NCBI Conserved Domain Search

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Conserved domains on [gi\|94967635\|ref\|YP_589683.1\|]
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

2e-49

192.73

95.70

5,15,0,34,50,34,38,89,72,18,107,91,128,235,222,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  16 NYRILGLLGAGGMGVVYRALDVKLERTVALKFLPeHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVM 95
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIK-KKKEKKKQVERILREIKILKRLNHPNIVKLYDVFEDED-KLYLVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  96 AYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSIS 174
cd00180      79 EYMSGGDLFDLLkKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLDSGGRKLTT 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 175 SGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPM---DEIPVDLLRIIYRALA 251
cd00180     159 FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGKGTPDelpPNISPEAKDLIKKLLV 238


                ....*..
gi 94967635 252 KEPELRY 258
cd00180     239 KDPEKRP 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132937

cd06606

STKc_MAPKKK

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15.

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

false

true

false

259

4e-37

151.93

89.58

6,30,15,30,61,45,46,107,92,57,164,151,53,217,205,7,224,214,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKrVLREARTASQLDHPNIGVIHGFEETDDGRVFIVMAYYEGETLARKI-AH 109
cd06606      16 VYLALSKDTGELVAVKSVELSSDSEEELES-LEREIRILSKLQHPNIVRYYGCEVTEENTLNIFMEYVSGGSLASLLkKF 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARL--STGASTQSISSGGTVGYMSPEQA 187
cd06606      95 GKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRlaSIAYSGGLKSVRGTPYWMAPEVI 174

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94967635 188 MGKMVDQHTDVWSLAVTLAEMITGRNPFVR-DSAAATV--IGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd06606     175 RGEEYGRASDIWSLGCTVIEMLTGKPPWSElGNPMALLykIGSSGEPPEIPEDLSEEAKDFLRKCLRRDPKKR 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

Protein Kinases (PKs), STE family, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The STE family is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPK kinase kinases (MAPKKKs), or MAPK kinase kinase kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli.

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

false

true

false

253

1e-36

150.77

90.12

7,29,14,20,52,34,32,85,66,18,104,84,3,107,89,112,219,203,25,244,229,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPehqTTNQDDRKRVLREARTASQLDHPNIGVIHGFEeTDDGRVFIVMAYYEGETLaRKI-- 107
cd05122      15 TVYKARHKKTGELVAVKVIK---LESDEEQEQILNEIQILKKCKHPNIVKYYGSY-LKKDELWIVMEYCDGGSL-DDLlk 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 108 AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQA 187
cd05122      90 STGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSAQLSDTKAKRNTFVGTPYWMAPEVI 169

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94967635 188 MGKMVDQHTDVWSLAVTLAEMITGRNPFVRDS--AAATVIGIVSDPPQPMDEIPVDLLR-IIYRALAKEPELR 257
cd05122     170 NGEPYGFKADIWSLGITAIEMAEGKPPYSELNpmKALFKIATNPPPGLPSPEKWSPEFRdFLKKCLQKDPEKR 242

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-36

148.51

91.29

14,29,15,27,58,42,24,82,67,2,86,69,22,108,92,27,135,120,80,229,200,7,238,207,8,246,216,4,253,220,8,264,228,7,274,235,13,290,248,4,297,252,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPEHQTTNQddRKRVLREARTASQLDHPNIGVIHG-FEetDDGRVFIVMAYYEGETLARKIA 108
cd06623      16 VVYKVRHKPTGKIYALKKIHVDGDEEF--RKQLLRELKTLRSCESPYVVKCYGaFY--KEGEISIVLEYMDGGSLADLLK 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 -HGPLPVPEAVDIAIQICDGLAAAHASA-IVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQ 186
cd06623      92 kVGKIPEPVLAYIARQILKGLDYLHTKRhIIHRDIKPSNLLINSKGEVKIADFGISKVLENTLDQCNTFVGTVTYMSPER 171

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 187 AMGKMVDQHTDVWSLAVTLAEMITGRNPFvrdsaaatvigivsDPPQPMDeiPVDLLRII-YRALakePELRYQNCgemL 265
cd06623     172 IQGESYSYAADIWSLGLTLLECALGKFPF--------------LPPGQPS--FFELMQAIcDGPP---PSLPAEEF---S 229

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967635 266 PELKDFrreVEVAVTAPPSTRRstlTAKElrpLLEH 301
cd06623     230 PEFRDF---ISACLQKDPKKRP---SAAE---LLQH 256

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

7e-33

137.76

95.28

6,15,0,33,49,33,39,89,72,18,107,91,123,230,216,6,237,222,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  16 NYRILGLLGAGGMGVVYRALDVKLERTVALKFLpEHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVM 95
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQI-SLEKIKEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSD-SLYIIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  96 AYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSIS 174
cd06627      79 EYAENGSLRQIIkKFGKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVATKLSDVSKDDES 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 175 SGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSD--PPQPMDeIPVDLLRIIYRALAK 252
cd06627     159 VVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQDdhPPLPEG-ISPELKDFLMQCFQK 237


                ....*
gi 94967635 253 EPELR 257
cd06627     238 DPNLR 242

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

9e-30

127.52

90.80

4,30,8,51,81,60,3,86,63,21,107,85,150

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIH-GFEetDDGRVFIVMAYYEGETLARKI-A 108
cd05123       9 VYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHyAFQ--TKEKLYLVMEYVNGGDLFTHLsK 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 HGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAM 188
cd05123      87 EGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAKEGIDDGVRTTTFCGTPEYLAPEVLQ 166

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967635 189 GKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05123     167 GKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRFPEFLSEEAKDLIKKLLTKDPTKR 235

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

7e-27

117.82

89.77

10,30,15,19,50,34,38,89,72,23,113,95,5,118,102,42,160,148,35,195,186,22,217,209,12,229,222,14,243,238,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPeHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAHG 110
cd06626      16 VYTAVNLDTGELMAVKEIR-IQDNDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHRE-KVYIFMEYCSGGTLEELLEHG 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 111 PLpVPEAV--DIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFG----LARLSTGASTQSISSGGTVGYMSP 184
cd06626      94 RI-LDEHVirVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGcavkLKNNTTTMGEEVQSLAGTPAYMAP 172

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 185 EQAMGKMVDQH---TDVWSLAVTLAEMITGRNPFVR-DSAAATVIGIVS-DPPQPMDEIPVDLL--RIIYRALAKEPELR 257
cd06626     173 EVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMFHVGAgHKPPIPDSLQLSPEgkDFLDRCLESDPKKR 252

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-26

116.81

88.89

7,30,16,43,73,60,4,77,65,7,86,72,23,109,96,55,164,160,12,176,183,81

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLD-HPNI-GVIHGFEetDDGRVFIVMAYYEGETLARKIA 108
cd05581      17 VYLAKEKETNKEYAIKVLDKRHLIKEKKVKYVKREKEVLTRLNgHPGIvKLYYTFQ--DEENLYFVLEYAENGELLEYIK 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 H-GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARL---------STGASTQSISSG-- 176
cd05581      95 KfGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVldpnsspesNKGKATNIDSQIek 174

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 177 ---------GTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIY 247
cd05581     175 nrrrrasfvGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYEFPPNFPPDAKDLIE 254

                       250
                ....*....|
gi 94967635 248 RALAKEPELR 257
cd05581     255 KLLVLDPQDR 264

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

5e-26

115.11

87.92

11,29,15,19,50,34,32,82,67,1,85,68,19,104,89,30,134,120,27,165,147,8,173,157,52,225,214,4,229,219,4,233,224,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLpeHQTTNQDDRKRVLREARTASQLDHPNIGVIHG-FeeTDDGRVFIVMAYYEGETLA--RK 106
cd06605      16 VVSKVRHRPTGKIMAVKTI--RLEINEAIQKQILRELDILHKCNSPYIVGFYGaF--YNNGDISICMEYMDGGSLDkiLK 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IAHGPLPVPEAVDIAIQICDGLAAAHAS-AIVHRDVKPSNVIITPRGVAKIVDFGLarlsTGASTQSI--SSGGTVGYMS 183
cd06605      92 EVQGRIPERILGKIAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGEIKLCDFGV----SGQLVNSLakTFVGTSSYMA 167

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 184 PEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVI-----GIVS-DPPQ-PMDEIPVDLLRIIYRALAKEPEL 256
cd06605     168 PERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPENDPPDGIfellqYIVNePPPRlPSGRFSPDFQDFVNLCLIKDPRE 247


                .
gi 94967635 257 R 257
cd06605     248 R 248

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

2e-25

113.08

79.79

9,29,33,20,52,53,25,77,79,7,86,86,31,118,117,4,122,124,39,161,164,11,173,175,67,240,245,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPehqTTNQDDRKRVLREARTASQLDHPNI-GVIHGFEetDDGRVFIVMAYYEGETLARKIA 108
cd06614      34 EVYTATDRATGKEVAIKKMR---LRKQPKKELIINEILIMKECKHPNIvNYYDSYL--VGDELWVVMEYMDGGSLTDIIT 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 HGPLPVPEAvDIAI---QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGL-ARLSTGASTQSiSSGGTVGYMSP 184
cd06614     109 QTFVRMNES-QIAYvcrEVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFaAQLTKEKSKRN-SMVGTPYWMAP 186

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 185 EQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPV---DLLRIIYRALAKEPELR 257
cd06614     187 EVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLITTKGIPPLKNPEKwspEFKDFLNKCLVKDPEKR 262

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-25

112.53

83.39

7,29,15,19,50,34,24,74,61,8,83,69,105,188,175,40,228,216,5,233,222,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLpeHQTTNQDDRKRVLREARTASQLDH---PNIGVIHGfEETDDGRVFIVMAYYEGETLARK 106
cd06917      16 AVYRGKHVPTGRVVALKII--NLDTPDDDVSDIQREVALLSQLRQsqpPNITKYYG-SYLKGPRLWIIMEYAEGGSVRTL 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQ 186
cd06917      93 MKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVAALLNQNSSKRSTFVGTPYWMAPEV 172

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94967635 187 AM-GKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIV-SDPPQ-PMDEIPVDLLRIIYRALAKEPELR 257
cd06917     173 ITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIPkSKPPRlEDNGYSKLLREFVAACLDEEPKER 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

7e-25

111.05

93.92

8,15,2,38,54,40,10,64,53,21,86,74,21,107,96,55,162,152,14,176,168,58,234,231,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  16 NYRILGLLGAGGMGVVYRALDVKLERTVALKFLPEHQTtNQDDRKRVLR---EARTASQLDHPNIGVIHGFEEtDDGRVF 92
cd06625       3 NWRRGKLLGQGAFGRVYLCYDVDTGRELAVKQVPFDPD-SPETKKEVNAlecEIQLLKNLQHERIVQYYGCLR-DDETLS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  93 IVMAYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLSTGAST 170
cd06625      81 IFMEYMPGGSVKDQLkAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASkRLQTICSS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 171 QSISSG--GTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQP-----MDEIPVDLL 243
cd06625     161 GTGMKSvtGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPqlpshVSPDARNFL 240


                ....*....
gi 94967635 244 RIIYRALAK 252
cd06625     241 RRTFVENAK 249

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

3e-24

109.14

92.34

11,29,9,6,35,18,16,53,34,24,77,62,3,85,65,15,100,89,78,178,169,32,210,202,5,216,207,14,230,224,4,235,228,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRAL---DVKLERTVALKFLPEHqtTNQDDRKRVLREARTASQLDHPNI----GVIhgfeeTDDGRVFIVMAYYEG-- 100
cd00192      10 EVYKGElkgKGGKKTPVAVKTLKED--ASDSEREDFLKEAKIMKKLGHPNIvrllGVC-----TEEEPLYLVLEYMEGgd 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 101 -------ETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSI 173
cd00192      83 lldflrkSRPVFSPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRDIYDDDYYRK 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 174 SSGGT--VGYMSPEQAMGKMVDQHTDVWSLAVTLAEMIT-GRNPFvRDSAAATVIGIVSD---PPQPmDEIPVDLLRIIY 247
cd00192     163 KGGGKlpIRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPY-PGLSNEEVLEYLRKgyrLPKP-ENCPDELYELML 240

                       250
                ....*....|
gi 94967635 248 RALAKEPELR 257
cd00192     241 SCWQEDPEDR 250

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

3e-24

109.12

89.43

7,30,8,46,78,54,7,85,62,24,109,87,53,164,140,12,176,162,54,230,218,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNigVIHGFEE-TDDGRVFIVMAYYEGETLARKIAH 109
cd05579       9 VFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPF--VVKLYYSfQGKKNLYLVMEYLPGGDLASLLEN 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 -GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLArlSTGASTQSISSG----------GT 178
cd05579      87 vGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLS--KVGLVRRQINLNddekedkrivGT 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 179 VGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSD--PPQPMDEIPVDLLRIIYRALAKEPEL 256
cd05579     165 PDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGkiEWPEDVEVSDEAKDLISKLLVPDPEK 244


                .
gi 94967635 257 R 257
cd05579     245 R 245

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

2e-23

106.81

87.79

9,30,8,51,81,60,3,86,63,21,107,85,56,163,142,11,176,153,49,225,204,4,229,213,13,245,226,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIH-GFEetDDGRVFIVMAYYEGETLARKI-A 108
cd05572       9 VELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYrTFK--DKKYIYFLMEYCLGGELWTILrD 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 HGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR-LSTGASTQSISsgGTVGYMSPEQA 187
cd05572      87 RGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKkLKSGQKTYTFC--GTPEYVAPEII 164

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967635 188 MGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVI--GIVS-----DPPQPMDEIPVDLlriIYRALAKEPELR 257
cd05572     165 LNKGYDFSVDYWSLGILLYELLTGSPPFGEDDEDPMKIynLILKgidklEFPKYIDKAAKDL---IKQLLRRNPEER 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

Serine/threonine kinases (STKs), plant MAP/ERK kinase kinase 1 (MEKK1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily is composed of plant mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks) including Arabidopsis thaliana MEKK1 and MAPKKK3. MEKK1 is a MAPKKK that phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death.

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

false

true

false

258

3e-23

105.97

78.68

9,63,50,19,83,69,25,108,95,64,173,159,17,192,176,4,196,183,38,236,221,8,244,233,13,258,246,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  64 REARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIA-HGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVK 142
cd06632      51 QEIALLSKLQHPNIVQYLG-TEREEDNLYIFLELVPGGSLAKLLKkYGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIK 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 143 PSNVIITPRGVAKIVDFGLARLSTGASTQSiSSGGTVGYMSPEQAMGKmvDQHT---DVWSLAVTLAEMITGRNPFVRDS 219
cd06632     130 GANILVDTNGVVKLADFGMAKQVVEFSFAK-SFKGSPYWMAPEVIAQQ--GGYGlaaDIWSLGCTVLEMATGKPPWSQLE 206

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 94967635 220 AAATVIGIVSDPPQPmdEIPVDLLR----IIYRALAKEPELRyQNCGEML 265
cd06632     207 GVAAVFKIGRSKELP--PIPDHLSDeakdFILKCLQRDPSLR-PTAAELL 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

STKc_PKN: Serine/Threonine Kinases (STKs), Protein Kinase N (PKN) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis.

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

false

true

false

324

6e-23

104.96

66.67

3,43,27,24,67,54,21,89,75,168

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREAR---TASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAHGPLPVPEAVDI 120
cd05589      28 AIKALKKGDIIARDEVESLMCEKRifeTANSERHPFLVNLFACFQTED-HVCFVMEYAAGGDLMMHIHTDVFSEPRAVFY 106

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 121 AIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWS 200
cd05589     107 AACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGFGDRTSTFCGTPEFLAPEVLTETSYTRAVDWWG 186

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967635 201 LAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05589     187 LGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSREAISIMRRLLRRNPERR 243

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-22

104.11

81.99

7,30,16,33,63,56,25,89,81,18,107,100,61,168,163,17,185,182,45,230,230,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVL-------REARTASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETL 103
cd06629      17 VYLALNVTTGEMMAVKQVELPATIAGRHDSRQKdmvkalrSEIETLKDLDHLNIVQYLGFETTEE-YLSIFLEYVPGGSI 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 104 ARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGA--STQSISSGGTVG 180
cd06629      96 GSCLrTYGRFEEQLVRFFTEQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGISKKSDDIydNDQNMSMQGSVF 175

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94967635 181 YMSPE--QAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSD---PPQPMDEIP 239
cd06629     176 WMAPEviHSYSQGYSAKVDIWSLGCVVLEMFAGRRPWSDEEAIAAMFKLGNKrsaPPIPPDVSM 239

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-22

102.50

80.14

12,52,36,30,82,67,18,100,88,18,118,108,44,162,154,10,176,164,39,227,203,8,237,211,11,250,222,7,258,229,25,284,254,5,294,259,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  53 TTNQDDRKRVLREARTASQLDHPNIGVIHG-FEETDDGRVFIVMAYYEG---ETLARKIAHGPLPVPEAV--DIAIQICD 126
cd06621      37 DPNPDLQKQILRELEINKSCKSPYIVKYYGaFLDESSSSIGIAMEYCEGgslDSIYKKVKKRGGRIGEKVlgKIAESVLK 116

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 127 GLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA--RLSTGASTQSissgGTVGYMSPEQAMGKMVDQHTDVWSLAVT 204
cd06621     117 GLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSgeLVNSLAGTFT----GTSFYMAPERIQGKPYSITSDVWSLGLT 192

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 205 LAEMITGRNPFvrdsaaatvigiVSDPPQPMdeIPVDLLRIIYRalAKEPELRyQNCGEMLPELKDFRREVEVAVTAPPs 284
cd06621     193 LLEVAQNRFPF------------PPEGEPPL--GPIELLSYIVN--MPNPELK-DEPGNGIKWSEEFKDFIKQCLEKDP- 254

                       250
                ....*....|....*..
gi 94967635 285 TRRSTltakeLRPLLEH 301
cd06621     255 TRRPT-----PWDMLEH 266

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

8e-22

101.08

87.98

7,43,28,38,82,66,40,122,107,41,163,149,11,176,160,40,216,203,42,261,245,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIHgFEETDDGRVFIVMAYYEGETLARKIAHGPLPVPEAVDIAI- 122
cd05578      29 AMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLW-YSFQDEEDMYLVVDLLLGGDLRYHLQQKVKFSEEQVKFYVc 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 123 QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR-LSTGASTQSISsgGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd05578     108 EIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIATkLTPDTLATSTS--GTPPYMAPEVFCRQGYSFAVDWWSL 185

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94967635 202 AVTLAEMITGRNPFV---RDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELRYqncGEMLPELKDF 271
cd05578     186 GVTAYEMLRGKRPYRghsRTPREEILAKFETADVLYPAGWSSEAIDAINKLLERDPQKRL---GDNLSDLKDH 255

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

1e-21

100.64

74.30

9,58,46,24,83,70,24,107,95,25,132,121,29,165,150,11,176,163,39,215,206,11,226,224,7,233,233,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  59 RKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAH-ASAI 136
cd06620      47 RKQILRELQIMHECRSPYIVSFYG-AFLNENNICMCMEFMDCGSLDRIYkKGGPIPVEILGKIAVAVVEGLTYLYnVHRI 125

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 137 VHRDVKPSNVIITPRGVAKIVDFGLarlsTGASTQSISSG--GTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNP 214
cd06620     126 MHRDIKPSNILVNSRGQIKLCDFGV----SGELINSIADTfvGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFP 201

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 215 F----VRDSAAATVIG-------IVSDPPQ--PMDEIPVDLLRIIYRALAKEPELR 257
cd06620     202 FafsnIDDDGQDDPMGildllqqIVQEPPPrlPSSDFPEDLRDFVDACLLKDPTER 257

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

2e-21

100.21

75.17

8,39,25,46,86,71,15,101,89,6,109,95,53,162,149,10,176,159,53,229,215,15,247,230,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEEtDDGRVFIVMAYYEGE---TLARKIahGPLPVPE 116
cd05580      26 GKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFK-DNSNLYMVMEFVPGGelfSLLRRS--GRFPEPV 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 117 AVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLSTGASTQSissgGTVGYMSPEQAMGKMVDQH 195
cd05580     103 ARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAkRVKGRTYTLC----GTPEYLAPEIILSKGYGKA 178

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 196 TDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVS---DPPQPMDEIPVDLLRiiyRALAKEPELRYQN 260
cd05580     179 VDWWALGILIYEMLAGYPPFFDDNPMKIYEKILSgkvRFPSFFSSDAKDLLR---NLLQVDLTKRLGN 243

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

8e-21

97.95

87.31

9,29,22,21,53,43,24,78,67,27,105,96,15,120,113,28,148,142,37,190,179,4,194,190,23,217,216,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPEhqtTNQDDRKRVLREARTASQLDHPNIgVIHGFEETDDGRVFIVMAYYEGETLAR--KI 107
cd06624      23 VVYAGRDLSTQVRIAIKEIPE---RDSRYSQPLHEEIALHSRLKHKNI-VQYLGSDSENGYFKIFMEQVPGGSLSAllRS 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 108 AHGPLPVPEAVDI--AIQICDGLAAAHASAIVHRDVKPSNVII-TPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSP 184
cd06624      99 KWGPLKDNESTIIfyTKQILEGLKYLHDNQIVHRDIKGDNVLVnTYSGVLKISDFGTSKRLAGINPCTETFTGTLQYMAP 178

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 185 EqamgkMVDQ-------HTDVWSLAVTLAEMITGRNPFVR---DSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEP 254
cd06624     179 E-----IIDKgprgygaPADIWSLGCTIIEMATGKPPFHElgePQAAMFKVGMFKIHPEIPESLSAEAKAFILRCFEPDP 253


                ...
gi 94967635 255 ELR 257
cd06624     254 DKR 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132950

cd06619

PKc_MKK5

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

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

false

true

false

279

1e-20

97.64

63.44

7,30,16,24,56,40,26,82,68,4,89,72,15,107,87,54,168,141,7,175,153,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTnqDDRKRVLREARTASQLDHPNIGVIHG--FEETddgRVFIVMAYYEGETLArkiA 108
cd06619      17 VYKAYHLLTRRILAVKVIPLDITV--ELQKQIMSELEILYKCDSPYIIGFYGafFVEN---RISICTEFMDGGSLD---V 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 HGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLarlstgaSTQSISS-----GGTVGYMS 183
cd06619      89 YRKIPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGV-------STQLVNSiaktyVGTNAYMA 161

                       170       180       190
                ....*....|....*....|....*....|..
gi 94967635 184 PEQAMGKMVDQHTDVWSLAVTLAEMITGRNPF 215
cd06619     162 PERISGEQYGIHSDVWSLGISFMELALGRFPY 193

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

4e-20

95.41

88.28

7,30,18,19,54,37,28,82,67,5,90,72,13,103,87,130,233,221,6,240,227,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPehqttNQDDRKRVLREARTASQLDHPNIGVIHG--FEETDdgrVFIVMAYYEGETL--ARK 106
cd06612      19 VYKAIHKETGQVVAIKVVP-----VEEDLQEIIKEISILKQCDSPYIVKYYGsyFKNTD---LWIVMEYCGAGSVsdIMK 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQ 186
cd06612      91 ITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAKRNTVIGTPFWMAPEV 170

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967635 187 AMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQ----PMDEIPvDLLRIIYRALAKEPELR 257
cd06612     171 IQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPPPtlsdPEKWSP-EFNDFVKKCLVKDPEER 244

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

5e-20

95.30

67.61

4,43,23,30,73,54,15,89,69,20,109,90,148

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTASQLD-HPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIA 121
cd05570      24 AIKVLKKDVVLQDDDVECTMTEKRVLALAGkHPFLTQLHSCFQTKD-RLFFVMEYVNGGDLMYHIQQqGRFPEPRARFYA 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd05570     103 AEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEGILGGVTTSTFCGTPDYIAPEILQGQPYGFSVDWWAL 182

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 202 AVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05570     183 GVLLYEMLAGQSPFDGDDEDELFQSILEDNVRYPRWLSKEAKSILKGFLTKNPEKR 238

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

2e-19

93.46

87.69

9,30,11,38,68,50,10,78,61,9,89,70,11,100,84,7,109,91,55,166,146,8,176,154,54,230,212,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREART-ASQLDHPNIG-VIHGFEETDdgRVFIVMAYYEG---ETLAR 105
cd05611      12 VYLAKKRSTGDYFAIKVLKKSDMIAKNQVTNVKAERAImMIQGESPYVAkLYYSFQSKD--YLYLVMEYLNGgdcASLIK 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 106 KIahGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLstGASTQSISsgGTVGYMSPE 185
cd05611      90 TL--GGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRN--GLENKKFV--GTPDYLAPE 163

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 186 QAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSD----PPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05611     164 TILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRrinwPEEVKEFCSPEAVDLINRLLCMDPAKR 239

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-19

92.34

77.82

8,30,21,19,50,40,20,72,60,11,83,76,19,102,98,16,119,114,3,122,120,63,185,188,47

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPeHQTTNQDDRKRVLREARTASqlDHPNIGVIHGF-----EETDDGRVFIVMAYYEGET--- 102
cd06608      22 VYKARHKKTGQLVAIKIMD-IIEDEEEEIEEEYNILRKYS--NHPNIATFYGAfikkgPPGSDDQLWLVMELCGGGSvtd 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 103 LARKIAHGPLPVPEAVdIAI---QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTV 179
cd06608      99 LVKGLRKKGKRLKEEW-IAYilrETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFGVSAQLDSTNGRRNTSIGTP 177

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 180 GYMSPE-----QAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPP 232
cd06608     178 YWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPLCDMHPMRALFKIPRNPP 235

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

8e-19

91.34

63.31

11,58,42,19,77,62,6,85,68,18,103,92,4,114,96,4,118,102,16,134,119,27,168,146,8,176,159,36,212,210,11,223,225,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  59 RKRVLREARTASQLDHPNI-GVIHGFeeTDDGRVFIVMAYYEGETL------ARKIahgplpvPEAV--DIAIQICDGLA 129
cd06615      43 RNQIIRELKVLHECNSPYIvGFYGAF--YSDGEISICMEHMDGGSLdqvlkkAGRI-------PENIlgKISIAVLRGLT 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 130 AAHAS-AIVHRDVKPSNVIITPRGVAKIVDFGLarlstgaSTQSISSG-----GTVGYMSPEQAMGKMVDQHTDVWSLAV 203
cd06615     114 YLREKhKIMHRDVKPSNILVNSRGEIKLCDFGV-------SGQLIDSMansfvGTRSYMSPERLQGTHYTVQSDIWSLGL 186

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 94967635 204 TLAEMITGR---------------NPFVRDSAAAT----VIGIVSDPPQPM 235
cd06615     187 SLVEMAIGRypipppdakeleamfGRPVSEGEAKEshrpVSGHPPDSPRPM 237

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

2e-18

89.90

63.67

5,56,42,7,63,54,19,83,73,25,108,99,55,163,160,52

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  57 DDRKRVL-----REARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIA-HGPLPVPEAVDIAIQICDGLAA 130
cd06628      43 QDRKRKMldalqREINLLKELHHENIVQYLG-SSQDAGHLNIFLEYVPGGSVAALLNnYGAFEESLVRNFVRQILKGLNY 121

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 131 AHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR------LSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVT 204
cd06628     122 LHNRGIIHRDIKGANILVDNKGGIKISDFGISKkleansLSTKTNGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCL 201

                       170
                ....*....|.
gi 94967635 205 LAEMITGRNPF 215
cd06628     202 VVEMFTGKHPF 212

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

2e-18

89.75

81.23

4,30,19,23,55,42,27,83,69,144,227,214,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTtnQDDRKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIAHG 110
cd06641      20 VFKGIDNRTQKVVAIKIIDLEEA--EDEIEDIQQEITVLSQCDSPYVTKYYG-SYLKDTKLWIIMEYLGGGSALDLLEPG 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 111 PLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGK 190
cd06641      97 PLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRNTFVGTPFWMAPEVIKQS 176

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 191 MVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGI-VSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd06641     177 AYDSKADIWSLGITAIELAKGEPPHSELHPMKVLFLIpKNNPPTLEGNYSKPLKEFVEACLNKEPSFR 244

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-18

89.30

98.12

16,16,2,33,49,36,9,61,45,21,82,67,6,90,73,10,100,87,61,161,149,15,176,166,9,185,178,4,191,182,24,228,206,4,233,210,2,243,212,12,256,224,31,290,255,4,297,259,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  17 YRILGLLGAGGMGVVYRALDVKLERTVALKFLP-EHQTTNQDDrkrVLREARTASQLDHPNIGVIHG-FEETDDgrVFIV 94
cd06610       3 YKLIEVIGSGATAVVQRAICLPNGEKVAIKRIDlEKCQTSMDE---LRKEIQAMSLCHHPNVVKYYTsFVVGDE--LWVV 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  95 MAYYEG----ETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGL-ARLSTGAS 169
cd06610      78 MPLMSGgsclDIMKYSYPQGGLDEAIIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVsASLADGGD 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 170 TQSISSG--GTVGYMSPE---QAMGkmVDQHTDVWSLAVTLAEMITGRNPFvrdsaaatvigivSDPPqPMdeipvdllR 244
cd06610     158 RTKVRKTfvGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPY-------------SKYP-PM--------K 213

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967635 245 IIYRALAKEPElRYQNCGEMLPELKDFRREVEVAVTAPPSTRRstlTAKElrpLLEH 301
cd06610     214 VLMLTLQNDPP-SLETEADYKKYSKSFRKMISKCLQKDPAKRP---TASE---LLKH 263

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 1 (MEKK1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MEKK1 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK1 activates the extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing.

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

false

true

false

268

5e-18

88.77

89.18

10,31,16,29,60,48,22,83,70,21,105,91,16,121,109,31,152,141,10,162,152,3,165,158,56,221,217,8,229,227,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  32 YRALDVKLERTVALKFLPEHQTTNQDDRK---RVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLArKIA 108
cd06630      17 YQARDVKTGTLMAVKQVTYVRNTSSEQEEvveALRKEIRLMARLNHPHIIRMLG-ATCEDSHFNLFVEWMAGGSVS-HLL 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 109 HGPLPVPEAVDIA--IQICDGLAAAHASAIVHRDVKPSNVIITPRG-VAKIVDFGLA-RLS---TGASTQSISSGGTVGY 181
cd06630      95 SKYGAFKEAVIINytEQLLRGLSYLHENQIIHRDVKGANLLIDSTGqRLRIADFGAAaRLAakgTGAGEFQGQLLGTIAF 174

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 182 MSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAA---ATVIGIVS--DPPQPMDEIPVDLLRIIYRALAKEPEL 256
cd06630     175 MAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHSnhlALIFKIASatTAPSIPEHLSPGLRDVTLRCLELQPED 254


                .
gi 94967635 257 R 257
cd06630     255 R 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

STKc_phototropin_like: Serine/Threonine Kinases (STKs), Phototropin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Included in this subfamily are plant phototropins and predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. N. crassa nrc-2 plays a role in growth and development by controlling entry into the conidiation program.

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

false

true

false

315

5e-18

88.77

92.06

8,29,15,59,89,74,22,111,99,51,162,178,71,233,251,25,259,276,10,269,288,10,279,301,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH 109
cd05574      16 RVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTET-YLCLVMDYCPGGELFRLLQR 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GP---LPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA------------------------ 162
cd05574      95 QPgkcFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSkqsdveptpvskalrkgsrgsvnk 174

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 163 ----RLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQ--PMD 236
cd05574     175 itteTFSEEPSFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETFSNILKKEVTfpGSP 254

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 94967635 237 EIPVDLLRIIYRALAKEPELRYqNCGEMLPELK--DFRREVEVAV---TAPP 283
cd05574     255 PVSSSARDLIRKLLVKDPSKRL-GSKRGAAEIKqhPFFKGVNWALirhTTPP 305

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

5e-18

88.50

88.89

9,30,18,19,52,37,36,89,73,15,105,88,4,109,94,83,192,180,24,217,204,12,229,220,3,232,225,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPehqTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLArKIAH- 109
cd06613      19 VYKARDIATGELAAVKVIK---LEPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRD-KLWIVMEYCGGGSLQ-DIYQv 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 -GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAM 188
cd06613      94 tGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVSAQLTATIAKRKSFIGTPYWMAPEVAA 173

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 189 GKMV---DQHTDVWSLAVTLAEMITGRNPFVrDSAAATVIGIVS----DPP--QPMDEIPVDLLRIIYRALAKEPELR 257
cd06613     174 VERKggyDGKCDIWALGITAIELAELQPPMF-DLHPMRALFLISksnfQPPklKDKEKWSPVFHDFIKKCLTKDPKKR 250

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-18

88.58

70.95

14,29,29,20,51,49,20,71,70,18,90,88,10,100,100,9,112,109,6,118,117,7,125,127,8,135,135,27,162,163,2,164,166,7,174,173,11,185,188,43,228,233,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPehQTTNQDDRKRVLREARTASQ-LDHPNIGVIHGFEETDDGrVFIVMAYYEG--ETLARK 106
cd06618      30 QVYKMRFKKTGHVMAVKQMR--RTGNKEENKRILMDLDVVLKsHDCPYIVKCYGYFITDSD-VFICMELMSTclDKLLKR 106

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IAHgplPVPEAV--DIAIQIC---DGLAAAHAsaIVHRDVKPSNVIITPRGVAKIVDFGLA-RL-STGASTQsisSGGTV 179
cd06618     107 IQG---PIPEDIlgKMTVAIVkalHYLKEKHG--VIHRDVKPSNILLDASGNVKLCDFGISgRLvDSKAKTR---SAGCA 178

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967635 180 GYMSPE----QAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIV--SDPPQP 234
cd06618     179 AYMAPEridpPDPNPKYDIRADVWSLGISLVELATGQFPYKNCKTEFEVLTKIlqEEPPSL 239

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

6e-18

88.43

74.34

5,48,35,29,78,64,31,109,96,54,163,156,52,215,210,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  49 PEHQTTNQDDRKRVLREARTASQLDHPNIgVIHGFEETDDGRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIAIQICDG 127
cd06631      36 TSNVLAAEKEYEKLQEEVDLLKSLKHVNI-VQYLGTCLDDNTISIFMEFVPGGSISSILNRfGPLPEPVFCKYTKQILDG 114

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 128 LAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR------LSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd06631     115 VAYLHNNCVVHRDIKGNNVMLMPNGIIKLIDFGCARrlawvgLHGTHSNMLKSMHGTPYWMAPEVINESGYGRKSDIWSI 194

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 94967635 202 AVTLAEMITGRNPF--VRDSAAATVIGIVSDPPQPMDE 237
cd06631     195 GCTVFEMATGKPPLasMDRLAAMFYIGAHRGLMPRLPD 232

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

9e-18

87.89

79.65

4,29,33,19,51,52,37,89,89,148,237,240,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLpehQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH 109
cd06648      34 IVCIATDKSTGRQVAVKKM---DLRKQQRRELLFNEVVIMRDYQHPNIVEMYSSYLVGD-ELWVVMEFLEGGALTDIVTH 109

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMG 189
cd06648     110 TRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPEVISR 189

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967635 190 KMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDE---IPVDLLRIIYRALAKEPELR 257
cd06648     190 LPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNLPPKLKNlhkVSPRLRSFLDRMLVRDPAQR 260

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

1e-17

87.29

71.17

5,16,2,33,49,36,2,54,38,28,82,67,1,85,68,129

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  17 YRILGLLGAGGMGVVYRALDVKLERTVALKFLP-EHqttNQDDRKRVLREARTASQLDHPNIGVIHG-FeeTDDGRVFIV 94
cd06609       3 FTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIDlEE---AEDEIEDIQQEIQFLSQCRSPYITKYYGsF--LKGSKLWII 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  95 MAYYEGETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSIS 174
cd06609      78 MEYCGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNT 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 94967635 175 SGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNP 214
cd06609     158 FVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPP 197

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-17

87.09

84.64

13,29,15,20,51,35,23,74,59,8,82,69,5,90,74,10,100,86,18,118,106,16,134,123,27,165,150,15,180,168,15,195,187,22,217,210,16,233,228,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  30 VVYRALDVKLERTVALKFLPehQTTNQDDRKRVLREARTASQLDH-PNIGVIHG--FEETDdgrVFIVMAYYEG--ETLA 104
cd06617      16 VVDKMRHVPTGTIMAVKRIR--ATVNSQEQKRLLMDLDISMRSSDcPYTVHFYGalFREGD---VWICMEVMDTslDKFY 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 105 RKIAHGPLPVPEAV--DIAIQICDGLAAAHAS-AIVHRDVKPSNVIITPRGVAKIVDFGLarlsTGASTQSISSGGTVG- 180
cd06617      91 KKVYKKGLTIPEDIlgKIAVSVVKALEYLHEKlSVIHRDVKPSNILINRNGQVKLCDFGI----SGYLVDSLAKTVDAGc 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 181 --YMSPEQAMGKMVDQH----TDVWSLAVTLAEMITGRNPFVR-DSAAATVIGIVSDPPQ--PMDEIPVDLLRIIYRALA 251
cd06617     167 kpYMAPERIDPEGNQKGydvrSDVWSLGITMIELATGRFPYDNwKTPFEQLKQVVEEPSPqlPAEKFSPEFQDFVNKCLR 246


                ....*.
gi 94967635 252 KEPELR 257
cd06617     247 KDYHER 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

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

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

false

true

false

277

2e-17

86.88

65.70

6,111,91,51,162,143,10,174,153,41,215,198,54,269,260,4,274,264,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 112 LPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLSTGASTQSisSGGTVGYMSPEQAMGK 190
cd05577      92 FDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLAvEFPEGKKIHG--RVGTVGYMAPEVLQNE 169

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 191 MVDQHTDVWSLAVTLAEMITGRNPF----VRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELRYQNCGEMLP 266
cd05577     170 VYDFSPDWFALGCLLYEMIAGHSPFrqrkEKVKKEEVDRRTLTDEVEYPDKFSEEAKSICEGLLQKDPEKRLGCRGEGAD 249

                       170       180
                ....*....|....*....|....*
gi 94967635 267 ELK--------DFRReVEVAVTAPP 283
cd05577     250 EVKehpffkdlNFQR-LEAGMLEPP 273

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

3e-17

85.86

71.98

8,30,14,8,39,22,9,50,31,37,89,68,19,108,88,55,163,144,15,178,161,32,210,194,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKlERTVALKFLpeHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDdgRVFIVMAYYEGETLARKIA-H 109
cd05060      15 VYLMKSGK-EVEVAVKTL--KQEHIAAGKKEFLREASVMAQLDHPCIVRLIGVCKGE--PLMLVMELAPLGPLLKYLKkR 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR-LSTGASTQSISSGGT--VGYMSPEQ 186
cd05060      90 REIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRaLGAGSDYYRATTAGRwpLKWYAPEC 169

                       170       180       190
                ....*....|....*....|....*....|
gi 94967635 187 AMGKMVDQHTDVWSLAVTLAEMIT-GRNPF 215
cd05060     170 INYGKFSSKSDVWSYGVTLWEAFSyGAKPY 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133171

cd05039

PTKc_Csk_like

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

false

true

false

256

3e-17

85.91

67.58

9,40,29,16,60,45,16,76,65,4,85,69,18,103,92,6,111,98,52,167,150,10,177,161,33,210,195,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  41 RTVALKFLPEHQTTNQddrkRVLREARTASQLDHPN----IGVIhgfeeTDDGRVFIVMAYYEGETL-----ARKIAHgp 111
cd05039      30 QKVAVKCLKDDSTAAQ----AFLAEASVMTTLRHPNlvqlLGVV-----LQGNPLYIVTEYMAKGSLvdylrSRGRAV-- 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 112 LPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARlstgASTQSISSGG-TVGYMSPEQAMGK 190
cd05039      99 ITLAQQLGFALDVCEGMEYLEEKNFVHRDLAARNVLVSEDLVAKVSDFGLAK----EASQGQDSGKlPVKWTAPEALREK 174

                       170       180
                ....*....|....*....|....*...
gi 94967635 191 MVDQHTDVWSLAVTLAEMIT-GRNPFVR 217
cd05039     175 KFSTKSDVWSFGILLWEIYSfGRVPYPR 202

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

8e-17

84.52

58.47

6,86,71,20,106,92,56,162,179,68,230,253,4,236,257,10,247,267,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  87 DDGRVFIVMAYYEGETLARK-IAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA--- 162
cd05573      72 DEEYLYLVMEYMPGGDLMTLlIKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCkkm 151

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 163 ----------------------------RLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNP 214
cd05573     152 kkagdseyylndshnlldsdrdnvlkrrRPKKQRRVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPP 231

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 94967635 215 FVRDSAAATVIGIVSD------PPQPmdEIPVDLLRIIyRALAKEPELRY 258
cd05573     232 FYSDTLQETYNKIMNWkeslyfPADV--KVSPEAIDLI-RRLLCDPEDRL 278

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

8e-17

84.33

81.23

5,30,19,23,55,42,27,83,69,132,216,201,12,228,215,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTtnQDDRKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIAHG 110
cd06642      20 VYKGIDNRTKEVVAIKIIDLEEA--EDEIEDIQQEITVLSQCDSPYITRYYG-SYLKGTKLWIIMEYLGGGSALDLLKPG 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 111 PLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGK 190
cd06642      97 PLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPFWMAPEVIKQS 176

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967635 191 MVDQHTDVWSLAVTLAEMITGRNPFvRDSAAATVIGIV--SDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd06642     177 AYDFKADIWSLGITAIELAKGEPPN-SDLHPMRVLFLIpkNSPPTLEGQYSKPFKEFVEACLNKDPRFR 244

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

9e-17

84.28

68.04

4,43,23,27,70,51,18,89,69,20,109,90,148

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTAS-QLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIA 121
cd05619      24 AIKALKKDVVLMDDDVECTMVEKRVLSlAWEHPFLTHLYCTFQTKE-NLFFVMEYLNGGDLMFHIQScHKFDLPRATFYA 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd05619     103 AEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCKENMLGDAKTCTFCGTPDYIAPEILLGQKYNTSVDWWSF 182

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 202 AVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05619     183 GVLLYEMLIGQSPFHGHDEEELFQSIRMDNPCYPRWLTREAKDILVKLFVREPERR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88488

cd05587

STKc_cPKC

STKc_cPKC: Serine/Threonine Kinases (STKs), Classical (or Conventional) Protein Kinase C (cPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC 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). 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, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. cPKCs are potent kinases for histones, myelin basic protein, and protamine. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia.

STKc_cPKC: Serine/Threonine Kinases (STKs), Classical (or Conventional) Protein Kinase...

false

true

false

324

1e-16

83.81

54.63

4,39,24,40,79,65,9,89,74,20,109,95,106

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGV-IHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEA 117
cd05587      25 DELYAIKILKKDVIIQDDDVECTMVEKRVLALPGKPPFLTqLHSCFQTMD-RLYFVMEYVNGGDLMYHIQQvGKFKEPHA 103

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 118 VDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTD 197
cd05587     104 VFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKENIFGGKTTRTFCGTPDYIAPEIIAYQPYGKSVD 183

                       170
                ....*....|....*...
gi 94967635 198 VWSLAVTLAEMITGRNPF 215
cd05587     184 WWAFGVLLYEMLAGQPPF 201

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

2e-16

83.42

54.65

5,42,28,35,77,64,7,86,71,17,103,89,58,164,147,63

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  43 VALKFLPEHQTTNQDDRKRVLREARTASQLDHPNI-GVIHGFEetDDGRVFIVMAYYEGETL-ARKIAHGPLPVPEAVDI 120
cd05600      29 VALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLvKLLYAFQ--DDEYLYLAMEYVPGGDFrTLLNNLGVLSEDHARFY 106

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 121 AIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLarlSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWS 200
cd05600     107 MAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGL---SKGIVTYANSVVGSPDYMAPEVLRGKGYDFTVDYWS 183

                       170       180
                ....*....|....*....|....*..
gi 94967635 201 LAVTLAEMITGRNPFVRDSAAATVIGI 227
cd05600     184 LGCMLYEFLCGFPPFSGSTPNETWENL 210

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132984

cd06653

STKc_MEKK3_like_1

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily, catalytic (c) domain, functionally uncharacterized subgroup 1. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The MEKK3-like subfamily is composed of MEKK3, MEKK2, and related proteins, all containing an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs.

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

false

true

false

264

2e-16

82.77

85.98

8,15,2,31,46,36,11,58,47,24,82,72,25,107,98,55,162,154,4,166,162,8,176,170,59

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  16 NYRILGLLGAGGMGVVYRALDVKLERTVALK---FLPEHQTTNQDdRKRVLREARTASQLDHPNIGVIHG-FEETDDGRV 91
cd06653       3 NWRLGKLLGRGAFGEVYLCYDADTGRELAVKqvpFDPDSQETSKE-VNALECEIQLLKNLRHDRIVQYYGcLRDPEEKKL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  92 FIVMAYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLST--- 166
cd06653      82 SIFVEYMPGGSIKDQLkAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASkRIQTicm 161

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 167 -GASTQSISsgGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPM 235
cd06653     162 sGTGIKSVT--GTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIATQPTKPM 229

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

3e-16

82.70

53.77

4,43,27,5,49,32,38,88,70,34,122,105,93

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLpEHQTTNQDDRKRVLREARTASQLDHPNIGVIHGFEETDdGRVFIVMAYYEGETLARKIAHGPLPVPEAVDIAI- 122
cd05582      28 AMKVL-KKATLKVRDRVRTKMERDILAEVNHPFIVKLHYAFQTE-GKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLa 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 123 QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLA 202
cd05582     106 ELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFG 185

                       170
                ....*....|...
gi 94967635 203 VTLAEMITGRNPF 215
cd05582     186 VLMFEMLTGSLPF 198

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88486

cd05585

STKc_YPK1_like

STKc_YPK1_like: Serine/Threonine Kinases (STKs), Yeast protein kinase 1 (YPK1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The YPK1-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 fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development.

STKc_YPK1_like: Serine/Threonine Kinases (STKs), Yeast protein kinase 1 (YPK1)-like...

false

true

false

312

3e-16

82.77

69.55

5,40,18,37,78,55,30,108,86,123,231,212,15,249,227,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  41 RTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIgVIHGFEETDDGRVFIVMAYYEGETLARKIA-HGPLPVPEAVD 119
cd05585      19 RIYALKTIRKAHIVSRSEVTHTLAERTVLAQVNCPFI-VPLKFSFQSPEKLYFVLAFINGGELFHHLQkEGRFDLSRARF 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 120 IAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVW 199
cd05585      98 YTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLNMKDDDRTNTFCGTPEYLAPELLLGHGYTKAVDWW 177

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967635 200 SLAVTLAEMITGRNPFVRDSAAATVIGIVSDP---PQPMDEIPVDLLRIIyraLAKEPELR 257
cd05585     178 TLGVLLYEMLTGLPPFYDENTNEMYRKILQEPlrfPDGFDRDAKDLLTGL---LNRDPTQR 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132982

cd06651

STKc_MEKK3

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

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

false

true

false

266

3e-16

82.43

88.72

9,30,17,16,46,36,11,58,47,24,82,72,25,107,98,55,162,154,4,166,162,8,176,170,58,234,233,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALK---FLPEHQTTNQDdRKRVLREARTASQLDHPNIGVIHG-FEETDDGRVFIVMAYYEGETLARK 106
cd06651      18 VYLCYDVDTGRELAAKqvqFDPESPETSKE-VSALECEIQLLKNLQHERIVQYYGcLRDRAEKTLTIFMEYMPGGSVKDQ 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 I-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLST----GASTQSISsgGTVG 180
cd06651      97 LkAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASkRLQTicmsGTGIRSVT--GTPY 174

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967635 181 YMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQP-----MDEIPVDLLRIIYRALAKEP 254
cd06651     175 WMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPTNPqlpshISEHARDFLGCIFVEARHRP 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132983

cd06652

STKc_MEKK2

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 2 (MEKK2) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MEKK2 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling.

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

false

true

false

265

3e-16

82.39

85.28

8,15,2,31,46,36,11,58,47,25,83,73,24,107,98,55,162,154,4,166,162,8,176,170,58

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  16 NYRILGLLGAGGMGVVYRALDVKLERTVALK---FLPEHQTTNQDdRKRVLREARTASQLDHPNIGVIHGF-EETDDGRV 91
cd06652       3 NWRLGKLLGQGAFGRVYLCYDADTGRELAVKqvqFDPESPETSKE-VNALECEIQLLKNLLHERIVQYYGClRDPMERTL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  92 FIVMAYYEGETLARKI-AHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLST--- 166
cd06652      82 SIFMEHMPGGSIKDQLkSYGALTENVTRKYTRQILEGVSYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASkRLQTicl 161

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967635 167 -GASTQSISsgGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQP 234
cd06652     162 sGTGMKSVT--GTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNP 228

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

4e-16

82.36

65.36

5,111,93,111,222,208,36,258,248,7,265,257,7,272,265,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 112 LPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKM 191
cd05608      94 FPEPRACFYTAQIILGLEHLHQHRIVYRDLKPENVLLDNDGNVRISDLGLAVELKDGQSKTKGYAGTPGFMAPELLQGEE 173

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 192 VDQHTDVWSLAVTLAEMITGRNPFVRDSAAA----TVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELRY----QNCGE 263
cd05608     174 YDYSVDYFTLGVTLYEMIAAKGPFRRRGEKVenkeVKRRILNDSVTYSEKFSAASKSICEGLLAKDPQKRLgfrdGNCDM 253

                       170       180
                ....*....|....*....|...
gi 94967635 264 ML--PELKDFR-REVEVAVTAPP 283
cd05608     254 LRahPFFSALNwRKLEAGILPPP 276

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

4e-16

82.39

46.55

6,58,46,24,83,70,26,109,97,25,134,123,27,165,150,11,176,163,38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  59 RKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIAIQICDGLAAAHAS-AI 136
cd06650      47 RNQIIRELQVLHECNSPYIVGFYG-AFYSDGEISICMEHMDGGSLDQVLKKaGRIPEQILGKVSIAVIKGLTYLREKhKI 125

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 137 VHRDVKPSNVIITPRGVAKIVDFGLarlsTGASTQSISSG--GTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNP 214
cd06650     126 MHRDVKPSNILVNSRGEIKLCDFGV----SGQLIDSMANSfvGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAIGRYP 201

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

4e-16

82.28

68.04

4,43,23,27,70,51,18,89,69,20,109,90,148

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTAS-QLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIA 121
cd05592      24 AIKALKKDVVLEDDDVECTMVERRVLIlAWEHPFLTHLFCTFQTKE-HLFFVMEYLNGGDLMFHIQSsGRFDEARARFYA 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd05592     103 AEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENINGEGKASTFCGTPDYIAPEILKGQKYNESVDWWSF 182

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 202 AVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05592     183 GVLLYEMLIGQSPFHGEDEDELFDSILNDRPHFPRWISKEAKDCLSKLFEREPTKR 238

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

4e-16

82.28

60.33

6,92,77,17,109,95,67,176,177,9,185,190,9,198,199,33,231,235,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  93 IVMAYYEGETLARKIAH-GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQ 171
cd05609      78 MVMEYVEGGDCATLLKNiGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIGLMSLTT 157

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 172 SISSG---------------GTVGYMSPE----QAMGKMVDQhtdvWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDP- 231
cd05609     158 NLYEGhiekdtrefldkqvcGTPEYIAPEvilrQGYGKPVDW----WAMGIILYEFLVGCVPFFGDTPEELFGQVISDDi 233

                       170       180
                ....*....|....*....|....*...
gi 94967635 232 --PQPMDEIPVDLLRIIYRALAKEPELR 257
cd05609     234 ewPEGDEALPADAQDLISRLLRQNPLER 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88516

cd05615

STKc_cPKC_alpha

STKc_cPKC_alpha: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC) subfamily, alpha isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC 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, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion.

STKc_cPKC_alpha: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC)...

false

true

false

323

4e-16

82.37

53.56

8,43,28,33,76,62,12,89,74,20,109,95,54,163,151,11,176,162,9,185,175,9,198,184,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTASQLDHPN-IGVIHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIA 121
cd05615      29 AIKILKKDVVIQDDDVECTMVEKRVLALQDKPPfLTQLHSCFQTVD-RLYFVMEYVNGGDLMYHIQQvGKFKEPQAVFYA 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR--LSTGASTQSISsgGTVGYMSPE----QAMGKMVDQh 195
cd05615     108 AEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGMCKehMVDGVTTRTFC--GTPDYIAPEiiayQPYGKSVDW- 184

                       170       180
                ....*....|....*....|
gi 94967635 196 tdvWSLAVTLAEMITGRNPF 215
cd05615     185 ---WAYGVLLYEMLAGQPPF 201

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

4e-16

82.40

46.83

7,58,46,24,83,70,28,112,98,6,118,106,16,134,123,27,165,150,11,176,163,38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  59 RKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIAHGPlPVPEAV--DIAIQICDGLAAAHAS-A 135
cd06649      47 RNQIIRELQVLHECNSPYIVGFYG-AFYSDGEISICMEHMDGGSLDQVLKEAK-RIPEEIlgKVSIAVLRGLAYLREKhQ 124

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 136 IVHRDVKPSNVIITPRGVAKIVDFGLarlsTGASTQSISSG--GTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRN 213
cd06649     125 IMHRDVKPSNILVNSRGEIKLCDFGV----SGQLIDSMANSfvGTRSYMSPERLQGTHYSVQSDIWSMGLSLVELAIGRY 200


                .
gi 94967635 214 P 214
cd06649     201 P 201

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

4e-16

82.02

81.23

5,30,19,23,55,42,27,83,69,131,215,200,13,228,215,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTtnQDDRKRVLREARTASQLDHPNIGVIHGfEETDDGRVFIVMAYYEGETLARKIAHG 110
cd06640      20 VFKGIDNRTQQVVAIKIIDLEEA--EDEIEDIQQEITVLSQCDSPYVTKYYG-SYLKGTKLWIIMEYLGGGSALDLLRAG 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 111 PLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGK 190
cd06640      97 PFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPFWMAPEVIQQS 176

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967635 191 MVDQHTDVWSLAVTLAEMITGRNPfVRDSAAATVIGIV--SDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd06640     177 AYDSKADIWSLGITAIELAKGEPP-NSDMHPMRVLFLIpkNNPPTLTGEFSKPFKEFIDACLNKDPSFR 244

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

6e-16

81.69

72.30

7,30,34,16,49,50,28,77,79,11,90,90,125,234,215,12,248,227,8,258,235,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKflpEHQTTNQDDRKRVLREARTASQLDHPNI-GVIHGFEETDDgrVFIVMAYYEGETLARKIAH 109
cd06655      35 VFTAIDVATGQEVAIK---QINLQKQPKKELIINEILVMKELKNPNIvNFLDSFLVGDE--LFVVMEYLAGGSLTDVVTE 109

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMG 189
cd06655     110 TCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTR 189

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 190 KMVDQHTDVWSLAVTLAEMITGRNPFvrdsaaatvigivsdppqpMDEIPVDLLRIIyrALAKEPELryQNCGEMLPELK 269
cd06655     190 KAYGPKVDIWSLGIMAIEMVEGEPPY-------------------LNENPLRALYLI--ATNGTPEL--QNPEKLSPIFR 246


                ..
gi 94967635 270 DF 271
cd06655     247 DF 248

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

7e-16

81.39

74.27

9,30,30,53,83,86,3,90,89,19,109,109,60,173,169,12,185,183,5,190,189,38,228,228,5,233,234,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIGVIHGF---EETddgrVFIVMAYYEGETLARKI 107
cd06607      31 VYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQQLRHPNTIEYKGCylrEHT----AWLVMEYCLGSASDILE 106

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 108 AH-GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGAStqsiSSGGTVGYMSPE- 185
cd06607     107 VHkKPLQEVEIAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFGSASLVSPAN----SFVGTPYWMAPEv 182

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 186 -QAMGK-MVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIV-SDPPQ-PMDEIPVDLLRIIYRALAKEPELR 257
cd06607     183 iLAMDEgQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAqNDSPTlSSNDWSDYFRNFVDSCLQKIPQDR 258

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

3e-15

79.51

72.03

11,87,70,26,113,98,5,118,105,12,130,118,31,165,149,11,176,162,10,186,173,10,196,188,19,215,210,13,228,224,29,257,255,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  88 DGRVFIVMAYYEGETLARKIAHGPLP--VPEAV--DIAIQICDGLAA-AHASAIVHRDVKPSNVIITPRGVAKIVDFGLa 162
cd06622      71 EGAVYMCMEYMDAGSLDKLYAGGVATegIPEDVlrRITYAVVKGLKFlKEEHNIIHRDVKPTNVLVNGNGQVKLCDFGV- 149

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 163 rlsTGASTQSISSG--GTVGYMSPEQ-AMGKMVDQHT-----DVWSLAVTLAEMITGRNPF---VRDSAAATVIGIV-SD 230
cd06622     150 ---SGNLVASLAKTniGCQSYMAPERiKSGGPNQNPTytvqsDVWSLGLSILEMALGRYPYppeTYANIFAQLSAIVdGD 226

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 94967635 231 PPQPMDEIPVDLLRIIYRALAKEPELR--YQNCGEMLPELKDFRREVEVA 278
cd06622     227 PPTLPSGYSDDAQDFVAKCLNKIPNRRptYAQLLEHPWLVKYKNADVDMA 276

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

4e-15

78.96

90.27

11,42,25,6,48,32,10,61,42,26,89,68,15,104,86,59,163,146,16,179,164,31,210,196,21,231,220,3,235,223,22,257,247,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  43 VALKFL-PEHQTTNQDDrkrVLREARTASQLDHPNIGVIHGFEETDdgRVFIVMAYYEGETLA---RKIAHGPLPVPEAV 118
cd05040      26 VAVKCLkSDKLSDIMDD---FLKEAAIMHSLDHENLIRLYGVVLTH--PLMMVTELAPLGSLLdrlRKDALGHFLISTLC 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 119 DIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR-LSTGASTQSISSGGTV--GYMSPEQAMGKMVDQH 195
cd05040     101 DYAVQIANGMRYLESKRFIHRDLAARNILLASDDKVKIGDFGLMRaLPQNEDHYVMEEHLKVpfAWCAPESLRTRTFSHA 180

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 196 TDVWSLAVTLAEMIT-GRNPFVRDSAAATVIGIVSDP---PQPmDEIPVDLLRIIYRALAKEPELR--YQNCGEMLPE 267
cd05040     181 SDVWMFGVTLWEMFTyGEEPWAGLSGSQILKKIDKEGerlERP-EACPQDIYNVMLQCWAHNPADRptFAALREFLPE 257

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

8e-15

78.04

58.79

7,43,29,34,77,64,11,90,75,19,109,96,51,160,148,25,185,175,3,188,182,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTASQLDHPNI-GVIHGFEETDDgrVFIVMAYYEGETLARKIAH--GPLPVPEAVDI 120
cd05601      30 AMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIpQLQYAFQDKDN--LYLVMEYHPGGDLLSLLNRyeDQFDESMAQFY 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 121 AIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFG-LARLSTGASTQSISSGGTVGYMSPE--QAM----GKMVD 193
cd05601     108 LAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFGsAAKLNANKMVNSKLPVGTPDYIAPEvlTSLngdsKSTYG 187

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 94967635 194 QHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVS 229
cd05601     188 VECDWWSLGVIAYEMIYGRSPFSEGTSAVTYSNIMN 223

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88498

cd05597

STKc_DMPK_like

STKc_DMPK_like: Serine/Threonine Kinases (STKs), Myotonic Dystrophy protein kinase (DMPK)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). Three isoforms of MRCK are known, named alpha, beta and gamma. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously.

STKc_DMPK_like: Serine/Threonine Kinases (STKs), Myotonic Dystrophy protein kinase (...

false

true

false

331

2e-14

76.90

58.31

9,86,71,30,118,101,3,121,108,39,160,148,25,185,175,10,195,188,34,229,227,23,253,250,9,267,259,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  87 DDGRVFIVMAYYEGETLARKIAHGPLPVPEavDIA----IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFG-L 161
cd05597      72 DENNLYLVMDYYVGGDLLTLLSKFEDRLPE--DMArfylAEMVLAIDSVHQLGYVHRDIKPDNVLLDKNGHIRLADFGsC 149

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 162 ARLSTGASTQSISSGGTVGYMSPE--QAMGKMVDQH---TDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVS-----DP 231
cd05597     150 LRLLADGTVQSNVAVGTPDYISPEilQAMEDGKGRYgpeCDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNhkehfQF 229

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 94967635 232 PQPMDEIPVDLLRIIYRALAKePELRYQNCGemlpeLKDFR 272
cd05597     230 PPDVTDVSEEAKDLIRRLICS-PETRLGRNG-----LQDFK 264

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-14

76.97

68.04

4,43,23,25,68,49,20,89,69,19,108,89,149

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREART-ASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIA-HGPLPVPEAVDIA 121
cd05620      24 AVKALKKDVVLIDDDVECTMVEKRVlALAWENPFLTHLYCTFQTKE-HLFFVMEFLNGGDLMFHIQdKGRFDLYRATFYA 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSL 201
cd05620     103 AEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGDNRASTFCGTPDYIAPEILQGLKYTFSVDWWSF 182

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967635 202 AVTLAEMITGRNPFVRDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRALAKEPELR 257
cd05620     183 GVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFERDPTRR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133176

cd05044

PTKc_c-ros

Catalytic Domain of the Protein Tyrosine Kinase, C-ros

false

true

false

270

2e-14

76.77

70.37

9,39,25,17,58,42,19,77,65,3,85,68,18,103,92,8,111,102,41,152,149,25,177,176,33,210,210,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLPEHQTTNQddRKRVLREARTASQLDHPNI----GVIhgfeeTDDGRVFIVMAYYEGETL------ARKIAH 109
cd05044      26 EIRVAVKTLRKGATDQE--KKEFLKEAHLMSNFNHPNIlkllGVC-----LLNEPQYLILELMEGGDLlsylrgARVTRF 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GP--LPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRG------VAKIVDFGLARLSTGASTQSISSGG--TV 179
cd05044      99 GPplLTLSELLDICLDVAKGCVYLERMHFIHRDLAARNCLVSEKTysdadrVVKIGDFGLARDIYKNDYYRKEGEGllPV 178

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 94967635 180 GYMSPEQAMGKMVDQHTDVWSLAVTLAEMIT-GRNPF 215
cd05044     179 RWMAPESLLDGIFTTQSDVWAFGVLMWEILTlGQQPY 215

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133173

cd05041

PTKc_Fes_like

Catalytic Domain of Fes-like Protein Tyrosine Kinases

false

true

false

251

2e-14

76.73

91.24

14,30,10,4,34,15,6,42,21,8,52,29,32,85,61,19,104,83,6,111,89,57,170,146,8,178,158,9,187,168,7,195,175,15,210,191,20,230,215,5,238,220,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRA-LDVKLErtVALKFLPEhqTTNQDDRKRVLREARTASQLDHPNIGVIHGFEeTDDGRVFIVMAYYEGETLA---RK 106
cd05041      11 VYKGvLKGKTE--VAVKTCRS--TLPPDLKRKFLQEAEILKQYDHPNIVKLIGVC-VQKQPIYIVMELVPGGSLLtflRK 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IAHGpLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGAstQSISSGGT----VGYM 182
cd05041      86 KKNR-LTVKKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEGG--IYTVSDGLkqipIKWT 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 183 SPEQA-MGKMVDQhTDVWSLAVTLAEMIT-GRNPFVRDSAAATVIGIVSD----PPQPMdeiPVDLLRIIYRALAKEPEL 256
cd05041     163 APEALnYGRYTSE-SDVWSYGILLWETFSlGDTPYPGMSNQQTRERIESGyrmpAPQLC---PEEIYRLMLQCWAYDPEN 238


                .
gi 94967635 257 R 257
cd05041     239 R 239

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-14

76.82

73.54

5,30,16,47,78,63,22,100,86,63,166,149,63,229,215,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  31 VYRALDVKLERTVALKFLPEHQTTNQDDRKRVLREARTASQLDHPNIgVIHGFEETDDGRVFIVMAYYEG-ETLARKIAH 109
cd05612      17 VYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFI-VNMYWTFHDDKFLYMLMEYVPGgELFSYLRKA 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 110 GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARlstGASTQSISSGGTVGYMSPEQAMG 189
cd05612      96 GKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAK---KVRDRTWTLCGTPEYLAPEIIQS 172

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 190 KMVDQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIVS---DPPQPMDEIPVDLLR 244
cd05612     173 KGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAgklEFPRHFDLRAKDLIK 230

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88517

cd05616

STKc_cPKC_beta

STKc_cPKC_beta: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC) subfamily, beta isoforms, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC 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, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis.

STKc_cPKC_beta: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC)...

false

true

false

323

2e-14

76.59

53.56

8,43,28,25,68,54,20,89,74,20,109,95,54,163,151,11,176,162,9,185,175,9,198,184,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREART-ASQLDHPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIAH-GPLPVPEAVDIA 121
cd05616      29 AIKILKKDVVIQDDDVECTMVEKRVlALSGKPPFLTQLHSCFQTMD-RLYFVMEYVNGGDLMYQIQQvGRFKEPHAVFYA 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 122 IQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR--LSTGASTQSISsgGTVGYMSPE----QAMGKMVDQh 195
cd05616     108 AEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKenMWDGVTTKTFC--GTPDYIAPEiiayQPYGKSVDW- 184

                       170       180
                ....*....|....*....|
gi 94967635 196 tdvWSLAVTLAEMITGRNPF 215
cd05616     185 ---WAFGVLLYEMLAGQAPF 201

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-14

76.48

86.35

8,7,11,39,49,50,28,77,79,11,90,90,125,234,215,12,248,227,8,258,235,13,271,249,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635   8 LTTGDLVGNYRILGLLGAGGMGVVYRALDVKLERTVALKflpEHQTTNQDDRKRVLREARTASQLDHPNI-GVIHGFEET 86
cd06647      12 VSVGDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIK---QMNLQQQPKKELIINEILVMRENKHPNIvNYLDSYLVG 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  87 DDgrVFIVMAYYEGETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLST 166
cd06647      89 DE--LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQIT 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 167 GASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFvrdsaaatvigivsdppqpMDEIPVDLLRII 246
cd06647     167 PEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPY-------------------LNENPLRALYLI 227

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967635 247 yrALAKEPELryQNCGEMLPELKDF-RREVEVAVTAPPSTR 286
cd06647     228 --ATNGTPEL--QNPEKLSAIFRDFlNRCLEMDVEKRGSAK 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133166

cd05034

PTKc_Src_like

Catalytic Domain of Src kinase-like Protein Tyrosine Kinases

false

true

false

261

3e-14

75.80

60.15

5,62,48,22,85,70,26,111,99,53,164,153,46,210,200,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  63 LREARTASQLDHPNIGVIHGFEeTDDGRVFIVMAYYEGETLARKIAHGP---LPVPEAVDIAIQICDGLAAAHASAIVHR 139
cd05034      49 LEEAQIMKKLRHDKLVQLYAVC-SEEEPIYIVTEYMSKGSLLDFLKSGEgkkLRLPQLVDMAAQIAEGMAYLESRNYIHR 127

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967635 140 DVKPSNVIITPRGVAKIVDFGLARL-STGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMIT-GRNPF 215
cd05034     128 DLAARNVLVGENLVCKVADFGLARLiEDDEYTAREGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTEIVTyGRVPY 205

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

4e-14

75.83

65.34

7,39,35,9,50,44,27,77,75,3,85,78,12,97,98,23,120,124,58,178,184,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLpeHQTTNQDDRKRVLREARTASQLDHPNI----GVIhgfeeTDDGRVFIVMAY--------YEGETLARKI 107
cd05032      36 ETRVAIKTV--NENASMRERIEFLNEASVMKEFNCHHVvrllGVV-----STGQPTLVIMELmargdlksYLRSRRPEAE 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 108 AHGPLPVPEAVDI---AIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGT--VGYM 182
cd05032     109 NNPGLGPPTLQEFiqmAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMARDIYETDYYRKGGKGLlpVRWM 188

                       170       180
                ....*....|....*....|....*...
gi 94967635 183 SPEQAMGKMVDQHTDVWSLAVTLAEMIT 210
cd05032     189 APESLKDGVFTTKSDVWSFGVVLWEMAT 216

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

5e-14

75.46

55.08

6,43,23,26,69,50,7,76,58,11,89,69,19,108,89,107,215,197,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTA-SQLDHPN-IGVIHGFEETDdgRVFIVMAYYEGETLARKIA-HGPLPVPEAVDI 120
cd05604      24 AVKVLQKKIVLNRKEQKHIMAERNVLlKNVKHPFlVGLHYSFQTTE--KLYFVLDFVNGGELFFHLQrERSFPEPRARFY 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 121 AIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWS 200
cd05604     102 AAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCKEGIAQSDTTTTFCGTPEYLAPEVIRKQPYDNTVDWWC 181

                       170       180
                ....*....|....*....|.
gi 94967635 201 LAVTLAEMITGRNPF-VRDSA 220
cd05604     182 LGAVLYEMLYGLPPFyCRDVA 202

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132947

cd06616

PKc_MKK4

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

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

false

true

false

288

5e-14

75.09

53.47

10,135,128,27,166,155,14,180,172,6,186,181,29,215,215,11,229,226,4,233,234,24,257,260,7,265,267,6,271,274,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 136 IVHRDVKPSNVIITPRGVAKIVDFGLArlstGASTQSISSGGTVG---YMSPEQ---AMGKMVDQHTDVWSLAVTLAEMI 209
cd06616     129 IIHRDVKPSNILLDRNGNIKLCDFGIS----GQLVDSIAKTRDAGcrpYMAPERidpSARDGYDVRSDVWSLGITLYEVA 204

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 210 TGRNPF-----VRDSAAATVIGivsDPPQ----PMDEIPVDLLRIIYRALAKEPELR--YQNCGEMlPELKDF-RREVEV 277
cd06616     205 TGKFPYpkwnsVFDQLTQVVKG---DPPIlsnsEEREFSPSFVNFINLCLIKDESKRpkYKELLEH-PFIKDYeERNVDV 280


                ..
gi 94967635 278 AV 279
cd06616     281 AA 282

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

6e-14

74.78

72.86

8,69,56,8,77,65,6,85,71,15,100,89,9,110,98,82,192,185,45,237,233,22,260,255,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  70 SQLDHPNI-GVIHGFeeTDDGRVFIVMAYYEG---ETLARKIAHgPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSN 145
cd06611      57 SECKHPNIvGLYEAY--FYENKLWILIEFCDGgalDSIMLELER-GLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGN 133

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 146 VIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMV-----DQHTDVWSLAVTLAEMITGRNPFVRDSA 220
cd06611     134 ILLTLDGDVKLADFGVSAKNKSTLQKRDTFIGTPYWMAPEVVACETFkdnpyDYKADIWSLGITLIELAQMEPPHHELNP 213

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 94967635 221 AATVIGIVSDPPQPMDE---IPVDLLRIIYRALAKEPELRYQnCGEML 265
cd06611     214 MRVLLKILKSEPPTLDQpskWSSSFNDFLKSCLVKDPDDRPT-AAELL 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

STKc_ROCK: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development.

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

false

true

false

370

8e-14

74.59

38.38

3,86,113,76,162,190,31,193,225,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  87 DDGRVFIVMAYYEGETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLA-RLS 165
cd05596     114 DDKYLYMVMEYMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCmKMD 193

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967635 166 TGASTQSISSGGTVGYMSPEQAMGKMVD----QHTDVWSLAVTLAEMITGRNPFVRDSAAAT 223
cd05596     194 ANGMVRCDTAVGTPDYISPEVLKSQGGDgyygRECDWWSVGVFLYEMLVGDTPFYADSLVGT 255

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

9e-14

74.62

67.80

8,39,23,13,52,37,25,77,63,8,87,71,35,122,107,106,228,217,11,240,228,4,247,232,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLPEHQ-TTNQDDRKRVLREARTASQLDHPNI-GVIHGFEEtdDGRVFIVMAYYEGETLARKIAHGPLPVPEA 117
cd05584      24 GKIFAMKVLKKATiVRNQKDTAHTKAERNILEAVKHPFIvDLIYAFQT--GGKLYLILEYLSGGELFMHLEREGIFMEDT 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 118 VDIAI-QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHT 196
cd05584     102 ACFYLsEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHEGTVTHTFCGTIEYMAPEILMRSGHGKAV 181

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967635 197 DVWSLAVTLAEMITGRNPFVRDSAAATVIGIV----SDPPQPMDEIPvDLLRiiyRALAKEPELR 257
cd05584     182 DWWSLGALMYDMLTGAPPFTAENRKKTIDKILkgklNLPPYLTPEAR-DLLK---KLLKRNPSSR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88503

cd05602

STKc_SGK1

STKc_SGK1: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK1 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. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia.

STKc_SGK1: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (...

false

true

false

325

9e-14

74.33

60.00

5,39,19,30,69,50,7,76,58,11,89,69,25,114,95,119

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  40 ERTVALKFLPEHQTTNQDDRKRVLREARTA-SQLDHPN-IGVIHGFEETDdgRVFIVMAYYEGETLARKIAHGPLPV-PE 116
cd05602      20 EKFYAVKVLQKKAILKKKEEKHIMSERNVLlKNVKHPFlVGLHFSFQTTD--KLYFVLDYINGGELFYHLQRERCFLePR 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 117 AVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQHT 196
cd05602      98 ARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEPNGTTSTFCGTPEYLAPEVLHKQPYDRTV 177

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 94967635 197 DVWSLAVTLAEMITGRNPFVRDSAAATVIGIVSDPPQ 233
cd05602     178 DWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQ 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88531

cd05630

STKc_GRK6

STKc_GRK6: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK6 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. GRK6 is widely expressed in many tissues. t is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis.

STKc_GRK6: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

285

1e-13

73.89

46.32

5,84,69,5,90,74,19,109,96,53,162,150,9,173,159,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  85 ETDDGrVFIVMAYYEGETLARKIAH---GPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGL 161
cd05630      70 ETKDA-LCLVLTLMNGGDLKFHIYHmgeAGFEEGRAVFYAAEICCGLEDLHQERIVYRDLKPENILLDDHGHIRISDLGL 148

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94967635 162 A-RLSTGASTQsiSSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPF 215
cd05630     149 AvHVPEGQTIK--GRVGTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPF 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132987

cd06656

STKc_PAK3

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

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

false

true

false

297

1e-13

73.99

70.71

4,5,9,47,55,56,22,77,79,11,90,90,129

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635   6 ATLTTGDLVGNYRILGLLGAGGMGVVYRALDVKLERTVALKFLPEHQttnQDDRKRVLREARTASQLDHPNI-GVIHGFE 84
cd06656      10 SIVSVGDPKKKYTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQ---QPKKELIINEILVMRENKNPNIvNYLDSYL 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  85 ETDDgrVFIVMAYYEGETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARL 164
cd06656      87 VGDE--LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQ 164

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94967635 165 STGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDS 219
cd06656     165 ITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNEN 219

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133190

cd05059

PTKc_Tec_like

Catalytic Domain of Tec-like Protein Tyrosine Kinases

false

true

false

256

2e-13

73.63

71.48

9,40,28,10,51,38,7,61,45,23,85,68,18,103,91,3,109,94,57,168,151,10,178,164,32,210,197,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  41 RTVALKFLPEhQTTNQDDrkrVLREARTASQLDHPNIGVIHGFEeTDDGRVFIVMAYYEGETL-----ARKiahGPLPVP 115
cd05059      29 IDVAIKMIRE-GAMSEDD---FIEEAKVMMKLSHPNLVQLYGVC-TKQRPIFIVTEYMANGCLlnflrQRR---GKFGTE 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 116 EAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTgaSTQSISSGGT---VGYMSPEQAMGKMV 192
cd05059     101 WLLDMCSDVCEAMEYLESNSFIHRDLAARNCLVGEDNVVKVSDFGLARYVL--DDQYTSSQGTkfpVKWAPPEVFNYSRF 178

                       170       180       190
                ....*....|....*....|....*....|...
gi 94967635 193 DQHTDVWSLAVTLAEMIT-GRNPFVRDSAAATV 224
cd05059     179 SSKSDVWSFGVLMWEVFSeGKMPYERFTNSEVV 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88518

cd05617

STKc_aPKC_zeta

STKc_aPKC_zeta: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, zeta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. There are two aPKC isoforms, zeta and iota. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells.

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

false

true

false

327

2e-13

73.17

54.74

4,37,17,36,73,54,15,89,69,19,108,89,107

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  38 KLERTVALKFLPEHQTTNQDDRKRVLREARTASQLD-HPNIGVIHGFEETDDgRVFIVMAYYEGETLARKIA-HGPLPVP 115
cd05617      18 KNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASsNPFLVGLHSCFQTTS-RLFLVIEYVNGGDLMFHMQrQRKLPEE 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 116 EAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPEQAMGKMVDQH 195
cd05617      97 HARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFS 176

                       170       180
                ....*....|....*....|
gi 94967635 196 TDVWSLAVTLAEMITGRNPF 215
cd05617     177 VDWWALGVLMFEMMAGRSPF 196

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

2e-13

72.83

70.95

4,5,10,47,55,57,22,77,80,11,90,91,129

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635   6 ATLTTGDLVGNYRILGLLGAGGMGVVYRALDVKLERTVALKFLPEHQttnQDDRKRVLREARTASQLDHPNI-GVIHGFE 84
cd06654      11 SIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIRQMNLQQ---QPKKELIINEILVMRENKNPNIvNYLDSYL 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  85 ETDDgrVFIVMAYYEGETLARKIAHGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARL 164
cd06654      88 VGDE--LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQ 165

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94967635 165 STGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMITGRNPFVRDS 219
cd06654     166 ITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNEN 220

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133180

cd05049

PTKc_Trk

Catalytic Domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases

false

true

false

280

3e-13

72.86

67.14

9,42,37,8,52,45,32,85,77,20,105,112,22,127,137,5,135,142,28,165,170,13,178,187,32,210,220,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  43 VALKFLPEhqTTNQDDRKRVLREARTASQLDHPNIGVIHGFEeTDDGRVFIVMAYYEGETLAR---------------KI 107
cd05049      38 VAVKTLKE--TASNDARKDFEREAELLTNFQHENIVKFYGVC-TEGDPPIMVFEYMEHGDLNKflrshgpdaaflkspDS 114

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 108 AHGPLPVPEAVDIAIQICDG---LAAAHasaIVHRDVKPSNVIITPRGVAKIVDFGLARlsTGASTQSISSGGT----VG 180
cd05049     115 PMGELTLSQLLQIAVQIASGmvyLASQH---FVHRDLATRNCLVGYDLVVKIGDFGMSR--DVYTTDYYRVGGHtmlpIR 189

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 94967635 181 YMSPEQAMGKMVDQHTDVWSLAVTLAEMIT-GRNPF 215
cd05049     190 WMPPESIMYRKFTTESDVWSFGVVLWEIFTyGKQPW 225

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

3e-13

72.66

61.81

6,87,76,35,122,112,41,163,154,29,192,185,36,228,226,6,235,232,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  88 DGRVFIVMAYYEGETLARKIAHGPLPVPEAVDIAI-QICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLAR-LS 165
cd05583      77 DTKLHLILDYVNGGELFTHLYQREHFTESEVRVYIaEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKeFL 156

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 166 TGASTQSISSGGTVGYMSPEQAMGKMV--DQHTDVWSLAVTLAEMITGRNPFVRDSAAATVIGIV-----SDPPQPmDEI 238
cd05583     157 AEEEERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDGEQNSQSEISrrilkSKPPFP-KTM 235

                       170
                ....*....|....*....
gi 94967635 239 PVDLLRIIYRALAKEPELR 257
cd05583     236 SAEARDFIQKLLEKDPKKR 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133200

cd05069

PTKc_Yes

Catalytic Domain of the Protein Tyrosine Kinase, Yes

false

true

false

260

3e-13

72.40

76.54

7,62,48,21,85,69,26,111,98,53,164,152,46,210,199,6,216,209,32,251,241,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  63 LREARTASQLDHPNIGVIHGFeeTDDGRVFIVMAYYEGETLARKIAHGP---LPVPEAVDIAIQICDGLAAAHASAIVHR 139
cd05069      49 LQEAQIMKKLRHDKLVPLYAV--VSEEPIYIVTEFMGKGSLLDFLKEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHR 126

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 140 DVKPSNVIITPRGVAKIVDFGLARL-STGASTQSISSGGTVGYMSPEQAMGKMVDQHTDVWSLAVTLAEMIT-GRNPFV- 216
cd05069     127 DLRAANILVGDNLVCKIADFGLARLiEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTkGRVPYPg 206

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 94967635 217 ---RDSAAATVIGIVSDPPQPMDEIPVDLLRIIYRalaKEPELR 257
cd05069     207 mvnREVLEQVERGYRMPCPQGCPESLHELMKLCWK---KDPDER 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88489

cd05588

STKc_aPKC

STKc_aPKC: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes.

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

false

true

false

329

3e-13

72.32

56.84

6,32,9,10,42,22,24,66,49,4,72,53,15,88,68,20,108,89,107

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  33 RALDVKLERT---VALKFLPEHQTTNQDDRKRVLREA---RTASqlDHPNIGVIHGFEETDdGRVFIVMAYYEGETLARK 106
cd05588      10 KVLLVELKKTrriYAMKVIKKELVNDDEDIDWVQTEKhvfETAS--NHPFLVGLHSCFQTE-SRLFFVIEFVSGGDLMFH 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635 107 IA-HGPLPVPEAVDIAIQICDGLAAAHASAIVHRDVKPSNVIITPRGVAKIVDFGLARLSTGASTQSISSGGTVGYMSPE 185
cd05588      87 MQrQRKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCKEGIRPGDTTSTFCGTPNYIAPE 166

                       170       180       190
                ....*....|....*....|....*....|
gi 94967635 186 QAMGKMVDQHTDVWSLAVTLAEMITGRNPF 215
cd05588     167 ILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88476

cd05575

STKc_SGK

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

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

false

true

false

323

4e-13

72.30

66.56

5,43,23,28,71,52,5,76,58,11,89,69,19,108,89,149

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967635  44 ALKFLPEHQTTNQDDRKRVLREARTASQ-LDHPN-IGVIHGFEETDdgRVFIVMAYYEGETLARKIA-HGPLPVPEAVDI 120
cd05575      24 AVKVLQKKAILKKNEQKHIMAERNVLLKn