NCBI Conserved Domain Search

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Conserved domains on [gi\|94968483\|ref\|YP_590531.1\|]
serine/threonine protein kinase [Candidatus Koribacter versatilis Ellin345]

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List of domain hits		?

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

29142

cd00180

S_TKc

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

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

true

256

2e-48

189.65

98.83

6,12,0,42,55,42,51,106,94,56,183,150,69,253,219,26,280,245,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  13 HYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQaLSRFQREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQ-VERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENvagsqtaia 171
cd00180      80 YMSGGDLFDLLKKRgRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLD--------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 santmtaagvqeQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTP 251
cd00180     151 ------------SGGRKLTTFVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGKGTP 218

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94968483 252 MvRMNPDVPPELERIVSKALEKDRNLRYqSANDMRAD 288
cd00180     219 D-ELPPNISPEAKDLIKKLLVKDPEKRP-TAEELLQH 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132935

cd05122

PKc_STE

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

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

false

true

false

253

6e-36

148.07

95.26

7,13,1,43,59,44,46,105,91,55,165,146,12,193,158,39,235,197,13,248,212,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALsrfQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEEQEQI---LNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagSQTAIAS 172
cd05122      79 CDGGSLDDLLKStGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSAQ-----LSDTKAK 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 173 ANTMTaagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFrggSTAEVFKAILDTA--PT 250
cd05122     154 RNTFV----------------GTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPY---SELNPMKALFKIAtnPP 214

                       250       260
                ....*....|....*....|....*...
gi 94968483 251 PMVRMNPDVPPELERIVSKALEKDRNLR 278
cd05122     215 PGLPSPEKWSPEFRDFLKKCLQKDPEKR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

9e-33

137.29

94.98

9,13,1,32,47,33,11,58,45,19,77,66,10,88,76,17,105,94,57,181,151,52,233,205,20,256,225,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARDSQALSR-FQREAQAASALNHPNICTI--HDIGEENGRAfIA 90
cd06606       2 WTRGKLLGRGSFGSVYLALSKDTGELVAVKSV--ELSSDSEEELEsLEREIRILSKLQHPNIVRYygCEVTEENTLN-IF 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  91 MEFLDGLTLKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENvagsqta 169
cd06606      79 MEYVSGGSLASLLKKfGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRLA------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 iasantmtaagvQEQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFR--GGSTAEVFKAILDT 247
cd06606     152 ------------SIAYSGGLKSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSelGNPMALLYKIGSSG 219

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968483 248 APTPMVrmnPDVPPELERIVSKALEKDRNLR 278
cd06606     220 EPPEIP---EDLSEEAKDFLRKCLRRDPKKR 247

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

3e-31

132.22

93.91

5,13,2,57,70,60,36,106,97,79,186,176,64,254,240,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALN-HPNICTIHDIGEENGRAFIAME 92
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLDKRHLIKEKKVKYVKREKEVLTRLNgHPGIVKLYYTFQDEENLYFVLE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTAIA 171
cd05581      83 YAENGELLEYIKKFgSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVLDPNSSPESNK 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 SANTMTAAGVQEQHlTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTp 251
cd05581     163 GKATNIDSQIEKNR-RRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYE- 240

                       250       260
                ....*....|....*....|....*..
gi 94968483 252 mvrMNPDVPPELERIVSKALEKDRNLR 278
cd05581     241 ---FPPNFPPDAKDLIEKLLVLDPQDR 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

STKc_AGC: Serine/Threonine Kinases (STKs), AGC (Protein Kinases A, G and C) family, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AGC family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase (PI3K). Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases.

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

false

true

false

250

2e-30

129.83

98.40

5,19,0,85,104,86,64,189,150,59,252,209,26,278,237,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 KHTIE-ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTaiasantmta 178
cd05123      81 FTHLSkEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAKEGIDDGVRT---------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 179 agvqeqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAptpmVRMNPD 258
cd05123     151 -----------TTFCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDK----LRFPEF 215

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968483 259 VPPELERIVSKALEKDRNLR--YQSANDMRA 287
cd05123     216 LSEEAKDLIKKLLTKDPTKRlgSGGAEEIKA 246

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

1e-29

126.94

93.56

11,11,0,33,44,35,12,60,47,39,99,92,28,131,120,29,160,150,2,170,152,8,192,160,40,232,203,17,256,220,4,260,229,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKF--LPDELARDSQALsrfqREAQAASALNHPNICTIHDIGEENGRAFI 89
cd06623       1 SDLERVKVLGQGSSGVVYKVRHKPTGKIYALKKihVDGDEEFRKQLL----RELKTLRSCESPYVVKCYGAFYKEGEISI 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  90 AMEFLDGLTL------KHTIEERSMEMDRILALAIEIADALDAAhaagIVHRDIKPANIFVTKRGHAKVLDFGLAKV-EN 162
cd06623      77 VLEYMDGGSLadllkkVGKIPEPVLAYIARQILKGLDYLHTKRH----IIHRDIKPSNLLINSKGEVKIADFGISKVlEN 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 163 vagsqtaiASANTMTAagvqeqhltspgstLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF---RGGSTAE 239
cd06623     153 --------TLDQCNTF--------------VGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFlppGQPSFFE 210

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94968483 240 VFKAILDTAPtpmvrmnPDVP-----PELERIVSKALEKDRNLR 278
cd06623     211 LMQAICDGPP-------PSLPaeefsPEFRDFISACLQKDPKKR 247

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

3e-28

122.29

88.57

5,11,0,119,130,122,35,165,160,25,190,189,60,252,249,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd05574       1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAA---GIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAG--- 165
cd05574      81 DYCPGGELFRLLQRQPGKCFPEEVARFYAAEVLLALEYLhllGIVYRDLKPENILLHEDGHIMLSDFDLSKQSDVEPtpv 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 166 SQTAIASANTMTAAGVQEQHLTSPG----STLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVF 241
cd05574     161 SKALRKGSRGSVNKITTETFSEEPSfrsnSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETF 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94968483 242 KAILDTAPTpmVRMNPDVPPELERIVSKALEKDRNLRYQSA 282
cd05574     241 SNILKKEVT--FPGSPPVSSSARDLIRKLLVKDPSKRLGSK 279

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132958

cd06627

STKc_Cdc7_like

Serine/threonine kinases (STKs), cell division control protein 7 (Cdc7)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane.

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

false

true

false

254

3e-24

109.26

95.28

9,12,0,33,47,33,5,52,39,52,104,93,25,130,118,28,165,146,14,193,160,51,244,213,7,256,220,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  13 HYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARD-SQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQI--SLEKIkEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTLKHTIE--ERSMEMDRILALAIEIADALDAAHAaGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagSQTA 169
cd06627      79 EYAENGSLRQIIKkfGKFPESLVAVYVYQVLQGLAYLHEQ-GVIHRDIKAANILTTKDGVVKLADFGVA-------TKLS 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 IASANTMTAAgvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAI--LDT 247
cd06627     151 DVSKDDESVV--------------GTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIvqDDH 216

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968483 248 APTPmvrmnPDVPPELERIVSKALEKDRNLR 278
cd06627     217 PPLP-----EGISPELKDFLMQCFQKDPNLR 242

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

3e-23

105.50

75.38

7,19,7,27,48,34,3,51,38,54,105,93,55,169,148,13,190,161,22,212,186,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPdeLAR-DSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd06626       8 IGGGTFGKVYTAVNLDTGELMAVKEIR--IQDnDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCSGGT 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagsqtaIASANTMT 177
cd06626      86 LEELLEHgRILDEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAVK---------LKNNTTTM 156

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 94968483 178 AAGVQeqhltspgSTLGTIAYMSPEQARAKDLDAR---TDLFSFGAVLYEMATGTLPF 232
cd06626     157 GEEVQ--------SLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPW 206

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

4e-23

105.32

94.57

5,12,0,88,100,89,58,168,147,10,190,157,43,234,200,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  13 HYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd05578       1 HFEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagsqtAIA 171
cd05578      81 LLLGGDLRyHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIA----------TKL 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 SANTMTAagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRgGSTAEVFKAILDTAPTP 251
cd05578     151 TPDTLAT------------STSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYR-GHSRTPREEILAKFETA 217

                       250       260
                ....*....|....*....|....*..
gi 94968483 252 MVRMNPDVPPELERIVSKALEKDRNLR 278
cd05578     218 DVLYPAGWSSEAIDAINKLLERDPQKR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88474

cd05573

STKc_ROCK_NDR_like

STKc_ROCK_NDR_like: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) and Nuclear Dbf2-Related (NDR)-like kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK- and NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis.

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

false

true

false

354

2e-22

103.01

80.23

7,13,2,32,45,36,22,69,58,27,96,91,9,110,100,49,159,159,112,272,271,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFL--PDELARDSQALSRFQREAQAASalNHPNICTIHDIGEENGRAFIAM 91
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILrkSDMLKRNQVAHVRAERDILADA--DSPWIVKLYYSFQDEEYLYLVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDG------LTLKHTIEErsmemDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK------ 159
cd05573      81 EYMPGgdlmtlLIKYDVFPE-----ETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCKkmkkag 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 160 ----VENVAGSQTAIASANTMTAAGVQEQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGG 235
cd05573     156 dseyYLNDSHNLLDSDRDNVLKRRRPKKQRRVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSD 235

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 94968483 236 STAEVFKAILDTAPTPMVRMNPDVPPELERIVSKALeKDRNLRYQSANDMRA 287
cd05573     236 TLQETYNKIMNWKESLYFPADVKVSPEAIDLIRRLL-CDPEDRLGSFEEIKS 286

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

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

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

false

true

false

265

4e-22

102.01

90.57

11,19,8,12,35,20,3,38,27,8,48,35,60,108,98,48,162,146,6,173,152,8,193,160,41,234,206,15,256,221,4,260,230,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAedtrLHR----FVALKFLPdeLARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLD 95
cd06605       9 LGAGNSGVVSKV----RHRptgkIMAVKTIR--LEINEAIQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICMEYMD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 GLTLKHTIEERSM---EMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGSQTaias 172
cd06605      83 GGSLDKILKEVQGripERILGKIAVAVLKGLTYLHEKHKIIHRDVKPSNILVNSRGEIKLCDFG------VSGQLV---- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 173 aNTMTAAGVqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRG-----GSTAEVFKAILDT 247
cd06605     153 -NSLAKTFV------------GTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPendppDGIFELLQYIVNE 219

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94968483 248 APtpmvrmnPDVP-----PELERIVSKALEKDRNLR 278
cd06605     220 PP-------PRLPsgrfsPDFQDFVNLCLIKDPRER 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs.

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

false

true

false

287

5e-22

101.52

85.02

8,11,18,35,49,53,81,130,136,38,173,174,3,192,177,53,246,230,8,255,238,3,258,242,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPdelARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd06614      19 ELYDNLEKIGEGASGEVYTATDRATGKEVAIKKMR---LRKQPKKELIINEILIMKECKHPNIVNYYDSYLVGDELWVVM 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAA--GIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTa 169
cd06614      96 EYMDGGSLTDIITQTFVRMNESQIAYVCREVLQGLEYLHsqNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSKR- 174

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 iasaNTMtaagvqeqhltspgstLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdTAP 249
cd06614     175 ----NSM----------------VGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLIT-TKG 233

                       250       260       270
                ....*....|....*....|....*....|
gi 94968483 250 TPMVRmNPD-VPPELERIVSKALEKDRNLR 278
cd06614     234 IPPLK-NPEkWSPEFKDFLNKCLVKDPEKR 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

3e-20

95.80

75.85

7,19,2,46,65,49,34,99,84,60,160,144,8,174,152,9,197,161,51,252,212,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQA-ASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05575       3 IGKGSFGKVLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVlLKNVKHPFLVGLHYSFQTKEKLYFVLDYVNGGE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 L-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTaiasanTMT 177
cd05575      83 LfFHLQRERSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCK-EGIAGSKT------TST 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 178 AAGVQEqhltspgstlgtiaYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAptpmVRMNP 257
cd05575     156 FCGTPE--------------YLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNKP----LRLRP 217

                       250       260       270
                ....*....|....*....|....*....|
gi 94968483 258 DVPPELERIVSKALEKDRNLRYQSANDMRA 287
cd05575     218 NISVSARHLLEGLLQKDRTKRLGAKNDFLE 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

STKc_MAST_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The MAST kinase subfamily includes MAST kinases, MAST-like (MASTL) kinases, and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which also contains an insert relative to MAST kinases like MASTL. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively.

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

false

true

false

265

4e-20

95.26

92.45

7,19,0,60,79,62,5,86,67,18,104,86,56,164,142,18,191,160,62,255,222,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHD--IGEENgrAFIAMEFLDGL 97
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYsfQGKKN--LYLVMEYLPGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  98 TLKHTIE-ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvaGSQTAIASANTM 176
cd05579      79 DLASLLEnVGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKV----GLVRRQINLNDD 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 TAAGVQeqhltspgsTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTPMVrmN 256
cd05579     155 EKEDKR---------IVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEWPE--D 223

                       250       260
                ....*....|....*....|..
gi 94968483 257 PDVPPELERIVSKALEKDRNLR 278
cd05579     224 VEVSDEAKDLISKLLVPDPEKR 245

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

5e-20

94.99

77.53

7,19,2,29,48,33,18,67,51,38,105,90,54,160,144,9,189,153,67,260,220,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDE--LARDSQALSRFQREAQAAsALNHPNICTIHDIGEENGRAFIAMEFLDGL 97
cd05592       3 LGKGSFGKVMLAELKGTNEYYAIKALKKDvvLEDDDVECTMVERRVLIL-AWEHPFLTHLFCTFQTKEHLFFVMEYLNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  98 TLKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTAiasantm 176
cd05592      82 DLMFHIQSsGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCK-ENINGEGKA------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 taagvqeqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTPMVRMN 256
cd05592     154 -------------STFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILNDRPHFPRWIS 220

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968483 257 pdvpPELERIVSKALEKDRNLRYQSANDMRA 287
cd05592     221 ----KEAKDCLSKLFEREPTKRLGMDGDIRQ 247

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

9e-20

94.25

93.75

8,13,4,35,50,39,6,59,45,45,104,92,52,162,144,6,168,151,8,192,159,52,245,211,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDElaRDSQALsrfQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd06612       5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVE--EDLQEI---IKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTIE--ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGSQT-AI 170
cd06612      80 CGAGSVSDIMKitNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFG------VSGQLTdTM 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 171 ASANTMtaagvqeqhltspgstLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIlDTAPT 250
cd06612     154 AKRNTV----------------IGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMI-PNKPP 216

                       250       260
                ....*....|....*....|....*...
gi 94968483 251 PMVRMNPDVPPELERIVSKALEKDRNLR 278
cd06612     217 PTLSDPEKWSPEFNDFVKKCLVKDPEER 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

STKc_cGK_PKG: Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or PKG) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm.

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

false

true

false

262

2e-19

93.33

79.39

5,19,0,87,106,88,53,159,142,11,193,153,45,238,200,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGEL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 KHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK-VENVAGSQTAIasantmt 177
cd05572      81 WTILRDRgLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKkLKSGQKTYTFC------- 153

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94968483 178 aagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTA--EVFKAILD 246
cd05572     154 ----------------GTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGEDDEDpmKIYNLILK 208

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132940

cd06609

STKc_MST3_like

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

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

false

true

false

274

2e-19

93.06

71.17

5,13,2,32,47,34,109,162,143,10,172,154,5,193,159,38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd06609       3 FTLLECIGKGSFGEVYKAIDKRTNQVVAIKVI--DLEEAEDEIEDIQQEIQFLSQCRSPYITKYYGSFLKGSKLWIIMEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGSQTAIAS- 172
cd06609      81 CGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFG------VSGQLTSTMSk 154

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 94968483 173 ANTMTaagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLP 231
cd06609     155 RNTFV----------------GTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPP 197

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-19

92.67

63.36

5,11,0,85,96,91,29,130,120,29,167,149,7,190,156,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd05600       1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDG------LTLKHTIEERSMEMDRILALAIEIADALDaahaaGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvag 165
cd05600      81 EYVPGgdfrtlLNNLGVLSEDHARFYMAEMFEAVDALHEL-----GYIHRDLKPENFLIDASGHIKLTDFGLSK------ 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 166 sqTAIASANtmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd05600     150 --GIVTYAN----------------SVVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETWENLK 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

3e-19

92.50

79.06

7,11,0,34,47,34,24,71,61,87,170,148,6,186,154,7,193,162,12,205,175,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARDSQALSRFQREAQAASALNH---PNICTIHDIGEENGRAF 88
cd06917       1 SLYQRLELIGRGAYGAVYRGKHVPTGRVVALKII--NLDTPDDDVSDIQREVALLSQLRQsqpPNITKYYGSYLKGPRLW 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  89 IAMEFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagsqt 168
cd06917      79 IIMEYAEGGSVRTLMKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA---------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 169 aiASANTMtaagvqeqhlTSPGSTL-GTIAYMSPEQAR-AKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILD 246
cd06917     149 --ALLNQN----------SSKRSTFvGTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIPK 216


                ...
gi 94968483 247 TAP 249
cd06917     217 SKP 219

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

7e-19

91.18

78.02

7,19,3,18,37,24,10,47,35,83,130,119,39,190,158,42,236,200,48,287,248,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLH---RFVALKFLPD-ELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLD 95
cd05584       4 LGKGGYGKVFQVRKVTGAdtgKIFAMKVLKKaTIVRNQKDTAHTKAERNILEAVKHPFIVDLIYAFQTGGKLYLILEYLS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 GLTLKHTIEERSMEMDRILALAIEIADALDAAHAA-GIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTAiasan 174
cd05584      84 GGELFMHLEREGIFMEDTACFYLSEISLALEHLHQqGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHEGTVTH----- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 175 tmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFrggsTAEVFKAILDTAPTPMVR 254
cd05584     159 ----------------TFCGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPF----TAENRKKTIDKILKGKLN 218

                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 94968483 255 MNPDVPPELERIVSKALEKDRNLRYQSANDmraDLARLKR 294
cd05584     219 LPPYLTPEARDLLKKLLKRNPSSRLGAGPG---DAAEVQS 255

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

1e-18

90.84

93.98

9,11,0,34,47,34,49,96,87,61,171,148,16,191,164,11,202,178,9,213,187,36,250,223,11,261,237,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd06610       1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIKRI--DLEKCQTSMDELRKEIQAMSLCHHPNVVKYYTSFVVGDELWVVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDG----LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLakvenvagsq 167
cd06610      79 PLMSGgsclDIMKYSYPQGGLDEAIIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGV---------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 168 taiaSANTMTAAGVQEQHLTspgsTLGTIAYMSPE---QARAKDLDArtDLFSFGAVLYEMATGTLPFRGGSTAEVFKAI 244
cd06610     149 ----SASLADGGDRTKVRKT----FVGTPCWMAPEvmeQVHGYDFKA--DIWSFGITAIELATGAAPYSKYPPMKVLMLT 218

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968483 245 LDTAPtPMVRMNPDVPP---ELERIVSKALEKD 274
cd06610     219 LQNDP-PSLETEADYKKyskSFRKMISKCLQKD 250

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-18

89.81

85.86

6,13,2,86,99,89,61,162,150,3,173,153,4,191,157,57,252,214,37

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd05580       3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVMEF 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTL-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenVAGsqtaias 172
cd05580      83 VPGGELfSLLRRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAKR--VKG------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 173 aNTMTaagvqeqhltspgsTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAptpm 252
cd05580     154 -RTYT--------------LCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKIYEKILSGK---- 214

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94968483 253 VRMNPDVPPELERIVSKALEKDRNLRYQSANDMRADL 289
cd05580     215 VRFPSFFSSDAKDLLRNLLQVDLTKRLGNLKNGVNDI 251

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

8e-18

87.73

76.63

10,11,2,37,51,39,23,76,62,7,83,71,17,100,94,6,111,100,45,162,145,7,169,153,7,192,160,12,204,175,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDElarDSQALSRFQREAQAASALNHPNIctIHDIGEE--NGRAFI 89
cd06613       3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLE---PGDDFEIIQQEISMLKECRHPNI--VAYFGSYlrRDKLWI 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  90 AMEFLDGLTLK------HTIEERsmemdRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenV 163
cd06613      78 VMEYCGGGSLQdiyqvtGPLSEL-----QIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFG------V 146

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94968483 164 AGSQTA-IASANTMtaagvqeqhltspgstLGTIAYMSPEQA---RAKDLDARTDLFSFGAVLYEMATGTLP 231
cd06613     147 SAQLTAtIAKRKSF----------------IGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPP 202

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

8e-18

87.81

85.47

12,8,11,38,48,49,19,68,68,3,71,73,22,93,99,5,98,106,8,110,114,49,159,165,10,193,175,16,209,195,29,238,225,11,250,236,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483   9 TTVSHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPdeLARDSQALSRFQREAQAASaLNH--PNICTIHDIGEENGR 86
cd06618      12 ADLNDLENLGEIGSGTCGQVYKMRFKKTGHVMAVKQMR--RTGNKEENKRILMDLDVVL-KSHdcPYIVKCYGYFITDSD 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  87 AFIAMEF----LDGLT--LKHTIEERsmemDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK- 159
cd06618      89 VFICMELmstcLDKLLkrIQGPIPED----ILGKMTVAIVKALHYLKEKHGVIHRDVKPSNILLDASGNVKLCDFGISGr 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 160 -VENVAGSQTAiasantmtaagvqeqhltspgstlGTIAYMSPEQARAKDL----DARTDLFSFGAVLYEMATGTLPFRG 234
cd06618     165 lVDSKAKTRSA------------------------GCAAYMAPERIDPPDPnpkyDIRADVWSLGISLVELATGQFPYKN 220

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 94968483 235 GSTA-EVFKAILDTAPtPMVRMNPDVPPELERIVSKALEKDRNLR 278
cd06618     221 CKTEfEVLTKILQEEP-PSLPPNEGFSPDFCSFVDLCLTKDHRKR 264

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

4e-17

85.55

93.41

9,17,5,29,46,36,53,100,89,6,106,97,54,180,151,8,190,159,19,209,179,23,235,202,23,258,226,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  18 ERLGGGGMGVVYKAEDTRLHRFVALKFLP--DELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLD 95
cd06632       6 ELLGSGSFGSVYEGLNLDDGDFFAVKEVSlaDDGQTGQEAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 GLTLkHTIEER--SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagsqtaiasa 173
cd06632      86 GGSL-AKLLKKygSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAKQ------------- 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 174 ntmtaagVQEQHLTSpgSTLGTIAYMSPEQARAKDL-DARTDLFSFGAVLYEMATGTLPFrggSTAEVFKAILDTAPTPM 252
cd06632     152 -------VVEFSFAK--SFKGSPYWMAPEVIAQQGGyGLAADIWSLGCTVLEMATGKPPW---SQLEGVAAVFKIGRSKE 219

                       250       260
                ....*....|....*....|....*..
gi 94968483 253 VRMNPD-VPPELERIVSKALEKDRNLR 278
cd06632     220 LPPIPDhLSDEAKDFILKCLQRDPSLR 246

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

5e-17

85.29

87.63

6,11,0,88,99,89,60,159,150,3,173,153,10,197,163,62,263,225,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd05612       1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTL-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK-VENvagsqta 169
cd05612      81 EYVPGGELfSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAKkVRD------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 iasaNTMTAAGVQEqhltspgstlgtiaYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAP 249
cd05612     154 ----RTWTLCGTPE--------------YLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKL 215

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94968483 250 TPMVRMNPDVppelERIVSKALEKDRNLRYQSANDMRADLARLK 293
cd05612     216 EFPRHFDLRA----KDLIKKLLVVDRTRRLGNMKNGADDVKNHK 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

5e-17

85.26

95.79

10,17,0,19,36,22,13,51,35,49,100,93,59,161,152,15,187,167,2,195,169,32,227,202,20,252,222,4,256,228,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  18 ERLGGGGMGVVYKAEDTRL---HRFVALKFLPDELarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFL 94
cd00192       1 KKLGEGAFGEVYKGELKGKggkKTPVAVKTLKEDA--SDSEREDFLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLK---------HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKveNVAG 165
cd00192      79 EGGDLLdflrksrpvFSPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSR--DIYD 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 166 SQTAIASANTMtaagvqeqhltSPgstlgtIAYMSPEQARAKDLDARTDLFSFGAVLYEMAT-GTLPFRGGSTAEVFKAI 244
cd00192     157 DDYYRKKGGGK-----------LP------IRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEVLEYL 219

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94968483 245 LDTaptpmVRMN--PDVPPELERIVSKALEKDRNLR 278
cd00192     220 RKG-----YRLPkpENCPDELYELMLSCWQEDPEDR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88505

cd05604

STKc_SGK3

STKc_SGK3: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK3 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). SGK3 is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling.

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

false

true

false

325

5e-17

85.09

74.46

7,19,2,47,66,50,34,100,85,59,167,144,10,190,154,56,249,210,4,254,214,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAA-SALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05604       3 IGKGSFGKVLLAKRKLDGKCYAVKVLQKKIVLNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTEKLYFVLDFVNGGE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqTAIASANTMT 177
cd05604      83 LFfHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCK--------EGIAQSDTTT 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 178 aagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDtapTPMVrMNP 257
cd05604     155 -------------TFCGTPEYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYGLPPFYCRDVAEMYDNILH---KPLV-LRP 217

                       250       260
                ....*....|....*....|....*..
gi 94968483 258 DVPPELERIVSKALEKDRNLRYQSAND 284
cd05604     218 GASLTAWSILEELLEKDRQRRLGAKED 244

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

2e-16

83.39

74.69

4,13,0,33,46,35,7,53,43,115,189,158,84

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLP--DELARDS-QALSRFQREAQAASALNHPNICTIHDIGEENGRAFIA 90
cd05589       1 FRCLAVLGRGHFGKVLLAEYKKTGELYAIKALKkgDIIARDEvESLMCEKRIFETANSERHPFLVNLFACFQTEDHVCFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  91 MEFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTai 170
cd05589      81 MEYAAGGDLMMHIHTDVFSEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGFGDRT-- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 171 asantmtaagvqeqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPT 250
cd05589     159 -------------------STFCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVR 219

                       250       260
                ....*....|....*....|...
gi 94968483 251 PMVRMNPDVPPELERIVSKALEK 273
cd05589     220 YPRFLSREAISIMRRLLRRNPER 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

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

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

false

true

false

318

2e-16

82.98

65.41

6,19,2,46,65,49,35,100,85,59,160,144,9,190,153,3,193,157,53

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQA-ASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05570       3 LGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDDDVECTMTEKRVlALAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTAiasantmt 177
cd05570      83 LMyHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK-EGILGGVTT-------- 153

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 178 aagvqeqhltspgSTL-GTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILD 246
cd05570     154 -------------STFcGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILE 210

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88503

cd05602

STKc_SGK1

STKc_SGK1: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK1 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three isoforms of SGK, named SGK1, SGK2, and SGK3. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia.

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

false

true

false

325

2e-16

82.80

74.46

7,19,2,26,51,28,19,70,54,29,99,84,60,160,144,3,183,147,65,252,212,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLpdelarDSQALSRFQREAQAASALN-------HPNICTIHDIGEENGRAFIAME 92
cd05602       3 IGKGSFGKVLLARHKSDEKFYAVKVL------QKKAILKKKEEKHIMSERNvllknvkHPFLVGLHFSFQTTDKLYFVLD 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTL-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVagsqtaia 171
cd05602      77 YINGGELfYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK-ENI-------- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 santmtaagvqeQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAptp 251
cd05602     148 ------------EPNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKP--- 212

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968483 252 mVRMNPDVPPELERIVSKALEKDRNLRYQSAND 284
cd05602     213 -LQLKPNITNSARHLLEGLLQKDRTKRLGAKDD 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132953

cd06622

PKc_MAPKK_PBS2_like

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, fungal PBS2-like proteins, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1.

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

false

true

false

286

5e-16

81.82

87.06

9,15,4,34,51,38,45,96,88,60,162,148,7,169,156,5,192,161,20,212,187,29,241,219,9,253,228,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  16 IVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLD 95
cd06622       5 VLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLEL--DESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 G-----LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGSQTA- 169
cd06622      83 AgsldkLYAGGVATEGIPEDVLRRITYAVVKGLKFLKEEHNIIHRDVKPTNVLVNGNGQVKLCDFG------VSGNLVAs 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 IASANtmtaagvqeqhltspgstLGTIAYMSPEQARAKDLDAR------TDLFSFGAVLYEMATGTLPFRGGSTAEVF-- 241
cd06622     157 LAKTN------------------IGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYANIFaq 218

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94968483 242 -KAILDTAPTpmvRMNPDVPPELERIVSKALEKDRNLR 278
cd06622     219 lSAIVDGDPP---TLPSGYSDDAQDFVAKCLNKIPNRR 253

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

6e-16

81.71

72.08

9,14,4,4,19,8,30,49,40,7,60,47,45,105,94,51,162,145,3,166,148,8,190,156,50,241,206,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  15 RIVErLGGGGMGVVYKAEDTRLHRFVALKFLPDEL--ARDSQALsrfqREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd06615       5 KLGE-LGAGNGGVVTKVLHRPSGLIMARKLIHLEIkpAIRNQII----RELKVLHECNSPYIVGFYGAFYSDGEISICME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEE--RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGsQTAI 170
cd06615      80 HMDGGSLDQVLKKagRIPENILGKISIAVLRGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFG------VSG-QLID 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 171 ASANtmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVfKAILDTAPT 250
cd06615     153 SMAN----------------SFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKEL-EAMFGRPVS 215

                       250
                ....*....|.
gi 94968483 251 PMVRMNPDVPP 261
cd06615     216 EGEAKESHRPV 226

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88520

cd05619

STKc_nPKC_theta

STKc_nPKC_theta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), theta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases.

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

false

true

false

316

6e-16

81.58

69.30

9,19,2,29,48,33,18,67,51,38,105,90,54,160,144,6,170,150,7,193,157,51,253,208,2,255,211,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDE--LARDSQALSRFQREAQAAsALNHPNICTIHDIGEENGRAFIAMEFLDGL 97
cd05619       3 LGKGSFGKVFLAELKGTNQFFAIKALKKDvvLMDDDVECTMVEKRVLSL-AWEHPFLTHLYCTFQTKENLFFVMEYLNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  98 TLKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSqtaiASANTM 176
cd05619      82 DLMFHIQScHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCK-ENMLGD----AKTCTF 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 TaagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIldtaptpmvRM- 255
cd05619     157 C----------------GTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEELFQSI---------RMd 211

                       250
                ....*....|
gi 94968483 256 NPDVPPELER 265
cd05619     212 NPCYPRWLTR 221

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

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

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

false

true

false

268

1e-15

80.29

93.28

9,17,5,26,43,34,63,106,98,43,149,142,7,167,149,16,189,165,55,244,222,7,256,229,4,260,237,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  18 ERLGGGGMGVVYKAEDTRLHRFVALK---FLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFL 94
cd06630       6 QQLGTGAFSSCYQARDVKTGTLMAVKqvtYVRNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWM 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGH-AKVLDFGlakvenvagsqTAIAS 172
cd06630      86 AGGSVSHLLSKYgAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFG-----------AAARL 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 173 ANTMTAAGVQEqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAI--LDTAPT 250
cd06630     155 AAKGTGAGEFQ------GQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHSNHLALIfkIASATT 228

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968483 251 PmvrmnPDVP----PELERIVSKALEKDRNLR 278
cd06630     229 A-----PSIPehlsPGLRDVTLRCLELQPEDR 255

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-15

80.39

52.83

4,57,43,51,108,95,51,160,146,10,190,156,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  58 RFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTLKHTIEERSM-EMDRILALAIEIADALDAAHAAGIVHRD 136
cd05582      44 RTKMERDILAEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMfTEEDVKFYLAELALALDHLHSLGIIYRD 123

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 137 IKPANIFVTKRGHAKVLDFGLAKvENVAGSQTAIasantmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLF 216
cd05582     124 LKPENILLDEEGHIKLTDFGLSK-ESIDHEKKAY--------------------SFCGTVEYMAPEVVNRRGHTQSADWW 182

                       170       180
                ....*....|....*....|....*....
gi 94968483 217 SFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd05582     183 SFGVLMFEMLTGSLPFQGKDRKETMTMIL 211

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

2e-15

79.78

68.99

10,16,5,29,48,34,10,58,45,21,79,68,23,102,94,29,131,125,25,162,150,4,168,154,4,172,159,5,193,164,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLpdeLARDSQALSR-FQREAQAASALNHPNICTIHD--IGEENGRAFIAMEF 93
cd06621       6 LSRLGEGAGGSVTKCRLKNTGMIFALKTI---TTDPNPDLQKqILRELEINKSCKSPYIVKYYGafLDESSSSIGIAMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHT---IEERSMEMDRILALAIEIADALDAAHAAG--IVHRDIKPANIFVTKRGHAKVLDFGlakvenVAGSqt 168
cd06621      83 CEGGSLDSIykkVKKRGGRIGEKVLGKIAESVLKGLSYLHSrkIIHRDIKPSNILLTRKGQVKLCDFG------VSGE-- 154

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94968483 169 AIAS-ANTMTaagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF 232
cd06621     155 LVNSlAGTFT----------------GTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPF 203

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-15

79.85

94.40

12,14,12,3,19,15,37,59,52,71,130,127,14,144,142,15,168,157,10,190,167,12,202,181,31,233,214,9,249,223,14,263,241,15,279,256,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  15 RIVerLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALsrfQREAQAASALNHPNICTIHDIGEENGRAFIAMEFL 94
cd06624      13 RVV--LGKGTYGVVYAGRDLSTQVRIAIKEIPERDSRYSQPL---HEEIALHSRLKHKNIVQYLGSDSENGYFKIFMEQV 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLKHTIEERSMEMDRILALAIEIADALDAAHAA----GIVHRDIKPANIFV-TKRGHAKVLDFGLAKvenvagsqtA 169
cd06624      88 PGGSLSALLRSKWGPLKDNESTIIFYTKQILEGLKYlhdnQIVHRDIKGDNVLVnTYSGVLKISDFGTSK---------R 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 IASANTMTAagvqeqhltspgSTLGTIAYMSPE--QARAKDLDARTDLFSFGAVLYEMATGTLPFR--GGSTAEVFKail 245
cd06624     159 LAGINPCTE------------TFTGTLQYMAPEiiDKGPRGYGAPADIWSLGCTIIEMATGKPPFHelGEPQAAMFK--- 223

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 94968483 246 dtapTPMVRMNPDVPPEL----ERIVSKALEKDRNLRyQSANDMRAD 288
cd06624     224 ----VGMFKIHPEIPESLsaeaKAFILRCFEPDPDKR-ASAHDLLQD 265

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

4e-15

78.82

89.62

4,22,6,24,46,31,61,107,93,56,188,149,90

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  23 GGMGVVYKAEDTRLHRFVALKFLP-DELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTLKH 101
cd05611       7 GAFGSVYLAKKRSTGDYFAIKVLKkSDMIAKNQVTNVKAERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLNGGDCAS 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 102 TIEERS-MEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVagsqtaiasantmtaag 180
cd05611      87 LIKTLGgLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLE----------------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 181 vqeqhltsPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTPMVRMNPDVP 260
cd05611     150 --------NKKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCS 221

                       250
                ....*....|....*...
gi 94968483 261 PELERIVSKALEKDRNLR 278
cd05611     222 PEAVDLINRLLCMDPAKR 239

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

4e-15

78.69

88.03

11,14,7,31,47,38,59,106,100,24,131,124,26,165,150,7,172,158,4,192,162,40,232,205,11,243,217,3,246,226,10,257,236,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  15 RIVERLGGGGMGVVYKAEDTRLHRFVALKFLpdELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFL 94
cd06620       8 ETISDLGAGNGGSVSKVKHIPTGTVMAKKVV--HIGAKSSVRKQILRELQIMHECRSPYIVSFYGAFLNENNICMCMEFM 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLKHTIEER---SMEMDRILALAIEIADALDAAHAAgIVHRDIKPANIFVTKRGHAKVLDFGLakvenvagSQTAIA 171
cd06620      86 DCGSLDRIYKKGgpiPVEILGKIAVAVVEGLTYLYNVHR-IMHRDIKPSNILVNSRGQIKLCDFGV--------SGELIN 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 S-ANTMtaagvqeqhltspgstLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF---RGGSTAEVFKA-ILD 246
cd06620     157 SiADTF----------------VGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFafsNIDDDGQDDPMgILD 220

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94968483 247 ------TAPTPMVRMNpDVPPELERIVSKALEKDRNLR 278
cd06620     221 llqqivQEPPPRLPSS-DFPEDLRDFVDACLLKDPTER 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88521

cd05620

STKc_nPKC_delta

STKc_nPKC_delta: Serine/Threonine Kinases (STKs), Novel Protein Kinase C (nPKC), delta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis.

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

false

true

false

316

4e-15

78.51

77.22

8,19,2,29,48,33,22,71,55,36,107,92,52,160,144,9,189,153,55,244,209,9,258,218,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDE--LARDSQALSRFQREAQAASALNhPNICTIHDIGEENGRAFIAMEFLDGL 97
cd05620       3 LGKGSFGKVLLAELKGKGEYFAVKALKKDvvLIDDDVECTMVEKRVLALAWEN-PFLTHLYCTFQTKEHLFFVMEFLNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  98 TLKHTIEERS-MEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTAiasantm 176
cd05620      82 DLMFHIQDKGrFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCK-ENVFGDNRA------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 taagvqeqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAI-LDTAPTPMVrm 255
cd05620     154 -------------STFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIrVDTPHYPRW-- 218

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968483 256 npdVPPELERIVSKALEKDRNLRYQSANDMR 286
cd05620     219 ---ITKESKDILEKLFERDPTRRLGVVGNIR 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

1e-14

77.16

86.69

8,19,9,29,50,38,8,58,50,48,106,99,53,159,153,12,190,165,42,235,207,16,254,223,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDElaRDSQALSR----FQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLD 95
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKQVPFD--PDSPETKKevnaLECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMP 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 GLTLKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK-VENVAGSQTAIAsa 173
cd06625      88 GGSVKDQLKAYgALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKrLQTICSSGTGMK-- 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 174 ntmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFrggSTAEVFKAILDTAPTPmv 253
cd06625     166 -----------------SVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPW---AEFEAMAAIFKIATQP-- 223

                       250
                ....*....|....*
gi 94968483 254 rMNPDVPPELERIVS 268
cd06625     224 -TNPQLPSHVSPDAR 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132947

cd06616

PKc_MKK4

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

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

false

true

false

288

1e-14

77.40

85.76

10,19,11,49,69,60,26,96,86,4,100,96,8,108,105,51,159,158,10,193,168,10,203,181,34,239,215,19,258,238,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASAlNHPNICTIHDIGEENGRAFIAMEFLDgLTL 99
cd06616      12 IGRGAFGTVNKMLHKPSGTIMAVKRIRSTVDEKEQKRLLMDLDVVMRSS-DCPYIVKFYGALFREGDCWICMELMD-ISL 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 K------HTIEERSM-EMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK--VENVAGSQTAi 170
cd06616      90 DkfykyvYEVLKSVIpEEILGKIAVATVKALNYLKEELKIIHRDVKPSNILLDRNGNIKLCDFGISGqlVDSIAKTRDA- 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 171 asantmtaagvqeqhltspgstlGTIAYMSPEQ---ARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTaeVFKAILDT 247
cd06616     169 -----------------------GCRPYMAPERidpSARDGYDVRSDVWSLGITLYEVATGKFPYPKWNS--VFDQLTQV 223

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94968483 248 APTPMVRMNPD----VPPELERIVSKALEKDRNLR 278
cd06616     224 VKGDPPILSNSeereFSPSFVNFINLCLIKDESKR 258

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

2e-14

76.89

66.97

4,13,2,90,103,94,53,176,147,37,213,190,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd05601       3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTI--EERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenvagsqtaia 171
cd05601      83 HPGGDLLSLLnrYEDQFDESMAQFYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFG--------------- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 172 santmTAAGVQEQHLTSPGSTLGTIAYMSPEQARAKDLDART------DLFSFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd05601     148 -----SAAKLNANKMVNSKLPVGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGTSAVTYSNIM 222


                .
gi 94968483 246 D 246
cd05601     223 N 223

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132942

cd06611

STKc_SLK_like

Serine/threonine kinases (STKs), Ste20-like kinase (SLK)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of the subfamily include SLK, STK10 (also called LOK for lymphocyte-oriented kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney (HEK) cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions.

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

false

true

false

280

2e-14

76.71

88.93

8,11,4,37,51,41,53,104,96,52,169,148,8,180,156,5,190,161,11,201,177,48,250,225,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDElarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd06611       5 DIWEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQIE---SEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTLKHTIE--ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenvagsqta 169
cd06611      82 EFCDGGALDSIMLelERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFG------------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 IASANTMTaagVQEQHltspgSTLGTIAYMSP-----EQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAI 244
cd06611     149 VSAKNKST---LQKRD-----TFIGTPYWMAPevvacETFKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKI 220

                       250       260       270
                ....*....|....*....|....*....|....
gi 94968483 245 LDTAPtPMVRMNPDVPPELERIVSKALEKDRNLR 278
cd06611     221 LKSEP-PTLDQPSKWSSSFNDFLKSCLVKDPDDR 253

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

2e-14

76.57

72.76

5,19,2,80,99,83,62,169,145,8,190,153,55,249,208,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05571       3 LGKGTFGKVILVREKATGKYYAMKILKKEVIIAKDEVAHTLTESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 -KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVEnvagsqtaIASANTMTa 178
cd05571      83 fFHLSRERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLCKEG--------ISDGATMK- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 179 agvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdtapTPMVRMNPD 258
cd05571     154 ------------TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELIL----MEEIRFPRT 217

                       250       260
                ....*....|....*....|
gi 94968483 259 VPPELERIVSKALEKDRNLR 278
cd05571     218 LSPEAKSLLAGLLKKDPKQR 237

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

4e-14

75.41

64.49

6,19,2,26,45,29,60,105,90,54,160,144,8,174,152,6,194,158,51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFL-PDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05591       3 LGKGSFGKVMLAELKGTDEVYAIKVLkKDVILQDDDVDCTMTEKRILALAAKHPFLTALHCCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LKHTIEE-RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTaiasanTMT 177
cd05591      83 LMFQIQRsRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCK-EGILNGVT------TTT 155

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94968483 178 AAGvqeqhltspgstlgTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd05591     156 FCG--------------TPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESIL 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133248

cd05148

PTKc_Srm_Brk

Catalytic Domain of the Protein Tyrosine Kinases, Srm and Brk

false

true

false

261

6e-14

75.16

97.70

10,11,5,21,33,26,15,51,41,50,101,94,59,180,153,4,185,157,42,227,200,19,246,221,5,256,226,14,278,240,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEdTRLHRFVALKFLPDElarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAM 91
cd05148       6 EEFTLERKLGSGYFGEVWEGL-WKNRVRVAIKILKSD---DLLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEPVYIIT 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  92 EFLDGLTLKH---TIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagsqt 168
cd05148      82 ELMEKGSLLAflrSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARL-------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 169 aiasantmtaagVQEQhLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMAT-GTLPFRGGSTAEVFKAILD- 246
cd05148     154 ------------IKED-VYLSSDKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQITAg 220

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 94968483 247 -TAPTPmvrmnPDVPPELERIVSKAlekdrnlrYQSANDMRADLARLKRDLDS 298
cd05148     221 yRMPCP-----AKCPQEIYKIMLEC--------WAAEPEDRPSFKALREELDN 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Byr2-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses.

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

false

true

false

267

6e-14

74.87

92.88

9,19,7,24,43,33,3,46,40,60,106,101,53,168,154,19,193,173,46,239,220,12,256,232,2,258,235,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALK--FLP----DELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEF 93
cd06628       8 IGSGSFGSVYLGMNAHSGELMAVKqvEIPsnsiGVQDRKRKMLDALQREINLLKELHHENIVQYLGSSQDAGHLNIFLEY 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqtAIAS 172
cd06628      88 VPGGSVAALLNNYgAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISK---------KLEA 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 173 ANTMTAAGVQEQHLTspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAE-VFKAILDTAPTP 251
cd06628     159 NSLSTKTNGARPSLQ------GSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFPDCTQMQaIFKIGTNASPEI 232

                       250       260
                ....*....|....*....|....*...
gi 94968483 252 mvrmnPD-VPPELERIVSKALEKDRNLR 278
cd06628     233 -----PSnASSEAKNFLRKTFEIDYNKR 255

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

6e-14

74.91

67.03

7,17,6,29,46,39,5,53,44,14,71,58,31,105,89,50,179,139,13,192,153,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  18 ERLGGGGMGVVYKAEDTRLHRFVALKFLP----DELARdsQALSRFQREAQAASalnhPNICTIHDIGEENGRAFIAMEF 93
cd06619       7 EILGHGNGGTVYKAYHLLTRRILAVKVIPlditVELQK--QIMSELEILYKCDS----PYIIGFYGAFFVENRISICTEF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  94 LDGLTLKHTieeRSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFglakvenvagsqtaiasa 173
cd06619      81 MDGGSLDVY---RKIPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDF------------------ 139

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 174 ntmtaaGVQEQHLTSPGST-LGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF 232
cd06619     140 ------GVSTQLVNSIAKTyVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

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

8e-14

74.30

66.67

6,16,9,33,51,42,54,105,98,53,165,151,9,190,160,44,234,214,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLPDELarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDG 96
cd06650      10 ISELGAGNGGVVFKVSHKPSGLIMARKLIHLEI--KPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  97 LTLKHTIEE--RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagSQTAIASAN 174
cd06650      88 GSLDQVLKKagRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVS-------GQLIDSMAN 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 175 tmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRG----------GSTAEVFKAI 244
cd06650     161 ----------------SFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAIGRYPIPPpdakelelmfGCPVEGDPAE 224


                ....*..
gi 94968483 245 LDTAPTP 251
cd06650     225 SETSPRP 231

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-13

74.02

82.46

7,18,25,28,49,53,30,79,86,4,86,90,72,165,162,4,183,166,66,250,232,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  19 RLGGGGMGVVYKAEDTRLHRFVALKFLPdelARDSQALSRFQREAQAASALNHPNICTIHD---IGEEngrAFIAMEFLD 95
cd06648      26 KIGEGSTGIVCIATDKSTGRQVAVKKMD---LRKQQRRELLFNEVVIMRDYQHPNIVEMYSsylVGDE---LWVVMEFLE 99

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  96 GLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagSQTAiasant 175
cd06648     100 GGALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFC-------AQVS------ 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 176 mtaagvqeQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPtPMVRM 255
cd06648     167 --------KEVPRRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNLP-PKLKN 237

                       250       260
                ....*....|....*....|...
gi 94968483 256 NPDVPPELERIVSKALEKDRNLR 278
cd06648     238 LHKVSPRLRSFLDRMLVRDPAQR 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88491

cd05590

STKc_nPKC_eta

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

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

false

true

false

320

1e-13

73.90

65.00

4,19,2,27,46,30,54,100,85,69,190,154,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLP-DELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05590       3 LGKGSFGKVMLARLKESGRLYAVKVLKkDVILQDDDVECTMTEKRILSLARNHPFLTQLYCCFQTPDRLFFVMEFVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVENVAGSQTAiasantmt 177
cd05590      83 LMfHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKTTS-------- 154

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94968483 178 aagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILD 246
cd05590     155 -------------TFCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILN 210

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

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

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

false

true

false

277

1e-13

74.16

86.64

4,19,0,85,104,88,54,159,142,8,188,150,90

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05577       1 LGKGGFGEVCACQVRATGKMYACKKLDKKRIKKRKGETMALNEKIILEKVSSPFIVSLAYAFETKDALCLVLTLMNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 KHTIE---ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkVENVAGSQtaiasantm 176
cd05577      81 KFHIYnvgNPGFDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLA-VEFPEGKK--------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 taagvqeqhltsPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPTPMVRMN 256
cd05577     151 ------------IHGRVGTVGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHSPFRQRKEKVKKEEVDRRTLTDEVEYP 218

                       250       260
                ....*....|....*....|..
gi 94968483 257 PDVPPELERIVSKALEKDRNLR 278
cd05577     219 DKFSEEAKSICEGLLQKDPEKR 240

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-13

73.86

58.97

5,19,2,46,65,49,35,100,85,59,178,144,10,190,154,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQA-ASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05588       3 IGRGSYAKVLLVELKKTRRIYAMKVIKKELVNDDEDIDWVQTEKHVfETASNHPFLVGLHSCFQTESRLFFVIEFVSGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqtaiasantmt 177
cd05588      83 LMfHMQRQRKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCK------------------ 144

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94968483 178 aAGVQEQHLTSpgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF 232
cd05588     145 -EGIRPGDTTS--TFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88500

cd05599

STKc_NDR_like

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

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

false

true

false

364

2e-13

73.01

81.04

10,11,0,34,45,36,22,69,58,27,96,88,3,101,91,58,159,162,18,177,184,69,246,256,6,252,263,16,271,279,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  12 SHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFL--PDELARDSQALSRFQREAQAASalNHPNICTIHDIGEENGRAFI 89
cd05599       1 DDFESIKVIGRGAFGEVRLVQKKDTGHIYAMKKLrkSEMLEKEQVAHVRAERDILAEA--DNPWVVKLYYSFQDENYLYL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  90 AMEFLDG---LTLkhTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAK------- 159
cd05599      79 IMEYLPGgdmMTL--LMKKDTFTEEETRFYIAETILAIDSIHKLGYIHRDIKPDNLLLDAKGHIKLSDFGLCTglkkshr 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 160 ------VENVAGSQTAIASANTMT----AAGVQEQHLTSPGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGT 229
cd05599     157 tefyriLSHALPSNFLDFISKPMSskrkAETWKRNRRALAYSTVGTPDYIAPEVFLQTGYNKECDWWSLGVIMYEMLVGY 236

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94968483 230 LPFRGGSTAEVFKAILD---TAPTPM-VRMNPDVPPELERIVSkalEKDRNLRYQSANDMRA 287
cd05599     237 PPFCSDNPQETYRKIINwkeTLQFPDeVPLSPEAKDLIKRLCC---EAERRLGNNGVNEIKS 295

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

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

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

false

true

false

277

2e-13

73.19

85.20

6,16,8,37,55,45,102,172,147,14,192,161,57,250,218,10,262,228,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSqaLSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDG 96
cd06641       9 LEKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  97 LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLakvenvagsqtaiasANTM 176
cd06641      87 GSALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGV---------------AGQL 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 TAAGVQEQHLtspgstLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPtPMVRMN 256
cd06641     152 TDTQIKRNTF------VGTPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLFLIPKNNP-PTLEGN 224

                       250       260
                ....*....|....*....|..
gi 94968483 257 PDVPpeLERIVSKALEKDRNLR 278
cd06641     225 YSKP--LKEFVEACLNKEPSFR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

STKc_MSK_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2.

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

false

true

false

288

3e-13

72.66

91.67

11,13,1,24,37,28,10,47,39,24,71,64,28,99,93,61,175,154,10,190,164,19,209,185,23,232,212,18,254,230,20,274,252,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLH---RFVALKFLPD-ELARDSQALSRFQREAQAASALNH-PNICTIHDIGEENGRAF 88
cd05583       2 FELLRVLGTGAYGKVFLVRKVGGHdagKLYAMKVLKKaTIVQKAKTAEHTRTERQVLEAVRRcPFLVTLHYAFQTDTKLH 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  89 IAMEFLDGLTL-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagsq 167
cd05583      82 LILDYVNGGELfTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKE------- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 168 taiasantMTAAGVQEQHltspgSTLGTIAYMSPEQARAKDL--DARTDLFSFGAVLYEMATGTLPF----RGGSTAEVF 241
cd05583     155 --------FLAEEEERAY-----SFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFtvdgEQNSQSEIS 221

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 94968483 242 KAILDTAPTpmvrMNPDVPPELERIVSKALEKD--RNLRYQSANDMRA 287
cd05583     222 RRILKSKPP----FPKTMSAEARDFIQKLLEKDpkKRLGANGADEIKN 265

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-13

72.77

58.01

5,16,9,33,51,42,54,105,98,53,165,151,9,190,160,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLPDELarDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDG 96
cd06649      10 ISELGAGNGGVVTKVQHKPSGLIMARKLIHLEI--KPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  97 LTLKHTIEE--RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagSQTAIASAN 174
cd06649      88 GSLDQVLKEakRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVS-------GQLIDSMAN 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94968483 175 tmtaagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLP 231
cd06649     161 ----------------SFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVELAIGRYP 201

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

4e-13

72.26

65.43

6,19,7,57,76,65,30,106,96,53,160,149,8,174,157,6,194,163,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICT-IHDIGEENGRAFIAMEFLDGLT 98
cd05587       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVIIQDDDVECTMVEKRVLALPGKPPFLTqLHSCFQTMDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LKHTIEER-SMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTaiasanTMT 177
cd05587      88 LMYHIQQVgKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCK-ENIFGGKT------TRT 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94968483 178 AAGvqeqhltspgstlgTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPT 250
cd05587     161 FCG--------------TPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVS 219

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

5e-13

71.54

91.64

11,13,7,33,46,46,14,69,60,9,78,75,18,96,98,62,163,160,14,193,174,9,202,188,30,244,218,6,250,225,15,265,250,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLP------DELARDSQALSRFQreaqaasalNHPNICTIH------DIG 81
cd06608       8 FELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDiiedeeEEIEEEYNILRKYS---------NHPNIATFYgafikkGPP 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  82 EENGRAFIAMEFLDG-----LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFG 156
cd06608      79 GSDDQLWLVMELCGGgsvtdLVKGLRKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFG 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 157 LAkvenvAGSQTAIASANTMTaagvqeqhltspgstlGTIAYMSPE-----QARAKDLDARTDLFSFGAVLYEMATGTLP 231
cd06608     159 VS-----AQLDSTNGRRNTSI----------------GTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPP 217

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 94968483 232 FrggstaevfkaiLDTAPT-PMVRMNPDVPPELER----------IVSKALEKD 274
cd06608     218 L------------CDMHPMrALFKIPRNPPPTLKSptnwskkfndFISECLIKN 259

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88496

cd05595

STKc_PKB_beta

STKc_PKB_beta: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, beta (or Akt2) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure.

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

false

true

false

323

6e-13

71.60

72.76

5,19,2,81,100,84,59,167,143,10,190,153,55,249,208,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05595       3 LGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 K-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqTAIASANTMTa 178
cd05595      83 FfHLSRERVFTEERARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCK--------EGISDGATMK- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 179 agvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdtapTPMVRMNPD 258
cd05595     154 ------------TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELIL----MEEIRFPRT 217

                       250       260
                ....*....|....*....|
gi 94968483 259 VPPELERIVSKALEKDRNLR 278
cd05595     218 LSPEAKSLLAGLLKKDPKQR 237

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

6e-13

71.68

88.57

10,15,4,34,51,38,20,71,59,29,100,93,58,165,151,13,193,164,9,202,177,30,232,208,14,247,222,10,258,232,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  16 IVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELarDSQALSRFQREAQAASALNH-PNICTIHDIGEENGRAFIAMEFL 94
cd06617       5 VIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATV--NSQEQKRLLMDLDISMRSSDcPYTVHFYGALFREGDVWICMEVM 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLK-----HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagSQTA 169
cd06617      83 DTSLDKfykkvYKKGLTIPEDILGKIAVSVVKALEYLHEKLSVIHRDVKPSNILINRNGQVKLCDFGIS-------GYLV 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 170 IASANTMTAagvqeqhltspgstlGTIAYMSPE----QARAKDLDARTDLFSFGAVLYEMATGTLPF-RGGSTAEVFKAI 244
cd06617     156 DSLAKTVDA---------------GCKPYMAPEridpEGNQKGYDVRSDVWSLGITMIELATGRFPYdNWKTPFEQLKQV 220

                       250       260       270
                ....*....|....*....|....*....|....
gi 94968483 245 LDtAPTPMVRMNPdVPPELERIVSKALEKDRNLR 278
cd06617     221 VE-EPSPQLPAEK-FSPEFQDFVNKCLRKDYHER 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

STKc_MAST: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also referred to as syntrophin-associated STK (SAST), while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3.

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

false

true

false

305

6e-13

71.50

52.46

5,130,120,30,168,150,19,187,171,54,241,226,10,253,236,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 131 GIVHRDIKPANIFVTKRGHAKVLDFGLAKVenvagsqtAIASANTMTAAGVQEQHLT--SPGSTLGTIAYMSPEQARAKD 208
cd05609     121 GIVHRDLKPDNLLITSMGHIKLTDFGLSKI--------GLMSLTTNLYEGHIEKDTRefLDKQVCGTPEYIAPEVILRQG 192

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 209 LDARTDLFSFGAVLYEMATGTLPFRGGSTAEVF-KAILDTAPTPmvRMNPDVPPELERIVSKALEKDRNLRYQSANDMRA 287
cd05609     193 YGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFgQVISDDIEWP--EGDEALPADAQDLISRLLRQNPLERLGTGGAFEV 270

                       170
                ....*....|
gi 94968483 288 DLARLKRDLD 297
cd05609     271 KQHRFFLGLD 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132986

cd06655

STKc_PAK2

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

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

false

true

false

296

1e-12

70.52

90.20

7,6,13,52,61,65,18,79,86,4,86,90,72,177,162,11,190,173,51,242,224,56

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483   7 IGTTVSHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRfqrEAQAASALNHPNICTIHD---IGEE 83
cd06655      14 IGDPKKKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKELIIN---EILVMKELKNPNIVNFLDsflVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  84 ngrAFIAMEFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenv 163
cd06655      91 ---LFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFC----- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 164 agsqtaiasantmtAAGVQEQHLTSpgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFkA 243
cd06655     163 --------------AQITPEQSKRS--TMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRAL-Y 225

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94968483 244 ILDTAPTPMVRMNPDVPPELERIVSKALEKDRNLRYQSANDMRADLARLKRDLDS 298
cd06655     226 LIATNGTPELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSS 280

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

1e-12

70.47

58.97

5,19,2,46,65,49,35,100,85,59,178,144,11,191,155,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQA-ASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05618       3 IGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEDIDWVQTEKHVfEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LK-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqtaiasantmt 177
cd05618      83 LMfHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCK------------------ 144

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94968483 178 aAGVQEQHLTSPgsTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPF 232
cd05618     145 -EGLRPGDTTST--FCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

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

2e-12

70.08

85.20

6,16,8,37,55,45,102,172,147,12,190,159,59,250,218,10,262,228,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSqaLSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDG 96
cd06642       9 LERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  97 LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLakvenvagsqtaiasANTM 176
cd06642      87 GSALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGV---------------AGQL 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 TAAGVQEQhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILDTAPtPMVRMN 256
cd06642     152 TDTQIKRN------TFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSP-PTLEGQ 224

                       250       260
                ....*....|....*....|..
gi 94968483 257 PDVPpeLERIVSKALEKDRNLR 278
cd06642     225 YSKP--FKEFVEACLNKDPRFR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88486

cd05585

STKc_YPK1_like

STKc_YPK1_like: Serine/Threonine Kinases (STKs), Yeast protein kinase 1 (YPK1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development.

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

false

true

false

312

2e-12

69.67

78.85

10,19,0,26,50,26,10,60,41,44,104,86,56,161,142,8,173,150,4,193,154,52,246,206,3,252,209,22,274,233,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLpdelaRDSQALSRFQ-----REAQAASALNHPNICTIHDIGEENGRAFIAMEFL 94
cd05585       1 IGKGSFGKVMQVRKKDTQRIYALKTI-----RKAHIVSRSEvthtlAERTVLAQVNCPFIVPLKFSFQSPEKLYFVLAFI 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  95 DGLTLKHTIE-ERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKVeNVAGSQTAiasa 173
cd05585      76 NGGELFHHLQkEGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKL-NMKDDDRT---- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 174 NTMTaagvqeqhltspgstlGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdTAPtpmV 253
cd05585     151 NTFC----------------GTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKIL-QEP---L 210

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94968483 254 RMNPDVPPELERIVSKALEKD--RNLRYQSANDMRA 287
cd05585     211 RFPDGFDRDAKDLLTGLLNRDptQRLGYNGAQEIKN 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

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

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

false

true

false

293

3e-12

69.55

91.13

7,6,13,40,49,53,30,79,86,4,86,90,72,177,162,11,190,173,55,246,228,52

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483   7 IGTTVSHYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPdelARDSQALSRFQREAQAASALNHPNICTIHD---IGEE 83
cd06647      14 VGDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMN---LQQQPKKELIINEILVMRENKHPNIVNYLDsylVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  84 ngrAFIAMEFLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAkvenv 163
cd06647      91 ---LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFC----- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 164 agsqtaiasantmtAAGVQEQHLTSpgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKA 243
cd06647     163 --------------AQITPEQSKRS--TMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYL 226

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94968483 244 ILdTAPTPMVRMNPDVPPELERIVSKALEKDRNLRYQSANDMRADLARLKRDLDS 298
cd06647     227 IA-TNGTPELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSS 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88517

cd05616

STKc_cPKC_beta

STKc_cPKC_beta: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC) subfamily, beta isoforms, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis.

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

false

true

false

323

3e-12

69.27

64.40

5,19,7,27,46,35,61,107,97,52,160,149,9,189,158,57

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLP-DELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLT 98
cd05616       8 LGKGSFGKVMLAERKGTDELYAIKILKkDVVIQDDDVECTMVEKRVLALSGKPPFLTQLHSCFQTMDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  99 LKHTIEERS-MEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvENVAGSQTAiasantmt 177
cd05616      88 LMYQIQQVGrFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGMCK-ENMWDGVTT-------- 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94968483 178 aagvqeqhltspGSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILD 246
cd05616     159 ------------KTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIME 215

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-12

69.28

89.36

7,12,5,34,49,39,56,105,97,51,169,148,8,185,156,16,201,177,48,250,225,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  13 HYRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPdelARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd06643       6 FWEIIGELGDGAFGKVYKAQNKETGVLAAAKVID---TKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEE--RSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenvagsqtaI 170
cd06643      83 FCAGGAVDAVMLEleRPLTEPQIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGDIKLADFG-------------V 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 171 ASANTMTaagvqeqhLTSPGSTLGTIAYMSP-----EQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd06643     150 SAKNTRT--------IQRRDSFIGTPYWMAPevvmcETSKDRPYDYKADVWSLGITLIEMAQIEPPHHELNPMRVLLKIA 221

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94968483 246 DTAPtPMVRMNPDVPPELERIVSKALEKDRNLRYQSA 282
cd06643     222 KSEP-PTLAQPSRWSSEFKDFLKKCLEKNVDARWTTT 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88504

cd05603

STKc_SGK2

STKc_SGK2: Serine/Threonine Kinases (STKs), Serum- and Glucocorticoid-induced Kinase (SGK) subfamily, SGK2 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three isoforms of SGK, named SGK1, SGK2, and SGK3. SGK2 shows a more restricted distribution that SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1.

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

false

true

false

321

4e-12

68.91

64.49

6,19,2,29,48,33,19,68,52,31,99,84,60,178,144,10,190,154,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDE--LARDSQALSRFQREAQAASaLNHPNICTIHDIGEENGRAFIAMEFLDGL 97
cd05603       3 IGKGSFGKVLLAKRKSDGSFYAVKVLQKKtiLKKKEQNHIMAERNVLLKN-LKHPFLVGLHYSFQTAEKLYFVLDYVNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  98 TL-KHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqtaiasantm 176
cd05603      82 ELfFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK----------------- 144

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94968483 177 taAGVQEQHLTSpgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAIL 245
cd05603     145 --EGVEPEETTS--TFCGTPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQMYDNIL 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88494

cd05593

STKc_PKB_gamma

STKc_PKB_gamma: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, gamma (or Akt3) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer.

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

false

true

false

325

5e-12

68.55

76.31

5,19,2,81,100,84,59,167,143,10,190,153,55,249,208,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05593       3 LGKGTFGKVILVREKASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 K-HTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqTAIASANTMTa 178
cd05593      83 FfHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCK--------EGITDAATMK- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 179 agvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdtapTPMVRMNPD 258
cd05593     154 ------------TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELIL----MEDIKFPRT 217

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968483 259 VPPELERIVSKALEKDRNLRYQSANDMRADLAR 291
cd05593     218 LSADAKSLLSGLLIKDPNKRLGGGPDDAKEIMR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88495

cd05594

STKc_PKB_alpha

STKc_PKB_alpha: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, alpha (or Akt1) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis.

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

false

true

false

324

6e-12

68.55

74.69

6,19,2,81,100,84,8,108,93,51,167,144,10,190,154,55,249,209,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  20 LGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSQALSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDGLTL 99
cd05594       3 LGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 100 K-HTIEERSM-EMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLAKvenvagsqTAIASANTMT 177
cd05594      83 FfHLSRERVFsEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCK--------EGIKDGATMK 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 178 aagvqeqhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILdtapTPMVRMNP 257
cd05594     155 -------------TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELIL----MEEIRFPR 217

                       250       260
                ....*....|....*....|....*..
gi 94968483 258 DVPPELERIVSKALEKDRNLRYQSAND 284
cd05594     218 TLSPEAKSLLSGLLKKDPKQRLGGGPD 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

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

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

false

true

false

370

1e-11

67.27

58.65

5,13,44,33,46,78,9,56,87,100,176,187,35,211,226,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLP-DELARDSQAlSRFQREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd05596      45 FDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLSkFEMIKRSDS-AFFWEERDIMAHANSEWIVQLHYAFQDDKYLYMVME 123

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenvagsqtaias 172
cd05596     124 YMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG---------------- 187

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94968483 173 antmTAAGVQEQHLTSPGSTLGTIAYMSPEQARAKDLDA----RTDLFSFGAVLYEMATGTLPFRGGSTAEVFKAILD 246
cd05596     188 ----TCMKMDANGMVRCDTAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMD 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88507

cd05606

STKc_beta_ARK

STKc_beta_ARK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, beta-adrenergic receptor kinase (beta-ARK) group, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism.

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

false

true

false

278

1e-11

66.97

44.96

5,130,116,28,181,144,21,202,166,37,241,203,11,252,215,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 131 GIVHRDIKPANIFVTKRGHAKVLDFGLAkvenvagsqtaiasantmtaagvQEQHLTSPGSTLGTIAYMSPE-QARAKDL 209
cd05606     117 FVVYRDLKPANILLDEHGHVRISDLGLA-----------------------CDFSKKKPHASVGTHGYMAPEvLQKGVAY 173

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 210 DARTDLFSFGAVLYEMATGTLPFRGGSTAEvfKAILDTAPTPM-VRMNPDVPPELERIVSKALEKDRNLR 278
cd05606     174 DSSADWFSLGCMLFKLLRGHSPFRQHKTKD--KHEIDRMTLTMnVELPDSFSPELRSLLEGLLQRDVNKR 241

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

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

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

false

true

false

277

2e-11

66.61

85.20

5,16,8,37,55,45,102,172,147,12,190,159,41,234,200,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  17 VERLGGGGMGVVYKAEDTRLHRFVALKFLPDELARDSqaLSRFQREAQAASALNHPNICTIHDIGEENGRAFIAMEFLDG 96
cd06640       9 LERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  97 LTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGLakvenvagsqtaiasANTM 176
cd06640      87 GSALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGV---------------AGQL 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483 177 TAAGVQEQhltspgSTLGTIAYMSPEQARAKDLDARTDLFSFGAVLYEMATGTLPfrgGSTAEVFKAILDTAPTPMVRMN 256
cd06640     152 TDTQIKRN------TFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPP---NSDMHPMRVLFLIPKNNPPTLT 222

                       250       260
                ....*....|....*....|..
gi 94968483 257 PDVPPELERIVSKALEKDRNLR 278
cd06640     223 GEFSKPFKEFIDACLNKDPSFR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

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

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

false

true

false

370

2e-11

66.62

58.65

5,13,44,34,47,79,8,56,87,100,176,187,35,211,226,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  14 YRIVERLGGGGMGVVYKAEDTRLHRFVALKFLPD-ELARDSQAlSRFQREAQAASALNHPNICTIHDIGEENGRAFIAME 92
cd05621      45 YDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLSKfEMIKRSDS-AFFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVME 123

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968483  93 FLDGLTLKHTIEERSMEMDRILALAIEIADALDAAHAAGIVHRDIKPANIFVTKRGHAKVLDFGlakvenvagsqtaias 172