catalytic Domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase

false

true

false

257

3e-14

75.50

80.54

11,32,0,15,47,16,6,53,24,28,83,52,10,95,62,8,103,71,15,118,89,61,184,150,6,196,156,7,209,163,32,241,196,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKAT-DSRLGR--SVALKFLPDDISHDPQAIERFRREARAAsaLNHPNICTIYdiGEYEGRPF-IAMEL 108
cd05040       1 KKLGDGSFGVVRRGEwSTSGGKviPVAVKCLKSDKLSDIMDDFLKEAAIMHS--LDHENLIRLY--GVVLTHPLmMVTEL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 109 LEGQTLKHRI---GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNavsaaE 185
cd05040      77 APLGSLLDRLrkdALGHFLISTLCDYAVQIANGMRYLESKRFIHRDLAARNILLASDDKVKIGDFGLMRALPQN-----E 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967801 186 TMATMpapvvsEDQLTSPgsslgtVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPFAAATAA 252
cd05040     152 DHYVM------EEHLKVP------FAWCAPESLRTRTFSHASDVWMFGVTLWEMFTyGEEPWAGLSGS 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132975

cd06644

STKc_STK10_LOK

Serine/threonine kinases (STKs), STK10 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The STK10 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. Other names for STK10 include lymphocyte-oriented kinase (LOK) and Xenopus polo-like kinase kinase 1 (xPlkk1). STK10 is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types.

Serine/threonine kinases (STKs), STK10 subfamily, catalytic (c) domain. STKs catalyze...

false

true

false

292

4e-14

75.45

85.96

8,29,15,4,34,19,27,64,46,63,127,111,52,199,163,24,223,192,47,271,239,21,293,260,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  30 VVAErLGGGGMGVVYKATDSRLGRSVALKFLPddiSHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELL 109
cd06644      16 IIGE-LGDGAFGKVYKAKNKETGALAAAKVIE---TKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFC 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 110 EGQTLKHRIGTRPMDITE--ILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNavsaaetm 187
cd06644      92 PGGAVDAIMLELDRGLTEpqIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSAKNVKT-------- 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 188 atmpapvvsedqLTSPGSSLGTVAYMSPEQARGEEL-----DARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE 262
cd06644     164 ------------LQRRDSFIGTPYWMAPEVVMCETMkdtpyDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSE 231

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967801 263 PKSASEVNhRIPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06644     232 PPTLSQPS-KWSMEFRDFLKTALDKHPETR-PSAAQL 266

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133248

cd05148

PTKc_Srm_Brk

Catalytic Domain of the Protein Tyrosine Kinases, Srm and Brk

false

true

false

261

6e-14

74.78

78.93

9,32,11,21,54,32,9,66,41,31,98,72,5,103,78,17,120,98,55,176,153,2,197,155,44,241,200,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRLGRsVALKFLPDDishDPQAIERFRREARAASALNHPNICTIYDIGEyEGRPF-IAMELLEG 111
cd05148      12 RKLGSGYFGEVWEGLWKNRVR-VAIKILKSD---DLLKQQDFQKEVQALKRLRHKHLISLFAVCS-VGEPVyIITELMEK 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 112 QTLKHRIGT---RPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtLKnavsaaetma 188
cd05148      87 GSLLAFLRSpegQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARL-IK---------- 155

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 189 tmpapvvseDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPFAAATAALMFDGI 258
cd05148     156 ---------EDVYLSSDKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQI 217

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88504

cd05603

STKc_SGK2

STKc_SGK2: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK2 isoform, 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. SGK2 shows a more restricted distribution that SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1.

STKc_SGK2: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (...

false

true

false

321

7e-14

74.69

33.33

3,133,103,41,178,144,12,206,156,54

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 134 QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlkNAVSAAETMATMpapvvsedqltspgssLGTVAYM 213
cd05603     104 EVASAIGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK----EGVEPEETTSTF----------------CGTPEYL 163

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 94967801 214 SPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILH 260
cd05603     164 APEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQMYDNILH 210

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133191

cd05060

PTKc_Syk_like

Catalytic Domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases

false

true

false

257

9e-14

74.31

79.77

11,32,0,15,47,16,7,54,25,9,65,34,27,94,61,10,104,72,6,110,79,64,179,143,7,196,150,9,207,159,34,241,194,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKAT-DSRLGRS--VALKFLPDDisHDPQAIERFRREARAASALNHPNICTIydIGEYEGRPFI-AMEL 108
cd05060       1 KELGHGNFGSVVKGVyLMKSGKEveVAVKTLKQE--HIAAGKKEFLREASVMAQLDHPCIVRL--IGVCKGEPLMlVMEL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 109 LE-GQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlknAVSAAETm 187
cd05060      77 APlGPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSR-----ALGAGSD- 150

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967801 188 atmpapvvsEDQLTSPGSslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPFAAATAA 252
cd05060     151 ---------YYRATTAGR--WPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSyGAKPYGEMKGA 205

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88508

cd05607

STKc_GRK7

STKc_GRK7: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK7 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. GRK7, also called iodopsin kinase, belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones.

STKc_GRK7: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

277

1e-13

73.91

70.04

4,34,0,84,118,87,55,174,142,13,207,155,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd05607       1 LGKGGFGEVCAVQVKNTGKMYACKKLDKKRLKKKSGEKMALLEKEILEKVNSPFIVNLAYAFESKTHLCLVMSLMNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRI---GTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkVTLKNAVSAAETMatmp 191
cd05607      81 KYHIynvGERGLEMERVIHYSAQITCGILHLHSMDIVYRDMKPENVLLDDQGNCRLSDLGLA-VELKDGKTITQRA---- 155

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94967801 192 apvvsedqltspgsslGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPF 246
cd05607     156 ----------------GTNGYMAPEILKEEPYSYPVDWFAMGCSIYEMVAGRTPF 194

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132980

cd06649

PKc_MEK2

MEK2 (MAPKK2 or MKK2): Protein kinases (PKs), MAP/ERK Kinase (MEK) 2 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). MEK2 is a dual-specificity PK that phosphorylates and activates 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 MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients.

MEK2 (MAPKK2 or MKK2): Protein kinases (PKs), MAP/ERK Kinase (MEK) 2 subfamily,...

false

true

false

331

1e-13

73.93

58.91

6,34,12,31,67,43,62,129,106,16,145,123,32,184,155,5,204,160,47

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIShdPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd06649      13 LGAGNGGVVTKVQHKPSGLIMARKLIHLEIK--PAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRIGTRPMDITEIL-DAGIQIANGLDAAHTK-SIVHRDIKPANIFLVEPGEAKILDFGLAKVTLknavsaaETMATmpa 192
cd06649      91 DQVLKEAKRIPEEILgKVSIAVLRGLAYLREKhQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLI-------DSMAN--- 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 94967801 193 pvvsedqltspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATA 251
cd06649     161 ------------SFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVELAIGRYPIPPPDA 207

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

1e-13

73.88

77.66

14,15,8,6,21,16,39,61,55,21,84,76,12,97,88,2,99,96,17,116,119,5,121,127,2,124,129,10,137,139,34,180,173,3,198,176,5,203,185,12,215,202,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  16 ASSLGL--VGRTISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpDDISHDPQAIERFRREARAASalNHPNICTIY 93
cd06639       9 SSMLGLesLGDPTDTWEIIETIGKGTYGKVYKVTNKKDGSLAAVKIL-DPISDVDEEIEAEYNILQSLP--NHPNVVKFY 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  94 DIGeYE------GRPFIAMELLEGQTLKH------RIGTR---PMdITEILDAGIQianGLDAAHTKSIVHRDIKPANIF 158
cd06639      86 GMF-YKadklvgGQLWLVLELCNGGSVTElvkgllICGQRldeAM-ISYILYGALL---GLQHLHNNRIIHRDVKGNNIL 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 159 LVEPGEAKILDFGlakvtlknaVSAaetmatmpapvvsedQLTSP----GSSLGTVAYMSP-----EQARGEELDARSDL 229
cd06639     161 LTTEGGVKLVDFG---------VSA---------------QLTSTrlrrNTSVGTPFWMAPeviacEQQYDYSYDARCDV 216

                       250
                ....*....|....*...
gi 94967801 230 FSLGVVLYEMATGQLPFA 247
cd06639     217 WSLGITAIELGDGDPPLF 234

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

2e-13

73.35

87.63

9,26,0,88,114,91,22,138,113,35,177,148,11,207,159,9,216,170,5,223,175,47,273,222,5,279,227,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  27 SHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAM 106
cd05612       1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEGQTL---KHRIGTRPMDITEILDAGIQIAngLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlKNAVSA 183
cd05612      81 EYVPGGELfsyLRKAGKFSNSTARFYAAEIVCA--LEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFA----KKVRDR 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 184 AETMAtmpapvvsedqltspgsslGTVAYMSPE--QARGEelDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHS 261
cd05612     155 TWTLC-------------------GTPEYLAPEiiQSKGH--GKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAG 213

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 94967801 262 EPKSASEVNhriPLAFDtLLNKAMEKDRDLRCQSAAELRADLKRLK 307
cd05612     214 KLEFPRHFD---LRAKD-LIKKLLVVDRTRRLGNMKNGADDVKNHK 255

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

2e-13

73.04

61.11

7,110,89,75,204,164,19,223,185,26,249,215,21,273,236,5,279,241,9,288,252,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNAVSAAEtmatm 190
cd05583      90 GELFTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLAEEEERAY----- 164

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 191 papvvsedqltspgSSLGTVAYMSPEQARGEEL--DARSDLFSLGVVLYEMATGQLPFAAA----TAALMFDGILHSEPK 264
cd05583     165 --------------SFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDgeqnSQSEISRRILKSKPP 230

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 94967801 265 SASEVNhriPLAFDtLLNKAMEKD--RDLRCQSAAELRA 301
cd05583     231 FPKTMS---AEARD-FIQKLLEKDpkKRLGANGADEIKN 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133199

cd05068

PTKc_Frk_like

Catalytic Domain of Fyn-related kinase-like Protein Tyrosine Kinases

false

true

false

261

3e-13

72.84

76.25

9,33,12,12,51,24,2,53,31,7,60,44,13,83,57,32,115,92,60,176,152,15,209,167,32,241,200,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  34 RLGGGGMGVVYKatdsrlGR-----SVALKFL------PDDISHDPQAIERfrrearaasaLNHPNICTIYDIGEYEGRP 102
cd05068      13 KLGAGQFGEVWE------GLwnnttPVAVKTLkpgtmdPKDFLAEAQIMKK----------LRHPKLIQLYAVCTLEEPI 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 103 FIAMELLEGQTLK---HRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtLKN 179
cd05068      77 YIVTELMKYGSLLeylQGGAGRALKLPQLIDMAAQVASGMAYLEAQNYIHRDLAARNVLVGENNICKVADFGLARV-IKE 155

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94967801 180 AVSAAETMATMPapvvsedqltspgsslgtVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPFAAATAA 252
cd05068     156 DIYEAREGAKFP------------------IKWTAPEAALYNRFSIKSDVWSFGILLTEIVTyGRMPYPGMTNA 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133164

cd05032

PTKc_InsR_like

Catalytic Domain of Insulin Receptor-like Protein Tyrosine Kinases

false

true

false

277

3e-13

72.36

75.45

6,34,13,17,51,35,16,69,51,46,115,108,59,192,167,49,241,217,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRL-----GRSVALKFLPDDISHDpqAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELL 109
cd05032      14 LGQGSFGMVYEGLAKGVvkgepETRVAIKTVNENASMR--ERIEFLNEASVMKEFNCHHVVRLLGVVSTGQPTLVIMELM 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 110 EGQTLK-----------HRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlk 178
cd05032      92 ARGDLKsylrsrrpeaeNNPGLGPPTLQEFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMAR---- 167

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967801 179 navsaaetmatmpaPVVSEDQLTSPGSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMAT-GQLPF 246
cd05032     168 --------------DIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATlAEQPY 222

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-13

72.06

68.24

5,21,14,39,62,53,23,86,76,87,191,163,11,204,174,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  22 VGRTISHYVVAERLGGGGMGVVYKATDSRLGRSVALKFLpdDISHDPQAIERFRREARAASALNhPNICTIYDIGEYEGR 101
cd06654      15 VGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIRQM--NLQQQPKKELIINEILVMRENKN-PNIVNYLDSYLVGDE 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 102 PFIAMELLEGQTLKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlknav 181
cd06654      92 LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFC-------- 163

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967801 182 saaetmatmpAPVVSEDQLTSpgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPF 246
cd06654     164 ----------AQITPEQSKRS--TMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPY 216

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88496

cd05595

STKc_PKB_beta

STKc_PKB_beta: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, beta (or Akt2) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB 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 PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure.

STKc_PKB_beta: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily,..

false

true

false

323

5e-13

71.98

67.18

6,34,2,84,119,86,12,131,100,42,177,142,13,206,155,56,262,214,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd05595       3 LGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 KHRIgTRPMDITEILDA--GIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlKNAVSAAETMATMpa 192
cd05595      83 FFHL-SRERVFTEERARfyGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLC----KEGISDGATMKTF-- 155

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967801 193 pvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSE---PKSAS 267
cd05595     156 --------------CGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEirfPRTLS 219

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

5e-13

71.88

49.39

7,102,76,9,111,89,25,138,114,33,181,147,4,194,151,33,227,190,33,260,231,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 103 FIAMELLEG----QTLKHRIGTRPMDITEILDAGIQIAngLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlk 178
cd05601      77 YLVMEYHPGgdllSLLNRYEDQFDESMAQFYLAELVLA--IHSLHQMGYVHRDIKPENILIDRTGHIKLADFG------- 147

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 179 navSAAEtmatmpapvVSEDQLTSPGSSLGTVAYMSPEQARGEELDARS------DLFSLGVVLYEMATGQLPFAAATAA 252
cd05601     148 ---SAAK---------LNANKMVNSKLPVGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGTSA 215

                       170       180
                ....*....|....*....|....
gi 94967801 253 LMFDGILH--------SEPKSASE 268
cd05601     216 VTYSNIMNfqrflkfpEDPKVSSD 239

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

6e-13

71.60

70.14

6,34,1,54,88,59,16,105,75,18,123,94,56,201,150,15,216,166,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPN----ICTIYDIGEYEGRPFIaMELLE 110
cd05606       2 IGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDcpfiVCMTYAFHTPDKLCFI-LDLMN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 111 GQTLKHRIGTRPM-DITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKNavsaaetmat 189
cd05606      81 GGDLHYHLSQHGVfSEAEMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKK---------- 150

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94967801 190 mpapvvsedqltSPGSSLGTVAYMSPE-QARGEELDARSDLFSLGVVLYEMATGQLPF 246
cd05606     151 ------------KPHASVGTHGYMAPEvLQKGVAYDSSADWFSLGCMLFKLLRGHSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88472

cd05571

STKc_PKB

STKc_PKB: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB 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). There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of PI3K and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis.

STKc_PKB: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily,...

false

true

false

323

6e-13

71.56

65.33

5,34,2,80,114,87,8,126,95,47,177,142,13,206,155,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQTL 114
cd05571       3 LGKGTFGKVILVREKATGKYYAMKILKKEVIIAKDEVAHTLTESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 115 -----KHRIGTRPmditEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlKNAVSAAETMAT 189
cd05571      83 ffhlsRERVFSED----RARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLC----KEGISDGATMKT 154

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967801 190 MpapvvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPK 264
cd05571     155 F----------------CGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIR 213

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

7e-13

71.09

95.85

12,32,5,18,51,23,9,60,35,55,115,93,10,127,103,47,185,150,16,204,166,47,251,214,4,255,223,14,275,237,3,279,240,13,293,253,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  33 ERLGGGGMGVVYKATDSRlGRSVALKFL---PDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELL 109
cd06631       6 EVLGKGAYGTVYCGLTNQ-GQLIAVKQVeldTSNVLAAEKEYEKLQEEVDLLKSLKHVNIVQYLGTCLDDNTISIFMEFV 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 110 EGQTLK---HRIGTRPMDIteILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKvtlknavsaaeT 186
cd06631      85 PGGSISsilNRFGPLPEPV--FCKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMPNGIIKLIDFGCAR-----------R 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 187 MATMPAPVVSEDQLTspgSSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATA-ALMF-----DGILH 260
cd06631     152 LAWVGLHGTHSNMLK---SMHGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASMDRlAAMFyigahRGLMP 228

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 94967801 261 SEPKSASEVnhriplAFDtLLNKAMEKDRDLRcQSAAEL 299
cd06631     229 RLPDSFSAA------AID-FVTSCLTRDQHER-PSALQL 259

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132964

cd06633

STKc_TAO3

Serine/threonine kinases (STKs), thousand-and-one amino acids 3 (TAO3) 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. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. TAO3 is also known as JIK (JNK inhibitory kinase) or KFC (kinase from chicken). It specifically activates c-Jun N-terminal kinase (JNK), presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis.

Serine/threonine kinases (STKs), thousand-and-one amino acids 3 (TAO3) subfamily,...

false

true

false

313

8e-13

70.82

82.43

10,28,22,60,90,82,8,98,92,17,115,113,19,137,132,38,200,170,6,206,177,10,216,189,5,221,195,41,264,236,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNicTIYDIGEY--EGRPFIAM 106
cd06633      23 FVGLHEIGHGSFGAVYFATNSHTNEVVAVKKMSYSGKQTNEKWQDIIKEVKFLQQLKHPN--TIEYKGCYlkEHTAWLVM 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 107 ELLEGQTLK----HRIGTRPMDITEILDAGIQianGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVtlknavs 182
cd06633     101 EYCLGSASDllevHKKPLQEVEIAAITHGALQ---GLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASK------- 170

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 183 aaetmatmpapvvsedqlTSPGSS-LGTVAYMSPE--QARGE-ELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGI 258
cd06633     171 ------------------SSPANSfVGTPYWMAPEviLAMDEgQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHI 232

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 94967801 259 LHSEpkSASEVNHRIPLAFDTLLNKAMEKDRDLRCQSAAELRADLKRLKR 308
cd06633     233 AQND--SPTLQSNEWTDSFRGFVDYCLQKIPQERPASAELLRHDFVRRDR 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

8e-13

70.99

82.08

11,34,22,54,90,76,8,98,86,17,115,107,19,137,126,34,181,160,3,199,163,7,206,171,10,216,183,5,221,189,51,274,240,34

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNicTIYDIGEY--EGRPFIAMELLEGQ 112
cd06607      23 IGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQQLRHPN--TIEYKGCYlrEHTAWLVMEYCLGS 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 113 TLK----HRIGTRPMDITEILDAGIQianGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGlakvtlknavSAAetma 188
cd06607     101 ASDilevHKKPLQEVEIAAICHGALQ---GLAYLHSHERIHRDIKAGNILLTEPGTVKLADFG----------SAS---- 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 189 tmpapvvsedqLTSPGSS-LGTVAYMSPE--QARGE-ELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPK 264
cd06607     164 -----------LVSPANSfVGTPYWMAPEviLAMDEgQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSP 232

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94967801 265 SASEVNHRipLAFDTLLNKAMEKDRDLRCQSAAELRADLKRLKR 308
cd06607     233 TLSSNDWS--DYFRNFVDSCLQKIPQDRPSSEELLKHRFVLRER 274

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

1e-12

70.73

50.82

5,103,77,8,111,88,25,138,113,41,179,155,21,206,176,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 104 IAMELLEG---QTLKHRIGTRPMDITEILDAGIQIAngLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTLKN- 179
cd05609      78 MVMEYVEGgdcATLLKNIGPLPVDMARMYFAETVLA--LEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIGLMSl 155

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 180 AVSAAETMATMPAPVVSEDQLtspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGIL 259
cd05609     156 TTNLYEGHIEKDTREFLDKQV------CGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVI 229


                ...
gi 94967801 260 HSE 262
cd05609     230 SDD 232

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88494

cd05593

STKc_PKB_gamma

STKc_PKB_gamma: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, gamma (or Akt3) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB 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 PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer.

STKc_PKB_gamma: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt...

false

true

false

325

1e-12

70.48

64.92

4,34,2,77,111,80,62,177,142,13,206,155,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDISHDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEG-QT 113
cd05593       3 LGKGTFGKVILVREKASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGgEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGTRPMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAkvtlKNAVSAAETMATMpap 193
cd05593      83 FFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLC----KEGITDAATMKTF--- 155

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 194 vvsedqltspgssLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEPK 264
cd05593     156 -------------CGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIK 213

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

1e-12

70.60

97.06

12,28,2,31,59,35,6,65,43,18,83,64,32,116,96,17,133,115,43,177,158,10,204,168,12,216,182,35,251,218,5,256,224,36,293,260,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  29 YVVAERLGGGGMGVVYKATDSRLGRSVALKF--LPDDIS--HDPQAIERFRREARAASA---LNHPNICTIYDIGEYEGR 101
cd06629       3 WVKGELIGKGTYGRVYLALNVTTGEMMAVKQveLPATIAgrHDSRQKDMVKALRSEIETlkdLDHLNIVQYLGFETTEEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 102 PFIAMELLEGQTLKhRIGTRPMDITEILDAGI--QIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTlKN 179
cd06629      83 LSIFLEYVPGGSIG-SCLRTYGRFEEQLVRFFteQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGISKKS-DD 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 180 AVSAAETMatmpapvvsedqltspgSSLGTVAYMSPE--QARGEELDARSDLFSLGVVLYEMATGQLPFAAATA-ALMFD 256
cd06629     161 IYDNDQNM-----------------SMQGSVFWMAPEviHSYSQGYSAKVDIWSLGCVVLEMFAGRRPWSDEEAiAAMFK 223

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94967801 257 -GILHSEPKSASEVNHRIPLAFDTLLNKAMEKDRDLRcQSAAEL 299
cd06629     224 lGNKRSAPPIPPDVSMNLSPVALDFLNACFTINPDNR-PTAREL 266

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88521

cd05620

STKc_nPKC_delta

STKc_nPKC_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), delta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC 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. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis.

STKc_nPKC_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), delta...

false

true

false

316

2e-12

70.04

66.77

5,34,2,31,65,34,56,121,91,55,193,146,9,205,155,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801  35 LGGGGMGVVYKATDSRLGRSVALKFLPDDIS-HDPQAIERFRREARAASALNHPNICTIYDIGEYEGRPFIAMELLEGQT 113
cd05620       3 LGKGSFGKVLLAELKGKGEYFAVKALKKDVVlIDDDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEFLNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967801 114 LKHRIGTR-PMDITEILDAGIQIANGLDAAHTKSIVHRDIKPANIFLVEPGEAKILDFGLAKVTlknavsaaetmatmpa 192
cd05620      83 LMFHIQDKgRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKEN---------------- 146

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967801 193 pVVSEDQLTSpgsSLGTVAYMSPEQARGEELDARSDLFSLGVVLYEMATGQLPFAAATAALMFDGILHSEP 263
cd05620     147 -VFGDNRAST---FCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQS