NCBI Conserved Domain Search

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Conserved domains on [gi\|117928194\|ref\|YP_872745.1\|]
serine/threonine protein kinase [Acidothermus cellulolyticus 11B]

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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

9e-51

196.58

90.23

4,16,0,40,57,40,167,225,207,20,245,228,3

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDpEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd00180        1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKK-KQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVME 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd00180       80 YMSGGDLFDLLKKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLDSGGRKLTTF 159

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVaYRHAHEDVPPPSSRVQSLPP-AID 248
cd00180      160 VGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDL-LEKILKGKGTPDELPPNISPeAKD 231

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132935

cd05122

PKc_STE

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

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

false

true

false

253

1e-37

153.08

84.98

4,17,1,43,63,44,19,84,63,2,86,67,149

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFdqGA--DGGHVYLVM 95
cd05122        2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEEQEQI---LNEIQILKKCKHPNIVKYY--GSylKKDELWIVM 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  96 EYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTAT 175
cd05122       77 EYCDGGSLDDLLKSTGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSAQLSDTKAKRNT 156

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 176 LIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPP 235
cd05122      157 FVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALFKIATNPPPG 216

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

3e-35

145.00

83.40

5,23,7,31,55,38,27,82,66,92,174,160,44,218,205,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFAtDPEFVARFIREAKAAAAFSHPNVVAVF-DQGADGGHVYLVMEYVVGET 102
cd06606        8 LGRGSFGSVYLALSKDTGELVAVKSVELSSD-SEEELESLEREIRILSKLQHPNIVRYYgCEVTEENTLNIFMEYVSGGS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTA--TLIGTV 180
cd06606       87 LASLLKKFGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRLASIAYSGGlkSVRGTP 166

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 181 AYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQG-DSPLAVAYRHAHEDVPPP 236
cd06606      167 YWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSElGNPMALLYKIGSSGEPPE 223

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

7e-33

137.53

89.20

2,23,0,213,236,216,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05123        1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYL 183
cd05123       81 FTHLSKEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAKEGIDDGVRTTTFCGTPEYL 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117928194 184 APEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP---SSRVQSL 243
cd05123      161 APEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRFPeflSEEAKDL 223

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-32

135.81

74.22

3,21,24,29,53,53,45,98,99,138

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHdvfATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYV-VG 100
cd06614       25 EKIGEGASGEVYTATDRATGKEVAIKKMR---LRKQPKKELIINEILIMKECKHPNIVNYYDSYLVGDELWVVMEYMdGG 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTV 180
cd06614      102 SLTDIITQTFVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSKRNSMVGTP 181

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 117928194 181 AYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP 236
cd06614      182 YWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLITTKGIPPL 237

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-31

130.83

87.80

2,16,0,33,50,33,190

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMhDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06627        1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQI-SLEKIKEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIILE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06627       80 YAENGSLRQIIKKFGKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVATKLSDVSKDDESV 159

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPPSSRV 240
cd06627      160 VGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQDDHPPLPEGI 223

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

6e-30

127.60

80.29

3,17,2,57,74,60,97,171,177,49

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFS-HPNVVAVFDQGADGGHVYLVME 96
cd05581        3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLDKRHLIKEKKVKYVKREKEVLTRLNgHPGIVKLYYTFQDEENLYFVLE 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTAS----- 171
cd05581       83 YAENGELLEYIKKFGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVLDPNSSpesnk 162

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 172 ---------------RTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05581      163 gkatnidsqieknrrRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSN 226

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-28

121.83

88.30

3,23,0,142,165,150,77,243,227,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05579        1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQA--------VNRTASRTAT 175
cd05579       81 ASLLENVGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKVglvrrqinLNDDEKEDKR 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 176 LIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPPSSRVQSlPPAIDAV 250
cd05579      161 IVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEWPEDVEVS-DEAKDLI 234

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-27

120.03

74.82

4,16,1,33,50,34,8,59,42,60,120,102,104

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMhDVFATDPEfVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06609        2 LFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVI-DLEEAEDE-IEDIQQEIQFLSQCRSPYITKYYGSFLKGSKLWIIME 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06609       80 YCGGGSCLDLLKPGKLDETYIAF-ILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNTF 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAV 224
cd06609      159 VGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRV 206

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

3e-27

118.70

77.54

5,14,15,8,22,25,38,63,63,56,120,119,107,229,226,10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  15 DGRYLIED--RIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVY 92
cd06648       16 DPRSYLDNfvKIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELL---FNEVVIMRDYQHPNIVEMYSSYLVGDELW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  93 LVMEYVVGETLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASR 172
cd06648       93 VVMEFLEGGALTDIVTHTRMNEEQIAT-VCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVPR 171

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 173 TATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRhaHEDVPPPSSR 239
cd06648      172 RKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKR--IRDNLPPKLK 236

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

6e-27

117.54

70.34

2,17,2,147,167,149,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd05580        3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVMEF 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQavnRTASRTATLI 177
cd05580       83 VPGGELFSLLRRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAK---RVKGRTYTLC 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 117928194 178 GTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAV 224
cd05580      160 GTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKI 206

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

1e-26

116.16

73.72

3,14,17,46,63,63,51,115,114,119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  15 DGRYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVYLV 94
cd06647       18 KKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQPKKELI---INEILVMRENKHPNIVNYLDSYLVGDELWVV 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  95 MEYVVGETLRDLLRRRGRLSpAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTA 174
cd06647       95 MEYLAGGSLTDVVTETCMDE-GQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRS 173

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 175 TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06647      174 TMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP 233

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

1e-26

116.38

76.53

5,23,8,27,52,35,23,75,61,44,120,105,73,193,179,41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHdvFATDPEFVARFIREAKAAAAFSH---PNVVAVFDQGADGGHVYLVMEYVVG 100
cd06917        9 IGRGAYGAVYRGKHVPTGRVVALKIIN--LDTPDDDVSDIQREVALLSQLRQsqpPNITKYYGSYLKGPRLWIIMEYAEG 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 ETLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTV 180
cd06917       87 GSVRTLMKAGPIAEKYISV-IIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVAALLNQNSSKRSTFVGTP 165

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 181 AYLAPEQVTRGVA-DARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06917      166 YWMAPEVITEGKYyDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIPKSKPP 220

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-26

115.67

74.43

2,23,0,145,169,145,50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05572        1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRtASRTATLIGTVAYL 183
cd05572       81 WTILRDRGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLKS-GQKTYTFCGTPEYV 159

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 117928194 184 APEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05572      160 APEIILNKGYDFSVDYWSLGILLYELLTGSPPFGED 195

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

3e-26

114.95

68.04

2,23,8,144,170,152,54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05612        9 LGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLMEYVPGGEL 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNrtaSRTATLIGTVAYL 183
cd05612       89 FSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAKKVR---DRTWTLCGTPEYL 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 117928194 184 APEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAV 224
cd05612      166 APEIIQSKGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGI 206

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-26

114.61

73.86

8,21,6,29,52,35,27,79,65,4,86,69,21,115,90,22,137,121,51,189,172,7,196,180,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHdvFATDPEFVARFIREAKAAAAFSHPNVV---AVFDqgaDGGHVYLVMEYV 98
cd06623        7 KVLGQGSSGVVYKVRHKPTGKIYALKKIH--VDGDEEFRKQLLRELKTLRSCESPYVVkcyGAFY---KEGEISIVLEYM 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  99 VGETLRDLLrrrgrlspAEALGILQPVLAALSAAHASGL---------IHRDVKPENVLLARDGRVKVADFGLAQAVNRT 169
cd06623       82 DGGSLADLL--------KKVGKIPEPVLAYIARQILKGLdylhtkrhiIHRDIKPSNLLINSKGEVKIADFGISKVLENT 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 117928194 170 ASRTATLIGTVAYLAPEQVtRGVADAR-SDVYAAGIMLFEMLTGAPPYQ 217
cd06623      154 LDQCNTFVGTVTYMSPERI-QGESYSYaADIWSLGLTLLECALGKFPFL 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

8e-26

113.76

76.63

7,30,9,11,41,23,10,52,33,9,62,42,38,100,88,79,179,169,32,211,202,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  31 TVYRARDMRLD---RPVAVKVMHDvFATDPEFVArFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG------- 100
cd00192       10 EVYKGELKGKGgkkTPVAVKTLKE-DASDSERED-FLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYMEGgdlldfl 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 -ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGT 179
cd00192       88 rKSRPVFSPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRDIYDDDYYRKKGGGK 167

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117928194 180 --VAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPYQG 218
cd00192      168 lpIRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPG 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132944

cd06613

STKc_MAP4K3_like

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

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

false

true

false

261

3e-25

112.00

84.67

4,16,3,32,51,35,135,186,172,4,190,177,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVmhdVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06613        4 DYELLQRIGSGTYGDVYKARDIATGELAAVKV---IKLEPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVME 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06613       81 YCGGGSLQDIYQVTGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVSAQLTATIAKRKSF 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 177 IGTVAYLAPE--QVTR-GVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPPS 237
cd06613      161 IGTPYWMAPEvaAVERkGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLISKSNFQPPK 224

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132986

cd06655

STKc_PAK2

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 2, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK2 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1.

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

false

true

false

296

5e-25

111.35

72.30

3,16,19,44,63,63,51,115,114,119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06655       20 KYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKELI---INEILVMKELKNPNIVNFLDSFLVGDELFVVME 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSpAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06655       97 YLAGGSLTDVVTETCMDE-AQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRSTM 175

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06655      176 VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP 233

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

8e-25

110.82

83.59

5,17,4,32,53,36,8,62,44,35,97,80,134,233,214,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMhdvfATDPEFVArFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd06612        5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVV----PVEEDLQE-IIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 -VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06612       80 cGAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAKRNTV 159

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEdvPPPS 237
cd06612      160 IGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNK--PPPT 218

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

2e-24

109.04

72.05

3,16,19,44,63,63,51,115,114,119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06656       20 KYTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKKELI---INEILVMRENKNPNIVNYLDSYLVGDELWVVME 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSpAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06656       97 YLAGGSLTDVVTETCMDE-GQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTM 175

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06656      176 VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP 233

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

2e-24

108.90

77.45

8,15,5,46,65,51,9,74,61,5,79,70,11,90,83,24,114,110,6,120,117,66,186,188,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  16 GRYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVArfirEAKAAAAFS-HPNVV----AVFDQGADGGH 90
cd06608        6 GIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDIIEDEEEEIEE----EYNILRKYSnHPNIAtfygAFIKKGPPGSD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  91 --VYLVMEYVVGETLRDLLRRRGRLS---PAEALG-ILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQ 164
cd06608       82 dqLWLVMELCGGGSVTDLVKGLRKKGkrlKEEWIAyILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFGVSA 161

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 165 AVNRTASRTATLIGTVAYLAPE-----QVTRGVADARSDVYAAGIMLFEMLTGAPPY 216
cd06608      162 QLDSTNGRRNTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPL 218

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

4e-24

108.17

80.08

6,17,2,33,52,35,65,117,103,44,161,151,12,174,163,19,193,183,32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHdvFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd06610        3 YKLIEVIGSGATAVVQRAICLPNGEKVAIKRID--LEKCQTSMDELRKEIQAMSLCHHPNVVKYYTSFVVGDELWVVMPL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAE---ALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFG----LAQAVNRTA 170
cd06610       81 MSGGSCLDIMKYSYPQGGLDeaiIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGvsasLADGGDRTK 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 117928194 171 SRTaTLIGTVAYLAPEQVTRGVA-DARSDVYAAGIMLFEMLTGAPPYQGDSPLAVA 225
cd06610      161 VRK-TFVGTPCWMAPEVMEQVHGyDFKADIWSFGITAIELATGAAPYSKYPPMKVL 215

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132990

cd06659

STKc_PAK6

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 6, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK6 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility.

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

false

true

false

297

5e-24

107.81

74.41

5,14,17,8,22,27,38,63,65,56,120,121,107,229,228,10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  15 DGRYLIED--RIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVY 92
cd06659       18 DPRSLLENyiKIGEGSTGIVCIAREKHSGRQVAVKMMDLRKQQRRELL---FNEVVIMRDYQHQNVVEMYKSYLVGEELW 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  93 LVMEYVVGETLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASR 172
cd06659       95 VLMEFLQGGALTDIVSQTRLNEEQIAT-VCESVLQALCYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDVPK 173

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 173 TATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRhaHEDVPPPSSR 239
cd06659      174 RKSLVGTPYWMAPEVISRTPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKR--LRDSPPPKLK 238

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

6e-24

107.63

74.29

4,17,2,157,174,190,53,227,245,15,243,260,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd05573        3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILADADSPWIVKLYYSFQDEEYLYLVMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTA--- 174
cd05573       83 MPGGDLMTLLIKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCKKMKKAGDSEYyln 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 175 ----------------------------TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAY 226
cd05573      163 dshnlldsdrdnvlkrrrpkkqrrvraySTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQETYN 242

                        250       260
                 ....*....|....*....|....
gi 117928194 227 R--HAHEDVPPPSSRVQSlPPAID 248
cd05573      243 KimNWKESLYFPADVKVS-PEAID 265

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

8e-24

107.12

72.30

3,16,20,44,63,64,51,115,115,119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  17 RYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVYLVME 96
cd06654       21 KYTRFEKIGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKKELI---INEILVMRENKNPNIVNYLDSYLVGDELWVVME 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSpAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd06654       98 YLAGGSLTDVVTETCMDE-GQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTM 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 117928194 177 IGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06654      177 VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTP 234

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

STKc_Yank1: Serine/Threonine Kinases (STKs), Yank1 or STK32A subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily contains uncharacterized STKs with similarity to the human protein designated Yank1 or STK32A.

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

false

true

false

258

3e-22

101.85

89.92

4,17,1,149,167,150,51,218,202,24,243,226,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd05578        2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVDL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVnRTASRTATLI 177
cd05578       82 LLGGDLRYHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIATKL-TPDTLATSTS 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 178 GTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQG-DSPLAVAYRHAHEDVPPPSSRVQSlPPAIDAV 250
cd05578      161 GTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGhSRTPREEILAKFETADVLYPAGWS-SEAIDAI 233

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

4e-22

101.62

72.83

7,21,6,29,52,35,27,79,66,7,90,73,30,120,105,43,163,149,8,174,157,42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHdvFATDPEFVARFIREAKAAAAFSHPNVV----AVFDQGAdgghVYLVMEY 97
cd06605        7 GELGAGNSGVVSKVRHRPTGKIMAVKTIR--LEINEAIQKQILRELDILHKCNSPYIVgfygAFYNNGD----ISICMEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALG--ILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTASrta 174
cd06605       81 MDGGSLDKILKEVQGRIPERILGkiAVAVLKGLTYLHEKHKIIHRDVKPSNILVNSRGEIKLCDFGVSgQLVNSLAK--- 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117928194 175 TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPY 216
cd06605      158 TFVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPY 199

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

8e-22

100.37

60.96

2,15,0,151,169,151,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  16 GRYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVM 95
cd05600        1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  96 EYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVnrtASRTAT 175
cd05600       81 EYVPGGDFRTLLNNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSKGI---VTYANS 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 117928194 176 LIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSP 221
cd05600      158 VVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTP 203

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

3e-21

98.85

86.54

5,23,3,27,50,32,24,75,56,88,167,144,78,245,223,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH--DVFATDPEFVARFIREAKAAAAFShPNVVAVFDQGADGGHVYLVMEYVVGE 101
cd05611        4 ISKGAFGSVYLAKKRSTGDYFAIKVLKksDMIAKNQVTNVKAERAIMMIQGES-PYVAKLYYSFQSKDYLYLVMEYLNGG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 TLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAqavnRTASRTATLIGTVA 181
cd05611       83 DCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLS----RNGLENKKFVGTPD 158

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 182 YLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPPSSRVQSLPP-AIDAV 250
cd05611      159 YLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPeAVDLI 228

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132988

cd06657

STKc_PAK4

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 4, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK4 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways.

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

false

true

false

292

6e-21

97.79

59.25

3,72,73,40,113,113,110,224,223,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  73 FSHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRlSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARD 152
cd06657       74 YQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRM-NEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHD 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 153 GRVKVADFGLAQAVNRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAvAYRHAHED 232
cd06657      153 GRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLK-AMKMIRDN 231

                        170
                 ....*....|....*
gi 117928194 233 VPPPSSRVQSLPPAI 247
cd06657      232 LPPKLKNLHKVSPSL 246

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

4e-20

94.92

61.95

2,23,2,27,50,30,169

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05570        3 LGKGSFGKVLLAELKGTDELYAIKVLKkDVVLQDDDVECTMTEKRVLALAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05570       83 LMYHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEGILGGVTTSTFCGTPDY 162

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05570      163 IAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGD 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132989

cd06658

STKc_PAK5

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 5, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK5 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria.

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

false

true

false

292

4e-20

95.11

71.23

4,22,28,38,63,66,60,124,126,99,224,225,11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  23 RIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVarfIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd06658       29 KIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELL---FNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGA 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQpVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd06658      106 LTDIVTHTRMNEEQIATVCLS-VLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKSLVGTPYW 184

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAvAYRHAHEDVPP 235
cd06658      185 MAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQ-AMRRIRDNLPP 236

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

6e-20

94.33

88.64

8,21,5,28,49,35,2,54,37,62,116,103,15,135,118,35,170,157,26,196,186,22,218,209,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVM--HDvfaTDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVV 99
cd06626        6 NKIGGGTFGKVYTAVNLDTGELMAVKEIriQD---NDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 100 GETLRDLLRRRGRLSPA----EALGILQPVLAALSAahasGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTA----S 171
cd06626       83 GGTLEELLEHGRILDEHvirvYTLQLLEGLAYLHSH----GIVHRDIKPANIFLDHNGVIKLGDFGCAVKLKNNTttmgE 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 172 RTATLIGTVAYLAPEQVTRGVADAR---SDVYAAGIMLFEMLTGAPPYQG-DSPLAVAYRHAHEDVPPPSSRVQSLPPAI 247
cd06626      159 EVQSLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMFHVGAGHKPPIPDSLQLSPEGK 238


                 .
gi 117928194 248 D 248
cd06626      239 D 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

STKc_p70S6K: Serine/Threonine Kinases (STKs), 70 kDa ribosomal protein S6 kinase (p70S6K) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta).

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

false

true

false

323

1e-19

93.49

62.23

3,23,3,16,39,22,13,52,36,168

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMR---LDRPVAVKVMHDV-FATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVV 99
cd05584        4 LGKGGYGKVFQVRKVTgadTGKIFAMKVLKKAtIVRNQKDTAHTKAERNILEAVKHPFIVDLIYAFQTGGKLYLILEYLS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 100 GETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGT 179
cd05584       84 GGELFMHLEREGIFMEDTACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHEGTVTHTFCGT 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 117928194 180 VAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05584      164 IEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAEN 204

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

4e-19

91.46

88.81

9,23,7,29,52,38,13,65,52,89,154,142,19,173,165,13,187,178,10,197,189,22,219,214,19,240,233,12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDV--FATDPEFVARFIR-EAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG 100
cd06630        8 LGTGAFSSCYQARDVKTGTLMAVKQVTYVrnTSSEQEEVVEALRkEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWMAG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGR-VKVADFGLAQAVNRTASRT----AT 175
cd06630       88 GSVSHLLSKYGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFGAAARLAAKGTGAgefqGQ 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 176 LIGTVAYLAPEqVTRGVADARS-DVYAAGIMLFEMLTGAPPYQGD---SPLAVAYRHAHEDVPPPSSrvQSLPPAIDAVV 251
cd06630      168 LLGTIAFMAPE-VLRGEQYGRScDVWSVGCVIIEMATAKPPWNAEkhsNHLALIFKIASATTAPSIP--EHLSPGLRDVT 244


                 .
gi 117928194 252 L 252
cd06630      245 L 245

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

4e-19

91.65

80.87

4,21,9,36,59,45,60,120,105,112,234,217,16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPefVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGE 101
cd06642       10 ERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 TLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVA 181
cd06642       88 SALDLLKPGPLEETYIAT-ILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPF 166

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928194 182 YLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDvpPPSSRVQSLPPAIDAV 250
cd06642      167 WMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNS--PPTLEGQYSKPFKEFV 233

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88483

cd05582

STKc_RSK_N

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks.

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

false

true

false

318

6e-19

91.18

45.60

1,73,55,145

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  74 SHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDG 153
cd05582       56 NHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEG 135

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 154 RVKVADFGLAQAVNRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQG 218
cd05582      136 HIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQG 200

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

9e-19

90.37

63.94

4,17,2,104,121,107,55,176,163,13,189,182,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd05601        3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGI-LQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATL 176
cd05601       83 HPGGDLLSLLNRYEDQFDESMAQFyLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFGSAAKLNANKMVNSKL 162

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 117928194 177 -IGTVAYLAPEQVT------RGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05601      163 pVGTPDYIAPEVLTslngdsKSTYGVECDWWSLGVIAYEMIYGRSPFSEGT 213

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

2e-18

89.73

75.81

5,21,9,36,59,45,50,113,95,8,121,106,105,227,211,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPefVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGE 101
cd06640       10 ERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 TLRDLLRRrgrlSPAEALGI---LQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIG 178
cd06640       88 SALDLLRA----GPFDEFQIatmLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVG 163

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 179 TVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYrHAHEDVPP 235
cd06640      164 TPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLF-LIPKNNPP 219

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

5e-18

88.02

44.75

2,73,59,42,116,101,103

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  74 SHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPaEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDG 153
cd05589       60 RHPFLVNLFACFQTEDHVCFVMEYAAGGDLMMHIHTDVFSEP-RAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEG 138

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928194 154 RVKVADFGLAQAVNRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05589      139 YVKIADFGLCKEGMGFGDRTSTFCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGD 204

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

6e-18

87.62

77.78

5,23,8,77,100,86,21,121,108,42,163,162,8,171,186,67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG-ET 102
cd05574        9 LGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVMDYCPGgEL 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGI-LQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA------------QAVNRT 169
cd05574       89 FRLLQRQPGKCFPEEVARFyAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSkqsdveptpvskALRKGS 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 170 AS----------------RTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDV 233
cd05574      169 RGsvnkittetfseepsfRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETFSNILKKEV 248


                 ....*
gi 117928194 234 PPPSS 238
cd05574      249 TFPGS 253

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

2e-17

86.40

69.71

5,23,22,58,86,80,5,91,90,80,175,170,13,188,186,50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVfdqgaDGGHV-----YLVMEYV 98
cd06607       23 IGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQQLRHPNTIEY-----KGCYLrehtaWLVMEYC 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  99 VGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASrtatLIG 178
cd06607       98 LGSASDILEVHKKPLQEVEIAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFGSASLVSPANS----FVG 173

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117928194 179 TVAYLAPEQV---TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPPSS 238
cd06607      174 TPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLSS 236

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-17

85.90

72.92

3,21,9,36,59,45,60,120,105,106

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPefVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGE 101
cd06641       10 EKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 TLRDLLRRRGRLSPAEALgILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVA 181
cd06641       88 SALDLLEPGPLDETQIAT-ILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRNTFVGTPF 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 117928194 182 YLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAY 226
cd06641      167 WMAPEVIKQSAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLF 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88492

cd05591

STKc_nPKC_epsilon

STKc_nPKC_epsilon: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), epsilon isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility.

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

false

true

false

321

2e-17

85.81

66.67

2,23,2,27,50,30,186

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05591        3 LGKGSFGKVMLAELKGTDEVYAIKVLKkDVILQDDDVDCTMTEKRILALAAKHPFLTALHCCFQTKDRLFFVMEYVNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05591       83 LMFQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGILNGVTTTTFCGTPDY 162

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP 236
cd05591      163 IAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYP 216

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

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

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

false

true

false

370

3e-17

85.76

54.32

4,23,50,100,124,150,47,171,198,15,186,217,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05596       51 IGRGAFGEVQLVRHKSSKQVYAMKLLSKFEMIKRSDSAFFWEERDIMAHANSEWIVQLHYAFQDDKYLYMVMEYMPGGDL 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQpVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTAS-RTATLIGTVAY 182
cd05596      131 VNLMSNYDIPEKWARFYTAE-VVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMDANGMvRCDTAVGTPDY 209

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117928194 183 LAPE----QVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05596      210 ISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADS 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88491

cd05590

STKc_nPKC_eta

STKc_nPKC_eta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), eta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM.

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

false

true

false

320

3e-17

85.45

61.88

2,23,2,27,50,30,170

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05590        3 LGKGSFGKVMLARLKESGRLYAVKVLKkDVILQDDDVECTMTEKRILSLARNHPFLTQLYCCFQTPDRLFFVMEFVNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05590       83 LMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKTTSTFCGTPDY 162

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05590      163 IAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAEN 200

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-17

84.98

55.70

2,44,23,6,50,30,169

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  45 AVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQ 123
cd05592       24 AIKALKkDVVLEDDDVECTMVERRVLILAWEHPFLTHLFCTFQTKEHLFFVMEYLNGGDLMFHIQSSGRFDEARARFYAA 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 124 PVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAG 203
cd05592      104 EIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENINGEGKASTFCGTPDYIAPEILKGQKYNESVDWWSFG 183

                        170
                 ....*....|....*.
gi 117928194 204 IMLFEMLTGAPPYQGD 219
cd05592      184 VLLYEMLIGQSPFHGE 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

STKc_ROCK2: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK2 (or ROK-alpha) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction.

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

false

true

false

370

5e-17

84.72

54.32

4,23,50,100,124,150,47,171,198,15,186,217,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05621       51 IGRGAFGEVQLVRHKSSQKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEYMPGGDL 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQpVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTAS-RTATLIGTVAY 182
cd05621      131 VNLMSNYDVPEKWAKFYTAE-VVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFGTCMKMDETGMvRCDTAVGTPDY 209

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117928194 183 LAPE----QVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05621      210 ISPEvlksQGGDGYYGRECDWWSVGVFLFEMLVGDTPFYADS 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132966

cd06635

STKc_TAO1

Serine/threonine kinases (STKs), thousand-and-one amino acids 1 (TAO1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MAP3K or MKKK) activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability.

Serine/threonine kinases (STKs), thousand-and-one amino acids 1 (TAO1) subfamily,...

false

true

false

317

5e-17

84.76

66.25

3,23,32,141,168,173,20,188,196,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd06635       33 IGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYCLGSAS 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQavnrTASRTATLIGTVAYL 183
cd06635      113 DLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSAS----IASPANSFVGTPYWM 188

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 184 APEQV---TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06635      189 APEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESP 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132976

cd06645

STKc_MAP4K3

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

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

false

true

false

267

8e-17

83.95

80.15

3,22,15,40,65,55,124,189,182,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  23 RIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARfirEAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd06645       16 RIGSGTYGDVYKARNVNTGELAAIKVIKLEPGEDFAVVQQ---EIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGGGS 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd06645       93 LQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYW 172

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 183 LAPEQVT---RGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP 236
cd06645      173 MAPEVAAverKGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPP 229

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132965

cd06634

STKc_TAO2

Serine/threonine kinases (STKs), thousand-and-one amino acids 2 (TAO2) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MAP3K or MKKK) activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 activates both 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. TAO2 contains a long C-terminal extension with autoinhibitory segments. It is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor (TNF), interleukin 1 (IL-1), and Toll-like receptor (TLR).

Serine/threonine kinases (STKs), thousand-and-one amino acids 2 (TAO2) subfamily,...

false

true

false

308

9e-17

83.95

68.18

3,23,22,143,170,165,18,188,186,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd06634       23 IGHGSFGAVYFARDVRNSEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQKLRHPNTIQYRGCYLREHTAWLVMEYCLGSAS 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVnrtaSRTATLIGTVAYL 183
cd06634      103 DLLEVHKKPLQEVEIAAVTHGALQGLAYLHSHNMIHRDVKAGNILLSEPGLVKLGDFGSASIM----APANXFVGTPYWM 178

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 184 APEQV---TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06634      179 APEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESP 232

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

1e-16

83.51

62.03

2,23,2,27,50,30,168

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05619        3 LGKGSFGKVFLAELKGTNQFFAIKALKkDVVLMDDDVECTMVEKRVLSLAWEHPFLTHLYCTFQTKENLFFVMEYLNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05619       83 LMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCKENMLGDAKTCTFCGTPDY 162

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQG 218
cd05619      163 IAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHG 198

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132967

cd06636

STKc_MAP4K4_6

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K4/MAP4K6 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4Ks (or MAPKKKKs) are involved in MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility.

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

false

true

false

282

1e-16

83.51

78.37

8,23,23,26,50,49,12,65,61,16,81,81,9,90,93,27,117,122,72,189,199,42,233,241,3

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMhDVFATDPEFVARfirEAKAAAAFSHPNVVAV----FDQGADGGH---VYLVME 96
cd06636       24 VGNGTYGQVYKGRHVKTGQLAAIKVM-DVTEDEEEEIKL---EINMLKKYSHHRNIATyygaFIKKSPPGHddqLWLVME 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  97 YVVGETLRDLLRRRGRLSPAE--ALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTA 174
cd06636      100 FCGAGSVTDLVKNTKGNALKEdwIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRN 179

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928194 175 TLIGTVAYLAPEQVT-----RGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEdvPPP 236
cd06636      180 TFIGTPYWMAPEVIAcdenpDATYDYRSDIWSLGITAIEMAEGAPPLCDMHPMRALFLIPRN--PPP 244

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

2e-16

82.66

60.80

2,23,7,27,50,35,169

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05587        8 LGKGSFGKVMLAERKGTDELYAIKILKkDVIIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05587       88 LMYHIQQVGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKENIFGGKTTRTFCGTPDY 167

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05587      168 IAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGE 204

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132955

cd06624

STKc_ASK

Serine/threonine kinases (STKs), apoptosis signal-regulating kinase (ASK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Subfamily members are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks) and include ASK1, ASK2, and MAPKKK15. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species (ROS)-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown.

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

false

true

false

268

2e-16

82.16

80.97

7,23,15,24,50,39,58,113,97,24,137,129,12,149,142,44,193,188,22,215,211,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKvmhDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd06624       16 LGKGTYGVVYAGRDLSTQVRIAIK---EIPERDSRYSQPLHEEIALHSRLKHKNIVQYLGSDSENGYFKIFMEQVPGGSL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRrrgrlSPAEALGILQPVLAALSAAHASGL--------IHRDVKPENVLL-ARDGRVKVADFGLAQAVNRTASRTA 174
cd06624       93 SALLR-----SKWGPLKDNESTIIFYTKQILEGLkylhdnqiVHRDIKGDNVLVnTYSGVLKISDFGTSKRLAGINPCTE 167

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 175 TLIGTVAYLAPEQVTRGVA--DARSDVYAAGIMLFEMLTGAPP-YQGDSPLAVAYRHAHEDVPPP 236
cd06624      168 TFTGTLQYMAPEIIDKGPRgyGAPADIWSLGCTIIEMATGKPPfHELGEPQAAMFKVGMFKIHPE 232

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

3e-16

82.19

68.91

2,64,54,102,166,162,76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  65 REAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKP 144
cd06628       55 REINLLKELHHENIVQYLGSSQDAGHLNIFLEYVPGGSVAALLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKG 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 145 ENVLLARDGRVKVADFGLAQAV------NRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQG 218
cd06628      135 ANILVDNKGGIKISDFGISKKLeanslsTKTNGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFPD 214

                        170       180
                 ....*....|....*....|....
gi 117928194 219 DSPLAVAYRHAHEDVPPPSSRVQS 242
cd06628      215 CTQMQAIFKIGTNASPEIPSNASS 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132970

cd06639

STKc_myosinIIIB

Serine/threonine kinases (STKs), class IIIB myosin subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities.

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

false

true

false

291

3e-16

81.97

80.07

7,15,21,48,66,69,18,84,89,3,87,95,13,100,112,85,185,202,46,233,248,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  16 GRYLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFireAKAAAAFSHPNVVAVFDQ--GAD---GGH 90
cd06639       22 DTWEIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEY---NILQSLPNHPNVVKFYGMfyKADklvGGQ 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  91 VYLVMEYVVG----ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAV 166
cd06639       99 LWLVLELCNGgsvtELVKGLLICGQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQL 178

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928194 167 NRTASRTATLIGTVAYLAP-----EQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEdvPPPSSR 239
cd06639      179 TSTRLRRNTSVGTPFWMAPeviacEQQYDYSYDARCDVWSLGITAIELGDGDPPLFDMHPVKTLFKIPRN--PPPTLL 254

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

3e-16

82.10

77.86

7,8,8,10,29,18,19,51,37,49,109,86,10,119,98,18,137,124,51,188,180,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194   9 LVGRLLDGRYliedriarggmATVYRARDMRLDRPVAVKVmhdVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADG 88
cd06611        9 IIGELGDGAF-----------GKVYKAQHKETGLFAAAKI---IQIESEEELEDFMVEIDILSECKHPNIVGLYEAYFYE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  89 GHVYLVMEYVVGetlrdllrrRGRLSPAEAL--GILQPVLAALSAAHASGL--------IHRDVKPENVLLARDGRVKVA 158
cd06611       75 NKLWILIEFCDG---------GALDSIMLELerGLTEPQIRYVCRQMLEALnflhshkvIHRDLKAGNILLTLDGDVKLA 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 159 DFGLAQAVNRTASRTATLIGTVAYLAPEQV-----TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDV 233
cd06611      146 DFGVSAKNKSTLQKRDTFIGTPYWMAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKSEP 225


                 .
gi 117928194 234 P 234
cd06611      226 P 226

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

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

false

true

false

279

4e-16

81.63

74.55

11,22,10,14,36,25,7,43,35,6,49,42,2,54,44,27,81,73,17,98,91,72,170,167,12,183,179,28,211,208,6,219,214,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  23 RIARGGMATVYRAR-DMRLDRP---VAVKVM-HDvfaTDPEFVARFIREAKAAAAFSHPNVVAV--FDQGADGGHVYLVM 95
cd05038       11 QLGEGHFGTVYLGTyDPPDDNTgeiVAVKKLnTS---GVEAHRQDFEREIEIMRTLDHENIVKYkgVSEEPGGRSLSLIM 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  96 EYV-VGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTA---- 170
cd05038       88 EYLpSGSLRDYLRRHRDQLNLKRLLLFALQIAKGMDYLGSKRLIHRDLAARNILVDSEDLVKISDFGLAKVLPEDKdyyy 167

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 171 SRTATLIGTVAYlAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPYQgdSPLA 223
cd05038      168 VKEPRESPIFWY-APECLRTGKFSSASDVWSYGVTLYEMFTyGEEPSL--SPPA 218

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

7e-16

80.93

71.43

8,22,7,27,51,34,28,79,65,9,89,74,11,100,88,20,120,109,43,163,153,8,174,161,51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  23 RIARGGMATVYRARDMRLDRPVAVKVMhdVFATDPEFVARFIREAKAAAAFSHPNVV---AVFDQGADGgHVYLVMEYVV 99
cd06621        8 RLGEGAGGSVTKCRLKNTGMIFALKTI--TTDPNPDLQKQILRELEINKSCKSPYIVkyyGAFLDESSS-SIGIAMEYCE 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 100 G---ETLRDLLRRRGRLSPAEALG-ILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTASrta 174
cd06621       85 GgslDSIYKKVKKRGGRIGEKVLGkIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSgELVNSLAG--- 161

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 117928194 175 TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVA 225
cd06621      162 TFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPPLG 212

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

7e-16

80.88

36.49

6,135,134,28,163,163,7,170,171,4,177,175,12,189,191,29,218,221,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 136 GLIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTA-SRTAtliGTVAYLAPEQVT----RGVADARSDVYAAGIMLFEM 209
cd06618      135 GVIHRDVKPSNILLDASGNVKLCDFGISgRLVDSKAkTRSA---GCAAYMAPERIDppdpNPKYDIRADVWSLGISLVEL 211

                         90       100       110
                 ....*....|....*....|....*....|.
gi 117928194 210 LTGAPPYQG-DSPLAVAYRHAHEDVPPPSSR 239
cd06618      212 ATGQFPYKNcKTEFEVLTKILQEEPPSLPPN 242

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

7e-16

80.75

53.82

4,90,79,75,165,155,28,193,185,26,219,215,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  91 VYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQA-VNRT 169
cd05583       80 LHLILDYVNGGELFTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEfLAEE 159

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 170 ASRTATLIGTVAYLAPEQVTRGVA--DARSDVYAAGIMLFEMLTGAPPYQGD----SPLAVAYRHAHEDVPPPSS 238
cd05583      160 EERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDgeqnSQSEISRRILKSKPPFPKT 234

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88523

cd05622

STKc_ROCK1

STKc_ROCK1: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring.

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

false

true

false

371

9e-16

80.48

59.30

6,9,31,14,23,50,77,102,127,15,117,143,54,171,198,15,186,217,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  10 VGRLLDGRYLIEDR-----IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQ 84
cd05622       32 INKIRDLRMKAEDYevvkvIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYA 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  85 GADGGHVYLVMEYVVGetLRDLLRRRGRLSPAE-ALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA 163
cd05622      112 FQDDRYLYMVMEYMPG--GDLVNLMSNYDVPEKwARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTC 189

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928194 164 QAVNRTAS-RTATLIGTVAYLAPE----QVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDS 220
cd05622      190 MKMNKEGMvRCDTAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADS 251

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

1e-15

80.10

29.17

5,136,128,27,163,156,7,170,164,4,177,168,11,188,182,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 137 LIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTA-SRTAtliGTVAYLAPEQV---TRGVADARSDVYAAGIMLFEMLT 211
cd06616      129 IIHRDVKPSNILLDRNGNIKLCDFGISgQLVDSIAkTRDA---GCRPYMAPERIdpsARDGYDVRSDVWSLGITLYEVAT 205


                 ....*..
gi 117928194 212 GAPPYQG 218
cd06616      206 GKFPYPK 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132964

cd06633

STKc_TAO3

Serine/threonine kinases (STKs), thousand-and-one amino acids 3 (TAO3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MAP3K or MKKK) activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. TAO3 is also known as JIK (JNK inhibitory kinase) or KFC (kinase from chicken). It specifically activates c-Jun N-terminal kinase (JNK), presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis.

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

false

true

false

313

1e-15

79.68

67.09

3,23,28,141,168,169,20,188,192,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd06633       29 IGHGSFGAVYFATNSHTNEVVAVKKMSYSGKQTNEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKEHTAWLVMEYCLGSAS 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQavnrTASRTATLIGTVAYL 183
cd06633      109 DLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSAS----KSSPANSFVGTPYWM 184

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 184 APEQV---TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06633      185 APEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSP 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132977

cd06646

STKc_MAP4K5

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 5 (MAPKKKK5 or MAP4K5) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity.

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

false

true

false

267

1e-15

79.69

82.02

3,17,10,45,65,55,124,189,182,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  18 YLIEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARfirEAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd06646       11 YELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSLIQQ---EIFMVKECKHCNIVAYFGSYLSREKLWICMEY 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLI 177
cd06646       88 CGGGSLQDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIAKRKSFI 167

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928194 178 GTVAYLAPEQVT---RGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP 236
cd06646      168 GTPYWMAPEVAAvekNGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMSKSNFQPP 229

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132968

cd06637

STKc_TNIK

Serine/threonine kinases (STKs),Traf2- and Nck-interacting kinase (TNIK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to mitogen-activated protein kinase (MAPK), kinase kinase kinase 4 (MAP4K4), and MAP4K6. MAP4Ks participate in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton.

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

false

true

false

272

2e-15

79.76

79.78

8,15,5,34,50,39,12,65,51,17,82,76,6,89,82,9,98,92,22,120,115,69,189,189,33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  16 GRYLIEDRIARGGMATVYRARDMRLDRPVAVKVMhDVFATDPEFVARfirEAKAAAAFSHPNVVAVF--------DQGAD 87
cd06637        6 GIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVM-DVTGDEEEEIKQ---EINMLKKYSHHRNIATYygafikknPPGMD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  88 GgHVYLVMEYV-VGETLRDLLRRRGRLSPAEALG-ILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQA 165
cd06637       82 D-QLWLVMEFCgAGSVTDLIKNTKGNTLKEEWIAyICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQ 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928194 166 VNRTASRTATLIGTVAYLAPEQVT-----RGVADARSDVYAAGIMLFEMLTGAPPYQGDSPL 222
cd06637      161 LDRTVGRRNTFIGTPYWMAPEVIAcdenpDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPM 222

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

2e-15

79.30

78.34

10,19,9,15,34,26,6,40,35,12,53,47,8,62,55,36,100,91,24,124,127,45,169,176,7,178,183,33,211,217,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  20 IEDRIARGGMATVYR--ARDMRL---DRPVAVKVMHDVfATDPEFVArFIREAKAAAAFSHPNVVAVFDQGADGGHVYLV 94
cd05032       10 LIRELGQGSFGMVYEglAKGVVKgepETRVAIKTVNEN-ASMRERIE-FLNEASVMKEFNCHHVVRLLGVVSTGQPTLVI 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  95 MEYVvgETLRDLLRRRGRLSPAEALGILQP------------VLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGL 162
cd05032       88 MELM--ARGDLKSYLRSRRPEAENNPGLGPptlqefiqmaaeIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGM 165

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117928194 163 AQAVNRT----ASRTATLigTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPYQGDS 220
cd05032      166 ARDIYETdyyrKGGKGLL--PVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATlAEQPYQGLS 226

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-15

79.41

67.97

7,43,30,8,51,39,5,61,44,38,99,83,67,166,153,10,178,163,33,211,197,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  44 VAVKVMHD-VFATDpefvaRFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVV-GETLRDLLRRRGRLSPAEALGI 121
cd05059       31 VAIKMIREgAMSED-----DFIEEAKVMMKLSHPNLVQLYGVCTKQRPIFIVTEYMAnGCLLNFLRQRRGKFGTEWLLDM 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 122 LQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAV---NRTASRTATLigTVAYLAPEQVTRGVADARSD 198
cd05059      106 CSDVCEAMEYLESNSFIHRDLAARNCLVGEDNVVKVSDFGLARYVlddQYTSSQGTKF--PVKWAPPEVFNYSRFSSKSD 183

                        170       180
                 ....*....|....*....|.
gi 117928194 199 VYAAGIMLFEMLT-GAPPYQG 218
cd05059      184 VWSFGVLMWEVFSeGKMPYER 204

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88476

cd05575

STKc_SGK

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

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

false

true

false

323

3e-15

78.85

60.06

2,23,2,49,72,52,144

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAA-FSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05575        3 IGKGSFGKVLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVLLKnVKHPFLVGLHYSFQTKEKLYFVLDYVNGGE 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05575       83 LFFHLQRERSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCKEGIAGSKTTSTFCGTPEY 162

                        170       180       190
                 ....*....|....*....|....*....|....
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPY 216
cd05575      163 LAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPF 196

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

4e-15

78.51

55.70

4,44,23,6,50,30,136,187,166,10,197,177,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  45 AVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQ 123
cd05620       24 AVKALKkDVVLIDDDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEFLNGGDLMFHIQDKGRFDLYRATFYAA 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 124 PVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYLAPEqVTRGVADARS-DVYAA 202
cd05620      104 EIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGDNRASTFCGTPDYIAPE-ILQGLKYTFSvDWWSF 182

                        170
                 ....*....|....*..
gi 117928194 203 GIMLFEMLTGAPPYQGD 219
cd05620      183 GVLLYEMLIGQSPFHGD 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88500

cd05599

STKc_NDR_like

STKc_NDR_like: Serine/Threonine Kinases (STKs), Nuclear Dbf2-Related (NDR) kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases.

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

false

true

false

364

4e-15

78.40

64.84

2,23,8,151,174,197,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05599        9 IGRGAFGEVRLVQKKDTGHIYAMKKLRKSEMLEKEQVAHVRAERDILAEADNPWVVKLYYSFQDENYLYLIMEYLPGGDM 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTA--------- 174
cd05599       89 MTLLMKKDTFTEEETRFYIAETILAIDSIHKLGYIHRDIKPDNLLLDAKGHIKLSDFGLCTGLKKSHRTEFyrilshalp 168

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928194 175 -----------------------------TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSP 221
cd05599      169 snfldfiskpmsskrkaetwkrnrralaySTVGTPDYIAPEVFLQTGYNKECDWWSLGVIMYEMLVGYPPFCSDNP 244

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

4e-15

78.48

58.97

2,23,2,51,74,54,142

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFS-HPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05588        3 IGRGSYAKVLLVELKKTRRIYAMKVIKKELVNDDEDIDWVQTEKHVFETASnHPFLVGLHSCFQTESRLFFVIEFVSGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05588       83 LMFHMQRQRKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCKEGIRPGDTTSTFCGTPNY 162

                        170       180       190
                 ....*....|....*....|....*....|....
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPY 216
cd05588      163 IAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132974

cd06643

STKc_SLK

Serine/threonine kinases (STKs), Ste20-like kinase (SLK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase (MAPKKK) by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration.

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

false

true

false

282

4e-15

78.14

74.82

4,26,15,24,53,39,47,100,87,93,193,185,41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  27 GGMATVYRARDMRLDRPVAVKVMHdvfATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG-ETLRD 105
cd06643       16 GAFGKVYKAQNKETGVLAAAKVID---TKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGgAVDAV 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 106 LLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYLAP 185
cd06643       93 MLELERPLTEPQIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSAKNTRTIQRRDSFIGTPYWMAP 172

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 186 EQVTRGVA-----DARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06643      173 EVVMCETSkdrpyDYKADVWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPP 226

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

5e-15

77.93

85.17

5,23,9,25,52,34,6,58,46,105,163,154,72,241,226,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVmhdvFATDPE------FVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd06625       10 LGQGAFGRVYLCYDVDTGRELAVKQ----VPFDPDspetkkEVNALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA---QAVNRTASRTA 174
cd06625       86 MPGGSVKDQLKAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASkrlQTICSSGTGMK 165

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 175 TLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPpssrvqSLPPAID 248
cd06625      166 SVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNP------QLPSHVS 233

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

8e-15

77.58

79.02

8,21,6,29,52,35,58,115,93,22,137,124,27,166,151,30,196,187,28,224,216,12,241,228,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARDMRLDRPVAVKVMHdvFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGE 101
cd06622        7 DELGKGNYGSVYKVLHRPTGVTMAMKEIR--LELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAG 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 TLRDLLRRRgrlspAEALGILQPVLAALSAAHASGL---------IHRDVKPENVLLARDGRVKVADFGLAQavNRTASR 172
cd06622       85 SLDKLYAGG-----VATEGIPEDVLRRITYAVVKGLkflkeehniIHRDVKPTNVLVNGNGQVKLCDFGVSG--NLVASL 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 173 TATLIGTVAYLAPEQVTRGVADAR------SDVYAAGIMLFEMLTGAPPYQGDSPLAV-AYRHAHEDVPPPssrvqSLPP 245
cd06622      158 AKTNIGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYANIfAQLSAIVDGDPP-----TLPS 232

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

9e-15

76.97

39.94

1,90,75,129

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  91 VYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTA 170
cd05615       76 LYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVDG 155

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 117928194 171 SRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05615      156 VTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGE 204

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133215

cd05084

PTKc_Fes

Catalytic Domain of the Protein Tyrosine Kinase, Fes

false

true

false

252

1e-14

76.51

78.17

8,21,0,15,37,15,5,42,21,12,56,33,44,100,78,63,163,142,16,179,159,32,211,192,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARdMRLDR-PVAVKVMHDVFAtdPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG 100
cd05084        1 ERIGRGNFGEVFSGR-LRADNtPVAVKSCRETLP--PELKAKFLMEARILKQYSHPNIVKLIGVCTQKQPIYIVMELVQG 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 -ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTASRTATLIG 178
cd05084       78 gDFLTFLRTEGPRLKVKELIRMAENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSrEEEDGVYSATGGMKQ 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 117928194 179 T-VAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPY 216
cd05084      158 IpVKWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPY 197

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

1e-14

76.62

72.76

8,31,14,8,40,22,11,53,33,29,84,62,1,85,64,87,172,152,7,179,161,32,211,194,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  32 VYRARDMRlDRPVAVKVMHDvfATDPEFVARFIREAKAAAAFSHPNVVAVFdqG-ADGGHVYLVMEYVVGETLRDLLRRR 110
cd05060       15 VYLMKSGK-EVEVAVKTLKQ--EHIAAGKKEFLREASVMAQLDHPCIVRLI--GvCKGEPLMLVMELAPLGPLLKYLKKR 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 111 GRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASR-TATLIGT--VAYLAPEQ 187
cd05060       90 REIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSDYyRATTAGRwpLKWYAPEC 169

                        170       180       190
                 ....*....|....*....|....*....|..
gi 117928194 188 VTRGVADARSDVYAAGIMLFEMLT-GAPPYQG 218
cd05060      170 INYGKFSSKSDVWSYGVTLWEAFSyGAKPYGE 201

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

1e-14

76.61

61.86

1,23,0,193

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05585        1 IGKGSFGKVMQVRKKDTQRIYALKTIRKAHIVSRSEVTHTLAERTVLAQVNCPFIVPLKFSFQSPEKLYFVLAFINGGEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYL 183
cd05585       81 FHHLQKEGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLNMKDDDRTNTFCGTPEYL 160

                        170       180       190
                 ....*....|....*....|....*....|...
gi 117928194 184 APEQVTRGVADARSDVYAAGIMLFEMLTGAPPY 216
cd05585      161 APELLLGHGYTKAVDWWTLGVLLYEMLTGLPPF 193

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

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

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

false

true

false

277

2e-14

76.47

29.60

2,135,114,31,167,145,51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 136 GLIHRDVKPENVLLARDGRVKVADFGLAQAVnRTASRTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPP 215
cd05577      115 RIVYRDLKPENILLDDHGHIRISDLGLAVEF-PEGKKIHGRVGTVGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHSP 193


                 ...
gi 117928194 216 YQG 218
cd05577      194 FRQ 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132969

cd06638

STKc_myosinIIIA

Serine/threonine kinases (STKs), class IIIA myosin subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells.

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

false

true

false

286

2e-14

76.20

81.47

7,19,21,44,66,65,16,82,86,19,101,107,18,119,127,66,185,198,46,233,244,10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  20 IEDRIARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFireAKAAAAFSHPNVVAVF-----DQGADGGHVYLV 94
cd06638       22 IIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEY---NILKALSDHPNVVKFYgmyykKDVKNGDQLWLV 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  95 MEYVVGE--TLRDLLRRRGRLSPAEAL--GILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTA 170
cd06638       99 LELCNGGsvTDLVKGFLKRGERMEEPIiaYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSTR 178

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928194 171 SRTATLIGTVAYLAP-----EQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEdvPPPSSRVQSL 243
cd06638      179 LRRNTSVGTPFWMAPeviacEQQLDSTYDARCDVWSLGITAIELGDGDPPLADLHPMRALFKIPRN--PPPTLHQPEL 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88519

cd05618

STKc_aPKC_iota

STKc_aPKC_iota: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, iota isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. There are two aPKC isoforms, zeta and iota. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions.

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

false

true

false

329

2e-14

75.87

58.97

4,23,2,51,74,54,112,187,166,10,197,177,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFS-HPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05618        3 IGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASnHPFLVGLHSCFQTESRLFFVIEYVNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05618       83 LMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTFCGTPNY 162

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 117928194 183 LAPEqVTRGVADARS-DVYAAGIMLFEMLTGAPPY 216
cd05618      163 IAPE-ILRGEDYGFSvDWWALGVLMFEMMAGRSPF 196

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

3e-14

75.82

60.99

2,23,7,27,50,35,169

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMH-DVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05616        8 LGKGSFGKVMLAERKGTDELYAIKILKkDVVIQDDDVECTMVEKRVLALSGKPPFLTQLHSCFQTMDRLYFVMEYVNGGD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05616       88 LMYQIQQVGRFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENMWDGVTTKTFCGTPDY 167

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 117928194 183 LAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05616      168 IAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGE 204

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-14

75.51

66.80

6,41,29,20,65,49,48,113,99,58,172,157,4,178,161,33,211,195,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  42 RPVAVKVMHDVFATDPEFVArfirEAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRL--SPAEAL 119
cd05039       30 QKVAVKCLKDDSTAAQAFLA----EASVMTTLRHPNLVQLLGVVLQGNPLYIVTEYMAKGSLVDYLRSRGRAviTLAQQL 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 120 GILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASrTATLigTVAYLAPEQVTRGVADARSDV 199
cd05039      106 GFALDVCEGMEYLEEKNFVHRDLAARNVLVSEDLVAKVSDFGLAKEASQGQD-SGKL--PVKWTAPEALREKKFSTKSDV 182

                        170
                 ....*....|....*...
gi 117928194 200 YAAGIMLFEMLT-GAPPY 216
cd05039      183 WSFGILLWEIYSfGRVPY 200

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-14

75.54

83.33

7,23,7,25,48,34,52,109,86,13,122,100,15,137,123,29,167,152,23,190,176,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKV--MHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGe 101
cd06632        8 LGSGSFGSVYEGLNLDDGDFFAVKEvsLADDGQTGQEAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVPG- 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 102 tlrdllrrRGRLSPAEALGIL-QPVLAALSAAHASGL--------IHRDVKPENVLLARDGRVKVADFGLAQAVnRTASR 172
cd06632       87 --------GSLAKLLKKYGSFpEPVIRLYTRQILLGLeylhdrntVHRDIKGANILVDTNGVVKLADFGMAKQV-VEFSF 157

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928194 173 TATLIGTVAYLAPEQVTR-GVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVPPP 236
cd06632      158 AKSFKGSPYWMAPEVIAQqGGYGLAADIWSLGCTVLEMATGKPPWSQLEGVAAVFKIGRSKELPP 222

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88499

cd05598

STKc_LATS

STKc_LATS: Serine/Threonine Kinases (STKs), Large Tumor Suppressor (LATS) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation.

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

false

true

false

376

3e-14

75.39

51.33

3,77,62,86,163,185,12,175,203,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  78 VVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKV 157
cd05598       63 VVKLYYSFQDKDNLYFVMDYIPGGDMMSLLIRLGIFEEDLARFYIAELTCAIESVHKMGFIHRDIKPDNILIDRDGHIKL 142

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 158 ADFGLA-------------------------------------QAVNRTASRTAT------LIGTVAYLAPEQVTRGVAD 194
cd05598      143 TDFGLCtgfrwthdskyyqkgdhhrqdsmepseewseidrcrlKPLERRRVRQHQrclahsLVGTPNYIAPEVLLRTGYT 222

                        170       180       190
                 ....*....|....*....|....*....|...
gi 117928194 195 ARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYR 227
cd05598      223 QLCDWWSVGVILYEMLVGQPPFLADTPAETQLK 255

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

3e-14

75.19

78.88

8,21,0,15,37,15,11,48,28,4,56,32,63,119,96,49,168,148,9,178,157,33,211,191,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  22 DRIARGGMATVYRARdMRLDRPVAVKV--MHDVfatdPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVV 99
cd05041        1 EKIGKGNFGDVYKGV-LKGKTEVAVKTcrSTLP----PDLKRKFLQEAEILKQYDHPNIVKLIGVCVQKQPIYIVMELVP 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 100 GETLRDLLRRRGRLSPAEAL-GILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNR---TASRTAT 175
cd05041       76 GGSLLTFLRKKKNRLTVKKLlQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEGgiyTVSDGLK 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 117928194 176 LIgTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPYQG 218
cd05041      156 QI-PIKWTAPEALNYGRYTSESDVWSYGILLWETFSlGDTPYPG 198

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

4e-14

75.30

76.34

8,20,5,29,51,34,58,114,92,6,120,99,43,163,143,8,174,151,42,216,196,4,220,204,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  21 EDRIARGGMATVYRARDMRLDRPVAVKVMhdVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG 100
cd06619        6 QEILGHGNGGTVYKAYHLLTRRILAVKVI--PLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 101 ETLRDLLRRrgrlsPAEALG-ILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLA-QAVNRTASrtaTLIG 178
cd06619       84 GSLDVYRKI-----PEHVLGrIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVStQLVNSIAK---TYVG 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117928194 179 TVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPY---QGDS----PLAVAYRHAHEDVP 234
cd06619      156 TNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPYpqiQKNQgslmPLQLLQCIVDEDPP 218

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

7e-14

74.33

59.33

4,23,2,51,74,54,112,187,166,10,197,177,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFS-HPNVVAVFDQGADGGHVYLVMEYVVGET 102
cd05617        3 IGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASsNPFLVGLHSCFQTTSRLFLVIEYVNGGD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 103 LRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAY 182
cd05617       83 LMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNY 162

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 117928194 183 LAPEqVTRGVADARS-DVYAAGIMLFEMLTGAPPY 216
cd05617      163 IAPE-ILRGEEYGFSvDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133165

cd05033

PTKc_EphR

Catalytic Domain of Ephrin Receptor Protein Tyrosine Kinases

false

true

false

266

8e-14

73.91

75.94

9,19,7,17,37,24,3,40,31,12,53,43,6,60,49,39,99,89,67,167,156,11,178,170,33,211,204,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  20 IEDRIARGGMATVYRARdMRL----DRPVAVKVMHDVfATDPEFvARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVM 95
cd05033        8 IEKVIGGGEFGEVCRGR-LKLpgkkEIDVAIKTLKAG-SSDKQR-LDFLTEASIMGQFDHPNIIRLEGVVTKSRPVMIIT 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  96 EYVV-GETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVnRTASRTA 174
cd05033       85 EYMEnGSLDKFLRENDGKFTVGQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRRL-EDSEATY 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 117928194 175 TLIG---TVAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPY 216
cd05033      164 TTKGgkiPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSyGERPY 209

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-13

73.05

61.63

5,23,8,94,117,103,54,171,158,15,187,173,10,197,189,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05597        9 IGRGAFGEVAVVKMKNTGQVYAMKILNKWEMLKRAETACFREERDVLVNGDRRWITNLHYAFQDENNLYLVMDYYVGGDL 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 104 RDLLRRRGRLSPAE-ALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTAS-RTATLIGTVA 181
cd05597       89 LTLLSKFEDRLPEDmARFYLAEMVLAIDSVHQLGYVHRDIKPDNVLLDKNGHIRLADFGSCLRLLADGTvQSNVAVGTPD 168

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 117928194 182 YLAPEqVTRGVADARS------DVYAAGIMLFEMLTGAPPYQGDS 220
cd05597      169 YISPE-ILQAMEDGKGrygpecDWWSLGVCMYEMLYGETPFYAES 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132975

cd06644

STKc_STK10_LOK

Serine/threonine kinases (STKs), STK10 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Other names for STK10 include lymphocyte-oriented kinase (LOK) and Xenopus polo-like kinase kinase 1 (xPlkk1). STK10 is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types.

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

false

true

false

292

2e-13

72.76

72.26

4,26,22,24,53,46,47,100,94,88,188,187,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  27 GGMATVYRARDMRLDRPVAVKVMHdvfATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVG-ETLRD 105
cd06644       23 GAFGKVYKAKNKETGALAAAKVIE---TKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGgAVDAI 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 106 LLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQAVNRTASRTATLIGTVAYLAP 185
cd06644      100 MLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSAKNVKTLQRRDSFIGTPYWMAP 179

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117928194 186 EQV-----TRGVADARSDVYAAGIMLFEMLTGAPPYQGDSPLAVAYRHAHEDVP 234
cd06644      180 EVVmcetmKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPP 233

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88511

cd05610

STKc_MASTL

STKc_MASTL: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST-like (MASTL) 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. 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. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. The human MASTL gene has also been labelled FLJ14813. A missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. To date, the function of MASTL is unknown.

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

false

true

false

669

2e-13

72.40

21.08

1,23,11,141

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEYVVGETL 103
cd05610       12 ISRGAFGKVYLGRKKNNSKLYAVKVVKKADMINKNMVHQVQAERDALALSKSPFIVHLYYSLQSANNVYLVMEYLIGGDV 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117928194 104 RDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGRVKVADFGLAQ 164
cd05610       92 KSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSK 152

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

3e-13

72.15

81.85

10,23,2,11,34,15,7,41,26,11,53,37,6,60,43,40,100,90,50,150,146,19,169,168,8,178,176,33,211,210,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYR--ARDMRLD----RPVAVKVMHDVfATDPEFvARFIREAKAAAAFSHPNVVAVFDQGADGGHVYLVMEY 97
cd05044        3 LGSGAFGEVYEgtAVDILGPgegeIRVAVKTLRKG-ATDQEK-KEFLKEAHLMSNFNHPNILKLLGVCLLNEPQYLILEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  98 VVG-------ETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLA------RDGRVKVADFGLAQ 164
cd05044       81 MEGgdllsylRGARVTRFGPPLLTLSELLDICLDVAKGCVYLERMHFIHRDLAARNCLVSektysdADRVVKIGDFGLAR 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928194 165 AVNRT---ASRTATLIgTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLT-GAPPYQGDSPLAV 224
cd05044      161 DIYKNdyyRKEGEGLL-PVRWMAPESLLDGIFTTQSDVWAFGVLMWEILTlGQQPYPALNNQEV 223

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

3e-13

72.27

60.66

4,74,59,91,165,152,6,171,171,68,240,239,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  75 HPNVVAVFDQGADGGHVYLVMEYVVGETLRDLLRRRGRLSPAEALGILQPVLAALSAAHASGLIHRDVKPENVLLARDGR 154
cd05609       60 NPFVVSMFCSFETRRHLCMVMEYVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGH 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194 155 VKVADFGLAQA--VNRTAS-------------RTATLIGTVAYLAPEQVTRGVADARSDVYAAGIMLFEMLTGAPPYQGD 219
cd05609      140 IKLTDFGLSKIglMSLTTNlyeghiekdtrefLDKQVCGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGD 219

                        170       180
                 ....*....|....*....|....*.
gi 117928194 220 SPLAVAYRHAHEDVPPPSSRvQSLPP 245
cd05609      220 TPEELFGQVISDDIEWPEGD-EALPA 244

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

3e-13

72.02

59.69

5,23,2,49,72,52,28,100,81,15,115,105,10,135,115,81

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928194  24 IARGGMATVYRARDMRLDRPVAVKVMHDVFATDPEFVARFIREAKAAAA-FSHPNV