NCBI Conserved Domain Search

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Conserved domains on [gi\|94968081\|ref\|YP_590129.1\|]
TPR repeat-containing serine/threonin protein kinase [Candidatus Koribacter versatilis Ellin345]

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List of domain hits		?

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

29142

cd00180

S_TKc

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

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

true

256

2e-50

196.19

98.44

5,7,0,37,45,37,53,98,91,56,172,147,65,238,212,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   8 HYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVaEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAME 87
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKK-EKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 YLDGVTLKHLI-GRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlv 166
cd00180      80 YMSGGDLFDLLkKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAK------------ 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 avtsdgLTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILgRVPVAPVR 246
cd00180     148 ------QLDSGGRKLTTFVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKIL-KGKGTPDE 220

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968081 247 LNPDVPHELERIISKALEKDRNLRYQSAAEMQ 278
cd00180     221 LPPNISPEAKDLIKKLLVKDPEKRPTAEELLQ 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

9e-36

147.31

94.98

8,8,1,35,44,36,39,83,76,17,100,94,61,177,155,47,227,202,13,240,221,4,248,225,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDvAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAF-IAME 87
cd06606       2 WTRGKLLGRGSFGSVYLALSKDTGELVAVKSVELS-SDSEEELESLEREIRILSKLQHPNIVRYYGCEVTEENTLnIFME 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 YLDGVTLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETesrlv 166
cd06606      81 YVSGGSLASLLKKfGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRLASIAY----- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 avtsdgltgehRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFrgeSSVETFEAILGRV------ 240
cd06606     156 -----------SGGLKSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPW---SELGNPMALLYKIgssgep 221

                       250       260       270
                ....*....|....*....|....*....|
gi 94968081 241 PVAPvrlnPDVPHELERIISKALEKDRNLR 270
cd06606     222 PEIP----EDLSEEAKDFLRKCLRRDPKKR 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

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

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

false

true

false

253

1e-35

146.92

95.26

7,8,1,43,54,44,44,98,89,56,163,145,2,169,147,8,182,155,54,237,209,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLarfQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEEQEQI---LNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLI-GRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesRLva 167
cd05122      79 CDGGSLDDLLkSTGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSA---------QL-- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 168 vtSDGLTGEHrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIlGRVPVAPVRL 247
cd05122     148 --SDTKAKRN-----TFVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALFKI-ATNPPPGLPS 219

                       250       260
                ....*....|....*....|...
gi 94968081 248 NPDVPHELERIISKALEKDRNLR 270
cd05122     220 PEKWSPEFRDFLKKCLQKDPEKR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

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

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

false

true

false

250

3e-34

142.54

94.00

6,14,0,84,98,87,22,122,109,33,171,142,9,182,151,67,253,218,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 KHLI---GRSPVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMsqeqetesrlvavtsd 171
cd05123      81 FTHLskeGRFDEERARFYAAEIVLALEYL--HSLGIIYRDLKPENILLDADGHIKLTDFGLAKE---------------- 142

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 GLTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPdv 251
cd05123     143 GIDDGVRTT--TFCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRFPEFLSE-- 218

                       250
                ....*....|....*....
gi 94968081 252 phELERIISKALEKDRNLR 270
cd05123     219 --EAKDLIKKLLTKDPTKR 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

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

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

false

true

false

279

1e-31

133.76

93.91

7,8,2,32,46,34,9,55,49,10,65,60,37,102,98,53,155,153,89,248,242,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLpedvaeDTATLARFQ------REARAASALN-HPNICSIFDIGEQEGR 81
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVL------DKRHLIKEKkvkyvkREKEVLTRLNgHPGIVKLYYTFQDEEN 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  82 AFIAMEYLDGVTLKHLIGRSP-VEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKM--SQE 158
cd05581      77 LYFVLEYAENGELLEYIKKFGsFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVldPNS 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 159 QETESRLVAVTSDGLTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILG 238
cd05581     157 SPESNKGKATNIDSQIEKNRRRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVK 236

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968081 239 RVPVAPvrlnPDVPHELERIISKALEKDRNLR 270
cd05581     237 LEYEFP----PNFPPDAKDLIEKLLVLDPQDR 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132954

cd06623

PKc_MAPKK_plant_like

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis. MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling, MKK2 is involved in cold and salt stress signaling, MKK4/MKK5 participates in innate immunity, and MKK7 regulates basal and systemic acquired resistance.

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

false

true

false

264

6e-31

131.18

95.83

9,6,0,35,43,35,59,102,96,52,167,148,10,182,158,42,224,203,17,248,220,5,253,230,17,271,247,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPedVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd06623       1 SDLERVKVLGQGSSGVVYKVRHKPTGKIYALKKIH--VDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGRSP--VEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesr 164
cd06623      79 EYMDGGSLADLLKKVGkiPEPVLAYIARQILKGLDYLHTKRHIIHRDIKPSNLLINSKGEVKIADFGISK---------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 165 lvaVTSDGLTGEHrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPF---RGESSVETFEAILGRVP 241
cd06623     149 ---VLENTLDQCN-----TFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFlppGQPSFFELMQAICDGPP 220

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94968081 242 vapvrlnPDVPH-----ELERIISKALEKDRNLRyQSAAEM 277
cd06623     221 -------PSLPAeefspEFRDFISACLQKDPKKR-PSAAEL 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

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

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

false

true

false

315

4e-30

128.83

91.11

7,6,0,99,105,102,56,161,160,17,178,181,6,184,191,61,247,252,30,278,282,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd05574       1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGRSPVEM---SKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQET-- 161
cd05574      81 DYCPGGELFRLLQRQPGKCfpeEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSKQSDVEPTpv 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 162 ESRLVAVTSDGLTGEHR----TSPGTT----MGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETF 233
cd05574     161 SKALRKGSRGSVNKITTetfsEEPSFRsnsfVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETF 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 94968081 234 EAILGRVPVAPVrlNPDVPHELERIISKALEKDRNLRYQSAAEMqADLKR 283
cd05574     241 SNILKKEVTFPG--SPPVSSSARDLIRKLLVKDPSKRLGSKRGA-AEIKQ 287

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

6e-28

121.45

96.23

6,14,0,83,97,86,23,122,109,49,181,158,64,247,222,19,266,243,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 KHL---IGRSPVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRLVAVTSD 171
cd05579      81 ASLlenVGSLDEDMARIYIAEIVLALEYL--HSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKVGLVRRQINLNDDEKED 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 gltgehrtspGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVrlNPDV 251
cd05579     159 ----------KRIVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEWPE--DVEV 226

                       250       260
                ....*....|....*....|....*....
gi 94968081 252 PHELERIISKALEKD--RNLRYQSAAEMQ 278
cd05579     227 SDEAKDLISKLLVPDpeKRLGAKSIEEIK 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

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

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

false

true

false

287

8e-28

120.78

91.29

10,0,6,7,7,19,33,42,52,6,49,58,56,105,116,47,152,164,14,185,178,56,243,234,7,250,242,20,271,262,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   1 MIGQIVS------HYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLpeDVAEDTaTLARFQREARAASALNHPNICSIFD 74
cd06614       7 ALKDIVSegdpreLYDNLEKIGEGASGEVYTATDRATGKEVAIKKM--RLRKQP-KKELIINEILIMKECKHPNIVNYYD 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  75 IGEQEGRAFIAMEYLDGVTLKHLIGRSPVEM--SKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGL 152
cd06614      84 SYLVGDELWVVMEYMDGGSLTDIITQTFVRMneSQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGF 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 153 -AKMSQEQETESRLVavtsdgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVE 231
cd06614     164 aAQLTKEKSKRNSMV-------------------GTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLR 224

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 94968081 232 TFEAILGRVPvaPVRLNPD-VPHELERIISKALEKDRNLRyQSAAEM 277
cd06614     225 ALFLITTKGI--PPLKNPEkWSPEFKDFLNKCLVKDPEKR-PSAEEL 268

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

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

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

false

true

false

258

2e-27

119.95

94.57

5,7,0,88,95,89,60,167,149,9,183,158,49,233,207,37

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   8 HYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAME 87
cd05578       1 HFEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 YLDGVTLK-HLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMsqeqetesrlv 166
cd05578      81 LLLGGDLRyHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIATK----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 aVTSDGLTGEhrtspgtTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETfEAILGRVPVAPVR 246
cd05578     150 -LTPDTLATS-------TSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGHSRTPR-EEILAKFETADVL 220

                       250       260
                ....*....|....*....|....
gi 94968081 247 LNPDVPHELERIISKALEKDRNLR 270
cd05578     221 YPAGWSSEAIDAINKLLERDPQKR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88493

cd05592

STKc_nPKC_theta_delta

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

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

false

true

false

316

2e-26

116.56

77.53

6,14,2,31,45,34,56,101,91,55,172,146,8,182,154,66,252,220,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVA-EDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05592       3 LGKGSFGKVMLAELKGTNEYYAIKALKKDVVlEDDDVECTMVERRVLILAWEHPFLTHLFCTFQTKEHLFFVMEYLNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIGRS-PVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSqeqetesrlvavtsdg 172
cd05592      83 LMFHIQSSgRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCKEN---------------- 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 173 LTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNpdvp 252
cd05592     147 INGEGKAS--TFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILNDRPHFPRWIS---- 220

                       250       260
                ....*....|....*....|....*..
gi 94968081 253 HELERIISKALEKDRNLRYQSAAEMQA 279
cd05592     221 KEAKDCLSKLFEREPTKRLGMDGDIRQ 247

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

4e-26

115.13

95.08

10,14,7,27,41,35,2,45,37,59,104,97,57,175,154,29,204,186,20,227,206,13,240,224,7,249,231,22,272,253,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLP-EDvaEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd06626       8 IGGGTFGKVYTAVNLDTGELMAVKEIRiQD--NDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCSGGT 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIGRSPVE-MSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETesrlvavtsdg 172
cd06626      86 LEELLEHGRILdEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAVKLKNNTT----------- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 173 ltgEHRTSPGTTMGTIAYMSPEQARGKELDAR---TDLFSFGVVLYEMSTGTLPFrgeSSVETFEAILGRV-----PVAP 244
cd06626     155 ---TMGEEVQSLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPW---SELDNEFQIMFHVgaghkPPIP 228

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968081 245 VRLnpDVPHELERIISKALEKDRNLRYqSAAEM 277
cd06626     229 DSL--QLSPEGKDFLDRCLESDPKKRP-TASEL 258

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-24

109.94

78.30

6,14,2,46,60,49,43,103,93,51,170,144,10,182,154,71,257,225,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARA-ASALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05570       3 LGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDDDVECTMTEKRVlALAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIGRSPV-EMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsDG 172
cd05570      83 LMYHIQQQGRfPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK----------------EG 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 173 LTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPDVP 252
cd05570     147 ILGGVTTS--TFCGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILEDNVRYPRWLSKEAK 224

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968081 253 HelerIISKALEKDRNLRYQSAAEMQADLKR 283
cd05570     225 S----ILKGFLTKNPEKRLGCGPTGEQDIKG 251

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-24

109.56

68.64

5,8,2,93,101,98,19,122,117,32,154,157,23,177,185,60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILADADSPWIVKLYYSFQDEEYLYLVMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGRS---PVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAK--------MSQ 157
cd05573      83 MPGGDLMTLLIKYdvfPEETARFYIAELVLAIDSV--HKLGFIHRDIKPDNILIDADGHIKLADFGLCKkmkkagdsEYY 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 158 EQETESRLVAVTSDGLTGEH-----RTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVET 232
cd05573     161 LNDSHNLLDSDRDNVLKRRRpkkqrRVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQET 240


                ....*
gi 94968081 233 FEAIL 237
cd05573     241 YNKIM 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

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

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

false

true

false

290

3e-24

109.07

89.31

9,8,2,90,98,95,22,122,117,32,163,149,7,182,156,55,237,212,5,243,217,10,257,227,28,285,257,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05580       3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVMEF 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLI---GRSPVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesRL 165
cd05580      83 VPGGELFSLLrrsGRFPEPVARFYAAQVVLALEYL--HSLDIVYRDLKPENLLLDSDGYIKITDFGFAK---------RV 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 166 VAVTSdgltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL-GRVPVaP 244
cd05580     152 KGRTY------------TLCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKIYEKILsGKVRF-P 218

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 94968081 245 VRLNPDVPHelerIISKALEKDRNLRYQSAAEMQADLKRLK--RDTD 289
cd05580     219 SFFSSDAKD----LLRNLLQVDLTKRLGNLKNGVNDIKNHPwfAGID 261

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

9e-24

107.52

81.23

8,6,0,42,50,42,16,66,61,87,155,148,9,177,157,2,182,159,15,197,175,27,227,202,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTatLARFQREARAASALNH---PNICSIFDIGEQEGRAF 83
cd06917       1 SLYQRLELIGRGAYGAVYRGKHVPTGRVVALKIINLDTPDDD--VSDIQREVALLSQLRQsqpPNITKYYGSYLKGPRLW 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  84 IAMEYLDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAkmSQEQETES 163
cd06917      79 IIMEYAEGGSVRTLMKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA--ALLNQNSS 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 RlvavtsdgltgehRTspgTTMGTIAYMSPEQAR-GKELDARTDLFSFGVVLYEMSTGTLPFrgeSSVETFEAILGRVPV 242
cd06917     157 K-------------RS---TFVGTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPY---SDVDAFRAMMLIPKS 217


                ....*...
gi 94968081 243 APVRLNPD 250
cd06917     218 KPPRLEDN 225

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

1e-23

106.95

78.35

5,7,0,31,38,32,10,50,42,51,101,94,66,185,160,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   8 HYRIVEQIGGGGMGVVYKAEDTRLHRLVALK-FLPEDVAEDTatLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKqISLEKIKEEA--LKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGRS-PVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRL 165
cd06627      79 EYAENGSLRQIIKKFgKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVATKLSDVSKDDES 158

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 94968081 166 VAvtsdgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPF 224
cd06627     159 VV------------------GTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPY 199

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

4e-23

105.32

87.63

4,6,0,88,94,89,60,175,149,76,255,225,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd05612       1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTL-KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrl 165
cd05612      81 EYVPGGELfSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAK----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 166 vavtsdgltgEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPV 245
cd05612     150 ----------KVRDRTWTLCGTPEYLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLEFPR 219

                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 94968081 246 RLNPDVphelERIISKALEKDRNLRYQSAAEMQADLKRLK 285
cd05612     220 HFDLRA----KDLIKKLLVVDRTRRLGNMKNGADDVKNHK 255

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

5e-23

104.88

79.01

5,14,0,84,98,85,57,172,142,8,182,150,44,226,196,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGEL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 KHLI-GRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMsqeqetesrlvavtsdgL 173
cd05572      81 WTILrDRGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKK-----------------L 143

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94968081 174 TGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRG--ESSVETFEAIL 237
cd05572     144 KSGQKTY--TFCGTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGEddEDPMKIYNLIL 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

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

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

false

true

false

265

2e-22

102.78

91.70

11,11,5,15,30,20,3,33,27,11,46,38,48,94,90,10,104,101,19,125,120,29,163,149,4,178,153,54,232,209,19,251,229,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAedtrLHR----LVALKFLPEDVaeDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAME 87
cd06605       6 LGELGAGNSGVVSKV----RHRptgkIMAVKTIRLEI--NEAIQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 YLDGVTL----KHLIGRSPVE-MSKLLGLAIEIADALDAAHtqGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqete 162
cd06605      80 YMDGGSLdkilKEVQGRIPERiLGKIAVAVLKGLTYLHEKH--KIIHRDVKPSNILVNSRGEIKLCDFGVSG-------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 163 sRLVAvtsdgltgehrTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVET--FEAILGRV 240
cd06605     150 -QLVN-----------SLAKTFVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPENDPPDgiFELLQYIV 217

                       250       260       270
                ....*....|....*....|....*....|.
gi 94968081 241 PVAPVRLNPDV-PHELERIISKALEKDRNLR 270
cd06605     218 NEPPPRLPSGRfSPDFQDFVNLCLIKDPRER 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88520

cd05619

STKc_nPKC_theta

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

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

false

true

false

316

3e-22

102.77

76.58

5,12,0,50,62,51,33,95,85,59,170,144,10,182,154,88

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAAS-ALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd05619       1 KMLGKGSFGKVFLAELKGTNQFFAIKALKKDVVLMDDDVECTMVEKRVLSlAWEHPFLTHLYCTFQTKENLFFVMEYLNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLK-HLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavts 170
cd05619      81 GDLMfHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCK---------------- 144

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 171 DGLTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPD 250
cd05619     145 ENMLGDAKTC--TFCGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEELFQSIRMDNPCYPRWLTRE 222

                       250       260
                ....*....|....*....|
gi 94968081 251 VPHELERIISKALEKDRNLR 270
cd05619     223 AKDILVKLFVREPERRLGVK 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

6e-22

101.44

95.79

9,12,0,19,31,22,12,45,34,50,95,93,57,162,150,19,187,169,32,219,202,18,237,221,7,248,228,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRL---HRLVALKFLPEDvaEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYL 89
cd00192       1 KKLGEGAFGEVYKGELKGKggkKTPVAVKTLKED--ASDSEREDFLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  90 DGVTLK---------HLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLakmsqeqe 160
cd00192      79 EGGDLLdflrksrpvFSPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGL-------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 161 teSRLVAVTSDGLTGEHRTSPgttmgtIAYMSPEQARGKELDARTDLFSFGVVLYEMST-GTLPFRGESSVETFEAIL-G 238
cd00192     151 --SRDIYDDDYYRKKGGGKLP------IRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEVLEYLRkG 222

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968081 239 RVPVAPvrlnPDVPHELERIISKALEKDRNLR 270
cd00192     223 YRLPKP----ENCPDELYELMLSCWQEDPEDR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

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

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

false

true

false

333

1e-21

100.37

63.36

4,6,0,97,103,98,51,170,149,7,182,156,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd05600       1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGRSPV-EMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrl 165
cd05600      81 EYVPGGDFRTLLNNLGVlSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSK----------- 149

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94968081 166 vavtsDGLTGEHrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05600     150 -----GIVTYAN-----SVVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETWENLK 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

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

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

false

true

false

323

1e-21

100.43

78.02

6,14,3,18,32,24,10,42,35,80,122,116,42,182,158,56,242,214,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLH---RLVALKFLPE-DVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLD 90
cd05584       4 LGKGGYGKVFQVRKVTGAdtgKIFAMKVLKKaTIVRNQKDTAHTKAERNILEAVKHPFIVDLIYAFQTGGKLYLILEYLS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  91 GVTLKHLIGRSPVEMSKLLGLAIEIADALDAA-HTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRlvavt 169
cd05584      84 GGELFMHLEREGIFMEDTACFYLSEISLALEHlHQQGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHEGTVTH----- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 170 sdgltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGrvpvAPVRLNP 249
cd05584     159 -------------TFCGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILK----GKLNLPP 221

                       250       260       270
                ....*....|....*....|....*....|....
gi 94968081 250 DVPHELERIISKALEKDRNLRYQSAAEMQADLKR 283
cd05584     222 YLTPEARDLLKKLLKRNPSSRLGAGPGDAAEVQS 255

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

5e-21

98.07

71.17

4,8,2,40,50,42,103,155,145,10,181,155,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTatLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd06609       3 FTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIDLEEAEDE--IEDIQQEIQFLSQCRSPYITKYYGSFLKGSKLWIIMEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAkmSQEQETESRLvav 168
cd06609      81 CGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGVS--GQLTSTMSKR--- 155

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 94968081 169 tsdgltgehrtspGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLP 223
cd06609     156 -------------NTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPP 197

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

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

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

false

true

false

324

1e-20

97.26

79.01

6,8,0,35,43,37,6,49,44,105,170,149,10,182,159,65,251,224,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPED--VAEDTA-TLARFQREARAASALNHPNICSIFDIGEQEGRAFIA 85
cd05589       1 FRCLAVLGRGHFGKVLLAEYKKTGELYAIKALKKGdiIARDEVeSLMCEKRIFETANSERHPFLVNLFACFQTEDHVCFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  86 MEYLDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrl 165
cd05589      81 MEYAAGGDLMMHIHTDVFSEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGLCK----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 166 vavtsDGLTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPV 245
cd05589     150 -----EGMGFGDRTS--TFCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYPR 222

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94968081 246 RLnpdvPHELERIISKALEKDRNLRYQSAAEMQADLKR 283
cd05589     223 FL----SREAISIMRRLLRRNPERRLGSGERDAEDVKK 256

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

1e-20

97.36

76.63

8,6,2,45,54,47,41,95,91,4,101,95,52,155,147,9,177,156,2,182,158,14,196,175,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLarfQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd06613       3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLEPGDDFEII---QQEISMLKECRHPNIVAYFGSYLRRDKLWIVM 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLK---HLIGrsPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAkmSQEQETES 163
cd06613      80 EYCGGGSLQdiyQVTG--PLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVS--AQLTATIA 155

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94968081 164 RlvavtsdgltgehRTspgTTMGTIAYMSPEQA---RGKELDARTDLFSFGVVLYEMSTGTLP 223
cd06613     156 K-------------RK---SFIGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPP 202

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88512

cd05611

STKc_Rim15_like

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, fungal Rim15-like kinases, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase.

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/...

false

true

false

260

2e-20

96.54

91.92

6,11,0,32,43,34,13,57,47,34,91,84,29,122,113,36,180,149,90

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPED--VAEDTATLARFQReARAASALNHPNICSIFDIGEQEGRAFIAMEYL 89
cd05611       1 LKPISKGAFGSVYLAKKRSTGDYFAIKVLKKSdmIAKNQVTNVKAER-AIMMIQGESPYVAKLYYSFQSKDYLYLVMEYL 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  90 DG---VTLKHLIGRSPVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEqetesrlv 166
cd05611      80 NGgdcASLIKTLGGLPEDWAKQYIAEVVLGVEDL--HQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLE-------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 avtsdgltgehrtsPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVR 246
cd05611     150 --------------NKKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEE 215

                       250       260
                ....*....|....*....|....
gi 94968081 247 LNPDVPHELERIISKALEKDRNLR 270
cd05611     216 VKEFCSPEAVDLINRLLCMDPAKR 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132941

cd06610

STKc_OSR1_SPAK

Serine/threonine kinases (STKs), oxidative stress response kinase (OSR1) and Ste20-related proline alanine-rich kinase (SPAK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates.

Serine/threonine kinases (STKs), oxidative stress response kinase (OSR1) and Ste20-...

false

true

false

266

4e-20

95.46

93.98

11,6,0,34,42,34,27,69,65,2,72,67,6,81,73,20,101,97,57,173,154,21,194,178,4,200,182,39,242,221,10,252,236,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLpeDVAEDTATLARFQREARAASALNHPNI----CSiFDIGEQegrA 82
cd06610       1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIKRI--DLEKCQTSMDELRKEIQAMSLCHHPNVvkyyTS-FVVGDE---L 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  83 FIAMEYLDGVTLKHLIGRS----PVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQE 158
cd06610      75 WVVMPLMSGGSCLDIMKYSypqgGLDEAIIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVSASLAD 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 159 qetesrlvavtsdglTGEHRTSPGTTMGTIAYMSPE---QARGkeLDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEA 235
cd06610     155 ---------------GGDRTKVRKTFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYSKYPPMKVLML 217

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94968081 236 ILGRvpvAPVRLNPDVP-----HELERIISKALEKD 266
cd06610     218 TLQN---DPPSLETEADykkysKSFRKMISKCLQKD 250

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-20

95.44

73.21

6,14,2,30,44,34,19,64,53,37,101,91,53,170,144,10,182,154,83

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDV--AEDTATLARFQREARAASAlNHPNICSIFDIGEQEGRAFIAMEYLDGV 92
cd05591       3 LGKGSFGKVMLAELKGTDEVYAIKVLKKDVilQDDDVDCTMTEKRILALAA-KHPFLTALHCCFQTKDRLFFVMEYVNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLKHLIGRS-PVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsD 171
cd05591      82 DLMFQIQRSrKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCK----------------E 145

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 GLTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPDV 251
cd05591     146 GILNGVTTT--TFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEA 223

                       250
                ....*....|....
gi 94968081 252 PHELERIISKALEK 265
cd05591     224 VSILKAFMTKNPNK 237

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

2e-19

93.48

93.75

8,8,4,33,43,37,8,54,45,43,97,90,55,155,145,9,179,154,62,243,216,6,249,223,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPedVAEDTATLarfQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd06612       5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVP--VEEDLQEI---IKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHL--IGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLakmSQEQETESRlv 166
cd06612      80 CGAGSVSDImkITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGV---SGQLTDTMA-- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 avtsdgltgehrtSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPvaPVR 246
cd06612     155 -------------KRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPP--PTL 219

                       250       260
                ....*....|....*....|....*
gi 94968081 247 LNP-DVPHELERIISKALEKDRNLR 270
cd06612     220 SDPeKWSPEFNDFVKKCLVKDPEER 244

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

3e-19

92.38

73.10

6,14,2,31,45,35,20,66,55,29,95,85,59,170,144,10,182,154,79

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVA--EDTATLARFQREARAASALNhPNICSIFDIGEQEGRAFIAMEYLDGV 92
cd05620       3 LGKGSFGKVLLAELKGKGEYFAVKALKKDVVliDDDVECTMVEKRVLALAWEN-PFLTHLYCTFQTKEHLFFVMEFLNGG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLK-HLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsD 171
cd05620      82 DLMfHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCK----------------E 145

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 GLTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPDV 251
cd05620     146 NVFGDNRAS--TFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKES 223

                       250
                ....*....|
gi 94968081 252 PHELERIISK 261
cd05620     224 KDILEKLFER 233

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

4e-19

92.10

86.41

10,11,5,29,42,34,32,74,68,23,97,101,6,108,107,42,171,149,9,180,159,47,237,206,10,247,224,13,260,247,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLpeDVAEDTATLARFQREARAASALNHPNICSIFD--IGEQEGRAFIAMEYL 89
cd06621       6 LSRLGEGAGGSVTKCRLKNTGMIFALKTI--TTDPNPDLQKQILRELEINKSCKSPYIVKYYGafLDESSSSIGIAMEYC 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  90 DGVTLKHL----------IGRSPVemsklLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFglakmsqeq 159
cd06621      84 EGGSLDSIykkvkkrggrIGEKVL-----GKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDF--------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 160 etesrlvavtsdGLTGEHRTS-PGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGEssvetfeailG 238
cd06621     150 ------------GVSGELVNSlAGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPE----------G 207

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 94968081 239 RVPVAPVRL--------NPDVPHELERIIS----------KALEKD 266
cd06621     208 EPPLGPIELlsyivnmpNPELKDEPGNGIKwseefkdfikQCLEKD 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

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

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

false

true

false

268

4e-19

91.85

93.28

9,12,5,26,38,34,62,100,97,44,144,142,9,162,151,9,173,160,5,181,165,56,240,221,17,257,242,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALK---FLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYL 89
cd06630       6 QQLGTGAFSSCYQARDVKTGTLMAVKqvtYVRNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWM 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  90 DGVTLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGH-AKILDFGLAkmsqeqeteSRLVA 167
cd06630      86 AGGSVSHLLSKyGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFGAA---------ARLAA 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 168 VTSDglTGEHRtspGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILgrvPVAPVRL 247
cd06630     157 KGTG--AGEFQ---GQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHSNHLALIF---KIASATT 228

                       250       260
                ....*....|....*....|....*..
gi 94968081 248 NPDVPHELER----IISKALEKDRNLR 270
cd06630     229 APSIPEHLSPglrdVTLRCLELQPEDR 255

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

1e-18

90.75

66.67

5,8,2,92,100,96,51,151,148,14,183,162,22,205,190,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05601       3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGR--SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFG-LAKMSQEQETESRL 165
cd05601      83 HPGGDLLSLLNRyeDQFDESMAQFYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFGsAAKLNANKMVNSKL 162

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94968081 166 vavtsdgltgehrtspgtTMGTIAYMSPEQARGKELDART------DLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05601     163 ------------------PVGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGTSAVTYSNIM 222

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

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

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

false

true

false

267

1e-18

90.28

95.13

9,14,7,24,38,33,9,47,46,53,100,100,54,163,154,17,183,171,57,247,228,6,253,238,17,271,255,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALK--FLPEDVAED----TATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd06628       8 IGSGSFGSVYLGMNAHSGELMAVKqvEIPSNSIGVqdrkRKMLDALQREINLLKELHHENIVQYLGSSQDAGHLNIFLEY 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesRLVA 167
cd06628      88 VPGGSVAALLNNyGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISK---------KLEA 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 168 VTSDGLTGEHRTSpgtTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVpvapvrl 247
cd06628     159 NSLSTKTNGARPS---LQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFPDCTQMQAIFKIGTNA------- 228

                       250       260       270
                ....*....|....*....|....*....|....
gi 94968081 248 NPDVPH----ELERIISKALEKDRNLRyQSAAEM 277
cd06628     229 SPEIPSnassEAKNFLRKTFEIDYNKR-PTAAEL 261

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-18

90.46

72.19

5,14,2,48,62,51,40,102,92,52,170,144,10,182,154,79

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAAS-ALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05590       3 LGKGSFGKVMLARLKESGRLYAVKVLKKDVILQDDDVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEFVNGGD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIGRSP-VEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsDG 172
cd05590      83 LMFHIQKSRrFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCK----------------EG 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 173 LTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPDVP 252
cd05590     147 IFNGKTTS--TFCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLSQDAV 224


                ....*....
gi 94968081 253 HELERIISK 261
cd05590     225 DILKAFMTK 233

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

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

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

false

true

false

258

3e-18

89.02

95.74

10,12,5,37,49,44,51,100,96,66,185,162,16,201,179,23,227,202,10,237,214,6,248,220,9,257,233,13,271,246,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTA--TLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLD 90
cd06632       6 ELLGSGSFGSVYEGLNLDDGDFFAVKEVSLADDGQTGqeAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  91 GVTLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRLVavt 169
cd06632      86 GGSLAKLLKKyGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAKQVVEFSFAKSFK--- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 170 sdgltgehrtspgttmGTIAYMSPEQARGKEL-DARTDLFSFGVVLYEMSTGTLPFrgeSSVETFEAIL--GRVPVApvr 246
cd06632     163 ----------------GSPYWMAPEVIAQQGGyGLAADIWSLGCTVLEMATGKPPW---SQLEGVAAVFkiGRSKEL--- 220

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94968081 247 lnPDVPHELER----IISKALEKDRNLRyQSAAEM 277
cd06632     221 --PPIPDHLSDeakdFILKCLQRDPSLR-PTAAEL 252

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-18

88.40

67.03

7,12,6,32,47,38,6,53,45,41,94,93,22,126,115,27,162,142,9,182,151,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVaedTATLAR-FQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06619       7 EILGHGNGGTVYKAYHLLTRRILAVKVIPLDI---TVELQKqIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDG 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTL-------KHLIGRSPVEMSKLLGLAIEIAdaldaahtqgIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqeteSR 164
cd06619      84 GSLdvyrkipEHVLGRIAVAVVKGLTYLWSLK----------ILHRDVKPSNMLVNTRGQVKLCDFGVS---------TQ 144

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 165 LVAVTSDgltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPF 224
cd06619     145 LVNSIAK-----------TYVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

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

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

false

true

false

277

6e-18

88.03

91.34

5,14,0,81,95,82,2,97,86,56,153,143,11,184,154,99

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05577       1 LGKGGFGEVCACQVRATGKMYACKKLDKKRIKKRKGETMALNEKIILEKVSSPFIVSLAYAFETKDALCLVLTLMNGGDL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 K-HL--IGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLA-KMSQEQETESRlvavts 170
cd05577      81 KfHIynVGNPGFDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLAvEFPEGKKIHGR------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 171 dgltgehrtspgttMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPD 250
cd05577     155 --------------VGTVGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHSPFRQRKEKVKKEEVDRRTLTDEVEYPDK 220

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968081 251 VPHELERIISKALEKDRNLRYQSAAEMQADLKR 283
cd05577     221 FSEEAKSICEGLLQKDPEKRLGCRGEGADEVKE 253

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

6e-18

87.98

88.81

7,10,4,34,46,38,58,104,103,20,126,123,27,162,150,9,182,159,22,204,187,71

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  11 IVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVaeDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLD 90
cd06622       5 VLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLEL--DESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  91 GVTLKHLIGRSPVE-------MSKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqeteS 163
cd06622      83 AGSLDKLYAGGVATegipedvLRRITYAVVKGLKFLKEEHN--IIHRDVKPTNVLVNGNGQVKLCDFGVS---------G 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 RLVAVTSDgltgehrtspgTTMGTIAYMSPEQARGKELDAR------TDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd06622     152 NLVASLAK-----------TNIGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYANIFAQLS 220

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94968081 238 GRVPVAPVRLNPDVPHELERIISKALEKDRNLRYQSAA 275
cd06622     221 AIVDGDPPTLPSGYSDDAQDFVAKCLNKIPNRRPTYAQ 258

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

6e-18

88.07

58.38

5,8,44,145,153,190,4,173,194,7,182,201,12,194,217,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05596      45 FDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLSKFEMIKRSDSAFFWEERDIMAHANSEWIVQLHYAFQDDKYLYMVMEY 124

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLA-KMSQeqetesrlva 167
cd05596     125 MPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCmKMDA---------- 194

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94968081 168 vtsdglTGEHRTSpgTTMGTIAYMSPE----QARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05596     195 ------NGMVRCD--TAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIM 260

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-17

86.94

78.62

7,14,3,10,24,16,18,48,34,3,51,42,56,107,99,57,182,156,67,253,223,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVY---KAEDTRLHRLVALKFLPEdvaedtATL-----ARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd05582       4 LGQGSFGKVFlvrKITGPDAGQLYAMKVLKK------ATLkvrdrVRTKMERDILAEVNHPFIVKLHYAFQTEGKLYLIL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGRSPVEMSK-LLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRl 165
cd05582      78 DFLRGGDLFTRLSKEVMFTEEdVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAY- 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 166 vavtsdgltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPV 245
cd05582     157 -----------------SFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGMPQ 219

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 94968081 246 RLNPdvphELERIISKALEKDRNLRYQSAAEMQADLKR 283
cd05582     220 FLSP----EAQSLLRALFKRNPANRLGAGPDGVEEIKR 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88488

cd05587

STKc_cPKC

STKc_cPKC: Serine/Threonine Kinases (STKs), Classical (or Conventional) Protein Kinase C (cPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. cPKCs are potent kinases for histones, myelin basic protein, and protamine. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia.

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

false

true

false

324

2e-17

86.12

76.54

7,14,7,54,68,62,31,99,98,6,109,104,45,175,149,10,185,162,63,252,225,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPN-ICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05587       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVIIQDDDVECTMVEKRVLALPGKPPfLTQLHSCFQTMDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIG-----RSPVEMskllGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvav 168
cd05587      88 LMYHIQqvgkfKEPHAV----FYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCK-------------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 169 tsdgltgEHRTSPGTTM---GTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPV 245
cd05587     150 -------ENIFGGKTTRtfcGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPK 222

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94968081 246 RLNpdvpHELERIISKALEKDRNLRYQSAAEMQADLK 282
cd05587     223 SLS----KEAVSICKGLLTKHPAKRLGCGPTGERDIR 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88523

cd05622

STKc_ROCK1

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

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

false

true

false

371

6e-17

84.72

66.85

6,8,44,145,153,190,6,166,196,5,182,201,21,203,226,57,261,283,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05622      45 YEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEY 124

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLA-KMSQEQetesrlvA 167
cd05622     125 MPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCmKMNKEG-------M 197

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 168 VTSDgltgehrtspgTTMGTIAYMSPEQARGKELDA----RTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVA 243
cd05622     198 VRCD-----------TAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSL 266

                       250       260
                ....*....|....*....|....*..
gi 94968081 244 PVRLNPDVPHELERIISkALEKDRNLR 270
cd05622     267 TFPDDNDISKEAKNLIC-AFLTDREVR 292

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

6e-17

84.72

58.38

5,8,44,145,153,190,4,173,194,7,182,201,21,203,226,34

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY 88
cd05621      45 YDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEY 124

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 LDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLA-KMSQeqetesrlva 167
cd05621     125 MPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFGTCmKMDE---------- 194

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 94968081 168 vtsdglTGEHRTSpgTTMGTIAYMSPEQARGKELDA----RTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05621     195 ------TGMVRCD--TAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIM 260

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

7e-17

84.63

75.85

6,14,2,46,60,49,34,94,84,60,170,144,10,182,154,57,243,211,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARA-ASALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05575       3 IGKGSFGKVLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVlLKNVKHPFLVGLHYSFQTKEKLYFVLDYVNGGE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 L-KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsDG 172
cd05575      83 LfFHLQRERSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCK----------------EG 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 173 LTGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRvpvaPVRLNPDVP 252
cd05575     147 IAGSKTTS--TFCGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNK----PLRLRPNIS 220

                       250       260
                ....*....|....*....|....*..
gi 94968081 253 HELERIISKALEKDRNLRYQSAAEMQA 279
cd05575     221 VSARHLLEGLLQKDRTKRLGAKNDFLE 247

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

7e-17

84.60

72.46

8,65,59,26,91,88,29,122,117,39,162,156,18,182,174,12,194,190,7,205,197,44,250,241,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  66 HPNICSIFDIGEQEGRAFIAMEYLDG---VTLKHLIGRSPVEMSKLLGLAIEIADALDaaHTQGIVHRDIKPPNIFVTKR 142
cd05609      60 NPFVVSMFCSFETRRHLCMVMEYVEGgdcATLLKNIGPLPVDMARMYFAETVLALEYL--HNYGIVHRDLKPDNLLITSM 137

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 143 GHAKILDFGLAKMSQEQETeSRLVAVTSDGLTGEHRTSpgTTMGTIAYMSPE----QARGKELdartDLFSFGVVLYEMS 218
cd05609     138 GHIKLTDFGLSKIGLMSLT-TNLYEGHIEKDTREFLDK--QVCGTPEYIAPEvilrQGYGKPV----DWWAMGIILYEFL 210

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94968081 219 TGTLPFRGESSVETFEAILGRVPVAPVRLNPdVPHELERIISKALEKDRNLRYQSAAEMQADLKRLKRDTD 289
cd05609     211 VGCVPFFGDTPEELFGQVISDDIEWPEGDEA-LPADAQDLISRLLRQNPLERLGTGGAFEVKQHRFFLGLD 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132951

cd06620

PKc_MAPKK_Byr1_like

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

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

false

true

false

284

1e-16

83.69

88.03

10,9,7,31,42,38,46,88,89,7,97,96,7,104,104,20,126,124,27,162,151,9,182,160,42,224,210,23,247,234,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  10 RIVEQIGGGGMGVVYKAEDTRLHRLVALKFLpeDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEY- 88
cd06620       8 ETISDLGAGNGGSVSKVKHIPTGTVMAKKVV--HIGAKSSVRKQILRELQIMHECRSPYIVSFYGAFLNENNICMCMEFm 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  89 ----LDGVTLKhlIGRSPVE-MSKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqeteS 163
cd06620      86 dcgsLDRIYKK--GGPIPVEiLGKIAVAVVEGLTYLYNVHR--IMHRDIKPSNILVNSRGQIKLCDFGVS---------G 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 RLVAVTSDgltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPF--------RGESSVETFEA 235
cd06620     153 ELINSIAD-----------TFVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFafsnidddGQDDPMGILDL 221

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94968081 236 ILGRVPVAPVRL-NPDVPHELERIISKALEKDRNLR 270
cd06620     222 LQQIVQEPPPRLpSSDFPEDLRDFVDACLLKDPTER 257

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-16

83.65

84.56

10,13,25,27,49,52,7,56,65,18,74,86,4,81,90,71,152,162,14,185,176,51,238,227,11,249,239,22,272,261,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  14 QIGGGGMGVVYKAEDTRLHRLVALKFLpedvaedtaTLARFQR------EARAASALNHPNICSIFD---IGEQegrAFI 84
cd06648      26 KIGEGSTGIVCIATDKSTGRQVAVKKM---------DLRKQQRrellfnEVVIMRDYQHPNIVEMYSsylVGDE---LWV 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  85 AMEYLDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGL-AKMSQEQETES 163
cd06648      94 VMEFLEGGALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFcAQVSKEVPRRK 173

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 RLVavtsdgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIlgRVPVA 243
cd06648     174 SLV-------------------GTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRI--RDNLP 232

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94968081 244 PVRLNP-DVPHELERIISKALEKDRNLRYqSAAEM 277
cd06648     233 PKLKNLhKVSPRLRSFLDRMLVRDPAQRA-TAAEL 266

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

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

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

false

true

false

288

1e-16

83.44

91.67

10,8,1,24,32,28,10,42,39,24,66,64,28,94,93,68,177,161,3,182,164,19,201,185,26,227,215,38,267,253,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLH---RLVALKFLPE-DVAEDTATLARFQREARAASALNH-PNICSIFDIGEQEGRAF 83
cd05583       2 FELLRVLGTGAYGKVFLVRKVGGHdagKLYAMKVLKKaTIVQKAKTAEHTRTERQVLEAVRRcPFLVTLHYAFQTDTKLH 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  84 IAMEYLDGVTL-KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETE 162
cd05583      82 LILDYVNGGELfTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLAEEEE 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 163 srlvavtsdgltgehRTSpgTTMGTIAYMSPEQARGKEL--DARTDLFSFGVVLYEMSTGTLPFRGE----SSVETFEAI 236
cd05583     162 ---------------RAY--SFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDgeqnSQSEISRRI 224

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94968081 237 LGRVPVAPVRLNPDVPHELERIISKALEKdrNLRYQSAAEMQA 279
cd05583     225 LKSKPPFPKTMSAEARDFIQKLLEKDPKK--RLGANGADEIKN 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

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

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

false

true

false

277

1e-16

83.59

85.20

5,11,8,37,50,45,103,153,149,13,185,162,38,226,200,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTatLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06641       9 LEKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLA-KMSQEQETESRLVavts 170
cd06641      87 GSALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAgQLTDTQIKRNTFV---- 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 171 dgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPfrgESSVETFEAILGRVPVAPVRLNPD 250
cd06641     163 ---------------GTPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPP---HSELHPMKVLFLIPKNNPPTLEGN 224

                       250       260
                ....*....|....*....|
gi 94968081 251 VPHELERIISKALEKDRNLR 270
cd06641     225 YSKPLKEFVEACLNKEPSFR 244

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

1e-16

83.50

72.76

5,14,2,80,94,83,60,170,143,10,182,153,67,253,220,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05571       3 LGKGTFGKVILVREKATGKYYAMKILKKEVIIAKDEVAHTLTESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 -KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsDGL 173
cd05571      83 fFHLSRERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLCK----------------EGI 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 174 TGEHRTSpgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPdvph 253
cd05571     147 SDGATMK--TFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLSP---- 220

                       250
                ....*....|....*..
gi 94968081 254 ELERIISKALEKDRNLR 270
cd05571     221 EAKSLLAGLLKKDPKQR 237

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

2e-16

83.32

94.30

8,14,9,27,41,38,54,95,93,59,163,152,9,178,161,46,230,207,28,258,239,12,271,251,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLP--EDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGV 92
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKQVPfdPDSPETKKEVNALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPGG 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLK-HLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesRLVAVTSD 171
cd06625      90 SVKdQLKAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASK---------RLQTICSS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 GltgehrTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFrgessvETFEAILGRVPVAPVRLNPDV 251
cd06625     161 G------TGMKSVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPW------AEFEAMAAIFKIATQPTNPQL 228

                       250       260       270
                ....*....|....*....|....*....|
gi 94968081 252 PHELERI----ISKALEKDRNLRyQSAAEM 277
cd06625     229 PSHVSPDarnfLRRTFVENAKKR-PSAEEL 257

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-16

82.79

85.20

4,11,8,37,50,45,103,171,148,53,227,201,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTatLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06642       9 LERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqetesrlvavtsd 171
cd06642      87 GSALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVA------------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 GLTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFrgeSSVETFEAILGRVPVAPVRLNPDV 251
cd06642     149 GQLTDTQIKRNTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPN---SDLHPMRVLFLIPKNSPPTLEGQY 225

                       250
                ....*....|....*....
gi 94968081 252 PHELERIISKALEKDRNLR 270
cd06642     226 SKPFKEFVEACLNKDPRFR 244

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

3e-16

82.41

86.46

12,12,9,51,64,60,26,91,86,4,95,96,6,101,104,4,105,109,19,126,128,33,165,161,7,185,168,10,195,181,35,232,216,18,250,238,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASAlNHPNICSIFDIGEQEGRAFIAMEYLDgV 92
cd06616      10 GEIGRGAFGTVNKMLHKPSGTIMAVKRIRSTVDEKEQKRLLMDLDVVMRSS-DCPYIVKFYGALFREGDCWICMELMD-I 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLK------HLIGRS--PVEM-SKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQetes 163
cd06616      88 SLDkfykyvYEVLKSviPEEIlGKIAVATVKALNYLKEELK--IIHRDVKPSNILLDRNGNIKLCDFGISGQLVDS---- 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 rlVAVTSDGltgehrtspgttmGTIAYMSPEQ---ARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVetFEAILGRV 240
cd06616     162 --IAKTRDA-------------GCRPYMAPERidpSARDGYDVRSDVWSLGITLYEVATGKFPYPKWNSV--FDQLTQVV 224

                       250       260       270
                ....*....|....*....|....*....|....
gi 94968081 241 PVAPVRLNPD----VPHELERIISKALEKDRNLR 270
cd06616     225 KGDPPILSNSeereFSPSFVNFINLCLIKDESKR 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133173

cd05041

PTKc_Fes_like

Catalytic Domain of Fes-like Protein Tyrosine Kinases

false

true

false

251

5e-16

81.74

93.63

10,12,0,15,28,15,21,51,36,55,106,93,45,154,138,6,173,144,44,217,189,20,237,211,5,248,216,2,250,219,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEdTRLHRLVALKFLPEDVAEDTAtlARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGV 92
cd05041       1 EKIGKGNFGDVYKGV-LKGKTEVAVKTCRSTLPPDLK--RKFLQEAEILKQYDHPNIVKLIGVCVQKQPIYIVMELVPGG 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLKHLIGRSPVEMS--KLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGlakMSQEQEtesrlvavts 170
cd05041      78 SLLTFLRKKKNRLTvkKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFG---MSREEE---------- 144

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 171 dglTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEM-STGTLPFRGESSVETFEAIL--GRVPVapvrl 247
cd05041     145 ---GGIYTVSDGLKQIPIKWTAPEALNYGRYTSESDVWSYGILLWETfSLGDTPYPGMSNQQTRERIEsgYRMPA----- 216

                       250       260
                ....*....|....*....|
gi 94968081 248 nPD-VPHELERIISKALEKD 266
cd05041     217 -PQlCPEEIYRLMLQCWAYD 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132946

cd06615

PKc_MEK

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

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

false

true

false

308

6e-16

81.33

70.78

7,13,7,33,48,40,49,97,92,7,104,100,20,126,120,30,176,150,55,232,205,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  14 QIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEdtATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVT 93
cd06615       8 ELGAGNGGVVTKVLHRPSGLIMARKLIHLEIKP--AIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHL---IGRSPVE-MSKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAKMSqeqetesrlvavt 169
cd06615      86 LDQVlkkAGRIPENiLGKISIAVLRGLTYLREKHK--IMHRDVKPSNILVNSRGEIKLCDFGVSGQL------------- 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 170 sdgltgeHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVEtFEAILGRVPVAPVRLNP 249
cd06615     151 -------IDSMANSFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKE-LEAMFGRPVSEGEAKES 222


                ...
gi 94968081 250 DVP 252
cd06615     223 HRP 225

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

9e-16

81.10

70.31

6,1,13,40,44,53,30,74,86,4,81,90,71,152,162,14,185,176,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   2 IGQIVSHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPedvAEDTATLARFQREARAASALNHPNICSIFD---IGEQ 78
cd06647      14 VGDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMN---LQQQPKKELIINEILVMRENKHPNIVNYLDsylVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  79 egrAFIAMEYLDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGL-AKMSQ 157
cd06647      91 ---LWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQITP 167

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94968081 158 EQETESRLVavtsdgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGES 228
cd06647     168 EQSKRSTMV-------------------GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNEN 219

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

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

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

false

true

false

277

1e-15

80.87

85.20

5,11,8,37,50,45,104,158,149,7,179,156,44,226,200,44

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTatLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06640       9 LERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeQETESRLvavtsd 171
cd06640      87 GSALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAG----QLTDTQI------ 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 172 gltgehrtSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPfrgESSVETFEAILGRVPVAPVRLNPDV 251
cd06640     157 --------KRNTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPP---NSDMHPMRVLFLIPKNNPPTLTGEF 225

                       250
                ....*....|....*....
gi 94968081 252 PHELERIISKALEKDRNLR 270
cd06640     226 SKPFKEFIDACLNKDPSFR 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

1e-15

80.46

78.85

7,14,0,28,42,32,10,56,42,38,94,81,69,181,150,58,243,208,23,266,233,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPE----DVAEDTATLArfqrEARAASALNHPNICSIFDIGEQEGRAFIAMEYLD 90
cd05585       1 IGKGSFGKVMQVRKKDTQRIYALKTIRKahivSRSEVTHTLA----ERTVLAQVNCPFIVPLKFSFQSPEKLYFVLAFIN 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  91 GVTL-KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESrlvavt 169
cd05585      77 GGELfHHLQKEGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLNMKDDDRT------ 150

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 170 sdgltgehrtspGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRvpvaPVRLNP 249
cd05585     151 ------------NTFCGTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQE----PLRFPD 214

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968081 250 DVPHELERIISKALEKD--RNLRYQSAAEMQA 279
cd05585     215 GFDRDAKDLLTGLLNRDptQRLGYNGAQEIKN 246

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

1e-15

80.11

83.11

13,10,18,32,42,51,5,50,56,12,63,68,3,66,73,21,88,94,13,101,109,2,103,112,61,183,173,11,194,188,32,226,221,13,242,234,8,250,244,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  11 IVEQIGGGGMGVVYKAEDTRLHRLVALKFLPE-DVAEDtatLARFQREARAASaLNH--PNICSIFDIGEQEGRAFIAME 87
cd06618      19 NLGEIGSGTCGQVYKMRFKKTGHVMAVKQMRRtGNKEE---NKRILMDLDVVL-KSHdcPYIVKCYGYFITDSDVFICME 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 yLDGVTLKHLIGRS--PV-EMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESR 164
cd06618      95 -LMSTCLDKLLKRIqgPIpEDILGKMTVAIVKALHYLKEKHGVIHRDVKPSNILLDASGNVKLCDFGISGRLVDSKAKTR 173

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 165 lvavtsdgltgehrtspgtTMGTIAYMSPE----QARGKELDARTDLFSFGVVLYEMSTGTLPFRG-ESSVETFEAILGR 239
cd06618     174 -------------------SAGCAAYMAPEridpPDPNPKYDIRADVWSLGISLVELATGQFPYKNcKTEFEVLTKILQE 234

                       250       260       270
                ....*....|....*....|....*....|...
gi 94968081 240 vpvAPVRLNPD--VPHELERIISKALEKDRNLR 270
cd06618     235 ---EPPSLPPNegFSPDFCSFVDLCLTKDHRKR 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88517

cd05616

STKc_cPKC_beta

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

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

false

true

false

323

2e-15

80.05

64.09

6,14,7,31,45,40,18,64,58,36,100,95,56,168,151,8,182,159,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVA--EDTATLARFQREARAASAlNHPNICSIFDIGEQEGRAFIAMEYLDGV 92
cd05616       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVViqDDDVECTMVEKRVLALSG-KPPFLTQLHSCFQTMDRLYFVMEYVNGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  93 TLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSqeqetesrlvavTSD 171
cd05616      87 DLMYQIQQvGRFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEN------------MWD 154

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94968081 172 GLTGEhrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05616     155 GVTTK------TFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIM 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133168

cd05036

PTKc_ALK_LTK

Catalytic Domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase

Catalytic Domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and...

false

true

false

277

2e-15

79.79

82.31

9,9,8,18,29,26,5,34,38,12,48,50,50,98,102,2,100,110,44,144,157,10,170,167,46,216,214,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  10 RIVEQIGGGGMGVVYKAEdtRLHRL-------VALKFLPEDVAEdtATLARFQREARAASALNHPNICSIFDIGEQEGRA 82
cd05036       9 TLLRALGHGAFGEVYEGL--YRGRDgdavelqVAVKTLPESCSE--QDESDFLMEALIMSKFNHQNIVRLIGVSFERLPR 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  83 FIAMEYLDGVTLKHLI--GR------SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGH---AKILDFG 151
cd05036      85 FILLELMAGGDLKSFLreNRprperpSSLTMKDLLFCARDVAKGCKYLEENHFIHRDIAARNCLLTCKGPgrvAKIADFG 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 152 LAKmsqeqetesrlvavtsDGLTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYE-MSTGTLPFRGESSV 230
cd05036     165 MAR----------------DIYRASYYRKGGRAMLPIKWMPPEAFLDGIFTSKTDVWSFGVLLWEiFSLGYMPYPGRTNQ 228


                ....*...
gi 94968081 231 ETFEAILG 238
cd05036     229 EVMEFVTG 236

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-15

79.72

72.62

7,14,2,26,45,28,8,54,36,11,65,54,41,106,96,52,176,148,63,243,211,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLpedvaEDTATLARfQREARAASALN-------HPNICSIFDIGEQEGRAFIAME 87
cd05602       3 IGKGSFGKVLLARHKSDEKFYAVKVL-----QKKAILKK-KEEKHIMSERNvllknvkHPFLVGLHFSFQTTDKLYFVLD 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  88 YLDGVTLKHLIGRSPVEMS-KLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEqetesrlv 166
cd05602      77 YINGGELFYHLQRERCFLEpRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIE-------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 167 avtsdgltgeHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRvpvaPVR 246
cd05602     149 ----------PNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNK----PLQ 214

                       250       260
                ....*....|....*....|....
gi 94968081 247 LNPDVPHELERIISKALEKDRNLR 270
cd05602     215 LKPNITNSARHLLEGLLQKDRTKR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132986

cd06655

STKc_PAK2

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

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

false

true

false

296

2e-15

79.77

90.20

6,1,13,52,56,65,96,152,162,14,185,176,51,238,227,19,257,247,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   2 IGQIVSHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARfqrEARAASALNHPNICSIFDIGEQEGR 81
cd06655      14 IGDPKKKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKELIIN---EILVMKELKNPNIVNFLDSFLVGDE 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  82 AFIAMEYLDGVTLKHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGL-AKMSQEQE 160
cd06655      91 LFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFcAQITPEQS 170

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 161 TESRLVavtsdgltgehrtspgttmGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIlgRV 240
cd06655     171 KRSTMV-------------------GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLI--AT 229

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 94968081 241 PVAPVRLNPDVPHELER-IISKALEKDRNLRYQSAAEMQADLKRLKRDTDS 290
cd06655     230 NGTPELQNPEKLSPIFRdFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSS 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133179

cd05048

PTKc_Ror

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan...

false

true

false

283

3e-15

79.42

84.81

8,4,2,29,33,36,17,52,53,42,94,96,8,102,107,21,123,141,31,170,172,47,217,220,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   5 IVSHYRIVEQIGGGGMGVVYKAEDTRLHR-----LVALKFLPEDVAEDTATlaRFQREARAASALNHPNICSIFDIGEQE 79
cd05048       3 PLSAVRFLEELGEGAFGKVYKGELTGPNErlsatSVAIKTLKENAEPKVQQ--EFRQEAELMSDLQHPNIVCLLGVCTKE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  80 GRAFIAMEYLDGVTL-KHLIGRSP---VEMSKLLGLAIEIADALDAAH-------------TQGIVHRDIKPPNIFVTKR 142
cd05048      81 QPTCMLFEYLAHGDLhEFLVRNSPhsdVGAESGDETVKSSLDCSDFLHiaiqiaagmeylsSHHFVHRDLAARNCLVGEG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 143 GHAKILDFGLAKmsqeqetesrlvavtsDGLTGEHRTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEM-STGT 221
cd05048     161 LTVKISDFGLSR----------------DIYSADYYRVQSKSLLPVRWMPPEAILYGKFTTESDIWSFGVVLWEIfSYGL 224

                       250
                ....*....|....*...
gi 94968081 222 LPFRGESSVETFEAILGR 239
cd05048     225 QPYYGFSNQEVIEMIRSR 242

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

3e-15

79.31

63.66

10,11,9,33,46,42,52,98,97,6,104,104,20,126,124,27,162,151,11,184,162,34,236,196,8,248,204,3,252,207,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVaeDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06650      10 ISELGAGNGGVVFKVSHKPSGLIMARKLIHLEI--KPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLI---GRSPVE-MSKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqeteSRLVA 167
cd06650      88 GSLDQVLkkaGRIPEQiLGKVSIAVIKGLTYLREKHK--IMHRDVKPSNILVNSRGEIKLCDFGVS---------GQLID 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 168 VTSDGLtgehrtspgttMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMStgtlpfrgessvetfeaiLGRVPVAPvrl 247
cd06650     157 SMANSF-----------VGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMA------------------IGRYPIPP--- 204

                       250
                ....*....|....*....
gi 94968081 248 nPDVpHELERIISKALEKD 266
cd06650     205 -PDA-KELELMFGCPVEGD 221

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

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

false

true

false

279

3e-15

79.32

72.76

8,7,4,19,26,27,20,48,47,34,82,83,15,97,100,57,164,157,11,175,169,6,187,175,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   8 HYRIVEQIGGGGMGVVYKA----EDTRLHRLVALKFLPEDVAEdtATLARFQREARAASALNHPNICSIFDIGEQEGRA- 82
cd05038       5 VLKLIKQLGEGHFGTVYLGtydpPDDNTGEIVAVKKLNTSGVE--AHRQDFEREIEIMRTLDHENIVKYKGVSEEPGGRs 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  83 -FIAMEYLDGVTLKHL--IGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeq 159
cd05038      83 lSLIMEYLPSGSLRDYlrRHRDQLNLKRLLLFALQIAKGMDYLGSKRLIHRDLAARNILVDSEDLVKISDFGLAK----- 157

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94968081 160 etesrLVAVTSDGLTG-EHRTSPgttmgtIAYMSPEQARGKELDARTDLFSFGVVLYEMST 219
cd05038     158 -----VLPEDKDYYYVkEPRESP------IFWYAPECLRTGKFSSASDVWSYGVTLYEMFT 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132942

cd06611

STKc_SLK_like

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

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

false

true

false

280

3e-15

79.40

91.79

8,6,4,34,43,38,57,100,97,52,152,150,11,182,161,11,193,177,48,243,225,8,251,234,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   7 SHYRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLpedVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAM 86
cd06611       5 DIWEIIGELGDGAFGKVYKAQHKETGLFAAAKII---QIESEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  87 EYLDGVTLKHLIGR--SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGL-AKMSQEQETES 163
cd06611      82 EFCDGGALDSIMLEleRGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVsAKNKSTLQKRD 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 164 rlvavtsdgltgehrtspgTTMGTIAYMSP-----EQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILG 238
cd06611     162 -------------------TFIGTPYWMAPevvacETFKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILK 222

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94968081 239 RVPvaPVRLNPDV-PHELERIISKALEKDRNLRYQSAAEMQ 278
cd06611     223 SEP--PTLDQPSKwSSSFNDFLKSCLVKDPDDRPTAAELLK 261

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-15

78.15

72.76

5,14,2,89,103,92,51,170,143,6,178,149,71,253,220,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDGVTL 94
cd05595       3 LGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGEL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  95 KHLIGRSPV-EMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKmsqeqetesrlvavtsDGL 173
cd05595      83 FFHLSRERVfTEERARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCK----------------EGI 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 174 TGEhrTSPGTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAILGRVPVAPVRLNPdvph 253
cd05595     147 SDG--ATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLSP---- 220

                       250
                ....*....|....*..
gi 94968081 254 ELERIISKALEKDRNLR 270
cd05595     221 EAKSLLAGLLKKDPKQR 237

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

8e-15

77.78

63.14

9,11,9,33,46,42,53,99,98,5,104,104,20,126,124,27,162,151,11,184,162,47,232,209,7,240,216,2

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  12 VEQIGGGGMGVVYKAEDTRLHRLVALKFLPEDVaeDTATLARFQREARAASALNHPNICSIFDIGEQEGRAFIAMEYLDG 91
cd06649      10 ISELGAGNGGVVTKVQHKPSGLIMARKLIHLEI--KPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLIG---RSPVE-MSKLLGLAIEIADALDAAHTqgIVHRDIKPPNIFVTKRGHAKILDFGLAkmsqeqeteSRLVA 167
cd06649      88 GSLDQVLKeakRIPEEiLGKVSIAVLRGLAYLREKHQ--IMHRDVKPSNILVNSRGEIKLCDFGVS---------GQLID 156

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94968081 168 VTSDGLtgehrtspgttMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVEtFEAILGRvPV 242
cd06649     157 SMANSF-----------VGTRSYMSPERLQGTHYSVQSDIWSMGLSLVELAIGRYPIPPPDAKE-LEAIFGR-PV 218

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133171

cd05039

PTKc_Csk_like

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

false

true

false

256

1e-14

77.44

73.83

7,12,11,14,28,25,24,56,49,33,89,83,9,98,94,67,186,161,31,217,193,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAedTRLHRLVALKFLPEDVAEDTATLArfqrEARAASALNHPNICSIFDIGEQEGRAFIAMEYL-DG 91
cd05039      12 ATIGKGEFGDVMLG--DYRGQKVAVKCLKDDSTAAQAFLA----EASVMTTLRHPNLVQLLGVVLQGNPLYIVTEYMaKG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  92 VTLKHLI--GRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRLvavt 169
cd05039      86 SLVDYLRsrGRAVITLAQQLGFALDVCEGMEYLEEKNFVHRDLAARNVLVSEDLVAKVSDFGLAKEASQGQDSGKL---- 161

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94968081 170 sdgltgehrtspgttmgTIAYMSPEQARGKELDARTDLFSFGVVLYEM-STGTLPF 224
cd05039     162 -----------------PVKWTAPEALREKKFSTKSDVWSFGILLWEIySFGRVPY 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88514

cd05613

STKc_MSK1_N

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

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

false

true

false

290

1e-14

77.36

87.24

9,7,0,25,32,28,27,61,55,5,66,64,28,94,93,71,182,164,19,201,185,24,225,211,2,227,215,38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   8 HYRIVEQIGGGGMGVVYKAEDTRLH---RLVALKFLPEDVAEDTATLARFQREARaaSALNH----PNICSIFDIGEQEG 80
cd05613       1 NFELLKVLGTGAYGKVFLVRKVSGHdsgKLYAMKVLKKATIVQKAKTTEHTRTER--QVLEHirqsPFLVTLHYAFQTDT 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  81 RAFIAMEYLDGVTL-KHLIGRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQ 159
cd05613      79 KLHLILDYINGGELfTHLSQRERFKEQEVQIYSGEIVLALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFGLSKEFHED 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 160 ETESRLvavtsdgltgehrtspgTTMGTIAYMSPEQARGKEL--DARTDLFSFGVVLYEMSTGTLPFR--GE--SSVETF 233
cd05613     159 EVERAY-----------------SFCGTIEYMAPDIVRGGDGghDKAVDWWSMGVLMYELLTGASPFTvdGEknSQAEIS 221

                       250       260       270
                ....*....|....*....|....*....|..
gi 94968081 234 EAILGRVPVAPVRLNPDVPHELERIISKALEK 265
cd05613     222 RRILKSEPPYPQEMSALAKDIIQRLLMKDPKK 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132955

cd06624

STKc_ASK

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

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

false

true

false

268

1e-14

77.15

94.40

12,9,12,3,14,15,37,54,52,44,98,100,41,139,142,15,163,157,7,179,164,15,194,183,4,200,187,24,229,211,26,255,241,15,271,256,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  10 RIVeqIGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLarfQREARAASALNHPNICSIFDIGEQEGRAFIAMEYL 89
cd06624      13 RVV--LGKGTYGVVYAGRDLSTQVRIAIKEIPERDSRYSQPL---HEEIALHSRLKHKNIVQYLGSDSENGYFKIFMEQV 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  90 DGVTLKHLI----GRSPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFV-TKRGHAKILDFGLAKmsqeqetesR 164
cd06624      88 PGGSLSALLrskwGPLKDNESTIIFYTKQILEGLKYLHDNQIVHRDIKGDNVLVnTYSGVLKISDFGTSK---------R 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 165 LVAVTSdgltgehrtSPGTTMGTIAYMSPE----QARGkeLDARTDLFSFGVVLYEMSTGTLPFrgessVETFEAILGRV 240
cd06624     159 LAGINP---------CTETFTGTLQYMAPEiidkGPRG--YGAPADIWSLGCTIIEMATGKPPF-----HELGEPQAAMF 222

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 94968081 241 PVAPVRLNPDVPHEL----ERIISKALEKDRNLRyQSAAEMQAD 280
cd06624     223 KVGMFKIHPEIPESLsaeaKAFILRCFEPDPDKR-ASAHDLLQD 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88516

cd05615

STKc_cPKC_alpha

STKc_cPKC_alpha: Serine/Threonine Kinases (STKs), Classical Protein Kinase C (cPKC) subfamily, alpha isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion.

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

false

true

false

323

1e-14

76.97

64.09

4,14,7,54,68,62,32,100,95,64,182,159,55

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  15 IGGGGMGVVYKAEDTRLHRLVALKFLPEDVAEDTATLARFQREARAASALNHPN-ICSIFDIGEQEGRAFIAMEYLDGVT 93
cd05615       8 LGKGSFGKVMLAERKGTDELYAIKILKKDVVIQDDDVECTMVEKRVLALQDKPPfLTQLHSCFQTVDRLYFVMEYVNGGD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  94 LKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQETESRlvavtsdg 172
cd05615      88 LMYHIQQvGKFKEPQAVFYAAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVDGVTTR-------- 159

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94968081 173 ltgehrtspgTTMGTIAYMSPEQARGKELDARTDLFSFGVVLYEMSTGTLPFRGESSVETFEAIL 237
cd05615     160 ----------TFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIM 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Bck1-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress.

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

false

true

false

272

2e-14

76.76

87.50

9,12,6,27,39,35,9,48,49,52,100,102,59,176,161,9,185,171,9,194,182,30,227,212,10,240,222,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  13 EQIGGGGMGVVYKAEDTRLHRLVALKF--LPEDVAEDT-----ATLARFQREARAASALNHPNICSIFDIGEQEGRAFIA 85
cd06629       7 ELIGKGTYGRVYLALNVTTGEMMAVKQveLPATIAGRHdsrqkDMVKALRSEIETLKDLDHLNIVQYLGFETTEEYLSIF 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081  86 MEYLDGVTLKHLIGR-SPVEMSKLLGLAIEIADALDAAHTQGIVHRDIKPPNIFVTKRGHAKILDFGLAKMSQEQetesr 164
cd06629      87 LEYVPGGSIGSCLRTyGRFEEQLVRFFTEQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGISKKSDDI----- 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081 165 lvavtsdgltgeHRTSPGTTM-GTIAYMSPE--QARGKELDARTDLFSFGVVLYEMSTGTLPFrgeSSVETFEAILgrvP 241
cd06629     162 ------------YDNDQNMSMqGSVFWMAPEviHSYSQGYSAKVDIWSLGCVVLEMFAGRRPW---SDEEAIAAMF---K 223

                       250       260
                ....*....|....*....|.
gi 94968081 242 VAPVRLNPDVPHELERIISKA 262
cd06629     224 LGNKRSAPPIPPDVSMNLSPV 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6). MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAPK signaling cascades are important in mediating cellular responses to extracellular signals.

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain....

false

true

false

275

2e-14

76.55

91.64

9,8,7,33,41,46,14,64,60,9,73,75,21,94,101,59,155,160,9,180,169,14,194,188,43,238,231,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968081   9 YRIVEQIGGGGMGVVYKAEDTRLHRLVALKFLP------EDVAEDTATLARFQrearaasalNHPNICSIF------DIG 76
cd06608       8 FELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDiiedeeEEIEEEYNILRKYS---------NHPNIATFYgafikkGPP 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|