NCBI Conserved Domain Search

NewSearch

CDD Home

Conserved domains on [gi\|94967294\|ref\|YP_589342.1\|]
serine/threonine protein kinase [Candidatus Koribacter versatilis Ellin345]

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



List of domain hits		?

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

29142

cd00180

S_TKc

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

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

true

256

4e-56

215.07

97.27

7,15,1,33,49,34,58,107,93,43,150,137,21,196,158,60,257,218,27,285,245,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd00180       2 YELLEKLGKGAFGKVYLARDKKTGELVAIKIIK-KKKEKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVMEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsa 173
cd00180      81 MSGGDLFDLLKKrGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGhVKIADFGLAKQLDSGGRKLTT-- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD 253
cd00180     159 -----------------------FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGK 215

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967294 254 PEPaSTLNPQVPRGVDHVIARCLAKDPEQRWqTARDL 290
cd00180     216 GTP-DELPPNISPEAKDLIKKLLVKDPEKRP-TAEEL 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

4e-43

171.96

94.98

10,21,7,36,58,43,32,90,76,17,107,94,43,150,138,21,194,159,43,237,203,14,257,217,14,271,235,13,285,248,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELkERFVREARAISSLNHPRICTLHDVGQQEGVDF-LVMEFLEGES 100
cd06606       8 LGRGSFGSVYLALSKDTGELVAVKSVELSSDSEEEL-ESLEREIRILSKLQHPNIVRYYGCEVTEENTLnIFMEYVSGGS 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsapllsg 178
cd06606      87 LASLLKKfGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGvVKLADFGCAKRLASIAYSGGL------- 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglsplspltmaGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAF-DGKSQIAVANSILEkdpepa 257
cd06606     160 ----------------KSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWsELGNPMALLYKIGS------ 217

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967294 258 STLNPQVPRGVDHV----IARCLAKDPEQRWqTARDL 290
cd06606     218 SGEPPEIPEDLSEEakdfLRKCLRRDPKKRP-TAEEL 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

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

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

false

true

false

253

3e-40

162.32

97.63

10,15,1,33,50,34,6,57,40,50,107,91,43,150,135,21,196,156,41,251,197,9,260,213,9,269,228,15,285,243,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghLSSNPElKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIK--LESDEE-QEQILNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsa 173
cd05122      79 CDGGSLDDLLKStGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGeVKLADFGVSAQLSDTKAKRNT-- 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFdgksqiavansileKD 253
cd05122     157 -----------------------FVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPY--------------SE 199

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 94967294 254 PEPASTL-------NPQVPRGVD------HVIARCLAKDPEQRWqTARDL 290
cd05122     200 LNPMKALfkiatnpPPGLPSPEKwspefrDFLKKCLQKDPEKRP-TAEEL 248

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

4e-38

155.25

94.00

5,21,0,86,107,87,43,150,131,21,196,152,58,258,210,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGESL 101
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 102 AQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsapllsga 179
cd05123      81 FTHLSKeGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGhIKLTDFGLAKEGIDDGVRTTT-------- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 ptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPepasT 259
cd05123     153 -----------------FCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKL----R 211

                       250       260
                ....*....|....*....|....
gi 94967294 260 LNPQVPRGVDHVIARCLAKDPEQR 283
cd05123     212 FPEFLSEEAKDLIKKLLTKDPTKR 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

STKc_PDK1: Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. PDK1 is essential for normal embryo development and is important in regulating cell volume.

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

false

true

false

279

1e-37

153.79

93.91

10,15,2,32,47,35,4,53,39,9,62,49,10,72,60,35,107,96,43,150,140,15,170,155,81,259,236,12,271,252,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVL-PGHLssNPELKERFV-REARAISSLN-HPRICTLHDVGQQEGVDFLV 92
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLdKRHL--IKEKKVKYVkREKEVLTRLNgHPGIVKLYYTFQDEENLYFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  93 MEFLEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTmaagt 170
cd05581      81 LEYAENGELLEYIKKfGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGhIKITDFGTAKVLDPN----- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 171 SSAPLLSGAPTMSGLSPLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSIL 250
cd05581     156 SSPESNKGKATNIDSQIEKNRRRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIV 235

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967294 251 EkdpepastLNPQVPRGVDHV----IARCLAKDPEQR 283
cd05581     236 K--------LEYEFPPNFPPDakdlIEKLLVLDPQDR 264

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

8e-34

141.19

96.59

14,16,3,31,49,34,58,108,92,6,114,99,3,117,103,14,131,118,19,150,138,17,168,155,5,197,160,40,237,203,18,255,223,8,267,231,17,285,248,5,291,253,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  17 EIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFL 96
cd06623       4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKKI--HVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYM 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  97 EGESLAQRLQKgALPIKE-VLK-IGVEVSEALEVAHR-AGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAaGTSS 172
cd06623      82 DGGSLADLLKK-VGKIPEpVLAyIARQILKGLDYLHTkRHIIHRDIKPSNLLINSKGeVKIADFGISKVLENTLD-QCNT 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 ApllsgaptmsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAF---DGKSQIAVANSI 249
cd06623     160 F------------------------VGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFlppGQPSFFELMQAI 215

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 94967294 250 LEKDPE--PASTLNPQvprgVDHVIARCLAKDPEQRWqTARDLgLELGW 296
cd06623     216 CDGPPPslPAEEFSPE----FRDFISACLQKDPKKRP-SAAEL-LQHPF 258

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

4e-31

132.37

99.21

10,15,1,44,60,45,47,107,93,43,150,137,8,160,145,12,195,157,58,260,215,9,269,228,14,284,242,6,291,248,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKErFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06627       2 YQLGDLIGKGAFGVVYKGLNLETGDFVAIKQISLEKIKEEALKS-IMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIILEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLakAVESTMAAGTSSa 173
cd06627      81 AENGSLRQIIKKfGKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGvVKLADFGV--ATKLSDVSKDDE- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD 253
cd06627     158 ----------------------SVVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQDD 215

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 94967294 254 pepastlNPQVPRGVD----HVIARCLAKDPEQRwQTARDLgLELGW 296
cd06627     216 -------HPPLPEGISpelkDFLMQCFQKDPNLR-PTAKQL-LKHPW 253

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

4e-30

128.83

86.67

5,20,7,87,107,97,43,150,141,38,188,182,70,260,252,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05574       8 LLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVMDYCPGGE 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK---GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSSAPLL 176
cd05574      88 LFRLLQRqpgKCFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGhIMLSDFDLSKQSDVEPTPVSKALRKG 167

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 177 SGAPTMSGLSPL---SPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD 253
cd05574     168 SRGSVNKITTETfseEPSFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETFSNILKKE 247

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94967294 254 PEPAStlNPQVPRGVDHVIARCLAKDPEQRWQTAR 288
cd05574     248 VTFPG--SPPVSSSARDLIRKLLVKDPSKRLGSKR 280

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-29

125.51

96.99

16,15,2,32,49,34,3,52,38,7,60,45,42,102,91,9,111,103,6,120,109,31,151,141,7,171,148,7,183,155,9,196,164,11,207,178,4,213,182,41,261,223,9,270,241,14,285,255,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLS-SNPELKErFVREARAISSLNHPRICTLHDVGQQEGVDFLVME 94
cd06610       3 YKLIEVIGSGATAVVQRAICLPNGEKVAIKRI--DLEkCQTSMDE-LRKEIQAMSLCHHPNVVKYYTSFVVGDELWVVMP 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  95 FLEGESLA----QRLQKGALP---IKEVLKigvEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLakavestm 166
cd06610      80 LMSGGSCLdimkYSYPQGGLDeaiIATILK---EVLKGLEYLHKNGQIHRDIKAGNILLDSDGSvKLADFGV-------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 167 aagtsSAPLLSGaptmsGLSPLSPLTmagaVVGTVQYMAPE---QVEGklADARSDIFALGATLYEAATGKRAFDGKSQI 243
cd06610     149 -----SASLADG-----GDRTKVRKT----FVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYSKYPPM 212

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967294 244 AVANSILEKDPepastlnPQVPRGVDH---------VIARCLAKDPEQRWqTARDL 290
cd06610     213 KVLMLTLQNDP-------PSLETEADYkkysksfrkMISKCLQKDPAKRP-TASEL 260

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

2e-28

123.19

91.32

12,19,6,28,49,34,65,114,100,2,116,103,16,132,120,18,150,139,7,175,146,8,192,154,42,236,196,16,252,217,4,261,221,7,268,233,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  20 SQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGE 99
cd06605       7 GELGAGNSGVVSKVRHRPTGKIMAVKTI--RLEINEAIQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICMEYMDGG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 100 SLAQRLQKGALPIKE-VL-KIGVEVSEALEVAHRA-GIVHRDLKPGNIMLTKTG-AKLMDFGlakavestmaagtssapl 175
cd06605      85 SLDKILKEVQGRIPErILgKIAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGeIKLCDFG------------------ 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 176 LSGAPTMSglsplspltMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKraFDGKSQIAVANSILEK--- 252
cd06605     147 VSGQLVNS---------LAKTFVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGR--FPYPPENDPPDGIFELlqy 215

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94967294 253 --DPEPastlnPQVPRGV-----DHVIARCLAKDPEQR 283
cd06605     216 ivNEPP-----PRLPSGRfspdfQDFVNLCLIKDPRER 248

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

8e-28

121.19

97.45

12,15,2,32,49,34,27,76,66,8,89,74,61,150,136,16,176,152,6,197,158,57,261,215,4,265,224,19,285,243,5,291,248,13,305,261,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRI-----CTLHDVGQqegvdF 90
cd06609       3 FTLLECIGKGSFGEVYKAIDKRTNQVVAIKVI--DLEEAEDEIEDIQQEIQFLSQCRSPYItkyygSFLKGSKL-----W 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  91 LVMEFLEGESLAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMaag 169
cd06609      76 IIMEYCGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGdVKLADFGVSGQLTSTM--- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 170 tssapllSGAPTMsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSI 249
cd06609     153 -------SKRNTF---------------VGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRVLFLI 210

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94967294 250 LEKDPepastlnPQVP-----RGVDHVIARCLAKDPEQRWqTARDLgLELGWSAQASPSStQITPVKRR 313
cd06609     211 PKNNP-------PSLEgnkfsKPFKDFVSLCLNKDPKERP-SAKEL-LKHKFIKKAKKTS-YLTLLIER 269

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

1e-27

120.29

92.45

7,21,0,86,107,87,43,150,131,11,161,144,13,193,157,70,264,227,5,270,232,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGESL 101
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 102 AQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKA--VESTMAAGTSSAPlls 177
cd05579      81 ASLLENvGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGhLKLTDFGLSKVglVRRQINLNDDEKE--- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 178 gaptmsglsplspltmAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPEPA 257
cd05579     158 ----------------DKRIVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEWP 221

                       250       260
                ....*....|....*....|....*.
gi 94967294 258 STLNPQvPRGVDhVIARCLAKDPEQR 283
cd05579     222 EDVEVS-DEAKD-LISKLLVPDPEKR 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132957

cd06626

STKc_MEKK4

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MEKK4 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK4 activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses.

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

false

true

false

264

2e-27

120.14

95.08

13,21,7,29,51,36,32,83,69,5,89,74,29,118,104,33,151,138,9,174,147,10,191,157,26,217,186,18,235,207,23,260,230,9,270,239,14,285,253,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHlSSNPELKERFVREARAISSLNHPRICTLHDVG-QQEGVdFLVMEFLEGES 100
cd06626       8 IGGGTFGKVYTAVNLDTGELMAVKEIRIQ-DNDPKTIKEIADEMKVLELLKHPNLVKYYGVEvHREKV-YIFMEYCSGGT 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKGALPIKEVLKI-GVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKavestmaagtssapLLSG 178
cd06626      86 LEELLEHGRILDEHVIRVyTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGViKLGDFGCAV--------------KLKN 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 APTMSGlsplsplTMAGAVVGTVQYMAPEQVEGKLADAR---SDIFALGATLYEAATGKR---AFDGKSQIAVANSILEK 252
cd06626     152 NTTTMG-------EEVQSLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRpwsELDNEFQIMFHVGAGHK 224

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94967294 253 DPEPAStlNPQVPRGVDhVIARCLAKDPEQRWqTARDL 290
cd06626     225 PPIPDS--LQLSPEGKD-FLDRCLESDPKKRP-TASEL 258

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

8e-27

117.70

86.41

14,15,20,32,49,52,7,57,59,57,114,121,3,120,124,31,151,156,8,172,164,12,196,176,38,234,223,3,240,226,4,245,230,6,251,237,9,267,246,17,285,263,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPElKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06614      21 YDNLEKIGEGASGEVYTATDRATGKEVAIKKM--RLRKQPK-KELIINEILIMKECKHPNIVNYYDSYLVGDELWVVMEY 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKE-----VLKigvEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAkavestmaag 169
cd06614      98 MDGGSLTDIITQTFVRMNEsqiayVCR---EVLQGLEYLHSQNVIHRDIKSDNILLSKDGSvKLADFGFA---------- 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 170 tssAPLLSGAPTMSGlsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGK---------RAFdgk 240
cd06614     165 ---AQLTKEKSKRNS------------MVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEppylnepplRAL--- 226

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 94967294 241 SQIAvANSILE-KDPEPASTLnpqvprgVDHVIARCLAKDPEQRWqTARDL 290
cd06614     227 FLIT-TKGIPPlKNPEKWSPE-------FKDFLNKCLVKDPEKRP-SAEEL 268

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

1e-26

116.87

94.19

5,15,1,105,120,107,30,150,138,9,185,147,57,243,204,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05578       2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVDL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKEVLKIGV-EVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAkavestmaagtssa 173
cd05578      82 LLGGDLRYHLQQKVKFSEEQVKFYVcEIVLALEYLHSKGIIHRDIKPDNILLDEQGhAHLTDFNIA-------------- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglSPLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQiAVANSILEKD 253
cd05578     148 ------------TKLTPDTLATSTSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGHSR-TPREEILAKF 214

                       250       260       270
                ....*....|....*....|....*....|
gi 94967294 254 PEPASTLNPQVPRGVDHVIARCLAKDPEQR 283
cd05578     215 ETADVLYPAGWSSEAIDAINKLLERDPQKR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

STKc_PKA: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA) subfamily, catalytic (c) subunit. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). This subfamily is composed of the cAMP-dependent proteins kinases, PKA and PRKX. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic (C) subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active C subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis.

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

false

true

false

290

2e-26

116.00

82.07

6,15,2,92,107,95,43,150,139,14,168,153,4,196,157,67,267,224,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05580       3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVMEF 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVEStmaaGTSSa 173
cd05580      83 VPGGELFSLLRRsGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGyIKITDFGFAKRVKG----RTYT- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD 253
cd05580     158 -----------------------LCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKIYEKILSGK 214

                       250       260       270
                ....*....|....*....|....*....|
gi 94967294 254 PEPASTLNPQvprgVDHVIARCLAKDPEQR 283
cd05580     215 VRFPSFFSSD----AKDLLRNLLQVDLTKR 240

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

112.77

96.55

12,15,4,33,50,37,9,60,46,47,107,94,43,150,138,21,196,159,11,207,172,7,214,180,22,236,203,2,240,205,29,269,236,14,284,250,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghLSSNPELKErFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06613       5 YELLQRIGSGTYGDVYKARDIATGELAAVKVIK--LEPGDDFEI-IQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsa 173
cd06613      82 CGGGSLQDIYQVtGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGdVKLADFGVSAQLTATIAKRKS-- 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagaVVGTVQYMAPE--QVEGKLA-DARSDIFALGATLYEAATGKRA-FDgkSQIAVANSI 249
cd06613     160 -----------------------FIGTPYWMAPEvaAVERKGGyDGKCDIWALGITAIELAELQPPmFD--LHPMRALFL 214

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94967294 250 LEKDPEPASTLNPQVPRGVD--HVIARCLAKDPEQRwQTARDL 290
cd06613     215 ISKSNFQPPKLKDKEKWSPVfhDFIKKCLTKDPKKR-PTAEKL 256

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-25

111.36

87.46

11,19,6,28,49,34,32,81,68,17,98,88,16,114,106,37,151,144,8,159,153,5,192,158,45,237,205,7,244,220,17,263,237,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  20 SQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHD--VGQQEGVDFLVMEFLE 97
cd06621       7 SRLGEGAGGSVTKCRLKNTGMIFALKTI--TTDPNPDLQKQILRELEINKSCKSPYIVKYYGafLDESSSSIGIAMEYCE 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 G---ESLAQRLQKGALPIKE--VLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLA-KAVEStmaagt 170
cd06621      85 GgslDSIYKKVKKRGGRIGEkvLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQvKLCDFGVSgELVNS------ 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 171 ssapllsgaptmsglsplspltMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAF--DGKSQIA---- 244
cd06621     159 ----------------------LAGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFppEGEPPLGpiel 216

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94967294 245 ----VANSILEKDPEPASTLNpqVPRGVDHVIARCLAKDPEQR 283
cd06621     217 lsyiVNMPNPELKDEPGNGIK--WSEEFKDFIKQCLEKDPTRR 257

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

7e-25

111.10

79.66

8,15,2,41,57,43,11,68,55,37,105,93,45,150,139,15,165,159,27,192,187,85,278,272,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPElKERFVREARAI-SSLNHPRICTLHDVGQQEGVDFLVME 94
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRN-QVAHVRAERDIlADADSPWIVKLYYSFQDEEYLYLVME 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  95 FLEGESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVEST-----MA 167
cd05573      82 YMPGGDLMTLLiKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGhIKLADFGLCKKMKKAgdseyYL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 168 AGTSSAPLLSGAPTMSGLSPLSPLT-MAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVA 246
cd05573     162 NDSHNLLDSDRDNVLKRRRPKKQRRvRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQETY 241

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94967294 247 NSILEKDPEPASTLNPQVPRGVDHVIARCLAkDPEQRWQTARDL 290
cd05573     242 NKIMNWKESLYFPADVKVSPEAIDLIRRLLC-DPEDRLGSFEEI 284

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

8e-25

111.05

90.84

6,21,0,86,107,87,43,150,131,20,196,151,41,237,194,13,252,207,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGESL 101
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGEL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 102 AQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTssapllsga 179
cd05572      81 WTILRDrGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGyVKLVDFGFAKKLKSGQKTYT--------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 ptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAF--DGKSQIAVANSILekDPEPA 257
cd05572     152 -----------------FCGTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFgeDDEDPMKIYNLIL--KGIDK 212

                       250       260
                ....*....|....*....|....*.
gi 94967294 258 STLNPQVPRGVDHVIARCLAKDPEQR 283
cd05572     213 LEFPKYIDKAAKDLIKQLLRRNPEER 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 1 (MST1) and MST2 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 (a MAPK kinase) and MEKK1 (a MAPK kinase kinase) by acting as a MAPK kinase kinase kinase (MAPKKKK). Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress.

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

false

true

false

256

1e-24

110.43

96.09

12,15,4,33,52,37,7,60,44,40,100,87,7,108,94,42,150,137,18,193,155,44,240,199,20,260,220,3,263,225,8,272,233,12,285,245,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghlsSNPELKErFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06612       5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVP----VEEDLQE-IIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGES---LAQRLQKgALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAgts 171
cd06612      80 CGAGSvsdIMKITNK-TLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGqAKLADFGVSGQLTDTMAK--- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 172 sapllsgaptmsglsplspltmAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFdgkSQIAVANSILE 251
cd06612     156 ----------------------RNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPY---SDIHPMRAIFM 210

                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 94967294 252 KDPEPASTL-NPQ--VPRGVDHViARCLAKDPEQRWqTARDL 290
cd06612     211 IPNKPPPTLsDPEkwSPEFNDFV-KKCLVKDPEERP-SAIQL 250

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

3e-24

109.29

93.82

14,13,5,35,52,40,19,71,60,11,82,75,7,89,84,11,100,98,14,114,114,36,150,151,22,197,173,17,214,195,20,253,215,1,255,216,7,262,228,6,268,248,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  14 GPYEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghlsSNPELKERFVREARAISSL-NHPRICTLHDV----GQQEGV 88
cd06608       6 GIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIMD----IIEDEEEEIEEEYNILRKYsNHPNIATFYGAfikkGPPGSD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  89 D--FLVMEFLEGES---LAQRLQKGALPIKE--VLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAK 160
cd06608      82 DqlWLVMELCGGGSvtdLVKGLRKKGKRLKEewIAYILRETLRGLAYLHENKVIHRDIKGQNILLTKEGeVKLVDFGVSA 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 161 AVESTMAAGTSSapllsgaptmsglsplspltmagavVGTVQYMAPEQVEGKLA-----DARSDIFALGATLYEAATGKr 235
cd06608     162 QLDSTNGRRNTS-------------------------IGTPYWMAPEVIACDEQpdasyDYRCDVWSLGITAIELADGK- 215

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967294 236 afdgksqiavansilekdPePASTLNP-----QVPRGV--------------DHVIARCLAKDPEQR 283
cd06608     216 ------------------P-PLCDMHPmralfKIPRNPpptlksptnwskkfNDFISECLIKNYEQR 263

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

3e-24

109.53

95.02

12,21,2,18,39,23,8,49,31,58,107,98,43,150,142,18,180,160,8,189,168,1,200,169,32,232,202,17,249,224,3,253,227,4,264,231,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLD---RSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEG 98
cd00192       3 LGEGAFGEVYKGELKGKGgkkTPVAVKTL--KEDASDSEREDFLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYMEG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  99 ESLAQRLQK---------GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAA 168
cd00192      81 GDLLDFLRKsrpvfspesSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLvVKIADFGLSRDIYDDDYY 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 169 gtssapllsgapTMSGLSPLsPltmagavvgtVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQIAVAN 247
cd00192     161 ------------RKKGGGKL-P----------IRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEVLE 217

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967294 248 SI-----LEKdPEPAstlnpqvPRGVDHVIARCLAKDPEQR 283
cd00192     218 YLrkgyrLPK-PENC-------PDELYELMLSCWQEDPEDR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132951

cd06620

PKc_MAPKK_Byr1_like

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

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

false

true

false

284

1e-23

107.19

90.14

12,16,7,31,49,38,58,107,97,21,128,121,3,133,124,18,151,143,7,171,150,6,191,156,56,247,216,5,252,225,8,260,234,23,284,257,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  17 EIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFL 96
cd06620       8 ETISDLGAGNGGSVSKVKHIPTGTVMAKKVV--HIGAKSSVRKQILRELQIMHECRSPYIVSFYGAFLNENNICMCMEFM 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  97 EGESLAQRLQK-GALPIKEVLKIGVEVSEALEV---AHRagIVHRDLKPGNIMLTKTGA-KLMDFGLakavestmaagts 171
cd06620      86 DCGSLDRIYKKgGPIPVEILGKIAVAVVEGLTYlynVHR--IMHRDIKPSNILVNSRGQiKLCDFGV------------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 172 SAPLLSgaptmsglsplsplTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVAN---- 247
cd06620     151 SGELIN--------------SIADTFVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFAFSNIDDDGQddpm 216

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 94967294 248 SILEK----DPEPASTL-NPQVPRGVDHVIARCLAKDPEQRwQTARDL 290
cd06620     217 GILDLlqqiVQEPPPRLpSSDFPEDLRDFVDACLLKDPTER-PTPQQL 263

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-23

105.98

90.36

10,15,6,32,49,38,8,58,46,56,114,104,36,150,141,21,196,162,13,209,180,44,255,224,9,264,234,20,285,254,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELkERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06611       7 WEIIGELGDGAFGKVYKAQHKETGLFAAAKII--QIESEEEL-EDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEF 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKE--VLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSs 172
cd06611      84 CDGGALDSIMLELERGLTEpqIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGdVKLADFGVSAKNKSTLQKRDT- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 apllsgaptmsglsplspltmagaVVGTVQYMAPEQV-----EGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVAN 247
cd06611     163 ------------------------FIGTPYWMAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLL 218

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94967294 248 SILEKDpePASTLNPQV-PRGVDHVIARCLAKDPEQRWqTARDL 290
cd06611     219 KILKSE--PPTLDQPSKwSSSFNDFLKSCLVKDPDDRP-TAAEL 259

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

7e-23

104.63

89.62

7,24,6,24,48,31,59,107,91,43,150,135,13,192,148,63,255,212,14,270,226,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  25 GGMGEVYRAKDLRLDRSVAIKVLP-GHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGESLAQ 103
cd05611       7 GAFGSVYLAKKRSTGDYFAIKVLKkSDMIAKNQVTNVKAERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLNGGDCAS 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 104 RLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVEstmaagtssapllsgapt 181
cd05611      87 LIKTlGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGhLKLTDFGLSRNGL------------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 182 msglsplspltMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPE-PASTL 260
cd05611     149 -----------ENKKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINwPEEVK 217

                       250       260
                ....*....|....*....|...
gi 94967294 261 NPQVPRGVDhVIARCLAKDPEQR 283
cd05611     218 EFCSPEAVD-LINRLLCMDPAKR 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

Serine/threonine kinases (STKs), Nak1 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also known as N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner.

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

false

true

false

277

2e-22

103.29

96.39

13,14,1,33,49,34,24,73,61,35,110,96,4,115,100,5,120,108,30,150,139,21,196,160,13,209,174,45,255,219,14,270,233,14,285,247,5,291,252,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  15 PYEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNH---PRICTLHDVGQQEGVDFL 91
cd06917       2 LYQRLELIGRGAYGAVYRGKHVPTGRVVALKII--NLDTPDDDVSDIQREVALLSQLRQsqpPNITKYYGSYLKGPRLWI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  92 VMEFLEGESLAQRLQKGalPIKEvLKIGV---EVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMA 167
cd06917      80 IMEYAEGGSVRTLMKAG--PIAE-KYISViirEVLVALKYIHKVGVIHRDIKAANILVTNTGnVKLCDFGVAALLNQNSS 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 168 AGTSsapllsgaptmsglsplspltmagaVVGTVQYMAPEQV-EGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVA 246
cd06917     157 KRST-------------------------FVGTPYWMAPEVItEGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAM 211

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967294 247 NSILEKDPePASTLNPQVPRGVDhVIARCLAKDPEQRWqTARDLgLELGWSAQASPSSTQI 307
cd06917     212 MLIPKSKP-PRLEDNGYSKLLRE-FVAACLDEEPKERL-SAEEL-LKSKWIKAHSKTPVSI 268

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

STKc_PKC: Serine/Threonine Kinases (STKs), Protein Kinase C (PKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs.

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

false

true

false

318

1e-21

101.08

74.21

8,21,2,48,69,51,38,107,90,43,150,134,10,162,144,10,195,154,57,260,211,9,269,224,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAIS-SLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05570       3 LGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDDDVECTMTEKRVLAlAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavESTMAAGTSSapllsg 178
cd05570      83 LMYHIQQqGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGhIKIADFGMCK--EGILGGVTTS------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglsplspltmagAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKdpepas 258
cd05570     155 -----------------TFCGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILED------ 211

                       250       260
                ....*....|....*....|....*....
gi 94967294 259 tlNPQVPRGVD----HVIARCLAKDPEQR 283
cd05570     212 --NVRYPRWLSkeakSILKGFLTKNPEKR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

STKc_Sid2p_Dbf2p: Serine/Threonine Kinases (STKs), ROCK- and NDR-like subfamily, fungal Sid2p- and Dbf2p-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Sid2p- and Dbf2p-like group is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis.

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

false

true

false

333

3e-21

99.22

60.66

4,13,0,92,105,93,45,150,139,12,190,151,51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  14 GPYEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVM 93
cd05600       1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  94 EFLEGESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVestmaagts 171
cd05600      81 EYVPGGDFRTLLnNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGhIKLTDFGLSKGI--------- 151

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 172 sapllsgaptmsglsplspLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKS 241
cd05600     152 -------------------VTYANSVVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGST 202

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

1e-20

97.34

65.72

8,21,3,20,41,26,7,51,33,9,61,42,2,63,47,57,120,105,30,150,136,10,185,146,66

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRS---VAIKVLPghlSSNPELKERfVR---EARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05582       4 LGQGSFGKVFLVRKITGPDAgqlYAMKVLK---KATLKVRDR-VRtkmERDILAEVNHPFIVKLHYAFQTEGKLYLILDF 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKEVLKIGV-EVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavestmaagtssa 173
cd05582      80 LRGGDLFTRLSKEVMFTEEDVKFYLaELALALDHLHSLGIIYRDLKPENILLDEEGhIKLTDFGLSK------------- 146

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967294 174 pllsgaptmsglSPLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILE 251
cd05582     147 ------------ESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILK 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88513

cd05612

STKc_PRKX_like

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

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

false

true

false

291

2e-20

96.85

83.85

8,15,2,32,49,34,9,58,45,49,107,95,43,150,139,15,193,154,59,260,213,9,269,226,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELK--ERFVREARAISSLNHPRICTLHDVGQQEGVDFLVM 93
cd05612       3 LERIETLGTGTFGRVYLVRHKASGAYYALKVL--AIPEVIRLKqvEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  94 EFLEGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTmaagts 171
cd05612      81 EYVPGGELFSYLRKaGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGhIKITDFGFAKKVRDR------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 172 sapllsgaptmsglsplspltmAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILE 251
cd05612     155 ----------------------TWTLCGTPEYLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILA 212

                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 94967294 252 KdpepastlNPQVPRGVD----HVIARCLAKDPEQRWQTARD 289
cd05612     213 G--------KLEFPRHFDlrakDLIKKLLVVDRTRRLGNMKN 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132956

cd06625

STKc_MEKK3_like

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

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

false

true

false

263

3e-20

96.03

92.02

9,21,9,29,51,38,9,60,50,45,105,96,45,150,142,20,183,162,4,196,166,58,260,224,9,269,237,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHlSSNPELKER---FVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEG 98
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKQVPFD-PDSPETKKEvnaLECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPG 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  99 ESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTssapll 176
cd06625      89 GSVKDQLkAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGnVKLGDFGASKRLQTICSSGT------ 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 177 sgaptmsGLSPlspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPep 256
cd06625     163 -------GMKS---------VTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPT-- 224

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967294 257 astlNPQVPRGVD----HVIARCLAKDPEQR 283
cd06625     225 ----NPQLPSHVSpdarNFLRRTFVENAKKR 251

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

4e-20

95.90

85.47

16,10,11,38,50,49,19,69,69,29,98,100,9,110,109,6,116,117,10,126,130,4,132,134,18,150,153,9,159,163,6,167,169,6,198,175,16,214,195,25,239,221,15,254,239,15,273,254,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  11 TKLGPYEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghLSSNPELKERFVREARAIS-SLNHPRICTLHDVGQQEGVD 89
cd06618      12 ADLNDLENLGEIGSGTCGQVYKMRFKKTGHVMAVKQMR--RTGNKEENKRILMDLDVVLkSHDCPYIVKCYGYFITDSDV 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  90 FLVMEFLEG--ESLAQRLQKgalPIKEVL--KIGVEVSEAL---EVAHraGIVHRDLKPGNIMLTKTG-AKLMDFGLA-K 160
cd06618      90 FICMELMSTclDKLLKRIQG---PIPEDIlgKMTVAIVKALhylKEKH--GVIHRDVKPSNILLDASGnVKLCDFGISgR 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 161 AVESTmaAGTSSApllsgaptmsglsplspltmagavvGTVQYMAPEQVEGKLA----DARSDIFALGATLYEAATGKRA 236
cd06618     165 LVDSK--AKTRSA-------------------------GCAAYMAPERIDPPDPnpkyDIRADVWSLGISLVELATGQFP 217

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 94967294 237 FDG-KSQIAVANSILEKDP---EPASTLNPQVPRGVDhviaRCLAKDPEQR 283
cd06618     218 YKNcKTEFEVLTKILQEEPpslPPNEGFSPDFCSFVD----LCLTKDHRKR 264

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

1e-19

94.05

89.12

11,20,25,37,60,62,21,81,86,7,91,93,59,150,153,16,179,169,6,197,175,52,251,227,11,262,239,22,285,261,5,291,266,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELkerFVREARAISSLNHPRICTLHD---VGQQEGVdflVMEFLE 97
cd06648      26 KIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRREL---LFNEVVIMRDYQHPNIVEMYSsylVGDELWV---VMEFLE 99

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 GESLAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMaagtssapll 176
cd06648     100 GGALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGrVKLSDFGFCAQVSKEV---------- 169

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 177 sgaPTMSGLsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSIleKDPEP 256
cd06648     170 ---PRRKSL------------VGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRI--RDNLP 232

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 94967294 257 ASTLNP-QVPRGVDHVIARCLAKDPEQRWqTARDLgLELGWSAQASPSS 304
cd06648     233 PKLKNLhKVSPRLRSFLDRMLVRDPAQRA-TAAEL-LNHPFLAKAGPPS 279

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132981

cd06650

PKc_MEK1

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

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

false

true

false

333

2e-19

93.56

67.87

9,15,6,32,49,38,58,107,97,20,127,118,24,151,143,7,171,150,6,191,156,46,237,205,16,255,221,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06650       7 FEKISELGAGNGGVVFKVSHKPSGLIMARKLI--HLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEH 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALE-VAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLakavestmaagtsS 172
cd06650      85 MDGGSLDQVLKKaGRIPEQILGKVSIAVIKGLTyLREKHKIMHRDVKPSNILVNSRGEiKLCDFGV-------------S 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 APLLSgaptmsglsplsplTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAF---DGKSQIAVANSI 249
cd06650     152 GQLID--------------SMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAIGRYPIpppDAKELELMFGCP 217

                       250
                ....*....|....*..
gi 94967294 250 LEKDpePASTLNPQVPR 266
cd06650     218 VEGD--PAESETSPRPR 232

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

4e-19

92.34

73.99

8,21,3,16,37,22,31,68,54,52,120,107,30,150,138,10,162,148,2,187,150,66,257,216,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLR---LDRSVAIKVLPGHLSSNPELKERFVREARAI-SSLNHPRICTLHDVGQQEGVDFLVMEFLE 97
cd05584       4 LGKGGYGKVFQVRKVTgadTGKIFAMKVLKKATIVRNQKDTAHTKAERNIlEAVKHPFIVDLIYAFQTGGKLYLILEYLS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 GESLAQRLQKGALPIKEVLKIGV-EVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavEStmaagtssapl 175
cd05584      84 GGELFMHLEREGIFMEDTACFYLsEISLALEHLHQQGIIYRDLKPENILLDAQGhVKLTDFGLCK--ES----------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 176 lsgaptmsglspLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDpe 255
cd05584     151 ------------IHEGTVTHTFCGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGK-- 216

                       250       260
                ....*....|....*....|....*...
gi 94967294 256 paSTLNPQVPRGVDHVIARCLAKDPEQR 283
cd05584     217 --LNLPPYLTPEARDLLKKLLKRNPSSR 242

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

5e-19

92.10

92.64

10,21,7,27,50,34,12,62,50,45,107,96,44,151,141,13,190,154,22,212,177,38,250,216,3,253,220,10,267,230,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPghLSSNPELKERFV----REARAISSLNHPRICTLHDVGQQEGVDFLVMEFLE 97
cd06632       8 LGSGSFGSVYEGLNLDDGDFFAVKEVS--LADDGQTGQEAVkqleQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 GESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKAVEStmaagtssapl 175
cd06632      86 GGSLAKLLKKyGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVvKLADFGMAKQVVE----------- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 176 lsgaptmsglsplspLTMAGAVVGTVQYMAPEQVEGK-LADARSDIFALGATLYEAATGKRAFDGKSQIAVANSIL-EKD 253
cd06632     155 ---------------FSFAKSFKGSPYWMAPEVIAQQgGYGLAADIWSLGCTVLEMATGKPPWSQLEGVAAVFKIGrSKE 219

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967294 254 -PEPASTLNPQvprgVDHVIARCLAKDPEQR 283
cd06632     220 lPPIPDHLSDE----AKDFILKCLQRDPSLR 246

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

1e-18

90.71

73.77

8,19,4,29,48,34,9,58,43,8,66,54,84,150,139,10,163,149,12,197,161,63,264,224,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  20 SQLGAGGMGEVYRAKDLRLDRSVAIKVLP-GHLSSNPELkERFVREAR---AISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05589       5 AVLGRGHFGKVLLAEYKKTGELYAIKALKkGDIIARDEV-ESLMCEKRifeTANSERHPFLVNLFACFQTEDHVCFVMEY 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKaveSTMAAGTSSAP 174
cd05589      84 AAGGDLMMHIHTDVFSEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGyVKIADFGLCK---EGMGFGDRTST 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 175 LlsgaptmsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDP 254
cd05589     161 F----------------------CGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEV 218

                       250       260
                ....*....|....*....|....*....
gi 94967294 255 EPASTLnpqvPRGVDHVIARCLAKDPEQR 283
cd05589     219 RYPRFL----SREAISIMRRLLRRNPERR 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group I, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others.

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

false

true

false

293

2e-18

89.96

91.47

14,8,16,9,20,25,27,49,52,7,57,59,24,81,86,5,89,91,62,151,154,11,172,165,10,197,175,45,242,226,18,267,244,17,285,261,5,291,266,14,306,280,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294   9 PGTKLGPYEiqsQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPElKERFVREARAISSLNHPRICTLHD---VGQQ 85
cd06647      17 PKKKYTRFE---KIGQGASGTVYTAIDVATGQEVAIKQM--NLQQQPK-KELIINEILVMRENKHPNIVNYLDsylVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  86 EgvdFLVMEFLEGESLAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKAVes 164
cd06647      91 L---WVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSvKLTDFGFCAQI-- 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 165 tmaagtssAPLLSGAPTMsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQ-- 242
cd06647     166 --------TPEQSKRSTM---------------VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlr 222

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967294 243 ----IAVANSILEKDPEPASTLnpqvprgVDHVIARCLAKDPEQRWqTARDLgLELGWSAQASPSSTqITPV 310
cd06647     223 alylIATNGTPELQNPEKLSAI-------FRDFLNRCLEMDVEKRG-SAKEL-LQHPFLKLAKPLSS-LTPL 284

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

3e-18

89.15

95.15

10,20,6,28,48,37,59,107,97,43,150,142,9,163,151,16,196,167,45,241,221,7,252,228,10,266,238,17,284,255,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLP---GHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLE 97
cd06630       7 QLGTGAFSSCYQARDVKTGTLMAVKQVTyvrNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWMA 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 GESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG--AKLMDFGLAkaveSTMAAGTSSAP 174
cd06630      87 GGSVSHLLSKyGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGqrLRIADFGAA----ARLAAKGTGAG 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 175 LLSGAptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKS---------QIAV 245
cd06630     163 EFQGQ-----------------LLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKhsnhlalifKIAS 225

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 94967294 246 ANSilekDPEPASTLNPqvprGVDHVIARCLAKDPEQRwQTARDL 290
cd06630     226 ATT----APSIPEHLSP----GLRDVTLRCLELQPEDR-PPSREL 261

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-18

88.78

85.66

9,18,5,30,50,35,54,107,89,43,150,133,18,195,151,44,239,197,3,242,205,12,261,217,6,267,228,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  19 QSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEG 98
cd06619       6 QEILGHGNGGTVYKAYHLLTRRILAVKVIP--LDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDG 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  99 ESLAQRlqkGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAgtssaplls 177
cd06619      84 GSLDVY---RKIPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGqVKLCDFGVSTQLVNSIAK--------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 178 gaptmsglsplspltmagAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDG--KSQ-----IAVANSIL 250
cd06619     152 ------------------TYVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPYPQiqKNQgslmpLQLLQCIV 213

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94967294 251 EKDPepastlnPQVPRG-----VDHVIARCLAKDPEQR 283
cd06619     214 DEDP-------PVLPVGqfsekFVHFITQCMRKQPKER 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88493

cd05592

STKc_nPKC_theta_delta

STKc_nPKC_theta_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), theta and delta-like isoforms, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types.

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

false

true

false

316

8e-18

88.06

76.90

8,21,2,48,69,51,37,106,89,44,150,134,11,180,145,4,190,149,62,260,211,18,278,233,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAIS-SLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05592       3 LGKGSFGKVMLAELKGTNEYYAIKALKKDVVLEDDDVECTMVERRVLIlAWEHPFLTHLFCTFQTKEHLFFVMEYLNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQ-KGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAvestmaagtssapllsg 178
cd05592      83 LMFHIQsSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGhIKIADFGMCKE----------------- 145

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 apTMSGlsplspLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKdpepas 258
cd05592     146 --NING------EGKASTFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILND------ 211

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967294 259 tlNPQVPRGVDHVIARCLAK----DPEQRWQTARDL 290
cd05592     212 --RPHFPRWISKEAKDCLSKlferEPTKRLGMDGDI 245

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

8e-18

87.79

93.77

14,20,1,10,30,15,7,38,22,9,49,31,39,89,70,18,107,89,39,146,129,15,165,144,13,183,157,5,201,162,31,232,194,10,243,204,10,253,217,3,261,220,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEV----YRAKDLRlDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVdFLVMEFL 96
cd05060       2 ELGHGNFGSVvkgvYLMKSGK-EVEVAVKTL--KQEHIAAGKKEFLREASVMAQLDHPCIVRLIGVCKGEPL-MLVMELA 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  97 EGESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIML-TKTGAKLMDFGLAKAvestMAAGTSSAP 174
cd05060      78 PLGPLLKYLKKrREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLvNRHQAKISDFGMSRA----LGAGSDYYR 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 175 LLSGaptmsGLSPLspltmagavvgtvQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQiAVANSILEKD 253
cd05060     154 ATTA-----GRWPL-------------KWYAPECINYGKFSSKSDVWSYGVTLWEAFSyGAKPYGEMKG-AEVIAMLESG 214

                       250       260       270
                ....*....|....*....|....*....|...
gi 94967294 254 ---PEPastlnPQVPRGVDHVIARCLAKDPEQR 283
cd05060     215 erlPRP-----EECPQEIYSIMLSCWKYRPEDR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

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

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

false

true

false

277

1e-17

87.44

86.64

6,20,10,27,49,37,101,150,139,18,193,157,61,257,218,26,284,244,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd06641      11 KIGKGSFGEVFKGIDNRTQKVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGS 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAgtssapllsga 179
cd06641      89 ALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGeVKLADFGVAGQLTDTQIK----------- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 ptmsglsplspltmAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPepaST 259
cd06641     158 --------------RNTFVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLFLIPKNNP---PT 220

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967294 260 LNPQVPRGVDHVIARCLAKDPEQRwQTARDL 290
cd06641     221 LEGNYSKPLKEFVEACLNKEPSFR-PTAKEL 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132973

cd06642

STKc_STK25_YSK1

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

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

false

true

false

277

1e-17

87.02

86.64

6,20,10,27,49,37,101,150,139,21,196,160,58,257,218,26,284,244,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd06642      11 RIGKGSFGEVYKGIDNRTKEVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGS 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsapllsga 179
cd06642      89 ALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGdVKLADFGVAGQLTDTQIKRNT-------- 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 ptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPepaST 259
cd06642     161 -----------------FVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSP---PT 220

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967294 260 LNPQVPRGVDHVIARCLAKDPEQRwQTARDL 290
cd06642     221 LEGQYSKPFKEFVEACLNKDPRFR-PTAKEL 250

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

86.79

85.99

12,20,21,78,99,99,16,115,117,35,150,153,7,171,160,11,197,171,12,209,187,4,214,191,47,261,239,6,270,245,13,284,258,6,291,264,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGeS 100
cd06607      22 EIGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQQLRHPNTIEYKGCYLREHTAWLVMEYCLG-S 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKGALPIKEV--LKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGlakavestmaagtsSAPLLS 177
cd06607     101 ASDILEVHKKPLQEVeiAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGtVKLADFG--------------SASLVS 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 178 GAPTMsglsplspltmagavVGTVQYMAPEQV----EGKLaDARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD 253
cd06607     167 PANSF---------------VGTPYWMAPEVIlamdEGQY-DGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQND 230

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 254 PEPASTLN-PQVPRGvdhVIARCLAKDPEQRwQTARDLgLELGWSAQASPSSTQITPVKR 312
cd06607     231 SPTLSSNDwSDYFRN---FVDSCLQKIPQDR-PSSEEL-LKHRFVLRERPPTVIIDLIQR 285

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

2e-17

86.70

90.54

14,8,16,9,20,25,27,49,52,7,57,59,24,81,86,5,89,91,62,151,154,11,172,165,10,197,175,45,242,226,18,267,244,16,284,260,6,291,266,14,306,280,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294   9 PGTKLGPYEiqsQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPElKERFVREARAISSLNHPRICTLHD---VGQQ 85
cd06655      17 PKKKYTRYE---KIGQGASGTVFTAIDVATGQEVAIKQI--NLQKQPK-KELIINEILVMKELKNPNIVNFLDsflVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  86 EgvdFLVMEFLEGESLAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKAVes 164
cd06655      91 L---FVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSvKLTDFGFCAQI-- 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 165 tmaagtssAPLLSGAPTMsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQ-- 242
cd06655     166 --------TPEQSKRSTM---------------VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlr 222

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967294 243 ----IAVANSILEKDPEPASTLnpqvprgVDHVIARCLAKDPEQRwQTARDLgLELGWSAQASPSSTqITPV 310
cd06655     223 alylIATNGTPELQNPEKLSPI-------FRDFLNRCLEMDVEKR-GSAKEL-LQHPFLKLAKPLSS-LTPL 284

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132980

cd06649

PKc_MEK2

MEK2 (MAPKK2 or MKK2): Protein kinases (PKs), MAP/ERK Kinase (MEK) 2 subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MEK2 is a dual-specificity PK that phosphorylates and activates the downstream targets, extracellular signal-regulated kinase (ERK) 1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients.

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

false

true

false

331

3e-17

86.26

58.31

7,15,6,32,49,38,67,116,106,11,127,118,24,151,143,7,171,150,6,191,156,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06649       7 FERISELGAGNGGVVTKVQHKPSGLIMARKLI--HLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEH 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKEVL-KIGVEVSEALE-VAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLakavestmaagtsS 172
cd06649      85 MDGGSLDQVLKEAKRIPEEILgKVSIAVLRGLAyLREKHQIMHRDVKPSNILVNSRGEiKLCDFGV-------------S 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967294 173 APLLSgaptmsglsplsplTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGK 234
cd06649     152 GQLID--------------SMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVELAIGR 199

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

3e-17

85.84

90.07

8,15,6,32,49,38,13,63,51,51,114,104,36,150,141,21,196,162,13,209,180,61,271,241,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVrEARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06643       7 WEIIGELGDGAFGKVYKAQNKETGVLAAAKVI--DTKSEEELEDYMV-EIDILASCDHPNIVKLLDAFYYENNLWILIEF 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKE--VLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSs 172
cd06643      84 CAGGAVDAVMLELERPLTEpqIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGdIKLADFGVSAKNTRTIQRRDS- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 apllsgaptmsglsplspltmagaVVGTVQYMAPEQV-----EGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVAN 247
cd06643     163 ------------------------FIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGITLIEMAQIEPPHHELNPMRVLL 218

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94967294 248 SILEKDPEPASTLNPQVPRGVDHvIARCLAKDPEQRWQTARDL 290
cd06643     219 KIAKSEPPTLAQPSRWSSEFKDF-LKKCLEKNVDARWTTTQLL 260

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

5e-17

85.47

86.99

9,15,13,33,51,46,47,98,96,10,109,106,41,150,148,8,158,157,6,190,163,19,209,187,60,270,247,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPghlSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06644      14 WEIIGELGDGAFGKVYKAKNKETGALAAAKVIE---TKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEF 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEG---ESLAQRLQKGaLPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGL-AKAVEStmaagt 170
cd06644      91 CPGgavDAIMLELDRG-LTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGdIKLADFGVsAKNVKT------ 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 171 ssapllsgaptmsglsplspLTMAGAVVGTVQYMAPEQV-----EGKLADARSDIFALGATLYEAATGKRAFDGKSQIAV 245
cd06644     164 --------------------LQRRDSFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRV 223

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 94967294 246 ANSILEKDPEPASTLNPQVPRGVDhVIARCLAKDPEQRWQTARDL 290
cd06644     224 LLKIAKSEPPTLSQPSKWSMEFRD-FLKTALDKHPETRPSAAQLL 267

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

6e-17

84.97

66.67

6,15,2,102,117,106,33,150,140,9,166,149,14,197,163,21,218,190,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05601       3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQKGALPIKEVLK--IGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAkavestmAAGTSS 172
cd05601      83 HPGGDLLSLLNRYEDQFDESMAqfYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGhIKLADFGSA-------AKLNAN 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 APLLSGAPtmsglsplspltmagavVGTVQYMAPEQVEGKLADARS------DIFALGATLYEAATGKRAFDGKSQIAVA 246
cd05601     156 KMVNSKLP-----------------VGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGTSAVTY 218


                ....
gi 94967294 247 NSIL 250
cd05601     219 SNIM 222

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132946

cd06615

PKc_MEK

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

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

false

true

false

308

8e-17

84.41

73.38

8,15,2,32,49,34,58,107,93,20,127,114,24,151,139,7,171,146,6,191,152,56,248,208,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd06615       3 FEKLGELGAGNGGVVTKVLHRPSGLIMARKLI--HLEIKPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEH 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQK-GALPIKEVLKIGVEVSEALE-VAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLakavestmaagtsS 172
cd06615      81 MDGGSLDQVLKKaGRIPENILGKISIAVLRGLTyLREKHKIMHRDVKPSNILVNSRGEiKLCDFGV-------------S 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 173 APLLSgaptmsglsplsplTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANsILEK 252
cd06615     148 GQLID--------------SMANSFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKELEA-MFGR 212

                       250
                ....*....|....*.
gi 94967294 253 DPEPASTLNPQVPRGV 268
cd06615     213 PVSEGEAKESHRPVSG 228

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

1e-16

84.26

77.20

10,21,2,35,56,42,11,71,53,37,108,91,42,150,134,10,185,144,53,238,199,10,248,216,4,260,220,9,269,233,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPE-----LKERFVREARAisslNHPRICTLHDVGQQEGVDFLVMEFL 96
cd05588       3 IGRGSYAKVLLVELKKTRRIYAMKVIKKELVNDDEdidwvQTEKHVFETAS----NHPFLVGLHSCFQTESRLFFVIEFV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  97 EGESLAQRLQKG-ALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavestmaagtssap 174
cd05588      79 SGGDLMFHMQRQrKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGhIKLTDYGMCK-------------- 144

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 175 llsgaptmsglSPLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFD--GKSQIAVANS---- 248
cd05588     145 -----------EGIRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDivGMSDNPDQNTedyl 213

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 94967294 249 ---ILEKdpepastlNPQVPRGVD----HVIARCLAKDPEQRWQTARDLGL 292
cd05588     214 fqvILEK--------QIRIPRSLSvkasSVLKGFLNKDPKERLGCHPQTGF 256

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

1e-16

84.21

87.85

12,15,1,21,36,25,11,47,37,26,73,64,32,105,97,45,150,143,10,164,153,6,190,159,24,214,185,23,237,210,3,240,215,23,267,238,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDL---RLDRSVAIKVL-PGHLSSNPELKERFVREARAISSLNH-PRICTLHDVGQQEGVDF 90
cd05583       2 FELLRVLGTGAYGKVFLVRKVgghDAGKLYAMKVLkKATIVQKAKTAEHTRTERQVLEAVRRcPFLVTLHYAFQTDTKLH 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  91 LVMEFLEGESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavesTMAA 168
cd05583      82 LILDYVNGGELFTHLyQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGhVVLTDFGLSK----EFLA 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 169 GTssapllsgaptmsglsplspLTMAGAVVGTVQYMAPEQVEGKLA--DARSDIFALGATLYEAATGKRAF--DGK--SQ 242
cd05583     158 EE--------------------EERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFtvDGEqnSQ 217

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967294 243 IAVANSILEKDPEPASTLNPQvprgVDHVIARCLAKDPEQR 283
cd05583     218 SEISRRILKSKPPFPKTMSAE----ARDFIQKLLEKDPKKR 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 4 (MST4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration.

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

false

true

false

277

1e-16

83.95

86.64

6,20,10,27,49,37,101,150,139,21,196,160,40,239,200,44,284,244,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd06640      11 RIGKGSFGEVFKGIDNRTQQVVAIKII--DLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGS 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSsapllsga 179
cd06640      89 ALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGdVKLADFGVAGQLTDTQIKRNT-------- 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 ptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAfdgKSQIAVANSILEKDPEPAST 259
cd06640     161 -----------------FVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPP---NSDMHPMRVLFLIPKNNPPT 220

                       250       260       270
                ....*....|....*....|....*....|.
gi 94967294 260 LNPQVPRGVDHVIARCLAKDPEQRwQTARDL 290
cd06640     221 LTGEFSKPFKEFIDACLNKDPSFR-PTAKEL 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132962

cd06631

STKc_YSK4

Serine/threonine kinases (STKs), yeast Sps1/Ste20-related kinase 4 (YSK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs (MKKKs or MAP3Ks) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.

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

false

true

false

265

1e-16

83.81

92.83

10,21,7,13,35,20,15,51,35,12,63,51,44,107,96,44,151,141,26,196,167,53,254,220,12,266,237,7,274,244,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKdLRLDRSVAIKVLPGHlSSNPELKERFVR----EARAISSLNHPRICTLHDVGQQEGVDFLVMEFLE 97
cd06631       8 LGKGAYGTVYCGL-TNQGQLIAVKQVELD-TSNVLAAEKEYEklqeEVDLLKSLKHVNIVQYLGTCLDDNTISIFMEFVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  98 GESLAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKAVESTMAAGTSSAPL 175
cd06631      86 GGSISSILNRfGPLPEPVFCKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMPNGIiKLIDFGCARRLAWVGLHGTHSNML 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 176 LSgaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSIlekdpE 255
cd06631     166 KS-------------------MHGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASMDRLAAMFYI-----G 221

                       250       260       270
                ....*....|....*....|....*....|...
gi 94967294 256 PASTLNPQVPR-----GVDHVIArCLAKDPEQR 283
cd06631     222 AHRGLMPRLPDsfsaaAIDFVTS-CLTRDQHER 253

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-16

83.50

76.64

9,21,2,48,69,51,38,108,89,9,117,100,33,150,134,10,162,144,11,196,155,57,258,212,4,262,217,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAIS-SLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05591       3 LGKGSFGKVMLAELKGTDEVYAIKVLKKDVILQDDDVDCTMTEKRILAlAAKHPFLTALHCCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKgALPIKEVLK--IGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavESTMAAGTSSAplls 177
cd05591      83 LMFQIQR-SRKFDEPRSrfYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGhCKLADFGMCK--EGILNGVTTTT---- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 178 gaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDpepa 257
cd05591     156 -------------------FCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDD---- 212

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967294 258 sTLNP-QVPRGVDHVIARCLAKDPEQRWQTARDLGLE 293
cd05591     213 -VLYPvWLSKEAVSILKAFMTKNPNKRLGCVASQGGE 248

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

83.32

92.16

14,21,15,24,55,39,13,68,59,39,107,100,7,114,109,32,146,142,5,151,148,9,180,157,7,192,164,22,214,188,24,238,214,15,260,229,9,269,242,14,284,256,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKvlpghlssnpELKERFVREARAI-------SSLNHPRICTLHDVGQQEGVDFLVME 94
cd06624      16 LGKGTYGVVYAGRDLSTQVRIAIK----------EIPERDSRYSQPLheeialhSRLKHKNIVQYLGSDSENGYFKIFME 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  95 FLEGESLAQRLQK--GALPIKE--VLKIGVEVSEALEVAHRAGIVHRDLKPGNIML-TKTGA-KLMDFGLAKavestmaa 168
cd06624      86 QVPGGSLSALLRSkwGPLKDNEstIIFYTKQILEGLKYLHDNQIVHRDIKGDNVLVnTYSGVlKISDFGTSK-------- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 169 gtssapllsgapTMSGLSPlspltMAGAVVGTVQYMAPEQVEGKLA--DARSDIFALGATLYEAATGKRAFD--GKSQIA 244
cd06624     158 ------------RLAGINP-----CTETFTGTLQYMAPEIIDKGPRgyGAPADIWSLGCTIIEMATGKPPFHelGEPQAA 220

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 94967294 245 VANSILEKDpepastlNPQVPRGVD----HVIARCLAKDPEQRwQTARDL 290
cd06624     221 MFKVGMFKI-------HPEIPESLSaeakAFILRCFEPDPDKR-ASAHDL 262

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88476

cd05575

STKc_SGK

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

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

false

true

false

323

2e-16

83.08

75.23

7,21,2,26,47,29,60,107,90,43,150,134,10,162,144,11,196,155,59,259,214,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVL-PGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05575       3 IGKGSFGKVLLAKHKEDGKFYAVKVLqKKAILKKNEQKHIMAERNVLLKNVKHPFLVGLHYSFQTKEKLYFVLDYVNGGE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavESTMAAGTSSApllsg 178
cd05575      83 LFFHLQReRSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGhVVLTDFGLCK--EGIAGSKTTST----- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPEpas 258
cd05575     156 ------------------FCGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNKPLR--- 214

                       250       260       270
                ....*....|....*....|....*....|..
gi 94967294 259 tLNPQVPRGVDHVIARCLAKDPEQRWQTARDL 290
cd05575     215 -LRPNISVSARHLLEGLLQKDRTKRLGAKNDF 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133245

cd05114

PTKc_Tec_Rlk

Catalytic Domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase

Catalytic Domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in...

false

true

false

256

2e-16

82.97

91.80

10,20,10,14,35,24,12,47,37,5,57,42,46,103,90,47,150,138,25,199,163,33,232,197,21,257,218,7,264,226,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKdLRLDRSVAIKVL-PGHLSsnpelKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGE 99
cd05114      11 ELGSGQFGVVHLGK-WRAQIKVAIKAInEGAMS-----EEDFIEEAKVMMKLSHPKLVQLYGVCTQQKPLYIVTEFMENG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 100 SLAQ--RLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAAGTSSAPLl 176
cd05114      85 CLLNylRQRQGKLSKDMLLSMCQDVCEGMEYLERNSFIHRDLAARNCLVSSTGvVKVSDFGMTRYVLDDEYTSSSGAKF- 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 177 sgaptmsglsplspltmagavvgTVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQIAVANSILEKDpe 255
cd05114     164 -----------------------PVKWSPPEVFNFSKYSSKSDVWSFGVLMWEVFTeGKMPFEKKSNYEVVEMISRGF-- 218

                       250       260
                ....*....|....*....|....*....
gi 94967294 256 paSTLNPQV-PRGVDHVIARCLAKDPEQR 283
cd05114     219 --RLYRPKLaSMTVYEVMYSCWHEKPEGR 245

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

83.04

72.84

9,21,7,57,78,65,29,107,95,43,150,139,10,162,149,10,195,159,57,260,216,9,269,226,6,275,235,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICT-LHDVGQQEGVDFLVMEFLEGES 100
cd05587       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVIIQDDDVECTMVEKRVLALPGKPPFLTqLHSCFQTMDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavESTMAAGTSSapllsg 178
cd05587      88 LMYHIQQvGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGhIKIADFGMCK--ENIFGGKTTR------ 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglsplspltmagAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKdpepas 258
cd05587     160 -----------------TFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMEH------ 216

                       250       260
                ....*....|....*....|....*....
gi 94967294 259 tlNPQVPRGVD-HVIARC---LAKDPEQR 283
cd05587     217 --NVSYPKSLSkEAVSICkglLTKHPAKR 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88472

cd05571

STKc_PKB

STKc_PKB: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of PI3K and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis.

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

false

true

false

323

3e-16

82.73

76.16

6,21,2,97,118,100,32,150,133,12,175,145,8,195,153,68,267,221,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGESL 101
cd05571       3 LGKGTFGKVILVREKATGKYYAMKILKKEVIIAKDEVAHTLTESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 102 AQRLQKGALPIKEVLKI-GVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVestmaagtssaplLSGA 179
cd05571      83 FFHLSRERVFSEDRARFyGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGhIKITDFGLCKEG-------------ISDG 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 180 PTMSglsplspltmagAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKDPEPAST 259
cd05571     150 ATMK------------TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRT 217

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94967294 260 LNPQvprgVDHVIARCLAKDPEQRWQTARDLGLEL 294
cd05571     218 LSPE----AKSLLAGLLKKDPKQRLGGGPEDAKEI 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133198

cd05067

PTKc_Lck_Blk

Catalytic Domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk

false

true

false

260

4e-16

82.19

90.38

12,20,12,14,35,26,12,47,39,6,58,45,30,89,75,20,109,98,40,149,139,26,199,165,33,232,199,16,249,215,4,253,222,5,263,227,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKdLRLDRSVAIKVL-PGHLSSnpelkERFVREARAISSLNHPRICTLHDVGQQEGVdFLVMEFLEGE 99
cd05067      13 KLGAGQFGEVWMGY-YNNHTKVAIKSLkEGTMSP-----EAFLAEANLMKQLQHERLVRLYAVVTQEPI-YIVTEYMENG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 100 SLAQRLQKGA---LPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKT-GAKLMDFGLAKAVESTMAAGTSSAPL 175
cd05067      86 SLVDFLKTPEgikLTINKLIDMAAQIAEGMAYIERKNYIHRDLRAANILVSETlCCKIADFGLARIIEDNEYTAREGAKF 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 176 lsgaptmsglsplspltmagavvgTVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQIAVANSiLEKD- 253
cd05067     166 ------------------------PIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTyGRIPYPGMTNPEVIRN-LERGy 220

                       250       260       270
                ....*....|....*....|....*....|..
gi 94967294 254 --PEPAStlnpqVPRGVDHVIARCLAKDPEQR 283
cd05067     221 rmPRPDN-----CPEELYELMRLCWKERPEER 247

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

4e-16

82.03

74.47

9,21,2,47,68,50,40,108,91,42,150,134,10,185,144,53,238,199,10,248,216,4,260,220,9,269,233,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAI-SSLNHPRICTLHDVGQQEGVDFLVMEFLEGES 100
cd05618       3 IGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEDIDWVQTEKHVFeQASNHPFLVGLHSCFQTESRLFFVIEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQKG-ALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKavestmaagtssapllsg 178
cd05618      83 LMFHMQRQrKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGhIKLTDYGMCK------------------ 144

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglSPLSPLTMAGAVVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFD--GKSQIAVANS-------I 249
cd05618     145 -------EGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDivGSSDNPDQNTedylfqvI 217

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94967294 250 LEKdpepastlNPQVPRGVD----HVIARCLAKDPEQR 283
cd05618     218 LEK--------QIRIPRSLSvkaaSVLKSFLNKDPKER 247

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

4e-16

82.03

85.76

15,21,11,24,49,35,10,59,47,9,68,57,29,98,86,3,101,95,26,127,122,24,151,147,8,159,156,6,167,162,6,183,168,4,202,172,12,214,187,25,245,212,7,252,227,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKvlpgHLSSNPELKE--RFVREARAI-SSLNHPRICTLHDVGQQEGVDFLVMEFLEg 98
cd06616      12 IGRGAFGTVNKMLHKPSGTIMAVK----RIRSTVDEKEqkRLLMDLDVVmRSSDCPYIVKFYGALFREGDCWICMELMD- 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  99 ESL------AQRLQKGALPIKEVLKIGVEVSEALE-VAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLA-KAVESTmaAG 169
cd06616      87 ISLdkfykyVYEVLKSVIPEEILGKIAVATVKALNyLKEELKIIHRDVKPSNILLDRNGNiKLCDFGISgQLVDSI--AK 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 170 TSSApllsgaptmsGLSPlspltmagavvgtvqYMAPEQVEGKLA---DARSDIFALGATLYEAATGKRAFDGksqiavA 246
cd06616     165 TRDA----------GCRP---------------YMAPERIDPSARdgyDVRSDVWSLGITLYEVATGKFPYPK------W 213

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 94967294 247 NSILEK--------DPEPASTLNPQVPRGVDHVIARCLAKDPEQR 283
cd06616     214 NSVFDQltqvvkgdPPILSNSEEREFSPSFVNFINLCLIKDESKR 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88514

cd05613

STKc_MSK1_N

STKc_MSK1_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK1, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkappaB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MEK1 is associated with the development of cerebral ischemic/hypoxic preconditioning.

STKc_MSK1_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

290

6e-16

81.60

87.24

10,15,1,22,37,26,31,70,57,3,73,64,32,105,97,45,150,143,14,188,157,26,214,185,23,237,212,26,267,238,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLR---LDRSVAIKVLPGHLSSNPELKERFVREARAIssLNH----PRICTLHDVGQQEGV 88
cd05613       2 FELLKVLGTGAYGKVFLVRKVSghdSGKLYAMKVLKKATIVQKAKTTEHTRTERQV--LEHirqsPFLVTLHYAFQTDTK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  89 DFLVMEFLEGESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVEStm 166
cd05613      80 LHLILDYINGGELFTHLsQRERFKEQEVQIYSGEIVLALEHLHKLGIIYRDIKLENILLDSNGhVVLTDFGLSKEFHE-- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 167 aagtssapllsgaptmsglsplSPLTMAGAVVGTVQYMAPEQVEGKLA--DARSDIFALGATLYEAATGKRAF----DGK 240
cd05613     158 ----------------------DEVERAYSFCGTIEYMAPDIVRGGDGghDKAVDWWSMGVLMYELLTGASPFtvdgEKN 215

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94967294 241 SQIAVANSILEKDPEPASTLNPQvprgVDHVIARCLAKDPEQR 283
cd05613     216 SQAEISRRILKSEPPYPQEMSAL----AKDIIQRLLMKDPKKR 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88515

cd05614

STKc_MSK2_N

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK2, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis.

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

false

true

false

332

1e-15

80.84

75.90

9,15,1,22,37,26,34,71,62,34,105,97,45,150,143,22,196,165,22,218,188,19,237,211,26,267,237,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKDLR---LDRSVAIKVLPGHLSSNPELKERFVREARAISSL--NHPRICTLHDVGQQEGVDF 90
cd05614       2 FELLKVLGTGAYGKVFLVRKVTghdTGKLYAMKVLQKAALVQKAKTVEHTRTERNVLEHvrQSPFLVTLHYAFQTEAKLH 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  91 LVMEFLEGESLAQRL-QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKAVESTMAA 168
cd05614      82 LILDYVSGGEMFTHLyQRDNFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGhVVLTDFGLSKEFLSEEKE 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 169 GTSSapllsgaptmsglsplspltmagaVVGTVQYMAPEQVEGKLADARS-DIFALGATLYEAATGKRAF----DGKSQI 243
cd05614     162 RTYS------------------------FCGTIEYMAPEIIRGKGGHGKAvDWWSLGILIFELLTGASPFtlegERNTQS 217

                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 94967294 244 AVANSILEKDPEPASTLNPQvprgVDHVIARCLAKDPEQR 283
cd05614     218 EVSRRILKCDPPFPSFIGPE----AQDLLHKLLRKDPKKR 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133248

cd05148

PTKc_Srm_Brk

Catalytic Domain of the Protein Tyrosine Kinases, Srm and Brk

false

true

false

261

1e-15

80.56

92.34

11,15,7,19,35,26,12,51,38,9,60,48,45,105,96,43,148,140,14,162,155,12,200,167,32,232,200,19,251,221,7,263,228,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  16 YEIQSQLGAGGMGEVYRAKdLRLDRSVAIKVLpghlSSNPELKER-FVREARAISSLNHPRICTLHDVGQQEGVDFLVME 94
cd05148       8 FTLERKLGSGYFGEVWEGL-WKNRVRVAIKIL----KSDDLLKQQdFQKEVQALKRLRHKHLISLFAVCSVGEPVYIITE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  95 FLEGESLAQRL---QKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTK-TGAKLMDFGLAKAV-ESTMAAG 169
cd05148      83 LMEKGSLLAFLrspEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEdLVCKVADFGLARLIkEDVYLSS 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 170 TSSAPllsgaptmsglsplspltmagavvgtVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQIAVANS 248
cd05148     163 DKKIP--------------------------YKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQ 216

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967294 249 ILE--KDPEPAStlnpqVPRGVDHVIARCLAKDPEQR 283
cd05148     217 ITAgyRMPCPAK-----CPQEIYKIMLECWAAEPEDR 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132948

cd06617

PKc_MKK3_6

Protein kinases (PKs), MAP kinase kinase 3 (MKK3) and MKK6 subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK3 and MKK6 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 plays roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma.

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

false

true

false

280

2e-15

79.77

88.93

15,16,3,38,55,41,42,98,83,3,101,90,7,109,97,5,114,103,2,116,106,14,130,121,20,150,142,7,157,153,14,201,167,13,214,184,25,239,210,12,252,222,17,270,239,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  17 EIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNpELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFL 96
cd06617       4 EVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQ-EQKRLLMDLDISMRSSDCPYTVHFYGALFREGDVWICMEVM 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  97 EgESL----AQRLQKGaLPIKE-VL-KIGVEVSEALEVAH-RAGIVHRDLKPGNIMLTKTG-AKLMDFG----LAKAVES 164
cd06617      83 D-TSLdkfyKKVYKKG-LTIPEdILgKIAVSVVKALEYLHeKLSVIHRDVKPSNILINRNGqVKLCDFGisgyLVDSLAK 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 165 TMAAGTSsapllsgaptmsglsplspltmagavvgtvQYMAPEQVEGKLA----DARSDIFALGATLYEAATGKRAFDG- 239
cd06617     161 TVDAGCK------------------------------PYMAPERIDPEGNqkgyDVRSDVWSLGITMIELATGRFPYDNw 210

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94967294 240 KSQIAVANSILEkDPEPASTLNPQVPRGVDhVIARCLAKDPEQR 283
cd06617     211 KTPFEQLKQVVE-EPSPQLPAEKFSPEFQD-FVNKCLRKDYHER 252

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

2e-15

79.67

73.07

8,21,7,57,78,65,29,107,95,43,150,139,10,163,149,12,197,161,56,253,220,15,275,235,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYRAKDLRLDRSVAIKVLPGHLSSNPELKERFVREARAISSLNHPRICT-LHDVGQQEGVDFLVMEFLEGES 100
cd05615       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVVIQDDDVECTMVEKRVLALQDKPPFLTqLHSCFQTVDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 101 LAQRLQK-GALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTG-AKLMDFGLAKaveSTMAAGTSSAPLlsg 178
cd05615      88 LMYHIQQvGKFKEPQAVFYAAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGhIKIADFGMCK---EHMVDGVTTRTF--- 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 179 aptmsglsplspltmagavVGTVQYMAPEQVEGKLADARSDIFALGATLYEAATGKRAFDGKSQIAVANSILEKD---PE 255
cd05615     162 -------------------CGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNvsyPK 222

                       250       260
                ....*....|....*....|....*...
gi 94967294 256 PASTLNPQVPRGVdhviarcLAKDPEQR 283
cd05615     223 SLSKEAVSICKGL-------MTKHPSKR 243

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

2e-15

79.66

88.32

13,13,21,34,53,55,2,55,59,16,71,76,15,86,96,18,111,114,14,125,140,22,147,163,25,197,188,9,206,202,43,250,245,6,257,251,5,262,257,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  14 GPYEIQSQLGAGGMGEVYRAKDLRLDRSVAIKVLpghlssNP--ELKERFVREARAISSL-NHPRICTLHDVGQQE---- 86
cd06639      22 DTWEIIETIGKGTYGKVYKVTNKKDGSLAAVKIL------DPisDVDEEIEAEYNILQSLpNHPNVVKFYGMFYKAdklv 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  87 -GVDFLVMEFLEGESLAQRlqkgalpIKEVLKIGVEVSEA------------LEVAHRAGIVHRDLKPGNIMLT-KTGAK 152
cd06639      96 gGQLWLVLELCNGGSVTEL-------VKGLLICGQRLDEAmisyilygallgLQHLHNNRIIHRDVKGNNILLTtEGGVK 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 153 LMDFGLAKAVESTMAAGTSSapllsgaptmsglsplspltmagavVGTVQYMAP-----EQVEGKLADARSDIFALGATL 227
cd06639     169 LVDFGVSAQLTSTRLRRNTS-------------------------VGTPFWMAPeviacEQQYDYSYDARCDVWSLGITA 223

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967294 228 YEAATGKRAFDGKSQIAVANSIlEKDPEPaSTLNP-QVPRGVDHVIARCLAKDPEQR 283
cd06639     224 IELGDGDPPLFDMHPVKTLFKI-PRNPPP-TLLHPeKWCRSFNHFISQCLIKDFEAR 278

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-15

79.47

94.81

13,21,2,11,32,15,7,39,26,8,49,34,52,101,94,46,147,141,4,151,151,13,170,164,8,182,172,5,200,177,32,232,210,17,249,232,4,261,236,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  22 LGAGGMGEVYR--AKDLRLD----RSVAIKVLpgHLSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05044       3 LGSGAFGEVYEgtAVDILGPgegeIRVAVKTL--RKGATDQEKKEFLKEAHLMSNFNHPNILKLLGVCLLNEPQYLILEL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESL--------AQRLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLT-KTGA------KLMDFGLAK 160
cd05044      81 MEGGDLlsylrgarVTRFGPPLLTLSELLDICLDVAKGCVYLERMHFIHRDLAARNCLVSeKTYSdadrvvKIGDFGLAR 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 161 AVEStmaagtSSAPLLSGaptmSGLSPlspltmagavvgtVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDG 239
cd05044     161 DIYK------NDYYRKEG----EGLLP-------------VRWMAPESLLDGIFTTQSDVWAFGVLMWEILTlGQQPYPA 217

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 94967294 240 KSQIAVANSI-----LEKDpepastlnPQVPRGVDHVIARCLAKDPEQR 283
cd05044     218 LNNQEVLQHVttggrLQSP--------ENCPDKLYNLMTNCWAKDPSER 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133180

cd05049

PTKc_Trk

Catalytic Domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases

false

true

false

280

4e-15

79.03

91.79

10,20,11,21,41,37,8,51,45,55,106,115,40,146,156,19,165,178,9,200,187,32,232,220,17,249,241,6,262,247,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKDLRLDRS-----VAIKVLPGhlSSNPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEF 95
cd05049      12 ELGEGAFGKVFLGECYHLEPEndkelVAVKTLKE--TASNDARKDFEREAELLTNFQHENIVKFYGVCTEGDPPIMVFEY 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  96 LEGESLAQRLQ---------------KGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIML-TKTGAKLMDFGLA 159
cd05049      90 MEHGDLNKFLRshgpdaaflkspdspMGELTLSQLLQIAVQIASGMVYLASQHFVHRDLATRNCLVgYDLVVKIGDFGMS 169

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 160 KAVEST---MAAGTSSAPllsgaptmsglsplspltmagavvgtVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKR 235
cd05049     170 RDVYTTdyyRVGGHTMLP--------------------------IRWMPPESIMYRKFTTESDVWSFGVVLWEIFTyGKQ 223

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 94967294 236 AFDGKSQIAVANSI----LEKDPEpastlnpQVPRGVDHVIARCLAKDPEQR 283
cd05049     224 PWYGLSNEEVIECItqgrLLQRPR-------TCPSEVYDIMLGCWKRDPQQR 268

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

4e-15

79.02

91.80

11,20,10,14,35,24,12,47,37,5,57,42,46,103,90,48,151,139,11,162,153,11,200,164,32,232,197,19,251,218,6,262,224,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKdLRLDRSVAIKVL-PGHLSsnpelKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGE 99
cd05059      11 ELGSGQFGVVRLGK-WRGKIDVAIKMIrEGAMS-----EDDFIEEAKVMMKLSHPNLVQLYGVCTKQRPIFIVTEYMANG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 100 SLAQ--RLQKGALPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLTKTGA-KLMDFGLAKAV---ESTMAAGTSSA 173
cd05059      85 CLLNflRQRRGKFGTEWLLDMCSDVCEAMEYLESNSFIHRDLAARNCLVGEDNVvKVSDFGLARYVlddQYTSSQGTKFP 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 174 pllsgaptmsglsplspltmagavvgtVQYMAPEQVEGKLADARSDIFALGATLYEAAT-GKRAFDGKSQIAVANSILE- 251
cd05059     165 ---------------------------VKWAPPEVFNYSRFSSKSDVWSFGVLMWEVFSeGKMPYERFTNSEVVESVHRg 217

                       250       260       270
                ....*....|....*....|....*....|...
gi 94967294 252 -KDPEPAstlnpQVPRGVDHVIARCLAKDPEQR 283
cd05059     218 yRLYRPK-----LASTEVYTIMCDCWQEKPEDR 245

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

5e-15

78.43

94.84

12,20,1,14,35,15,6,41,22,11,54,33,52,106,86,3,109,90,38,147,129,23,182,152,7,200,159,30,230,190,7,242,197,20,262,219,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294  21 QLGAGGMGEVYRAKdLRLDRS-VAIKVLPGHLSsnPELKERFVREARAISSLNHPRICTLHDVGQQEGVDFLVMEFLEGE 99
cd05084       2 RIGRGNFGEVFSGR-LRADNTpVAVKSCRETLP--PELKAKFLMEARILKQYSHPNIVKLIGVCTQKQPIYIVMELVQGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967294 100 SLAQRLQ-KGA-LPIKEVLKIGVEVSEALEVAHRAGIVHRDLKPGNIMLT-KTGAKLMDFGLAKAVESTMAAGTssapll 176