NCBI Conserved Domain Search

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Conserved domains on [gi\|94967068\|ref\|YP_589116.1\|]
serine/threonine protein kinase [Candidatus Koribacter versatilis Ellin345]

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List of domain hits		?

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

29142

cd00180

S_TKc

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

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

true

256

4e-61

231.63

96.48

5,17,0,37,57,37,110,167,151,7,177,158,61,238,220,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  18 RYEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIA 97
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKK---EKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLV 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK----SGAQLT 173
cd00180      78 MEYMSGGDLFDLLKKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKqldsGGRKLT 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 174 TggdVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPD-LETKVHPAVAAILR 252
cd00180     158 T---FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGKGTPDeLPPNISPEAKDLIK 234

                       250
                ....*....|...
gi 94967068 253 KALSKHPSDRYQA 265
cd00180     235 KLLVKDPEKRPTA 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132935

cd05122

PKc_STE

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

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

false

true

false

253

2e-46

182.74

95.26

5,18,1,34,57,35,109,169,144,8,177,156,72,249,229,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFdvhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKL-----ESDEEQEQILNEIQILKKCKHPNIVKYYGSYLKKDELWIVM 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTGGD- 177
cd05122      77 EYCDGGSLDDLLKSTGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVS---AQLSDTKAk 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 178 ---VLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKVHPAVAA-ILRK 253
cd05122     154 rntFVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALFKIATNPPPGLPSPEKWSPEFRdFLKK 233


                ....*....
gi 94967068 254 ALSKHPSDR 262
cd05122     234 CLQKDPEKR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

7e-46

180.82

93.05

5,23,6,29,55,35,33,88,69,79,167,151,52,219,204,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFdvhGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAG-EQEGTFYIAMECVE 102
cd06606       7 LLGRGSFGSVYLALSKDTGELVAVKSVEL---SSDSEEELESLEREIRILSKLQHPNIVRYYGCEvTEENTLNIFMEYVS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 103 GNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK---SGAQLTTGGDVL 179
cd06606      84 GGSLASLLKKFGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKrlaSIAYSGGLKSVR 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFT-APNISTIIYKIVNEPLPPDLETKVHPAVAAILRKALSKH 258
cd06606     164 GTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSeLGNPMALLYKIGSSGEPPEIPEDLSEEAKDFLRKCLRRD 243


                ....
gi 94967068 259 PSDR 262
cd06606     244 PKKR 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132958

cd06627

STKc_Cdc7_like

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

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

false

true

false

254

3e-43

172.04

95.28

7,17,0,34,53,34,4,58,38,52,112,90,9,121,101,45,166,147,71,238,218,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  18 RYEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdVHGIeKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIA 97
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQIS--LEKI-KEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYII 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLseQRFLTLDRT--IDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIA-KSGAQLTT 174
cd06627      78 LEYAENGSLRQII--KKFGKFPESlvAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVAtKLSDVSKD 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 175 GGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPdLETKVHPAVAAILRKA 254
cd06627     156 DESVVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQDDHPP-LPEGISPELKDFLMQC 234


                ....*...
gi 94967068 255 LSKHPSDR 262
cd06627     235 FQKDPNLR 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

1e-41

166.81

95.60

4,24,0,30,56,30,115,171,146,64,237,210,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKK--ILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQ-LTTGGDVLGTPN 183
cd05123      79 DLFTHLSKEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAKEGIDdGVRTTTFCGTPE 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 184 YISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHPSDRY 263
cd05123     159 YLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKL--RFPEFLSEEAKDLIKKLLTKDPTKRL 236


                ...
gi 94967068 264 QAG 266
cd05123     237 GSG 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132954

cd06623

PKc_MAPKK_plant_like

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

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

false

true

false

264

4e-39

158.52

92.42

6,19,3,30,53,33,85,138,119,29,170,148,8,178,160,46,224,209,38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  20 EVESVIGRGAMAVVYKAVDPTIGRTVALKTmrfdVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAME 99
cd06623       4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKK----IHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLE 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHAN-GVIHRDIKPANIMITRSGVVKIMDFGIAKsgaQLTTGGDV 178
cd06623      80 YMDGGSLADLLKKVGKIPEPVLAYIARQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISK---VLENTLDQ 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 ----LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNIS---TIIYKIVNEPLPPDLETKVHPAVAAIL 251
cd06623     157 cntfVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPPGQPsffELMQAICDGPPPSLPAEEFSPEFRDFI 236

                       250
                ....*....|.
gi 94967068 252 RKALSKHPSDR 262
cd06623     237 SACLQKDPKKR 247

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

6e-37

151.21

84.32

8,18,20,33,56,53,54,111,107,11,122,120,44,169,164,8,177,176,57,235,233,6,241,241,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06614      21 YDNLEKIGEGASGEVYTATDRATGKEVAIKKMR-----LRKQPKKELIINEILIMKECKHPNIVNYYDSYLVGDELWVVM 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLsEQRFLTLDRTI--DIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTGG 176
cd06614      96 EYMDGGSLTDII-TQTFVRMNESQiaYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFA---AQLTKEK 171

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 D----VLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLET--KVHPAVAAI 250
cd06614     172 SkrnsMVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLITTKG-IPPLKNpeKWSPEFKDF 250

                       250
                ....*....|..
gi 94967068 251 LRKALSKHPSDR 262
cd06614     251 LNKCLVKDPEKR 262

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-33

140.31

98.57

8,18,2,33,52,35,15,68,50,8,76,59,91,167,171,66,233,239,5,242,244,20,264,264,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfDVHGIEKNEVLSRFRnEARAAGKL-LHPNLVTIYDAGEQEGTFYIA 97
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLD-KRHLIKEKKVKYVKR-EKEVLTRLnGHPGIVKLYYTFQDEENLYFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK---------- 167
cd05581      81 LEYAENGELLEYIKKFGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKvldpnsspes 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 168 -----------SGAQLTTGGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNE--P 234
cd05581     161 nkgkatnidsqIEKNRRRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLeyE 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94967068 235 LPPDletkVHPAVAAILRKALSKHPSDRyqAGADLVGALKSYQ 277
cd05581     241 FPPN----FPPDAKDLIEKLLVLDPQDR--LGVNGYDELKAHP 277

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

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

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

false

true

false

265

4e-33

138.40

96.98

5,24,0,29,54,29,8,63,37,113,176,159,86,264,245,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDvHGIEKNEVlSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKA-DMIRKNQV-DQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGG-------- 176
cd05579      79 DLASLLENVGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKVGLVRRQINlnddeked 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 -DVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKVHPAVAAILRKAL 255
cd05579     159 kRIVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEWPEDVEVSDEAKDLISKLL 238

                       250       260
                ....*....|....*....|.
gi 94967068 256 SKHPSDRyqAGADLVGALKSY 276
cd05579     239 VPDPEKR--LGAKSIEEIKNH 257

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

7e-32

134.22

92.91

5,23,6,29,52,36,104,156,141,19,175,165,50,225,218,37

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRF-DVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVE 102
cd06630       7 QLGTGAFSSCYQARDVKTGTLMAVKQVTYvRNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWMA 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 103 GNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSG-VVKIMDFGIAKSGAQLTTG-----G 176
cd06630      87 GGSVSHLLSKYGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGqRLRIADFGAAARLAAKGTGagefqG 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 DVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNIST---IIYKIVNEPLPPDLETKVHPAVAAILRK 253
cd06630     167 QLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHSNhlaLIFKIASATTAPSIPEHLSPGLRDVTLR 246


                ....*....
gi 94967068 254 ALSKHPSDR 262
cd06630     247 CLELQPEDR 255

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

1e-31

133.44

68.93

5,18,2,33,51,36,3,56,39,6,63,45,116,179,193,53

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMR-FDVhgIEKNEVlSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIA 97
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRkSDM--LKRNQV-AHVRAERDILADADSPWIVKLYYSFQDEEYLYLV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGGD 177
cd05573      80 MEYMPGGDLMTLLIKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCKKMKKAGDSEY 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 178 VL--------------------------------GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNIST 225
cd05573     160 YLndshnlldsdrdnvlkrrrpkkqrrvraystvGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQE 239


                ....*..
gi 94967068 226 IIYKIVN 232
cd05573     240 TYNKIMN 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132957

cd06626

STKc_MEKK4

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

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

false

true

false

264

2e-31

132.85

93.94

7,24,7,30,57,37,117,174,159,24,198,186,22,220,209,11,231,222,7,239,229,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06626       8 IGGGTFGKVYTAVNLDTGELMAVKEIRIQD---NDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCSGG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTT-----GGDVL 179
cd06626      85 TLEELLEHGRILDEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAVKLKNNTTtmgeeVQSLA 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 GTPNYISPEMVKGDPIDGR---SDLFSAAVILHEMLLGERPFTA-PNISTIIYKIV--NEPLPPDlETKVHPAVAAILRK 253
cd06626     165 GTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMFHVGagHKPPIPD-SLQLSPEGKDFLDR 243

                       250
                ....*....|..
gi 94967068 254 ALSKHPSDRYQA 265
cd06626     244 CLESDPKKRPTA 255

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

9e-31

130.63

90.00

7,18,6,33,56,39,56,112,96,53,165,150,25,190,180,44,235,224,13,248,239,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06611       7 WEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQ-----IESEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSE-QRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGG 176
cd06611      82 EFCDGGALDSIMLElERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVsAKNKSTLQKRD 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 DVLGTPNYISPEMV-----KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLETKVHPAVA--A 249
cd06611     162 TFIGTPYWMAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKSE-PPTLDQPSKWSSSfnD 240

                       250
                ....*....|....*...
gi 94967068 250 ILRKALSKHPSDRYQAGA 267
cd06611     241 FLKSCLVKDPDDRPTAAE 258

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-30

129.59

94.19

7,18,1,37,56,38,10,67,48,99,166,149,9,177,158,43,221,201,29,250,232,12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEVLSRFrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd05578       2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKC-VEKGSVRNVL-NELQILQSLEHPFLVNLWYSFQDEEDMYLVV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIA--KSGAQLTTGg 176
cd05578      80 DLLLGGDLRYHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIAtkLTPDTLATS- 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 dVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTApNISTIIYKIVNEPLPPDLETKVHPAVAAI--LRKA 254
cd05578     159 -TSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRG-HSRTPREEILAKFETADVLYPAGWSSEAIdaINKL 236


                ....*...
gi 94967068 255 LSKHPSDR 262
cd05578     237 LERDPQKR 244

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-30

129.16

93.16

4,24,9,34,58,44,4,63,48,105,168,157,97

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIE-KNEVlSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKQVPFDPDSPEtKKEV-NALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPG 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKS----GAQLTTGGDVL 179
cd06625      89 GSVKDQLKAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRlqtiCSSGTGMKSVT 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKVHPAVAAILRKALSKHP 259
cd06625     169 GTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPQLPSHVSPDARNFLRRTFVENA 248


                ....*.
gi 94967068 260 SDRYQA 265
cd06625     249 KKRPSA 254

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

7e-30

127.43

96.23

11,19,3,45,68,48,54,122,103,16,138,120,27,167,147,2,170,149,4,174,155,44,218,204,16,235,220,9,244,230,18,273,248,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  20 EVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVLSrfrnEARAAGKLLHPNLVTIYDAGEQEGTFYIAME 99
cd06605       4 ETLGELGAGNSGVVSKVRHRPTGKIMAVKTIRLEINEAIQKQILR----ELDILHKCNSPYIVGFYGAFYNNGDISICME 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTI-DIMTQICAGLDYAHAN-GVIHRDIKPANIMITRSGVVKIMDFGIakSGaQLTT--G 175
cd06605      80 YMDGGSLDKILKEVQGRIPERILgKIAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGEIKLCDFGV--SG-QLVNslA 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 GDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPF-----TAPNISTIIYKIVNEPlPPDLETKVH-PAVAA 249
cd06605     157 KTFVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYppendPPDGIFELLQYIVNEP-PPRLPSGRFsPDFQD 235

                       250       260       270
                ....*....|....*....|....*....|....
gi 94967068 250 ILRKALSKHPSDRyqagadlvgalKSYQALLTQP 283
cd06605     236 FVNLCLIKDPRER-----------PSYKELLEHP 258

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

2e-29

126.00

92.64

4,24,7,86,112,93,13,125,108,65,190,174,72

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06632       8 LGSGSFGSVYEGLNLDDGDFFAVKEVSLADDGQTGQEAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVPGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLseQRFLTLDRTIDIM--TQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGGDVLGTP 182
cd06632      88 SLAKLL--KKYGSFPEPVIRLytRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAKQVVEFSFAKSFKGSP 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMV-KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKVHPAVAAILRKALSKHPSD 261
cd06632     166 YWMAPEVIaQQGGYGLAADIWSLGCTVLEMATGKPPWSQLEGVAAVFKIGRSKELPPIPDHLSDEAKDFILKCLQRDPSL 245


                .
gi 94967068 262 R 262
cd06632     246 R 246

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

4e-29

125.25

94.48

6,18,2,32,52,34,115,170,149,9,179,159,57,238,216,37,275,261,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd05580       3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKIL--SKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKsgaQLTTGGDV 178
cd05580      81 EFVPGGELFSLLRRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAK---RVKGRTYT 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 L-GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPpdLETKVHPAVAAILRKALSK 257
cd05580     158 LcGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKIYEKILSGKVR--FPSFFSSDAKDLLRNLLQV 235

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967068 258 HPSDRYQAGADLVGALKS--------YQALLTQPIPTSVVP 290
cd05580     236 DLTKRLGNLKNGVNDIKNhpwfagidWIALLQKKIEAPFVP 276

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-28

123.12

95.38

5,24,3,27,52,30,119,174,149,61,235,212,28,265,240,11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRfDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05611       4 ISKGAFGSVYLAKKRSTGDYFAIKVLK-KSDMIAKNQVTNVKAERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLNGG 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQlttGGDVLGTPNY 184
cd05611      83 DCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLE---NKKFVGTPDY 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 185 ISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPL--PPDLETKVHPAVAAILRKALSKHPSDR 262
cd05611     160 LAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRInwPEEVKEFCSPEAVDLINRLLCMDPAKR 239

                       250
                ....*....|....
gi 94967068 263 YqaGADLVGALKSY 276
cd05611     240 L--GANGYQEIKSH 251

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-28

123.14

93.75

8,18,4,34,52,40,7,68,47,31,99,79,67,169,146,8,177,158,57,235,215,5,240,222,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRF--DVHGIEKnevlsrfrnEARAAGKLLHPNLVTIYDAGEQEGTFYI 96
cd06612       5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVeeDLQEIIK---------EISILKQCDSPYIVKYYGSYFKNTDLWI 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  97 AME-CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTG 175
cd06612      76 VMEyCGAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVS---GQLTDT 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 GD----VLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLE--TKVHPAVAA 249
cd06612     153 MAkrntVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKP-PPTLSdpEKWSPEFND 231

                       250
                ....*....|...
gi 94967068 250 ILRKALSKHPSDR 262
cd06612     232 FVKKCLVKDPEER 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

1e-27

119.93

95.40

14,23,1,14,37,18,24,65,42,49,114,99,53,167,156,12,181,168,2,183,171,8,195,179,3,198,186,14,212,201,6,220,207,6,226,214,7,233,225,5,242,230,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAV---DPTIGRTVALKTMRFDVHGIEKNEvlsrFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMEC 100
cd00192       2 KLGEGAFGEVYKGElkgKGGKKTPVAVKTLKEDASDSERED----FLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEY 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 101 VEGNTLQALLSEQR--------FLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK----S 168
cd00192      78 MEGGDLLDFLRKSRpvfspessTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRdiydD 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 169 GAQLTTGGDVLgtPN-YISPEMVKgdpiDGR----SDLFSAAVILHEML-LGERPFtaPNISTI-IYKIVNE----PLPP 237
cd00192     158 DYYRKKGGGKL--PIrWMAPESLK----DGKfttkSDVWSFGVLLWEIFtLGGTPY--PGLSNEeVLEYLRKgyrlPKPE 229

                       250       260
                ....*....|....*....|....*
gi 94967068 238 DletkVHPAVAAILRKALSKHPSDR 262
cd00192     230 N----CPDELYELMLSCWQEDPEDR 250

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

3e-27

118.80

78.93

8,23,1,31,56,32,16,72,51,3,77,54,92,172,146,7,179,157,56,235,215,7,246,222,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARA---AGKllHPNLVTIYDAGEQEGTFYIAMEC 100
cd05570       2 VLGKGSFGKVLLAELKGTDELYAIKVLKKDV--VLQDDDVECTMTEKRVlalAGK--HPFLTQLHSCFQTKDRLFFVMEY 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 101 VEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGaqlTTGGDVL- 179
cd05570      78 VNGGDLMYHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEG---ILGGVTTs 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 ---GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPL--PPDLETKvhpaVAAILRKA 254
cd05570     155 tfcGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILEDNVryPRWLSKE----AKSILKGF 230

                       250       260
                ....*....|....*....|..
gi 94967068 255 LSKHPSDRYQAGADLVGALKSY 276
cd05570     231 LTKNPEKRLGCGPTGEQDIKGH 252

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-26

117.00

97.32

7,17,3,34,56,37,110,169,147,6,175,157,15,190,175,45,235,221,5,240,228,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  18 RYEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIA 97
cd06613       4 DYELLQRIGSGTYGDVYKARDIATGELAAVKVIK-----LEPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTG-- 175
cd06613      79 MEYCGGGSLQDIYQVTGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVS---AQLTATia 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 --GDVLGTPNYISPEMV---KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPL-PPDLE--TKVHPAV 247
cd06613     156 krKSFIGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLISKSNFqPPKLKdkEKWSPVF 235

                       250       260
                ....*....|....*....|..
gi 94967068 248 AAILRKALSKHPSDRYQAGADL 269
cd06613     236 HDFIKKCLTKDPKKRPTAEKLL 257

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

1e-26

116.89

87.30

5,23,7,27,52,34,61,113,97,61,174,187,88,262,277,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05574       8 LLGKGDVGRVYLVRLKGTGKLFALKVL--DKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVMDYCPG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQ--RFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTT------- 174
cd05574      86 GELFRLLQRQpgKCFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSKQSDVEPTpvskalr 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 175 ----------------------GGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVN 232
cd05574     166 kgsrgsvnkittetfseepsfrSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETFSNILK 245

                       250       260       270
                ....*....|....*....|....*....|....*..
gi 94967068 233 EPLPPDLETKVHPAVAAILRKALSKHPSDR--YQAGA 267
cd05574     246 KEVTFPGSPPVSSSARDLIRKLLVKDPSKRlgSKRGA 282

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-26

115.22

87.46

10,22,6,31,57,37,30,87,69,30,118,99,5,123,109,42,167,151,8,175,160,45,220,211,8,229,219,7,236,231,26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVYKAVDPTIGRTVALKTMRFDvhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDA--GEQEGTFYIAMEC 100
cd06621       7 SRLGEGAGGSVTKCRLKNTGMIFALKTITTD----PNPDLQKQILRELEINKSCKSPYIVKYYGAflDESSSSIGIAMEY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 101 VEGNTLQALLSEQRFLTlDRTID-----IMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIakSGAQLTTG 175
cd06621      83 CEGGSLDSIYKKVKKRG-GRIGEkvlgkIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGV--SGELVNSL 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 -GDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTA------PNISTIIYkIVNEPLP-----PDLETKV 243
cd06621     160 aGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPegepplGPIELLSY-IVNMPNPelkdePGNGIKW 238

                       250
                ....*....|....*....
gi 94967068 244 HPAVAAILRKALSKHPSDR 262
cd06621     239 SEEFKDFIKQCLEKDPTRR 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

5e-26

114.85

90.18

13,24,26,26,52,52,11,65,63,1,67,64,47,115,111,51,169,162,5,176,167,2,178,175,39,217,215,9,228,224,13,241,239,24,266,263,5,275,268,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLsrFrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06648      27 IGEGSTGIVCIATDKSTGRQVAVKKM--DLRKQQRRELL--F-NEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGG 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRfLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTggDV------ 178
cd06648     102 ALTDIVTHTR-MNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFC---AQVSK--EVprrksl 175

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERP-FTAPNISTIiyKIVNEPLPPDLET--KVHPAVAAILRKAL 255
cd06648     176 VGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPyFNEPPLQAM--KRIRDNLPPKLKNlhKVSPRLRSFLDRML 253

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94967068 256 SKHPSDRYQAgADLVGalksYQALLTQPIPTSVVP 290
cd06648     254 VRDPAQRATA-AELLN----HPFLAKAGPPSSIVP 283

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

2e-25

113.30

88.45

12,17,4,4,24,8,24,48,37,12,60,50,11,78,61,33,111,98,7,123,105,43,169,148,7,176,159,14,190,174,44,235,218,9,244,228,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  18 RYEVesvIGRGAMAVVYKAVDPTIGRTVALK-----TMRFDVHGIEKN-EVLSRFRNEARaagkllhPNLVTIYDAGEQE 91
cd06917       5 RLEL---IGRGAYGAVYRGKHVPTGRVVALKiinldTPDDDVSDIQREvALLSQLRQSQP-------PNITKYYGSYLKG 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  92 GTFYIAMECVEGNTLQALLS----EQRFLTLdrtidIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAk 167
cd06917      75 PRLWIIMEYAEGGSVRTLMKagpiAEKYISV-----IIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 168 sgAQLTTGG----DVLGTPNYISPEMV-KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLETK 242
cd06917     149 --ALLNQNSskrsTFVGTPYWMAPEVItEGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIPKSK-PPRLEDN 225

                       250       260
                ....*....|....*....|....
gi 94967068 243 VH-PAVAAILRKALSKHPSDRYQA 265
cd06917     226 GYsKLLREFVAACLDEEPKERLSA 249

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

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

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

false

true

false

262

2e-25

112.59

96.56

6,24,0,27,53,27,114,167,144,7,177,151,49,226,201,11,237,213,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRfdVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVK--KRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK---SGAQLTTggdVLGT 181
cd05572      79 ELWTILRDRGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKklkSGQKTYT---FCGT 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 182 PNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTI-IYKIVNEPLPP-DLETKVHPAVAAILRKALSKHP 259
cd05572     156 PEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGEDDEDPMkIYNLILKGIDKlEFPKYIDKAAKDLIKQLLRRNP 235

                       250
                ....*....|....*...
gi 94967068 260 SDRYQAGADLVGALKSYQ 277
cd05572     236 EERLGNLKGGIKDIKKHK 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

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

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

false

true

false

275

3e-25

112.37

84.73

11,16,5,34,52,39,9,61,54,7,77,61,8,85,75,25,112,100,11,123,117,43,169,160,6,175,170,18,193,193,41,235,234,4

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  17 GRYEVESVIGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNE------VLSRFRNearaagkllHPNLVTIY----- 85
cd06608       6 GIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIM--DIIEDEEEEieeeynILRKYSN---------HPNIATFYgafik 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  86 -DAGEQEGTFYIAMECVEGNTLQALLseQRFLTLDRTID------IMTQICAGLDYAHANGVIHRDIKPANIMITRSGVV 158
cd06608      75 kGPPGSDDQLWLVMELCGGGSVTDLV--KGLRKKGKRLKeewiayILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEV 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 159 KIMDFGIAksgAQLTTG----GDVLGTPNYISPEMVKGD-----PIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYK 229
cd06608     153 KLVDFGVS---AQLDSTngrrNTSIGTPYWMAPEVIACDeqpdaSYDYRCDVWSLGITAIELADGKPPLCDMHPMRALFK 229

                       250
                ....*....|
gi 94967068 230 IVNEPlPPDL 239
cd06608     230 IPRNP-PPTL 238

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

4e-25

111.90

84.88

9,22,4,31,54,35,10,65,45,6,71,54,44,116,98,56,172,155,60,232,216,10,245,226,29,274,263,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVYKAVDPTIGRTVALKTMRFDvHGIEKNEVLSrFRNEAR---AAGKLLHPNLVTIYDAGEQEGTFYIAME 99
cd05589       5 AVLGRGHFGKVLLAEYKKTGELYAIKALKKG-DIIARDEVES-LMCEKRifeTANSERHPFLVNLFACFQTEDHVCFVME 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFlTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQL-TTGGDV 178
cd05589      83 YAAGGDLMMHIHTDVF-SEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGFgDRTSTF 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVN-EPLPPDLETKvhpAVAAILRKALSK 257
cd05589     162 CGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNdEVRYPRFLSR---EAISIMRRLLRR 238

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 94967068 258 HPSDRYQAGADLVGALK--------SYQALLTQPIPTSVVP 290
cd05589     239 NPERRLGSGERDAEDVKkqpffrdiNWDALLARRIPPPFVP 279

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132983

cd06652

STKc_MEKK2

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

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

false

true

false

265

6e-25

111.28

95.09

5,23,8,64,87,74,89,176,167,58,234,229,4,238,246,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDA--GEQEGTFYIAMECV 101
cd06652       9 LLGQGAFGRVYLCYDADTGRELAVKQVQFDPESPETSKEVNALECEIQLLKNLLHERIVQYYGClrDPMERTLSIFMEHM 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 102 EGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGG----D 177
cd06652      89 PGGSIKDQLKSYGALTENVTRKYTRQILEGVSYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLSGtgmkS 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 178 VLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEP----LPPD-------------LE 240
cd06652     169 VTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPtnpvLPPHvsdhcrdflkrifVE 248

                       250
                ....*....|..
gi 94967068 241 TKVHPAVAAILR 252
cd06652     249 AKLRPSADELLR 260

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

8e-25

110.87

95.86

9,18,2,44,66,46,45,111,94,55,169,149,8,177,164,17,194,182,24,218,207,15,235,222,6,241,233,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVlsrfRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06610       3 YKLIEVIGSGATAVVQRAICLPNGEKVAIKRIDLEKCQTSMDEL----RKEIQAMSLCHHPNVVKYYTSFVVGDELWVVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLS---EQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTG 175
cd06610      79 PLMSGGSCLDIMKysyPQGGLDEAIIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVS---ASLADG 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 GD-------VLGTPNYISPEMVKGDP-IDGRSDLFSAAVILHEMLLGERPF-TAPNISTIIYKIVNEplPPDLET----- 241
cd06610     156 GDrtkvrktFVGTPCWMAPEVMEQVHgYDFKADIWSFGITAIELATGAAPYsKYPPMKVLMLTLQND--PPSLETeadyk 233

                       250       260
                ....*....|....*....|....
gi 94967068 242 KVHPAVAAILRKALSKHPSDRYQA 265
cd06610     234 KYSKSFRKMISKCLQKDPAKRPTA 257

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

9e-25

110.77

72.67

6,24,8,30,56,38,113,171,151,52,223,207,5,228,214,29,258,243,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05600       9 VGQGGYGQVFLAKKKDTGEIVALKRMKKSL--LFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAMEYVPGG 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGaqLTTGGDVLGTPNY 184
cd05600      87 DFRTLLNNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSKGI--VTYANSVVGSPDY 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 185 ISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNI----STIIY--KIVNEPLPPDLETKVHPAVAAILRKALSKh 258
cd05600     165 MAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPnetwENLKYwkETLQRPVYDDPRFNLSDEAWDLITKLIND- 243


                ....*..
gi 94967068 259 PSDRYQA 265
cd05600     244 PSRRFGS 250

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

1e-24

109.95

81.79

5,18,2,33,58,35,5,63,45,111,176,156,59,237,215,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgieKNEVL-----SRFRNEARAAGKLLHPNLVTIYDAGEQEGT 93
cd05612       3 LERIETLGTGTFGRVYLVRHKASGAYYALKVLA-------IPEVIrlkqvEHVHNEKSILSEISHPFIVNMYWTFHDDKF 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  94 FYIAMECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLT 173
cd05612      76 LYMLMEYVPGGELFSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAKKVRDRT 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 174 TggDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRK 253
cd05612     156 W--TLCGTPEYLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKL--EFPRHFDLRAKDLIKK 231


                ....*....
gi 94967068 254 ALSKHPSDR 262
cd05612     232 LLVVDRTRR 240

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132940

cd06609

STKc_MST3_like

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

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

false

true

false

274

2e-24

109.24

87.96

12,17,1,36,54,37,11,68,48,12,81,60,4,90,64,4,94,74,21,118,95,4,122,101,44,169,145,6,175,155,59,235,214,5,240,220,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  18 RYEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDvHGIEKNEVLSRfrnEARAAGKLLHPNlVTIYdageqEGTF--- 94
cd06609       2 LFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIDLE-EAEDEIEDIQQ---EIQFLSQCRSPY-ITKY-----YGSFlkg 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  95 ---YIAMECVEGNTLQALLSEQRFltlDRTI--DIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksg 169
cd06609      72 sklWIIMEYCGGGSCLDLLKPGKL---DETYiaFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGVS--- 145

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 170 AQLTTG----GDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLE-TKVH 244
cd06609     146 GQLTSTmskrNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRVLFLIPKNN-PPSLEgNKFS 224

                       250
                ....*....|....*...
gi 94967068 245 PAVAAILRKALSKHPSDR 262
cd06609     225 KPFKDFVSLCLNKDPKER 242

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

5e-24

108.47

66.97

7,18,2,40,60,42,55,116,97,7,123,106,41,167,147,12,179,164,20,199,190,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEknEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd05601       3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQ--ETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFlTLDRTID--IMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGiakSGAQLTTGG 176
cd05601      81 EYHPGGDLLSLLNRYED-QFDESMAqfYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFG---SAAKLNANK 156

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967068 177 DVL-----GTPNYISPEMVKGDPIDGRS------DLFSAAVILHEMLLGERPFTAPNISTIIYKIVN 232
cd05601     157 MVNsklpvGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGTSAVTYSNIMN 223

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

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

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

false

true

false

267

6e-24

108.00

84.27

5,22,5,36,58,45,109,167,161,51,220,212,6,226,220,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIE----KNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06628       6 ALIGSGSFGSVYLGMNAHSGELMAVKQVEIPSNSIGvqdrKRKMLDALQREINLLKELHHENIVQYLGSSQDAGHLNIFL 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK-------SGAQ 171
cd06628      86 EYVPGGSVAALLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKkleanslSTKT 165

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967068 172 LTTGGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFtaPNISTI--IYKIVNEPLP 236
cd06628     166 NGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPF--PDCTQMqaIFKIGTNASP 230

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-24

107.74

75.54

4,23,1,28,52,29,121,173,151,62,237,213,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRfDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05575       2 VIGKGSFGKVLLAKHKEDGKFYAVKVLQ-KKAILKKNEQKHIMAERNVLLKNVKHPFLVGLHYSFQTKEKLYFVLDYVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLT-TGGDVLGTP 182
cd05575      81 GELFFHLQRERSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCKEGIAGSkTTSTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHPSDR 262
cd05575     161 EYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNKPL--RLRPNISVSARHLLEGLLQKDRTKR 238


                ....*..
gi 94967068 263 YQAGADL 269
cd05575     239 LGAKNDF 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

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

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

false

true

false

272

1e-23

107.19

93.01

8,23,7,38,61,50,49,110,105,3,113,110,4,125,114,54,179,171,11,190,184,43,233,231,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNE-----VLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06629       8 LIGKGTYGRVYLALNVTTGEMMAVKQVELPATIAGRHDsrqkdMVKALRSEIETLKDLDHLNIVQYLGFETTEEYLSIFL 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALL------SEQ--RFLTldrtidimTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGA 170
cd06629      88 EYVPGGSIGSCLrtygrfEEQlvRFFT--------EQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGISKKSD 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 171 QLTTGGDVL---GTPNYISPEMV--KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNE----PLPPDLET 241
cd06629     160 DIYDNDQNMsmqGSVFWMAPEVIhsYSQGYSAKVDIWSLGCVVLEMFAGRRPWSDEEAIAAMFKLGNKrsapPIPPDVSM 239

                       250       260
                ....*....|....*....|.
gi 94967068 242 KVHPAVAAILRKALSKHPSDR 262
cd06629     240 NLSPVALDFLNACFTINPDNR 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132990

cd06659

STKc_PAK6

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

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

false

true

false

297

1e-23

107.04

86.53

8,24,28,26,52,54,12,67,66,47,115,113,50,165,164,69,235,233,6,241,241,24,270,265,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLSrfrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06659      29 IGEGSTGIVCIAREKHSGRQVAVKMM--DLRKQQRRELLF---NEVVIMRDYQHQNVVEMYKSYLVGEELWVLMEFLQGG 103

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRfLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGGDVLGTPN 183
cd06659     104 ALTDIVSQTR-LNEEQIATVCESVLQALCYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFcAQISKDVPKRKSLVGTPY 182

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 184 YISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLET--KVHPAVAAILRKALSKHPSD 261
cd06659     183 WMAPEVISRTPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSP-PPKLKNahKISPVLRDFLERMLTREPQE 261

                       250       260
                ....*....|....*....|....*....
gi 94967068 262 RYQAgadlvGALKSYQALLTQPIPTSVVP 290
cd06659     262 RATA-----QELLDHPFLLQTGLPECLVP 285

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132982

cd06651

STKc_MEKK3

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

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

false

true

false

266

1e-23

107.08

84.96

4,23,8,62,85,74,5,92,79,84,176,167,67

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIY----DAGEQegTFYIAME 99
cd06651       9 LLGQGAFGRVYLCYDVDTGRELAAKQVQFDPESPETSKEVSALECEIQLLKNLQHERIVQYYgclrDRAEK--TLTIFME 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGG--- 176
cd06651      87 YMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICMSGtgi 166

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967068 177 -DVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKV 243
cd06651     167 rSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPTNPQLPSHI 234

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132984

cd06653

STKc_MEKK3_like_1

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

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

false

true

false

264

1e-23

106.65

89.39

3,23,8,64,87,74,89,176,167,77

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDA--GEQEGTFYIAMECV 101
cd06653       9 LLGRGAFGEVYLCYDADTGRELAVKQVPFDPDSQETSKEVNALECEIQLLKNLRHDRIVQYYGClrDPEEKKLSIFVEYM 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 102 EGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGG----D 177
cd06653      89 PGGSIKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMSGtgikS 168

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967068 178 VLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPPDLETKVHPAVAAILRK 253
cd06653     169 VTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIATQPTKPMLPDGVSDACRDFLKQ 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132988

cd06657

STKc_PAK4

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

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

false

true

false

292

2e-23

106.65

87.67

9,24,27,26,52,53,12,67,65,47,115,112,50,165,163,52,217,216,9,228,225,13,241,240,24,276,264,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLSrfrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06657      28 IGEGSTGIVCIATVKSSGKLVAVKKM--DLRKQQRRELLF---NEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGG 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRfLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGGDVLGTPN 183
cd06657     103 ALTDIVTHTR-MNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFcAQVSKEVPRRKSLVGTPY 181

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 184 YISPEMVKGDPIDGRSDLFSAAVILHEMLLGERP-FTAPNISTIiyKIVNEPLPPDLET--KVHPAVAAILRKALSKHPS 260
cd06657     182 WMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPyFNEPPLKAM--KMIRDNLPPKLKNlhKVSPSLKGFLDRLLVRDPA 259

                       250       260       270
                ....*....|....*....|....*....|....*
gi 94967068 261 DRYQAgadlvgalksyQALLTQPIPTSVVPGTPIV 295
cd06657     260 QRATA-----------AELLKHPFLAKAGPPSCIV 283

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-23

106.16

77.22

5,23,1,32,56,33,123,179,157,54,233,212,9,245,221,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05592       2 VLGKGSFGKVMLAELKGTNEYYAIKALKKDVV-LEDDDVECTMVERRVLILAWEHPFLTHLFCTFQTKEHLFFVMEYLNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGGDVL-GTP 182
cd05592      81 GDLMFHIQSSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENINGEGKASTFcGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNE-PLPPDLETKvhpAVAAILRKALSKHPSD 261
cd05592     161 DYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILNDrPHFPRWISK---EAKDCLSKLFEREPTK 237


                ....*...
gi 94967068 262 RYQAGADL 269
cd05592     238 RLGMDGDI 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132975

cd06644

STKc_STK10_LOK

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

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

false

true

false

292

6e-23

104.73

91.78

8,18,13,33,56,46,56,112,103,53,165,157,25,190,187,44,235,231,6,241,239,25,277,264,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06644      14 WEIIGELGDGAFGKVYKAKNKETGALAAAKVIE-----TKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMI 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSE-QRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGG 176
cd06644      89 EFCPGGAVDAIMLElDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVsAKNVKTLQRRD 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 DVLGTPNYISPEMV-----KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLET--KVHPAVAA 249
cd06644     169 SFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSE-PPTLSQpsKWSMEFRD 247

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 94967068 250 ILRKALSKHPSDRYQAGadlvgalksyqALLTQPIPTSVVPGTPI 294
cd06644     248 FLKTALDKHPETRPSAA-----------QLLEHPFVSSVTSNRPL 281

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

7e-23

104.34

74.92

5,23,1,32,56,33,6,63,39,106,169,146,66,237,212,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEVlSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05595       2 LLGKGTFGKVILVREKATGRYYAMKILRKEVI-IAKDEV-AHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG-AQLTTGGDVLGTP 182
cd05595      80 GELFFHLSRERVFTEERARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGiSDGATMKTFCGTP 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHPSDR 262
cd05595     160 EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEI--RFPRTLSPEAKSLLAGLLKKDPKQR 237


                ....*.
gi 94967068 263 YQAGAD 268
cd05595     238 LGGGPS 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

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

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

false

true

false

323

4e-22

101.97

78.95

8,22,1,12,34,16,17,58,33,12,70,47,7,77,58,102,179,161,56,235,219,5,244,224,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVY---KAVDPTIGRTVALKTMRfdvhgieKNEVLSRFRNEA--RAAGKLL----HPNLVTIYDAGEQEGT 93
cd05584       2 KVLGKGGYGKVFqvrKVTGADTGKIFAMKVLK-------KATIVRNQKDTAhtKAERNILeavkHPFIVDLIYAFQTGGK 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  94 FYIAMECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLT 173
cd05584      75 LYLILEYLSGGELFMHLEREGIFMEDTACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHEG 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 174 TGGDVL-GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPL--PPDLEtkvhPAVAAI 250
cd05584     155 TVTHTFcGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLnlPPYLT----PEARDL 230

                       250       260
                ....*....|....*....|....*.
gi 94967068 251 LRKALSKHPSDRYQAGADLVGALKSY 276
cd05584     231 LKKLLKRNPSSRLGAGPGDAAEVQSH 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132974

cd06643

STKc_SLK

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

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

false

true

false

282

5e-22

101.64

88.65

7,18,6,32,55,38,57,112,96,53,165,150,25,190,180,44,235,224,5,240,231,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMrfdvhGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd06643       7 WEIIGELGDGAFGKVYKAQNKETGVLAAAKVI-----DTKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSE-QRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGG 176
cd06643      82 EFCAGGAVDAVMLElERPLTEPQIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGDIKLADFGVsAKNTRTIQRRD 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 DVLGTPNYISPEMV-----KGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPlPPDLE--TKVHPAVAA 249
cd06643     162 SFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSE-PPTLAqpSRWSSEFKD 240

                       250
                ....*....|....*.
gi 94967068 250 ILRKALSKHPSDRYQA 265
cd06643     241 FLKKCLEKNVDARWTT 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132989

cd06658

STKc_PAK5

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

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

false

true

false

292

1e-21

100.50

88.01

10,24,29,26,52,55,12,67,67,47,115,114,50,165,165,52,217,218,9,228,227,13,241,242,24,276,266,8,284,280,6

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMrfDVHGIEKNEVLSrfrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06658      30 IGEGSTGIVCIATEKHTGKQVAVKKM--DLRKQQRRELLF---NEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGG 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRfLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGAQLTTGGDVLGTPN 183
cd06658     105 ALTDIVTHTR-MNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFcAQVSKEVPKRKSLVGTPY 183

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 184 YISPEMVKGDPIDGRSDLFSAAVILHEMLLGERP-FTAPNISTIiyKIVNEPLPPDLET--KVHPAVAAILRKALSKHPS 260
cd06658     184 WMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPyFNEPPLQAM--RRIRDNLPPRVKDshKVSSVLRGFLDLMLVREPS 261

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967068 261 DRYQAgadlvgalksyQALLTQPI------PTSVVP 290
cd06658     262 QRATA-----------QELLQHPFlklagpPSCIVP 286

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-21

100.45

74.92

5,23,1,32,56,33,10,67,43,105,172,149,63,237,212,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEVLSRFrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05571       2 LLGKGTFGKVILVREKATGKYYAMKILKKEVI-IAKDEVAHTL-TESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQL-TTGGDVLGTP 182
cd05571      80 GELFFHLSRERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLCKEGISDgATMKTFCGTP 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHPSDR 262
cd05571     160 EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEI--RFPRTLSPEAKSLLAGLLKKDPKQR 237


                ....*.
gi 94967068 263 YQAGAD 268
cd05571     238 LGGGPE 243

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

3e-21

99.00

85.20

6,24,11,29,57,40,53,111,93,55,169,148,6,175,158,53,229,211,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDvhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06641      12 IGKGSFGEVFKGIDNRTQKVVAIKIIDLE----EAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLsEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTG----GDVLG 180
cd06641      88 SALDLL-EPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVA---GQLTDTqikrNTFVG 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 181 TPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYkIVNEPLPPDLETKVHPAVAAILRKALSKHPS 260
cd06641     164 TPFWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLF-LIPKNNPPTLEGNYSKPLKEFVEACLNKEPS 242


                ....*
gi 94967068 261 DRYQA 265
cd06641     243 FRPTA 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88489

cd05588

STKc_aPKC

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

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

false

true

false

329

3e-21

98.90

74.77

7,23,1,30,53,32,22,77,54,95,172,150,46,218,204,16,234,223,8,246,231,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFD-VHGIEKNEVLSRFRNEARAAGKllHPNLVTIYDAGEQEGTFYIAMECVE 102
cd05588       2 VIGRGSYAKVLLVELKKTRRIYAMKVIKKElVNDDEDIDWVQTEKHVFETASN--HPFLVGLHSCFQTESRLFFVIEFVS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 103 GNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQL-TTGGDVLGT 181
cd05588      80 GGDLMFHMQRQRKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCKEGIRPgDTTSTFCGT 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 182 PNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPF--------TAPNISTIIYKIVNEP---LPPDLETKvhpaVAAI 250
cd05588     160 PNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFdivgmsdnPDQNTEDYLFQVILEKqirIPRSLSVK----ASSV 235

                       250
                ....*....|..
gi 94967068 251 LRKALSKHPSDR 262
cd05588     236 LKGFLNKDPKER 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88500

cd05599

STKc_NDR_like

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

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

false

true

false

364

4e-21

98.81

75.27

6,18,2,33,52,35,10,63,45,104,167,180,7,174,195,58,232,255,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfDVHGIEKNEVlSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAM 98
cd05599       3 FESIKVIGRGAFGEVRLVQKKDTGHIYAMKKLR-KSEMLEKEQV-AHVRAERDILAEADNPWVVKLYYSFQDENYLYLIM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  99 ECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAK----------- 167
cd05599      81 EYLPGGDMMTLLMKKDTFTEEETRFYIAETILAIDSIHKLGYIHRDIKPDNLLLDAKGHIKLSDFGLCTglkkshrtefy 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 168 --------------------SGAQLTT--------GGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFT 219
cd05599     161 rilshalpsnfldfiskpmsSKRKAETwkrnrralAYSTVGTPDYIAPEVFLQTGYNKECDWWSLGVIMYEMLVGYPPFC 240

                       250       260       270
                ....*....|....*....|....*....|....*.
gi 94967068 220 APNISTIIYKIVN--EPLPPDLETKVHPAVAAILRK 253
cd05599     241 SDNPQETYRKIINwkETLQFPDEVPLSPEAKDLIKR 276

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

5e-21

98.20

58.49

11,18,44,32,50,77,4,56,81,5,63,86,15,78,102,34,112,143,5,125,148,39,164,191,5,171,196,20,191,219,8,199,228,33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTM-RFDVhgIEKNEvlSRFRNEARAAGKLLH-PNLVTIYDAGEQEGTFYI 96
cd05622      45 YEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLsKFEM--IKRSD--SAFFWEERDIMAFANsPWVVQLFYAFQDDRYLYM 120

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  97 AMECVEGNTLQALLSE-------QRFLTldrtidimTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFG----I 165
cd05622     121 VMEYMPGGDLVNLMSNydvpekwARFYT--------AEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGtcmkM 192

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94967068 166 AKSGaqLTTGGDVLGTPNYISPEMVK---GDPIDGRS-DLFSAAVILHEMLLGERPFTAPNISTIIYKIVN 232
cd05622     193 NKEG--MVRCDTAVGTPDYISPEVLKsqgGDGYYGREcDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMN 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88505

cd05604

STKc_SGK3

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

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

false

true

false

325

7e-21

97.80

75.08

5,23,1,27,57,28,18,75,52,94,169,147,66,237,213,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMrfdvhgiEKNEVLSRFRNEARAAGK------LLHPNLVTIYDAGEQEGTFYIA 97
cd05604       2 VIGKGSFGKVLLAKRKLDGKCYAVKVL-------QKKIVLNRKEQKHIMAERnvllknVKHPFLVGLHYSFQTTEKLYFV 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  98 MECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG-AQLTTGG 176
cd05604      75 LDFVNGGELFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCKEGiAQSDTTT 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 177 DVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALS 256
cd05604     155 TFCGTPEYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYGLPPFYCRDVAEMYDNILHKPL--VLRPGASLTAWSILEELLE 232

                       250
                ....*....|...
gi 94967068 257 KHPSDRYQAGADL 269
cd05604     233 KDRQRRLGAKEDF 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132962

cd06631

STKc_YSK4

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

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

false

true

false

265

8e-21

97.67

94.34

8,23,6,17,41,23,21,62,45,48,112,93,10,122,105,54,176,162,3,179,169,41,220,211,45

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTiGRTVALKTMRFDVHGIEKNEV-LSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVE 102
cd06631       7 VLGKGAYGTVYCGLTNQ-GQLIAVKQVELDTSNVLAAEKeYEKLQEEVDLLKSLKHVNIVQYLGTCLDDNTISIFMEFVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 103 GNTLQALLseQRFLTLDRTI--DIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGG---D 177
cd06631      86 GGSISSIL--NRFGPLPEPVfcKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMPNGIIKLIDFGCARRLAWVGLHGthsN 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 178 VL----GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTA-PNISTIIYKIVNEPLPPDLETKVHPAVAAILR 252
cd06631     164 MLksmhGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASmDRLAAMFYIGAHRGLMPRLPDSFSAAAIDFVT 243

                       250
                ....*....|...
gi 94967068 253 KALSKHPSDRYQA 265
cd06631     244 SCLTRDQHERPSA 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

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

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

false

true

false

370

8e-21

97.70

71.35

14,18,44,32,50,77,4,56,81,5,63,86,10,75,96,5,80,104,32,112,143,5,125,148,39,164,191,5,171,196,20,191,219,8,199,228,35,234,267,10,246,277,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTM-RFDVhgIEKNEvlSRFRNEARAAgkLLHPN---LVTIYDAGEQEGTF 94
cd05596      45 FDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLsKFEM--IKRSD--SAFFWEERDI--MAHANsewIVQLHYAFQDDKYL 118

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  95 YIAMECVEGNTLQALLSE-------QRFLTldrtidimTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFG--- 164
cd05596     119 YMVMEYMPGGDLVNLMSNydipekwARFYT--------AEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGtcm 190

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 165 -IAKSGaqLTTGGDVLGTPNYISPEMVK---GDPIDGRS-DLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEP----L 235
cd05596     191 kMDANG--MVRCDTAVGTPDYISPEVLKsqgGDGYYGREcDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMDHKnsltF 268

                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 94967068 236 PPDLETKVHpaVAAILRKALSKHPSDRYQAGADLVGALKSYQ 277
cd05596     269 PDDIEISKQ--AKDLICAFLTDREVRLGRNGVDEIKSHPFFK 308

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

8e-21

97.41

76.60

8,24,0,27,52,27,15,68,42,38,106,81,9,116,90,63,179,154,57,236,212,2,241,214,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRfDVHGIEKNEVLSRFRnEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd05585       1 IGKGSFGKVMQVRKKDTQRIYALKTIR-KAHIVSRSEVTHTLA-ERTVLAQVNCPFIVPLKFSFQSPEKLYFVLAFINGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TL-QALLSEQRFlTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGGDVL-GTP 182
cd05585      79 ELfHHLQKEGRF-DLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLNMKDDDRTNTFcGTP 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLP-PDletKVHPAVAAILRKALSKHPSD 261
cd05585     158 EYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRfPD---GFDRDAKDLLTGLLNRDPTQ 234


                ....*
gi 94967068 262 RYQAG 266
cd05585     235 RLGYN 239

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-20

96.63

74.06

5,23,1,31,54,36,18,77,54,93,170,148,66,238,214,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDV----HGIEKNEVLSRFRNEARAagkllHPNLVTIYDAGEQEGTFYIAME 99
cd05590       2 VLGKGSFGKVMLARLKESGRLYAVKVLKKDVilqdDDVECTMTEKRILSLARN-----HPFLTQLYCCFQTPDRLFFVME 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGA-QLTTGGDV 178
cd05590      77 FVNGGDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIfNGKTTSTF 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPpdLETKVHPAVAAILRKALSKH 258
cd05590     157 CGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVV--YPTWLSQDAVDILKAFMTKN 234


                ....
gi 94967068 259 PSDR 262
cd05590     235 PTMR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88519

cd05618

STKc_aPKC_iota

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

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

false

true

false

329

1e-20

96.67

74.77

7,23,1,31,56,32,21,77,54,95,172,150,48,220,206,14,234,223,8,246,231,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARAAGKLL-HPNLVTIYDAGEQEGTFYIAMECVE 102
cd05618       2 VIGRGSYAKVLLVRLKKTERIYAMKVVKKEL--VNDDEDIDWVQTEKHVFEQASnHPFLVGLHSCFQTESRLFFVIEYVN 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 103 GNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQL-TTGGDVLGT 181
cd05618      80 GGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPgDTTSTFCGT 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 182 PNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTA--------PNISTIIYKIVNEP---LPPDLETKvhpaVAAI 250
cd05618     160 PNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIvgssdnpdQNTEDYLFQVILEKqirIPRSLSVK----AASV 235

                       250
                ....*....|..
gi 94967068 251 LRKALSKHPSDR 262
cd05618     236 LKSFLNKDPKER 247

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

2e-20

96.57

79.25

5,23,2,11,34,16,17,54,33,116,170,150,65,237,215,39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVY---KAVDPTIGRTVALKTMRfdvHGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMEC 100
cd05582       3 VLGQGSFGKVFlvrKITGPDAGQLYAMKVLK---KATLKVRDRVRTKMERDILAEVNHPFIVKLHYAFQTEGKLYLILDF 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 101 VEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGA-QLTTGGDVL 179
cd05582      80 LRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIdHEKKAYSFC 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHP 259
cd05582     160 GTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKL--GMPQFLSPEAQSLLRALFKRNP 237

                       250
                ....*....|....*..
gi 94967068 260 SDRYQAGADLVGALKSY 276
cd05582     238 ANRLGAGPDGVEEIKRH 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132938

cd06607

STKc_TAO

Serine/threonine kinases (STKs), thousand-and-one amino acids (TAO) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MAP3K or MKKK) activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3.

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

false

true

false

307

2e-20

96.80

76.87

10,24,22,29,55,51,109,167,160,21,188,185,5,194,190,16,212,206,4,216,212,15,231,228,2,235,230,6,241,237,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDvhGIEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06607      23 IGHGSFGAVYFARDVRTNEVVAIKKMSYS--GKQSNEKWQDIIKEVRFLQQLRHPNTIEYKGCYLREHTAWLVMEYCLGS 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGiakSGAQLTTGGDVLGTPNY 184
cd06607     101 ASDILEVHKKPLQEVEIAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFG---SASLVSPANSFVGTPYW 177

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 185 ISPE----MVKGDpIDGRSDLFSAAVILHEmlLGER--PFTAPNISTIIYKIV-NEplPPDLET-KVHPAVAAILRKALS 256
cd06607     178 MAPEvilaMDEGQ-YDGKVDVWSLGITCIE--LAERkpPLFNMNAMSALYHIAqND--SPTLSSnDWSDYFRNFVDSCLQ 252


                ....*.
gi 94967068 257 KHPSDR 262
cd06607     253 KIPQDR 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

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

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

false

true

false

370

2e-20

96.28

65.41

12,6,35,9,18,44,32,50,77,4,56,81,5,63,86,15,78,102,34,112,143,5,125,148,46,171,196,20,191,219,8,199,228,35,234,267,10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068   7 RKSDMPTETigrYEVESVIGRGAMAVVYKAVDPTIGRTVALKTM-RFDVhgIEKNEvlSRFRNEARAAGKLLH-PNLVTI 84
cd05621      36 RKLQMKAED---YDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLsKFEM--IKRSD--SAFFWEERDIMAFANsPWVVQL 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  85 YDAGEQEGTFYIAMECVEGNTLQALLSE-------QRFLTldrtidimTQICAGLDYAHANGVIHRDIKPANIMITRSGV 157
cd05621     109 FCAFQDDKYLYMVMEYMPGGDLVNLMSNydvpekwAKFYT--------AEVVLALDAIHSMGLIHRDVKPDNMLLDKHGH 180

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 158 VKIMDFGIAKSGAQ--LTTGGDVLGTPNYISPEMVK---GDPIDGRS-DLFSAAVILHEMLLGERPFTAPNISTIIYKIV 231
cd05621     181 LKLADFGTCMKMDEtgMVRCDTAVGTPDYISPEVLKsqgGDGYYGREcDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIM 260

                       250
                ....*....|....*..
gi 94967068 232 NEP----LPPDLETKVH 244
cd05621     261 DHKnslnFPEDVEISKH 277

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88494

cd05593

STKc_PKB_gamma

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

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

false

true

false

325

2e-20

96.29

74.46

5,23,1,32,56,33,10,67,43,102,169,146,66,237,212,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEVLSRFrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05593       2 LLGKGTFGKVILVREKASGKYYAMKILKKEVI-IAKDEVAHTL-TESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG-AQLTTGGDVLGTP 182
cd05593      80 GELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGiTDAATMKTFCGTP 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLppDLETKVHPAVAAILRKALSKHPSDR 262
cd05593     160 EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDI--KFPRTLSADAKSLLSGLLIKDPNKR 237


                ....*.
gi 94967068 263 YQAGAD 268
cd05593     238 LGGGPD 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88504

cd05603

STKc_SGK2

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

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

false

true

false

321

2e-20

96.26

76.64

6,22,0,32,56,32,19,75,52,98,173,151,62,235,215,6,245,221,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARAAGK-LLHPNLVTIYDAGEQEGTFYIAMECV 101
cd05603       1 KVIGKGSFGKVLLAKRKSDGSFYAVKVLQKKT--ILKKKEQNHIMAERNVLLKnLKHPFLVGLHYSFQTAEKLYFVLDYV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 102 EGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLT-TGGDVLG 180
cd05603      79 NGGELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCKEGVEPEeTTSTFCG 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 181 TPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPL--PPDLETkvhpAVAAILRKALSKH 258
cd05603     159 TPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQMYDNILHKPLqlPGGKTV----AACDLLVGLLHKD 234

                       250
                ....*....|..
gi 94967068 259 PSDRYQAGADLV 270
cd05603     235 QRRRLGAKADFL 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88488

cd05587

STKc_cPKC

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

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

false

true

false

324

4e-20

95.37

75.31

6,22,5,32,56,37,24,80,62,90,170,153,61,231,216,11,246,227,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  23 SVIGRGAMAVVYKAVDPTIGRTVALKTMRFDVhgIEKNEVLSRFRNEARAAGKLLHPN-LVTIYDAGEQEGTFYIAMECV 101
cd05587       6 MVLGKGSFGKVMLAERKGTDELYAIKILKKDV--IIQDDDVECTMVEKRVLALPGKPPfLTQLHSCFQTMDRLYFVMEYV 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 102 EGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGA-QLTTGGDVLG 180
cd05587      84 NGGDLMYHIQQVGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKENIfGGKTTRTFCG 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 181 TPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIV--NEPLPPDLETKvhpaVAAILRKALSKH 258
cd05587     164 TPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMehNVSYPKSLSKE----AVSICKGLLTKH 239

                       250
                ....*....|
gi 94967068 259 PSDRYQAGAD 268
cd05587     240 PAKRLGCGPT 249

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

5e-20

94.86

68.66

7,78,62,58,136,121,29,167,150,11,178,162,44,222,217,12,235,229,14,249,244,13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  79 PNLVTIYDAGEQEGTFYIAMECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAH-ANGVIHRDIKPANIMITRSGV 157
cd06620      63 PYIVSFYGAFLNENNICMCMEFMDCGSLDRIYKKGGPIPVEILGKIAVAVVEGLTYLYnVHRIMHRDIKPSNILVNSRGQ 142

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 158 VKIMDFGIakSGAQLTTGGDV-LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPN-----------IST 225
cd06620     143 IKLCDFGV--SGELINSIADTfVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFAFSNidddgqddpmgILD 220

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 94967068 226 IIYKIVNEPlPPDLETKVHPAVAA-ILRKALSKHPSDR 262
cd06620     221 LLQQIVQEP-PPRLPSSDFPEDLRdFVDACLLKDPTER 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88518

cd05617

STKc_aPKC_zeta

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

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

false

true

false

327

7e-20

94.36

74.62

8,23,1,11,34,16,38,77,54,95,172,150,48,220,202,8,228,213,6,234,221,8,246,229,16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVY----KAVDPTIGRTVALKTMRFDVHGIEKNEVLSRFRNEARAagkllHPNLVTIYDAGEQEGTFYIAME 99
cd05617       2 VIGRGSYAKVLlvrlKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASS-----NPFLVGLHSCFQTTSRLFLVIE 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQL-TTGGDV 178
cd05617      77 YVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPgDTTSTF 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 179 LGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTA----PNISTIIY---KIVNEP--LPPDLETKvhpaVAA 249
cd05617     157 CGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIitdnPDMNTEDYlfqVILEKPirIPRFLSVK----ASH 232

                       250
                ....*....|...
gi 94967068 250 ILRKALSKHPSDR 262
cd05617     233 VLKGFLNKDPKER 245

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

1e-19

93.90

73.83

7,23,1,32,56,33,6,62,42,12,77,54,92,169,147,65,234,213,8,245,221,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgIEKNEV---LSRFRNEARAAGkllHPNLVTIYDAGEQEGTFYIAMEC 100
cd05591       2 VLGKGSFGKVMLAELKGTDEVYAIKVLKKDVI-LQDDDVdctMTEKRILALAAK---HPFLTALHCCFQTKDRLFFVMEY 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 101 VEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG-AQLTTGGDVL 179
cd05591      78 VNGGDLMFQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGiLNGVTTTTFC 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 180 GTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEP-LPPDLETKvhpAVAAILRKALSKH 258
cd05591     158 GTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDvLYPVWLSK---EAVSILKAFMTKN 234


                ....
gi 94967068 259 PSDR 262
cd05591     235 PNKR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

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

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

false

true

false

305

1e-19

93.45

86.56

8,18,2,33,57,35,20,77,59,92,169,152,6,175,173,15,190,192,5,199,197,37,236,235,31

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  19 YEVESVIGRGAMAVVYKAVDPTIGRTVALKTMRfdvhgiEKNEVLSRFRNEARAAGKLL----HPNLVTIYDAGEQEGTF 94
cd05609       3 FETIKLISNGAYGAVYLVRHKETRQRFAMKKIN------KQNLILRNQIQQVFVERDILtfaeNPFVVSMFCSFETRRHL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  95 YIAMECVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG-AQLT 173
cd05609      77 CMVMEYVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIGlMSLT 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 174 TG---------------GDVLGTPNYISPEMV----KGDPIdgrsDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEP 234
cd05609     157 TNlyeghiekdtrefldKQVCGTPEYIAPEVIlrqgYGKPV----DWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDD 232

                       250       260       270
                ....*....|....*....|....*....|....
gi 94967068 235 LP-PDLETKVHPAVAAILRKALSKHPSDRYQAGA 267
cd05609     233 IEwPEGDEALPADAQDLISRLLRQNPLERLGTGG 266

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

2e-19

93.14

77.22

7,23,1,31,54,36,18,77,54,92,169,150,5,177,155,53,230,209,12,245,221,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDV----HGIEKNEVLSRFRNEARAagkllHPNLVTIYDAGEQEGTFYIAME 99
cd05619       2 MLGKGSFGKVFLAELKGTNQFFAIKALKKDVvlmdDDVECTMVEKRVLSLAWE-----HPFLTHLYCTFQTKENLFFVME 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 100 CVEGNTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSG----AQLTTg 175
cd05619      77 YLNGGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCKENmlgdAKTCT- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 176 gdVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKI-VNEPLPPDLETKvhpAVAAILRKA 254
cd05619     156 --FCGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEELFQSIrMDNPCYPRWLTR---EAKDILVKL 230

                       250
                ....*....|....*
gi 94967068 255 LSKHPSDRYQAGADL 269
cd05619     231 FVREPERRLGVKGDI 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88521

cd05620

STKc_nPKC_delta

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

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

false

true

false

316

2e-19

92.76

75.00

5,23,1,35,59,36,120,179,157,51,230,209,12,245,221,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  24 VIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEkNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEG 103
cd05620       2 VLGKGSFGKVLLAELKGKGEYFAVKALKKDVVLID-DDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEFLNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 104 NTLQALLSEQRFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAKSGAQLTTGGDVL-GTP 182
cd05620      81 GDLMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGDNRASTFcGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 183 NYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKI-VNEPLPPDLETKvhpAVAAILRKALSKHPSD 261
cd05620     161 DYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIrVDTPHYPRWITK---ESKDILEKLFERDPTR 237


                .
gi 94967068 262 R 262
cd05620     238 R 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132987

cd06656

STKc_PAK3

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

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

false

true

false

297

2e-19

92.86

79.12

7,11,16,10,24,26,35,59,64,10,77,74,36,114,110,51,165,162,71,239,233,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  12 PTETIGRYEVesvIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEK---NEVLSRFRNEaraagkllHPNLVTIYDAG 88
cd06656      17 PKKKYTRFEK---IGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKKEliiNEILVMRENK--------NPNIVNYLDSY 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  89 EQEGTFYIAMECVEGNTLQALLSEQrFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AK 167
cd06656      86 LVGDELWVVMEYLAGGSLTDVVTET-CMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQ 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 168 SGAQLTTGGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPpdlETKVHPAV 247
cd06656     165 ITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP---ELQNPERL 241

                       250
                ....*....|
gi 94967068 248 AAILRKALSK 257
cd06656     242 SAVFRDFLNR 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132985

cd06654

STKc_PAK1

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 1, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK1 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 1, catalytic (c) domain....

false

true

false

296

2e-19

92.48

79.39

7,11,17,10,24,27,35,59,65,10,77,75,36,114,111,51,165,163,71,239,234,18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  12 PTETIGRYEVesvIGRGAMAVVYKAVDPTIGRTVALKTMRFDVHGIEK---NEVLSRFRNEaraagkllHPNLVTIYDAG 88
cd06654      18 PKKKYTRFEK---IGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKKEliiNEILVMRENK--------NPNIVNYLDSY 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  89 EQEGTFYIAMECVEGNTLQALLSEQrFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AK 167
cd06654      87 LVGDELWVVMEYLAGGSLTDVVTET-CMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQ 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 168 SGAQLTTGGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLPpdlETKVHPAV 247
cd06654     166 ITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTP---ELQNPEKL 242

                       250
                ....*....|
gi 94967068 248 AAILRKALSK 257
cd06654     243 SAIFRDFLNR 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

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

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

false

true

false

293

3e-19

92.66

70.65

6,24,26,31,57,57,7,67,64,47,115,111,51,169,162,4,173,170,63

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDVHgiEKNEVLSrfrNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06647      27 IGQGASGTVYTAIDVATGQEVAIKQMNLQQQ--PKKELII---NEILVMRENKHPNIVNYLDSYLVGDELWVVMEYLAGG 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRfLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLT----TGGDVLG 180
cd06647     102 SLTDVVTETC-MDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFC---AQITpeqsKRSTMVG 177

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 94967068 181 TPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLP 236
cd06647     178 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP 233

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

3e-19

92.48

73.31

6,11,16,10,24,26,24,50,50,14,67,64,46,114,110,51,165,162,71

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  12 PTETIGRYEVesvIGRGAMAVVYKAVDPTIGRTVALKtmRFDVHGIEKNEVLSrfrNEARAAGKLLHPNLVTIYDAGEQE 91
cd06655      17 PKKKYTRYEK---IGQGASGTVFTAIDVATGQEVAIK--QINLQKQPKKELII---NEILVMKELKNPNIVNFLDSFLVG 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  92 GTFYIAMECVEGNTLQALLSEQrFLTLDRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGI-AKSGA 170
cd06655      89 DELFVVMEYLAGGSLTDVVTET-CMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFcAQITP 167

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967068 171 QLTTGGDVLGTPNYISPEMVKGDPIDGRSDLFSAAVILHEMLLGERPFTAPNISTIIYKIVNEPLP 236
cd06655     168 EQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTP 233

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

3e-19

92.04

85.20

6,24,11,29,57,40,61,119,101,47,169,148,6,175,158,59,235,217,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068  25 IGRGAMAVVYKAVDPTIGRTVALKTMRFDvhgiEKNEVLSRFRNEARAAGKLLHPNLVTIYDAGEQEGTFYIAMECVEGN 104
cd06640      12 IGKGSFGEVFKGIDNRTQQVVAIKIIDLE----EAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGG 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967068 105 TLQALLSEQRFLTLdRTIDIMTQICAGLDYAHANGVIHRDIKPANIMITRSGVVKIMDFGIAksgAQLTTG----GDVLG 180