NCBI Conserved Domain Search

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Conserved domains on [gi\|116620426\|ref\|YP_822582.1\|]
adenylate/guanylate cyclase [Solibacter usitatus Ellin6076]

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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

1e-48

190.80

98.05

5,7,0,37,45,37,51,96,89,69,166,158,60,227,218,33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426    8 RYRLAEKLGEGGLGAVYRARDIRLGRDVALKFLQPALaQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVME 87
cd00180         1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKK-EKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVME 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   88 LIEGQTLRQ-LSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENi 166
cd00180        80 YMSGGDLFDlLKKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLDSGGRKLTT- 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  167 LMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPvSRYRGDVPATVHRILARAL 246
cd00180       159 FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKGKGTP-DELPPNISPEAKDLIKKLL 237

                         250
                  ....*....|....
gi 116620426  247 TKDRELRYASADLM 260
cd00180       238 VKDPEKRPTAEELL 251

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

3e-36

149.61

92.49

6,22,15,20,45,35,52,97,88,56,153,145,2,157,147,60,218,207,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPalaQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL-SGGR 101
cd05122        16 VYKARHKKTGELVAVKVIKL---ESDEEQEQILNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEYCDGGSLDDLlKSTG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLpeSSLVTQENILMGTMAYMSPEQAI 180
cd05122        93 PLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSaQL--SDTKAKRNTFVGTPYWMAPEVIN 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHgLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd05122       171 GEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALF-KIATNPPPGLPSPEKWSPEFRDFLKKCLQKDPEKRPTAEELL 249

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

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

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

false

true

false

250

2e-33

140.61

90.80

4,22,8,74,96,83,58,155,141,69,228,210,25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQ-LSGGR 101
cd05123         9 VYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHYAFQTKEKLYLVMEYVNGGDLFThLSKEG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPEQAIG 181
cd05123        89 RFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAK-EGIDDGVRTTTFCGTPEYLAPEVLQG 167

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 116620426  182 AAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPepvsRYRGDVPATVHRILARALTKDRELR 253
cd05123       168 KGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKL----RFPEFLSEEAKDLIKKLLTKDPTKR 235

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

2e-32

137.29

72.20

6,22,15,18,41,33,37,78,71,20,98,94,9,109,103,45,154,149,53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLqPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEED-DGSLFIVMELIEGQTLRQLS--- 98
cd06606        16 VYLALSKDTGELVAVKSV-ELSSDSEEELESLEREIRILSKLQHPNIVRYYGCEVTeENTLNIFMEYVSGGSLASLLkkf 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK-LPESSLVTQENILMGTMAYMSPE 177
cd06606        95 GKLPEPVIR--RYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKrLASIAYSGGLKSVRGTPYWMAPE 172

                         170       180       190
                  ....*....|....*....|....*....|
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd06606       173 VIRGEEYGRASDIWSLGCTVIEMLTGKPPW 202

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

2e-32

136.84

88.89

6,22,16,43,65,60,32,97,95,10,109,105,57,166,181,59,229,240,24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALN-HPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---S 98
cd05581        17 VYLAKEKETNKEYAIKVLDKRHLIKEKKVKYVKREKEVLTRLNgHPGIVKLYYTFQDEENLYFVLEYAENGELLEYikkF 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENI------------ 166
cd05581        97 GSFDEKCTR--FYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVLDPNSSPESNKgkatnidsqiek 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  167 -------LMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEpvsrYRGDVPATVH 239
cd05581       175 nrrrrasFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYE----FPPNFPPDAK 250

                         250
                  ....*....|....
gi 116620426  240 RILARALTKDRELR 253
cd05581       251 DLIEKLLVLDPQDR 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

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

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

false

true

false

287

2e-29

126.95

82.58

10,22,34,16,40,50,7,48,57,58,106,127,5,121,132,31,152,164,3,157,167,54,211,222,5,218,227,35,254,262,9

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKflQPALAQDeGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06614        35 VYTATDRATGKEVAIK--KMRLRKQ-PKKELIINEILIMKECKHPNIVNYYDSYLVGDELWVVMEYMDGGSLTDIITQTF 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLA------------RALQYctaaadalraAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLpeSSLVTQENILMG 169
cd06614       112 VRMNesqiayvcrevlQGLEY----------LHSQNVIHRDIKSDNILLSKDGSVKLADFGFaAQL--TKEKSKRNSMVG 179

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  170 TMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGEN-YRAVLhgLLNTEPEPVSRYRGDVPATVHRILARALTK 248
cd06614       180 TPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPpLRALF--LITTKGIPPLKNPEKWSPEFKDFLNKCLVK 257

                         250
                  ....*....|....*
gi 116620426  249 DRELRyASADLMLSD 263
cd06614       258 DPEKR-PSAEELLQH 271

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132954

cd06623

PKc_MAPKK_plant_like

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

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

false

true

false

264

6e-29

125.40

69.70

4,22,16,19,43,35,83,126,120,35,162,155,45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpaLAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06623        17 VYKVRHKPTGKIYALKKIH--VDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGSLADLLKKVG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLARALQYCTAAADALRAAHHKG--IIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVtQENILMGTMAYMSPEQAI 180
cd06623        95 KIPEPVLAYIARQILKGLDYLHTKrhIIHRDIKPSNLLINSKGEVKIADFGISKVLENTLD-QCNTFVGTVTYMSPERIQ 173

                         170       180
                  ....*....|....*....|....*..
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd06623       174 GESYSYAADIWSLGLTLLECALGKFPF 200

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

5e-28

122.35

92.52

9,22,15,21,44,36,53,97,92,9,108,101,45,153,147,7,162,154,61,223,219,5,235,224,18,254,242,8

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPAlAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SG 99
cd06627        16 VYKGLNLETGDFVAIKQISLE-KIKEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTSDSLYIILEYAENGSLRQIikkFG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLAraLQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLvtQENILMGTMAYMSPEQ 178
cd06627        95 KFPESLV--AVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVAtKLSDVSK--DDESVVGTPYWMAPEV 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  179 AIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTE----PEPVSryrgdvpATVHRILARALTKDRELRy 254
cd06627       171 IEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIVQDDhpplPEGIS-------PELKDFLMQCFQKDPNLR- 242


                  ....*...
gi 116620426  255 ASADLMLS 262
cd06627       243 PTAKQLLK 250

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

1e-26

117.59

76.72

4,22,8,74,96,83,68,166,151,45,211,202,7

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQ-LSGGR 101
cd05572         9 VELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRTFKDKKYIYFLMEYCLGGELWTiLRDRG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQEniLMGTMAYMSPEQAIG 181
cd05572        89 LLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLKSGQKTYT--FCGTPEYVAPEIILN 166

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 116620426  182 AAVDPRCDLWSLGIVLYELLTGRLPFTGEN------YRAVLHG 218
cd05572       167 KGYDFSVDYWSLGILLYELLTGSPPFGEDDedpmkiYNLILKG 209

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

2e-25

113.75

80.00

4,22,8,75,97,86,10,109,96,45,154,148,72

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SG 99
cd05579         9 VFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLASLlenVG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK-------LPESSLVTQENILMGTMA 172
cd05579        89 SLDEDMAR--IYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKvglvrrqINLNDDEKEDKRIVGTPD 166

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 116620426  173 YMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEP 226
cd05579       167 YIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGETPEEIFQNILNGKIEW 220

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-24

110.71

75.58

5,35,28,60,95,89,58,153,148,10,166,158,43,209,207,16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCTA 114
cd05578        29 AMKYMNKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYSFQDEEDMYLVVDLLLGGDLRyHLQQKVKFSEEQVKFYVCE 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  115 AADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLVTQeniLMGTMAYMSPEQAIGAAVDPRCDLWSL 193
cd05578       109 IVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIAtKLTPDTLATS---TSGTPPYMAPEVFCRQGYSFAVDWWSL 185

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 116620426  194 GIVLYELLTGRLPFTG------ENYRAVLHGLLNTEPE 225
cd05578       186 GVTAYEMLRGKRPYRGhsrtprEEILAKFETADVLYPA 223

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

5e-24

108.96

92.42

8,22,15,19,44,34,7,51,43,47,98,91,57,155,151,32,187,186,22,209,209,15,225,224,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRR--ERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLS-G 99
cd06626        16 VYTAVNLDTGELMAVKEIR---IQDNDPKtiKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEYCSGGTLEELLeH 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKL---PESSLVTQENILMGTMAYMSP 176
cd06626        93 GRILDEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAVKlknNTTTMGEEVQSLAGTPAYMAP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  177 EQAIGAAVDPR---CDLWSLGIVLYELLTGRLPFTG-ENYRAVLHGLLNTEPePVSRYRGDVPATVHRILARALTKDREL 252
cd06626       173 EVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMFHVGAGHK-PPIPDSLQLSPEGKDFLDRCLESDPKK 251


                  ....*...
gi 116620426  253 RYASADLM 260
cd06626       252 RPTASELL 259

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

8e-24

108.68

81.72

6,22,16,75,97,93,5,103,98,59,166,157,45,211,206,9,228,215,38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL--SGG 100
cd05580        17 VMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNSNLYMVMEFVPGGELFSLlrRSG 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPmPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTqeniLMGTMAYMSPEQAI 180
cd05580        97 RF-PEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAKRVKGRTYT----LCGTPEYLAPEIIL 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGEN----YRAVLHGLLntepepvsRYRGDVPATVHRILARALTKDRELRYAS 256
cd05580       172 SKGYGKAVDWWALGILIYEMLAGYPPFFDDNpmkiYEKILSGKV--------RFPSFFSSDAKDLLRNLLQVDLTKRLGN 243

                         250
                  ....*....|
gi 116620426  257 ADLMLSDLRN 266
cd05580       244 LKNGVNDIKN 253

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

1e-23

107.79

90.19

8,22,16,19,43,35,48,91,87,34,126,121,35,164,156,50,214,211,11,225,224,13,242,237,18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpaLAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEG----QTLRQLS 98
cd06605        17 VSKVRHRPTGKIMAVKTIR--LEINEAIQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICMEYMDGgsldKILKEVQ 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGRPMPLARALQYCTAAADALRAAHHKgIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVtqeNILMGTMAYMSPEQ 178
cd06605        95 GRIPERILGKIAVAVLKGLTYLHEKHK-IIHRDVKPSNILVNSRGEIKLCDFGVSGQLVNSLA---KTFVGTSSYMAPER 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  179 AIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRA-----VLHGLLNTEPE--PVSRYRGDVPATVhrilARALTKDRE 251
cd06605       171 IQGNDYGVKSDVWSLGLSLIELATGRFPYPPENDPPdgifeLLQYIVNEPPPrlPSGRFSPDFQDFV----NLCLIKDPR 246


                  ....*....
gi 116620426  252 LRYASADLM 260
cd06605       247 ERPSYKELL 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

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

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

false

true

false

318

1e-22

104.55

67.61

6,35,23,25,60,49,35,95,85,59,154,147,8,166,155,58,228,213,25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPALAQDEGRRERFLNEARA-AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCT 113
cd05570        24 AIKVLKKDVVLQDDDVECTMTEKRVlALAGKHPFLTQLHSCFQTKDRLFFVMEYVNGGDLMyHIQQQGRFPEPRARFYAA 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  114 AAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK---LPESSLVTqeniLMGTMAYMSPEQAIGAAVDPRCDL 190
cd05570       104 EIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKegiLGGVTTST----FCGTPDYIAPEILQGQPYGFSVDW 179

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116620426  191 WSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPepvsRYRGDVPATVHRILARALTKDRELR 253
cd05570       180 WALGVLLYEMLAGQSPFDGDDEDELFQSILEDNV----RYPRWLSKEAKSILKGFLTKNPEKR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

1e-22

104.44

76.17

9,6,0,42,48,46,15,66,61,32,100,93,7,109,100,13,122,117,37,160,154,20,180,175,31,211,207,4

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426    7 SRYRLAEKLGEGGLGAVYRARDIRLGRDVALKFLQPALAQDE----GRRERFLNEARAAAAlnhPGIATIHSIEEDDGSL 82
cd06917         1 SLYQRLELIGRGAYGAVYRGKHVPTGRVVALKIINLDTPDDDvsdiQREVALLSQLRQSQP---PNITKYYGSYLKGPRL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   83 FIVMELIEGQTLRQLSggRPMPLARalQYCTAAADALRAA----HHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPES 158
cd06917        78 WIIMEYAEGGSVRTLM--KAGPIAE--KYISVIIREVLVAlkyiHKVGVIHRDIKAANILVTNTGNVKLCDFGVAALLNQ 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 116620426  159 SlVTQENILMGTMAYMSPEQAI-GAAVDPRCDLWSLGIVLYELLTGRLPFTGEN-YRAV 215
cd06917       154 N-SSKRSTFVGTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDaFRAM 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132979

cd06648

STKc_PAK_II

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group II, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival.

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

false

true

false

285

1e-22

104.45

80.70

5,25,37,21,49,58,103,152,162,3,157,165,67,225,232,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   26 ARDIRLGRDVALKFLQPALAQdegRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPL 105
cd06648        38 ATDKSTGRQVAVKKMDLRKQQ---RRELLFNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALTDIVTHTRMNE 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  106 ARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLpeSSLVTQENILMGTMAYMSPEQAIGAAV 184
cd06648       115 EQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFcAQV--SKEVPRRKSLVGTPYWMAPEVISRLPY 192

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 116620426  185 DPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPePVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06648       193 GTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNLP-PKLKNLHKVSPRLRSFLDRMLVRDPAQRATAAELL 267

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

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

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

false

true

false

293

2e-22

103.83

84.64

6,7,19,34,44,53,108,152,162,3,155,166,4,162,170,55,218,225,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426    8 RYRLAEKLGEGGLGAVYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVME 87
cd06647        20 KYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMN---LQQQPKKELIINEILVMRENKHPNIVNYLDSYLVGDELWVVME 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   88 LIEGQTLRQLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKL-PESSlvtQEN 165
cd06647        97 YLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQItPEQS---KRS 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  166 ILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHgLLNTEPEPVSRYRGDVPATVHRILARA 245
cd06647       174 TMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALY-LIATNGTPELQNPEKLSAIFRDFLNRC 252

                         250
                  ....*....|....*
gi 116620426  246 LTKDRELRYASADLM 260
cd06647       253 LEMDVEKRGSAKELL 267

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

2e-22

103.80

83.49

6,22,16,70,92,89,63,155,166,9,164,188,61,225,250,3,231,253,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQ---TLRQLSG 99
cd05574        17 VYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVMDYCPGGelfRLLQRQP 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKL--------------PESSLVTQE- 164
cd05574        97 GKCFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLSKQsdveptpvskalrkGSRGSVNKIt 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  165 ------------NILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPE-PVSryr 231
cd05574       177 tetfseepsfrsNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETFSNILKKEVTfPGS--- 253

                         250       260
                  ....*....|....*....|....*.
gi 116620426  232 GDVPATVHRILARALTKDRELRYASA 257
cd05574       254 PPVSSSARDLIRKLLVKDPSKRLGSK 279

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

2e-22

103.45

58.86

3,22,16,74,96,91,58,158,149,63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQ-LSGGR 101
cd05600        17 VFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAMEYVPGGDFRTlLNNLG 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlpesSLVTQENILMGTMAYMSPEQAIG 181
cd05600        97 VLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSK----GIVTYANSVVGSPDYMAPEVLRG 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 116620426  182 AAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLN 221
cd05600       173 KGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETWENLKY 212

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-22

103.27

78.72

5,22,34,19,44,53,110,154,165,5,162,170,55,218,225,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06655        35 VFTAIDVATGQEVAIKQIN---LQKQPKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAGGSLTDVVTETC 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK--LPESSlvtQENILMGTMAYMSPEQAI 180
cd06655       112 MDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAqiTPEQS---KRSTMVGTPYWMAPEVVT 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHgLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06655       189 RKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALY-LIATNGTPELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELL 267

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

1e-21

101.05

91.95

13,22,10,10,32,23,11,44,34,8,53,42,38,91,84,5,96,94,63,163,157,9,172,171,5,181,176,7,188,187,14,202,202,7,209,213,16,232,229,21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLG---RDVALKFLQPAlAQDEGRRErFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEG----QTLR 95
cd00192        11 VYKGELKGKGgkkTPVAVKTLKED-ASDSERED-FLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYMEGgdllDFLR 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   96 Q-----LSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSlvtqENILMGT 170
cd00192        89 KsrpvfSPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRDIYDD----DYYRKKG 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  171 MA-----YMSPEqaigAAVDPRC----DLWSLGIVLYELLT-GRLPFTG----ENYRAVLHGLLNTEPEpvsryrgDVPA 236
cd00192       165 GGklpirWMAPE----SLKDGKFttksDVWSFGVLLWEIFTlGGTPYPGlsneEVLEYLRKGYRLPKPE-------NCPD 233

                         250
                  ....*....|....*..
gi 116620426  237 TVHRILARALTKDRELR 253
cd00192       234 ELYELMLSCWQEDPEDR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

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

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

false

true

false

275

2e-21

100.81

71.64

10,22,21,20,46,41,18,64,60,11,75,77,22,97,104,7,104,121,7,121,128,31,152,160,3,157,163,20,177,188,30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPalaqDEGRRERFLNEARAAAAL-NHPGIATIHSI------EEDDGSLFIVMELIEGQTLR 95
cd06608        22 VYKARHKKTGQLVAIKIMDI----IEDEEEEIEEEYNILRKYsNHPNIATFYGAfikkgpPGSDDQLWLVMELCGGGSVT 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   96 QL-----SGGRPMP----------LARALQYctaaadalraAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLpeSS 159
cd06608        98 DLvkglrKKGKRLKeewiayilreTLRGLAY----------LHENKVIHRDIKGQNILLTKEGEVKLVDFGVsAQL--DS 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 116620426  160 LVTQENILMGTMAYMSPE-----QAIGAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd06608       166 TNGRRNTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPL 218

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88513

cd05612

STKc_PRKX_like

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

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

false

true

false

291

4e-21

99.55

81.44

6,22,16,72,94,89,60,158,149,53,211,206,9,221,215,12,240,227,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGGR 101
cd05612        17 VYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLMEYVPGGELfSYLRKAG 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlpesSLVTQENILMGTMAYMSPEQAIG 181
cd05612        97 KFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAK----KVRDRTWTLCGTPEYLAPEIIQS 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  182 AAVDPRCDLWSLGIVLYELLTGRLPFTGEN----YRAVLHGLLnTEPEPVSRYRGDvpatvhrILARALTKDRELRYASA 257
cd05612       173 KGHGKAVDWWALGILIYEMLVGYPPFFDDNpfgiYEKILAGKL-EFPRHFDLRAKD-------LIKKLLVVDRTRRLGNM 244


                  ....*....
gi 116620426  258 DLMLSDLRN 266
cd05612       245 KNGADDVKN 253

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

4e-21

99.23

71.90

6,6,0,35,43,35,61,104,106,7,121,113,32,153,146,2,157,148,49

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426    7 SRYRLAEKLGEGGLGAVYRARDIRLGRDVALKFLQpaLAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVM 86
cd06609         1 ELFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVID--LEEAEDEIEDIQQEIQFLSQCRSPYITKYYGSFLKGSKLWIIM 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   87 ELIEGQTLRQLSGGRPMP----------LARALQYctaaadalraAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KL 155
cd06609        79 EYCGGGSCLDLLKPGKLDetyiafilreVLLGLEY----------LHEEGKIHRDIKAANILLSEEGDVKLADFGVSgQL 148

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 116620426  156 peSSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLP 206
cd06609       149 --TSTMSKRNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPP 197

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

4e-21

99.54

75.14

6,22,16,75,97,94,11,110,105,44,154,179,71,227,250,14,241,265,17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SG 99
cd05573        17 VWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILADADSPWIVKLYYSFQDEEYLYLVMEYMPGGDLMTLlikYD 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARAlqYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK------------------------- 154
cd05573        97 VFPEETARF--YIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCKkmkkagdseyylndshnlldsdrdn 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  155 -----LPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEpvSR 229
cd05573       175 vlkrrRPKKQRRVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFYSDTLQETYNKIMNWKES--LY 252

                         250       260       270
                  ....*....|....*....|....*....|
gi 116620426  230 YRGDVPATVHRI-LARALTKDRELRYASAD 258
cd05573       253 FPADVKVSPEAIdLIRRLLCDPEDRLGSFE 282

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

2e-20

97.36

98.85

10,5,1,34,39,37,13,52,51,7,65,58,32,97,91,63,161,154,17,181,171,3,184,180,22,206,203,47,254,250,9

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426    6 QSRYRLAEKLGEGGLGAVYRARDIRLGRDVALKF--LQPALAQDEGRRE-RFLNEARaaaalnHPGIATIHSIEEDDGSL 82
cd06613         2 QEDYELLQRIGSGTYGDVYKARDIATGELAAVKVikLEPGDDFEIIQQEiSMLKECR------HPNIVAYFGSYLRRDKL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   83 FIVMELIEGQTLRQL-SGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLv 161
cd06613        76 WIVMEYCGGGSLQDIyQVTGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVSAQLTATI- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  162 TQENILMGTMAYMSPEQaigAAV------DPRCDLWSLGIVLYELLTGRLP-FTGENYRAVLHGLLNTEPEPVSRYRGDV 234
cd06613       155 AKRKSFIGTPYWMAPEV---AAVerkggyDGKCDIWALGITAIELAELQPPmFDLHPMRALFLISKSNFQPPKLKDKEKW 231

                         250       260
                  ....*....|....*....|....*....
gi 116620426  235 PATVHRILARALTKDRELRyASADLMLSD 263
cd06613       232 SPVFHDFIKKCLTKDPKKR-PTAEKLLQH 259

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

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

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

false

true

false

324

2e-20

97.26

67.90

6,35,27,8,43,37,5,50,42,9,59,54,95,155,149,69,228,218,29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPA--LAQDEgrRERFLNEAR---AAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQ 110
cd05589        28 AIKALKKGdiIARDE--VESLMCEKRifeTANSERHPFLVNLFACFQTEDHVCFVMEYAAGGDLMMHIHTDVFSEPRAVF 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDL 190
cd05589       106 YAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGLCK-EGMGFGDRTSTFCGTPEFLAPEVLTETSYTRAVDW 184

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116620426  191 WSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPepvsRYRGDVPATVHRILARALTKDRELRYASA 257
cd05589       185 WGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEV----RYPRFLSREAISIMRRLLRRNPERRLGSG 247

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

4e-20

96.33

78.45

5,22,34,19,44,53,110,154,165,5,162,170,55,218,225,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06656        35 VYTAIDIATGQEVAIKQMN---LQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETC 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK--LPESSlvtQENILMGTMAYMSPEQAI 180
cd06656       112 MDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAqiTPEQS---KRSTMVGTPYWMAPEVVT 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHgLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06656       189 RKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALY-LIATNGTPELQNPERLSAVFRDFLNRCLEMDVDRRGSAKELL 267

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

5e-20

95.56

78.72

5,22,35,19,44,54,110,154,166,5,162,171,55,218,226,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06654        36 VYTAMDVATGQEVAIRQMN---LQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETC 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK--LPESSlvtQENILMGTMAYMSPEQAI 180
cd06654       113 MDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAqiTPEQS---KRSTMVGTPYWMAPEVVT 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHgLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06654       190 RKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALY-LIATNGTPELQNPEKLSAIFRDFLNRCLDMDVEKRGSAKELL 268

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

9e-20

94.99

60.44

4,62,51,33,95,85,60,156,145,68,228,213,29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   63 ALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTA 141
cd05592        52 AWEHPFLTHLFCTFQTKEHLFFVMEYLNGGDLMfHIQSSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDR 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  142 EDRVKVLDFGLAKLpESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLN 221
cd05592       132 DGHIKIADFGMCKE-NINGEGKASTFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILN 210

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 116620426  222 TEPepvsRYRGDVPATVHRILARALTKDRELRYASA 257
cd05592       211 DRP----HFPRWISKEAKDCLSKLFEREPTKRLGMD 242

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

9e-20

95.00

75.00

7,22,11,21,46,32,10,57,42,9,66,56,25,91,84,16,109,100,43,157,143,63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPAlaqDEGRRERFLNeARAAAALNH-----PGIATIHSIEEDDGSLFIVMELIEG---QTL 94
cd05611        12 VYLAKKRSTGDYFAIKVLKKS---DMIAKNQVTN-VKAERAIMMiqgesPYVAKLYYSFQSKDYLYLVMEYLNGgdcASL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   95 RQLSGGRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLaklpeSSLVTQENILMGTMAYM 174
cd05611        88 IKTLGGLPEDWAK--QYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGL-----SRNGLENKKFVGTPDYL 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 116620426  175 SPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLL 220
cd05611       161 APETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNIL 206

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

1e-19

94.42

86.07

6,22,20,19,44,39,53,97,94,63,161,157,19,180,181,52,233,233,28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL--SGG 100
cd06611        21 VYKAQHKETGLFAAAKIIQ---IESEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALDSImlELE 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLvTQENILMGTMAYMSPEQAI 180
cd06611        98 RGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKSTL-QKRDTFIGTPYWMAPEVVA 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 -----GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPVSRYRGdVPATVHRILARALTKDRELRYA 255
cd06611       177 cetfkDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKSEPPTLDQPSK-WSSSFNDFLKSCLVKDPDDRPT 255


                  ....*.
gi 116620426  256 SADLML 261
cd06611       256 AAELLK 261

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

3e-19

93.17

77.44

5,25,39,16,44,55,108,152,164,3,157,167,64,222,231,38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   26 ARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPL 105
cd06659        40 AREKHSGRQVAVKMMD---LRKQQRRELLFNEVVIMRDYQHQNVVEMYKSYLVGEELWVLMEFLQGGALTDIVSQTRLNE 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  106 ARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLpeSSLVTQENILMGTMAYMSPEQAIGAAV 184
cd06659       117 EQIATVCESVLQALCYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFcAQI--SKDVPKRKSLVGTPYWMAPEVISRTPY 194

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 116620426  185 DPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNtEPEPVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06659       195 GTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRD-SPPPKLKNAHKISPVLRDFLERMLTREPQERATAQELL 269

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

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

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

false

true

false

268

4e-19

93.00

91.79

8,23,16,15,38,34,58,96,93,48,144,142,22,166,167,44,210,214,11,221,226,9,233,235,27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   24 YRARDIRLGRDVALK---FLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQ-LSG 99
cd06630        17 YQARDVKTGTLMAVKqvtYVRNTSSEQEEVVEALRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWMAGGSVSHlLSK 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDR-VKVLDFGLAKLPESSLVTQENI---LMGTMAYMS 175
cd06630        97 YGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFGAAARLAAKGTGAGEFqgqLLGTIAFMA 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  176 PEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGE---NYRAVLHGLLN-TEPEPVSRYrgdVPATVHRILARALTKDRE 251
cd06630       177 PEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEkhsNHLALIFKIASaTTAPSIPEH---LSPGLRDVTLRCLELQPE 253


                  ....*....
gi 116620426  252 LRYASADLM 260
cd06630       254 DRPPSRELL 262

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

6e-19

92.34

61.30

8,31,23,13,44,40,5,49,47,9,63,56,32,102,88,5,107,101,47,155,148,58,213,210,11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   32 GRDVALKFLQPAL----AQDEG--RRERFLNEAraaaaLNHPGIATIHSIEEDDGSLFIVMELIEGQTLRqlsggrpMPL 105
cd05584        24 GKIFAMKVLKKATivrnQKDTAhtKAERNILEA-----VKHPFIVDLIYAFQTGGKLYLILEYLSGGELF-------MHL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  106 AR--------ALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPE 177
cd05584        92 ERegifmedtACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCK-ESIHEGTVTHTFCGTIEYMAPE 170

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYR----AVLHGLLNTEP 224
cd05584       171 ILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKktidKILKGKLNLPP 221

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

7e-19

92.00

75.94

5,22,10,40,62,51,33,95,85,70,166,155,57,227,212,41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAA-ALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGG 100
cd05590        11 VMLARLKESGRLYAVKVLKKDVILQDDDVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEFVNGGDLMfHIQKS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPEQAI 180
cd05590        91 RRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKTTST-FCGTPDYIAPEILQ 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEpepvSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd05590       170 EMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDE----VVYPTWLSQDAVDILKAFMTKNPTMRLGSLTLG 245


                  ....*...
gi 116620426  261 LSDLRNWH 268
cd05590       246 GEEAILRH 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132949

cd06618

PKc_MKK7

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 (not included in this subfamily) and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade.

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs...

false

true

false

296

1e-18

91.28

62.84

8,78,85,13,91,101,33,125,134,28,153,163,11,167,174,10,177,188,36,213,225,11,225,236,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   79 DGSLFIVMELIEG---QTLRQLSGGRPMPLARALQYCTAAADALRAAHHkGIIHRDIKSSNIMVTAEDRVKVLDFGLA-K 154
cd06618        86 DSDVFICMELMSTcldKLLKRIQGPIPEDILGKMTVAIVKALHYLKEKH-GVIHRDVKPSNILLDASGNVKLCDFGISgR 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  155 LPESSLVTQEnilMGTMAYMSPE----QAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYR-AVLHGLLNTEPePVSR 229
cd06618       165 LVDSKAKTRS---AGCAAYMAPEridpPDPNPKYDIRADVWSLGISLVELATGQFPYKNCKTEfEVLTKILQEEP-PSLP 240

                         170       180       190
                  ....*....|....*....|....*....|.
gi 116620426  230 YRGDVPATVHRILARALTKDRELRYASADLM 260
cd06618       241 PNEGFSPDFCSFVDLCLTKDHRKRPKYRELL 271

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88492

cd05591

STKc_nPKC_epsilon

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

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

false

true

false

321

2e-18

90.82

50.16

5,60,49,35,95,85,59,154,146,9,166,155,45,211,204,6

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   61 AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMV 139
cd05591        50 ALAAKHPFLTALHCCFQTKDRLFFVMEYVNGGDLMfQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  140 TAEDRVKVLDFGLAK--LPESSLVTQeniLMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGEN----YR 213
cd05591       130 DAEGHCKLADFGMCKegILNGVTTTT---FCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNeddlFE 206


                  ....
gi 116620426  214 AVLH 217
cd05591       207 SILH 210

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-18

90.44

51.27

4,62,51,33,95,85,59,156,144,4,160,149,64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   63 ALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTA 141
cd05619        52 AWEHPFLTHLYCTFQTKENLFFVMEYLNGGDLMfHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDT 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  142 EDRVKVLDFGLAKlpESSL-VTQENILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLL 220
cd05619       132 DGHIKIADFGMCK--ENMLgDAKTCTFCGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEELFQSIR 209


                  ....
gi 116620426  221 NTEP 224
cd05619       210 MDNP 213

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

4e-18

89.51

93.26

9,22,15,19,41,35,21,62,61,29,91,93,16,109,109,44,153,154,13,166,171,45,211,217,17,232,234,30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQ-PALAQDEGRRERFLNEARAAA-----ALNHPGIATIHSIEEDDGSLFIVMELIEG---QT 93
cd06628        16 VYLGMNAHSGELMAVKQVEiPSNSIGVQDRKRKMLDALQREinllkELHHENIVQYLGSSQDAGHLNIFLEYVPGgsvAA 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   94 LRQLSGGRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLVTQENI----LM 168
cd06628        96 LLNNYGAFEESLVR--NFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISkKLEANSLSTKTNGarpsLQ 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  169 GTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGEN-YRAVLHGLLNTEPEPVSryrgDVPATVHRILARALT 247
cd06628       174 GSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFPDCTqMQAIFKIGTNASPEIPS----NASSEAKNFLRKTFE 249

                         250
                  ....*....|....*
gi 116620426  248 KDRELRYASADLMLS 262
cd06628       250 IDYNKRPTAAELLKH 264

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

5e-18

89.22

46.49

2,53,89,124,177,217,44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   54 FLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIK 133
cd05596        90 FWEERDIMAHANSEWIVQLHYAFQDDKYLYMVMEYMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVK 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  134 SSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPE----QAIGAAVDPRCDLWSLGIVLYELLTGRLPFTG 209
cd05596       170 PDNMLLDKSGHLKLADFGTCMKMDANGMVRCDTAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYA 249

                         170
                  ....*....|..
gi 116620426  210 ENYRAVLHGLLN 221
cd05596       250 DSLVGTYSKIMD 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

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

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

false

true

false

288

7e-18

88.83

73.61

5,39,41,23,66,64,28,94,93,90,184,185,29,213,218,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   40 LQPALAQDEGRRERFLNEARAAAalnhPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGGRPMPLARALQYCTAAADA 118
cd05583        42 VQKAKTAEHTRTERQVLEAVRRC----PFLVTLHYAFQTDTKLHLILDYVNGGELfTHLYQREHFTESEVRVYIAEIVLA 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  119 LRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPEQAIGAAV--DPRCDLWSLGIV 196
cd05583       118 LDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLAEEEERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVL 197

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 116620426  197 LYELLTGRLPFTGENYR----AVLHGLLNTEPEPVSRYRGDVPATVHRILARALTK 248
cd05583       198 TFELLTGASPFTVDGEQnsqsEISRRILKSKPPFPKTMSAEARDFIQKLLEKDPKK 253

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

9e-18

88.25

48.08

6,74,68,23,97,97,4,101,103,9,113,112,40,153,153,9,166,162,44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   75 IEEDDGSLFIVMELIEGQTLRQL------SGGR--PMPLARALQyctAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVK 146
cd06621        69 LDESSSSIGIAMEYCEGGSLDSIykkvkkRGGRigEKVLGKIAE---SVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVK 145

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 116620426  147 VLDFGLA-KLPESSLVTqeniLMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGE 210
cd06621       146 LCDFGVSgELVNSLAGT----FTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPE 206

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132956

cd06625

STKc_MEKK3_like

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

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

false

true

false

263

1e-17

88.33

79.85

4,22,17,30,52,49,43,95,93,63,158,158,69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRE--RFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSG 99
cd06625        18 VYLCYDVDTGRELAVKQVPFDPDSPETKKEvnALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPGGSVKdQLKA 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPES--SLVTQENILMGTMAYMSPE 177
cd06625        98 YGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTicSSGTGMKSVTGTPYWMSPE 177

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPV 227
cd06625       178 VISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPQ 227

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88502

cd05601

STKc_CRIK

STKc_CRIK: Serine/Threonine Kinases (STKs), Citron Rho-interacting kinase (CRIK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. CRIK is also called citron kinase. It contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. CRIK, an effector of the small GTPase Rho, plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension.

STKc_CRIK: Serine/Threonine Kinases (STKs), Citron Rho-interacting kinase (CRIK)...

false

true

false

330

1e-17

88.06

62.73

6,22,16,77,99,95,52,151,148,13,165,161,12,177,175,3,180,182,41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSG--G 100
cd05601        17 VQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQYAFQDKDNLYLVMEYHPGGDLLSLLNryE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFG-LAKLPESSLVTQEnILMGTMAYMSPE-- 177
cd05601        97 DQFDESMAQFYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFGsAAKLNANKMVNSK-LPVGTPDYIAPEvl 175

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 116620426  178 QAI----GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLN 221
cd05601       176 TSLngdsKSTYGVECDWWSLGVIAYEMIYGRSPFSEGTSAVTYSNIMN 223

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

1e-17

87.77

76.71

4,31,44,10,44,54,110,155,164,69,225,233,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   32 GRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQY 111
cd06657        45 GKLVAVKKMD---LRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAV 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLW 191
cd06657       122 CLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCA-QVSKEVPRRKSLVGTPYWMAPELISRLPYGPEVDIW 200

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116620426  192 SLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPePVSRYRGDVPATVHRILARALTKDRELRYASADLM 260
cd06657       201 SLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLP-PKLKNLHKVSPSLKGFLDRLLVRDPAQRATAAELL 268

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-17

87.79

80.82

9,31,46,10,44,56,110,155,166,52,219,218,5,224,224,14,243,238,18,268,256,9,277,266,7,284,275,7

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   32 GRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQY 111
cd06658        47 GKQVAVKKMD---LRKQQRRELLFNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIATV 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLW 191
cd06658       124 CLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCA-QVSKEVPKRKSLVGTPYWMAPEVISRLPYGTEVDIW 202

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  192 SLGIVLYELLTGRLPFtgenyravlhglLNTEP-EPVSRYRGDVPATVhrilaRALTKDRELRYASADLMLsdlrnwhVM 270
cd06658       203 SLGIMVIEMIDGEPPY------------FNEPPlQAMRRIRDNLPPRV-----KDSHKVSSVLRGFLDLML-------VR 258

                         250       260
                  ....*....|....*....|....
gi 116620426  271 RPSSDAT-ETLVETP--TQGGPPS 291
cd06658       259 EPSQRATaQELLQHPflKLAGPPS 282

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88486

cd05585

STKc_YPK1_like

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

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

false

true

false

312

2e-17

87.01

72.44

7,24,12,6,32,18,62,94,81,65,160,146,51,211,201,6,224,207,3,228,210,28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   25 RARDIRlgRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGGRPM 103
cd05585        13 RKKDTQ--RIYALKTIRKAHIVSRSEVTHTLAERTVLAQVNCPFIVPLKFSFQSPEKLYFVLAFINGGELfHHLQKEGRF 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  104 PLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSlVTQENILMGTMAYMSPEQAIGAA 183
cd05585        91 DLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLNMKD-DDRTNTFCGTPEYLAPELLLGHG 169

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116620426  184 VDPRCDLWSLGIVLYELLTGRLPFTGEN----YRAVLHgllntepEPVsRYRGDVPATVHRILARALTKDRELRYAS 256
cd05585       170 YTKAVDWWTLGVLLYEMLTGLPPFYDENtnemYRKILQ-------EPL-RFPDGFDRDAKDLLTGLLNRDPTQRLGY 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133201

cd05070

PTKc_Fyn_Yrk

Catalytic Domain of the Protein Tyrosine Kinases, Fyn and Yrk

false

true

false

260

2e-17

86.98

82.69

8,34,32,15,53,47,26,80,73,17,97,93,105,202,199,14,224,213,5,229,219,2,231,225,22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   35 VALKFLQPALAQDEGrrerFLNEARAAAALNHPGIATIHSIEEDDgSLFIVMELIEGQTLRQL---SGGRPMPLARALQY 111
cd05070        33 VAVKTLKPGTMSPES----FLEEAQIMKKLRHDKLVQLYAVVSEE-PIYIVTEYMSKGSLLDFlkdGEGRALKLPNLVDM 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLW 191
cd05070       108 AAQVAAGMAYIERMNYIHRDLRSANILVGDGLVCKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVW 187

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 116620426  192 SLGIVLYELLT-GRLPFTGENYRAVLhgllntepEPVSR-YR----GDVPATVHRILARALTKDRELR 253
cd05070       188 SFGILLTELVTkGRVPYPGMNNREVL--------EQVERgYRmpcpQDCPISLHELMLQCWKKDPEER 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-17

86.96

56.53

5,22,10,38,60,49,35,95,85,59,154,147,8,166,155,41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARA-AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGG 100
cd05588        11 VLLVELKKTRRIYAMKVIKKELVNDDEDIDWVQTEKHVfETASNHPFLVGLHSCFQTESRLFFVIEFVSGGDLMfHMQRQ 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK---LPESSLVTqeniLMGTMAYMSPE 177
cd05588        91 RKLPEEHARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCKegiRPGDTTST----FCGTPNYIAPE 166

                         170       180       190
                  ....*....|....*....|....*....|
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd05588       167 ILRGEDYGFSVDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132946

cd06615

PKc_MEK

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

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

false

true

false

308

3e-17

86.34

60.71

6,50,42,47,97,91,4,101,96,24,126,120,35,164,155,47,212,202,27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   51 RERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL--SGGR-PMPLARALQYCTAAADALRAAHHKgI 127
cd06615        43 RNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVlkKAGRiPENILGKISIAVLRGLTYLREKHK-I 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  128 IHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVtqeNILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd06615       122 MHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMA---NSFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPI 198

                         170       180       190
                  ....*....|....*....|....*....|..
gi 116620426  208 TGENyRAVLHGLLNTEPEPVSRYRGDVPATVH 239
cd06615       199 PPPD-AKELEAMFGRPVSEGEAKESHRPVSGH 229

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132941

cd06610

STKc_OSR1_SPAK

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

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

false

true

false

266

4e-17

86.22

71.43

11,22,16,19,43,35,30,73,66,6,80,72,17,97,95,9,106,112,5,121,117,31,152,149,11,163,161,14,177,178,4,183,182,24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpaLAQDEGRRERFLNEARAAAALNHPGIATIH-SIEEDDgSLFIVMELIEGQTLRQL---- 97
cd06610        17 VQRAICLPNGEKVAIKRID--LEKCQTSMDELRKEIQAMSLCHHPNVVKYYtSFVVGD-ELWVVMPLMSGGSCLDImkys 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   98 --SGGRPMPLA--------RALQYctaaadalraAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLPESSLVTQ-EN 165
cd06610        94 ypQGGLDEAIIatilkevlKGLEY----------LHKNGQIHRDIKAGNILLDSDGSVKLADFGVsASLADGGDRTKvRK 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 116620426  166 ILMGTMAYMSPE---QAIGaaVDPRCDLWSLGIVLYELLTGRLPF 207
cd06610       164 TFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPY 206

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

4e-17

86.17

59.12

4,31,23,19,51,42,43,94,86,65,160,151,60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   32 GRDVALKFLQPALAQDEGRrERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGGRPMPLARALQ 110
cd05582        24 GQLYAMKVLKKATLKVRDR-VRTKMERDILAEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLfTRLSKEVMFTEEDVKF 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSlVTQENILMGTMAYMSPEQAIGAAVDPRCDL 190
cd05582       103 YLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDH-EKKAYSFCGTVEYMAPEVVNRRGHTQSADW 181

                         170       180       190
                  ....*....|....*....|....*....|
gi 116620426  191 WSLGIVLYELLTGRLPFTGENYRAVLHGLL 220
cd05582       182 WSFGVLMFEMLTGSLPFQGKDRKETMTMIL 211

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-17

86.00

49.65

6,122,122,2,126,124,35,164,159,50,214,220,7,222,227,4,227,231,32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  123 HHkgIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVtqeNILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLT 202
cd06620       123 HR--IMHRDIKPSNILVNSRGQIKLCDFGVSGELINSIA---DTFVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELAL 197

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 116620426  203 GRLPFTGENYRA-----------VLHGLLNtEPEPvSRYRGDVPATVHRILARALTKDRELRYASADL 259
cd06620       198 GKFPFAFSNIDDdgqddpmgildLLQQIVQ-EPPP-RLPSSDFPEDLRDFVDACLLKDPTERPTPQQL 263

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

9e-17

85.09

71.69

6,22,10,41,63,52,32,95,85,59,155,144,52,207,200,17,232,217,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAA-LNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGG 100
cd05604        11 VLLAKRKLDGKCYAVKVLQKKIVLNRKEQKHIMAERNVLLKnVKHPFLVGLHYSFQTTEKLYFVLDFVNGGELFfHLQRE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPEQAI 180
cd05604        91 RSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCK-EGIAQSDTTTTFCGTPEYLAPEVIR 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPF----TGENYRAVLHGLLNTEPepvsryrgDVPATVHRILARALTKDRELRYAS 256
cd05604       170 KQPYDNTVDWWCLGAVLYEMLYGLPPFycrdVAEMYDNILHKPLVLRP--------GASLTAWSILEELLEKDRQRRLGA 241


                  ..
gi 116620426  257 AD 258
cd05604       242 KE 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132953

cd06622

PKc_MAPKK_PBS2_like

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

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

false

true

false

286

1e-16

84.13

85.31

10,22,16,19,43,35,57,100,98,25,126,123,34,161,157,5,168,162,19,187,187,25,212,219,6,221,225,17,242,242,18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpaLAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGG-- 100
cd06622        17 VYKVLHRPTGVTMAMKEIR--LELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGSLDKLYAGgv 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 ----RPMPLARALQYCTAAADALRAAHHKgIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLvTQENIlmGTMAYMSP 176
cd06622        95 ategIPEDVLRRITYAVVKGLKFLKEEHN-IIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASL-AKTNI--GCQSYMAP 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  177 EQAIGAAVDPR------CDLWSLGIVLYELLTGRLPFTGENY-------RAVLHGllnTEPEPVSRYRGDVPATVhrilA 243
cd06622       171 ERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYanifaqlSAIVDG---DPPTLPSGYSDDAQDFV----A 243

                         250
                  ....*....|....*..
gi 116620426  244 RALTKDRELRYASADLM 260
cd06622       244 KCLNKIPNRRPTYAQLL 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88488

cd05587

STKc_cPKC

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

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

false

true

false

324

2e-16

83.81

61.11

9,35,28,36,71,65,24,95,92,9,106,101,48,163,149,4,167,161,10,177,175,7,188,182,33,221,218,8

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPALAQDEGRRERFLNEARAAAALNHPGIAT-IHSIEEDDGSLFIVMELIEGQTLR---QLSGGRPMPlaRALQY 111
cd05587        29 AIKILKKDVIIQDDDVECTMVEKRVLALPGKPPFLTqLHSCFQTMDRLYFVMEYVNGGDLMyhiQQVGKFKEP--HAVFY 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlpesslvtqENIL--------MGTMAYMSPE----QA 179
cd05587       107 AAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCK---------ENIFggkttrtfCGTPDYIAPEiiayQP 177

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 116620426  180 IGAAVdprcDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLN---TEPEPVSR 229
cd05587       178 YGKSV----DWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMEhnvSYPKSLSK 226

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

3e-16

83.19

53.50

5,32,20,28,60,49,35,95,85,59,154,147,5,163,152,44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   33 RDVALKFLQPALAQDEGRRERFLNEARA-AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQ 110
cd05618        21 RIYAMKVVKKELVNDDEDIDWVQTEKHVfEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGDLMfHMQRQRKLPEEHARF 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK---LPESSlvtqENILMGTMAYMSPEQAIGAAVDPR 187
cd05618       101 YSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKeglRPGDT----TSTFCGTPNYIAPEILRGEDYGFS 176

                         170       180
                  ....*....|....*....|
gi 116620426  188 CDLWSLGIVLYELLTGRLPF 207
cd05618       177 VDWWALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

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

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

false

true

false

305

3e-16

83.05

62.30

9,81,75,10,91,88,16,109,104,53,162,171,15,177,190,7,188,197,35,223,235,2,231,237,2,233,241,24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   82 LFIVMELIEG---QTLRQLSGGRPMPLARalQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPES 158
cd05609        76 LCMVMEYVEGgdcATLLKNIGPLPVDMAR--MYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIGLM 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  159 SLVT--------------QENILMGTMAYMSPE----QAIGAAVdprcDLWSLGIVLYELLTGRLPFTGENYRAVLHGLL 220
cd05609       154 SLTTnlyeghiekdtrefLDKQVCGTPEYIAPEvilrQGYGKPV----DWWAMGIILYEFLVGCVPFFGDTPEELFGQVI 229

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 116620426  221 NTE---PEpvsryrGD--VPATVHRILARALTKDRELRYASA 257
cd05609       230 SDDiewPE------GDeaLPADAQDLISRLLRQNPLERLGTG 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132947

cd06616

PKc_MKK4

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

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

false

true

false

288

4e-16

82.80

52.78

9,110,113,15,126,128,27,153,156,11,167,167,11,178,181,31,209,217,9,218,230,10,234,240,4,239,244,21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKgIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLVTQEnilMGTMAYMSPEQ---AIGAAVDP 186
cd06616       114 VATVKALNYLKEELK-IIHRDVKPSNILLDRNGNIKLCDFGISgQLVDSIAKTRD---AGCRPYMAPERidpSARDGYDV 189

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  187 RCDLWSLGIVLYELLTGRLPFTG-----ENYRAVLHG----LLNTEPEPVSryrgdvPATVhRILARALTKDRELRYASA 257
cd06616       190 RSDVWSLGITLYEVATGKFPYPKwnsvfDQLTQVVKGdppiLSNSEEREFS------PSFV-NFINLCLIKDESKRPKYK 262


                  ...
gi 116620426  258 DLM 260
cd06616       263 ELL 265

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

4e-16

83.08

72.14

7,22,10,41,63,52,31,94,84,60,154,147,8,166,155,41,207,200,13,228,213,30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAA-LNHPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGG 100
cd05575        11 VLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVLLKnVKHPFLVGLHYSFQTKEKLYFVLDYVNGGELfFHLQRE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK---LPESSLVTqeniLMGTMAYMSPE 177
cd05575        91 RSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCKegiAGSKTTST----FCGTPEYLAPE 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLTGRLPF----TGENYRAVLHGLLntepepvsRYRGDVPATVHRILARALTKDRELR 253
cd05575       167 VLRKQPYDRTVDWWCLGAVLYEMLYGLPPFysrdTAEMYDNILNKPL--------RLRPNISVSARHLLEGLLQKDRTKR 238


                  ....*
gi 116620426  254 YASAD 258
cd05575       239 LGAKN 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133173

cd05041

PTKc_Fes_like

Catalytic Domain of Fes-like Protein Tyrosine Kinases

false

true

false

251

4e-16

82.89

74.90

7,22,10,5,28,15,20,50,35,43,93,82,7,102,89,60,162,150,40,202,191,7

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARdIRLGRDVALKFLQPALAQDEgrRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQT----LRQLS 98
cd05041        11 VYKGV-LKGKTEVAVKTCRSTLPPDL--KRKFLQEAEILKQYDHPNIVKLIGVCVQKQPIYIVMELVPGGSlltfLRKKK 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGrpMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVT-QENILMGTMAYMSPE 177
cd05041        88 NR--LTVKKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEGGIYTvSDGLKQIPIKWTAPE 165

                         170       180       190
                  ....*....|....*....|....*....|...
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLT-GRLPFTG 209
cd05041       166 ALNYGRYTSESDVWSYGILLWETFSlGDTPYPG 198

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-16

82.79

54.72

3,53,89,124,177,217,70,248,287,5

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   54 FLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIK 133
cd05622        90 FWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVK 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  134 SSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPE----QAIGAAVDPRCDLWSLGIVLYELLTGRLPFTG 209
cd05622       170 PDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYA 249

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 116620426  210 ENYRAVLHGLLNTEPEPVSRYRGDVPATVHRILARALTkDRELR 253
cd05622       250 DSLVGTYSKIMNHKNSLTFPDDNDISKEAKNLICAFLT-DREVR 292

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

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

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

false

true

false

370

5e-16

82.41

54.86

7,53,89,100,153,190,8,162,198,15,177,217,46,223,268,2,232,270,7,239,278,14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   54 FLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIK 133
cd05621        90 FWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEYMPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVK 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  134 SSNIMVTAEDRVKVLDFGLA-KLPESSLVtQENILMGTMAYMSPE----QAIGAAVDPRCDLWSLGIVLYELLTGRLPFT 208
cd05621       170 PDNMLLDKHGHLKLADFGTCmKMDETGMV-RCDTAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLFEMLVGDTPFY 248

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 116620426  209 GENYRAVLHGLLNTE-----PEpvsryrgDVPATVH-RILARALTKDRELR 253
cd05621       249 ADSLVGTYSKIMDHKnslnfPE-------DVEISKHaKNLICAFLTDREVR 292

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88516

cd05615

STKc_cPKC_alpha

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

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

false

true

false

323

6e-16

82.37

54.80

7,35,28,36,71,65,24,95,92,9,106,101,59,166,160,11,177,175,7,188,182,23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPALAQDEGRRERFLNEARAAAALNHPGIAT-IHSIEEDDGSLFIVMELIEGQTLR---QLSGGRPMPlaRALQY 111
cd05615        29 AIKILKKDVVIQDDDVECTMVEKRVLALQDKPPFLTqLHSCFQTVDRLYFVMEYVNGGDLMyhiQQVGKFKEP--QAVFY 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPE----QAIGAAVdpr 187
cd05615       107 AAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVDGVTTRT-FCGTPDYIAPEiiayQPYGKSV--- 182

                         170       180
                  ....*....|....*....|....
gi 116620426  188 cDLWSLGIVLYELLTGRLPFTGEN 211
cd05615       183 -DWWAYGVLLYEMLAGQPPFDGED 205

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

6e-16

82.36

47.78

4,60,49,35,95,85,59,154,147,8,166,155,45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   61 AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMV 139
cd05620        50 ALAWENPFLTHLYCTFQTKEHLFFVMEFLNGGDLMfHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVML 129

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 116620426  140 TAEDRVKVLDFGLAK---LPESSLVTqeniLMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLPFTGEN 211
cd05620       130 DRDGHIKIADFGMCKenvFGDNRAST----FCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDD 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88478

cd05577

STKc_GRK

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

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

false

true

false

277

6e-16

82.25

90.25

5,22,8,73,95,82,3,98,87,55,153,143,11,167,154,104

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLS--G 99
cd05577         9 VCACQVRATGKMYACKKLDKKRIKKRKGETMALNEKIILEKVSSPFIVSLAYAFETKDALCLVLTLMNGGDLKfHIYnvG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  100 GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLVTQEnilMGTMAYMSPEQ 178
cd05577        89 NPGFDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLAvEFPEGKKIHGR---VGTVGYMAPEV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  179 AIGAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASAD 258
cd05577       166 LQNEVYDFSPDWFALGCLLYEMIAGHSPFRQRKEKVKKEEVDRRTLTDEVEYPDKFSEEAKSICEGLLQKDPEKRLGCRG 245

                         250
                  ....*....|...
gi 116620426  259 LMLSDLRNWHVMR 271
cd05577       246 EGADEVKEHPFFK 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132970

cd06639

STKc_myosinIIIB

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

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

false

true

false

291

6e-16

82.36

67.35

10,22,37,32,55,69,7,64,76,11,75,89,4,79,96,21,100,120,9,109,131,43,152,175,8,162,183,14,176,202,31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFlNEARAAAalNHPGIATIHSI--EEDD---GSLFIVMELIEGQTLRQL 97
cd06639        38 VYKVTNKKDGSLAAVKILDPISDVDEEIEAEY-NILQSLP--NHPNVVKFYGMfyKADKlvgGQLWLVLELCNGGSVTEL 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   98 SGG---RPMPLARAL--QYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLPESSLvtQENILMGTM 171
cd06639       115 VKGlliCGQRLDEAMisYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVsAQLTSTRL--RRNTSVGTP 192

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 116620426  172 AYMSP-----EQAIGAAVDPRCDLWSLGIVLYELLTGRLPF 207
cd06639       193 FWMAPeviacEQQYDYSYDARCDVWSLGITAIELGDGDPPL 233

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

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

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

false

true

false

256

1e-15

81.16

92.19

6,22,18,20,47,38,50,97,90,63,161,153,50,211,204,5,218,209,45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPalaqdEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL--SGG 100
cd06612        19 VYKAIHKETGQVVAIKVVPV-----EEDLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGAGSVSDImkITN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  101 RPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLvTQENILMGTMAYMSPEQAI 180
cd06612        94 KTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTM-AKRNTVIGTPFWMAPEVIQ 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  181 GAAVDPRCDLWSLGIVLYELLTGRLPFTGEN-YRAVLhgLLNTEPEPVSRYRGDVPATVHRILARALTKDRELRYASADL 259
cd06612       173 EIGYNNKADIWSLGITAIEMAEGKPPYSDIHpMRAIF--MIPNKPPPTLSDPEKWSPEFNDFVKKCLVKDPEERPSAIQL 250


                  ....
gi 116620426  260 MLSD 263
cd06612       251 LQHP 254

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

1e-15

81.31

76.36

10,62,57,35,97,95,11,110,106,44,158,150,9,167,161,10,177,176,7,188,183,21,209,205,8,217,217,16,240,233,21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   63 ALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SGGRPMPLARAlqYCTAAADALRAAHHKGIIHRDIKSSNIMV 139
cd06632        58 KLQHPNIVQYLGTEREEDNLYIFLELVPGGSLAKLlkkYGSFPEPVIRL--YTRQILLGLEYLHDRNTVHRDIKGANILV 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  140 TAEDRVKVLDFGLAKlpesSLVTQENIL--MGTMAYMSPE-----QAIGAAVdprcDLWSLGIVLYELLTGRLPFTG-EN 211
cd06632       136 DTNGVVKLADFGMAK----QVVEFSFAKsfKGSPYWMAPEviaqqGGYGLAA----DIWSLGCTVLEMATGKPPWSQlEG 207

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 116620426  212 YRAVLH----GLLNTEPEPVSRYRGDvpatvhrILARALTKDRELRYASADLML 261
cd06632       208 VAAVFKigrsKELPPIPDHLSDEAKD-------FILKCLQRDPSLRPTAAELLE 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88524

cd05623

STKc_MRCK_alpha

STKc_MRCK_alpha: Serine/Threonine Kinases (STKs), DMPK-like subfamily, DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK) alpha isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCKalpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway.

STKc_MRCK_alpha: Serine/Threonine Kinases (STKs), DMPK-like subfamily, DMPK-related...

false

true

false

332

1e-15

81.26

57.83

9,68,62,20,88,83,14,102,98,49,151,148,10,162,158,15,177,175,3,180,181,41,227,222,14,241,242,12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   69 IATIHSIEEDDGSLFIVMEL-IEGQTLRQLSGGRP-MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVK 146
cd05623        63 ITTLHYAFQDENNLYLVMDYyVGGDLLTLLSKFEDrLPEDMARFYLAEMVIAIDSVHQLHYVHRDIKPDNILMDMNGHIR 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  147 VLDFG-LAKLPESSLVtQENILMGTMAYMSPE--QAI---GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLL 220
cd05623       143 LADFGsCLKLMEDGTV-QSSVAVGTPDYISPEilQAMedgKGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIM 221

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 116620426  221 NtepepvSRYRGDVPATVHRI------LARALTKDRELR 253
cd05623       222 N------HKERFQFPAQVTDVsedakdLIRRLICSREHR 254

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-15

81.19

70.28

10,22,10,21,43,33,9,54,42,18,72,61,7,80,68,14,94,83,60,155,143,22,177,169,7,188,176,35,227,211,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPA--LAQDEGRRErfLNEARAAAALNHPGIATI-HSIEEDDgSLFIVMELIEGQTL-RQLS 98
cd05571        11 VILVREKATGKYYAMKILKKEviIAKDEVAHT--LTESRVLQNTRHPFLTALkYSFQTHD-RLCFVMEYANGGELfFHLS 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKlPESSLVTQENILMGTMAYMSPE- 177
cd05571        88 RERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLCK-EGISDGATMKTFCGTPEYLAPEv 166

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116620426  178 ---QAIGAAVdprcDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEpepvSRYRGDVPATVHRILARALTKDRELR 253
cd05571       167 ledNDYGRAV----DWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEE----IRFPRTLSPEAKSLLAGLLKKDPKQR 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88498

cd05597

STKc_DMPK_like

STKc_DMPK_like: Serine/Threonine Kinases (STKs), Myotonic Dystrophy protein kinase (DMPK)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). Three isoforms of MRCK are known, named alpha, beta and gamma. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously.

STKc_DMPK_like: Serine/Threonine Kinases (STKs), Myotonic Dystrophy protein kinase (...

false

true

false

331

2e-15

80.75

45.32

7,68,62,20,88,83,11,99,95,52,151,149,9,162,158,15,177,175,4,181,182,30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   69 IATIHSIEEDDGSLFIVMEL-IEGQTLRQLSG-GRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVK 146
cd05597        63 ITNLHYAFQDENNLYLVMDYyVGGDLLTLLSKfEDRLPEDMARFYLAEMVLAIDSVHQLGYVHRDIKPDNVLLDKNGHIR 142

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 116620426  147 VLDFG--LAKLPESSLvtQENILMGTMAYMSPE--QAIG---AAVDPRCDLWSLGIVLYELLTGRLPFTGEN 211
cd05597       143 LADFGscLRLLADGTV--QSNVAVGTPDYISPEilQAMEdgkGRYGPECDWWSLGVCMYEMLYGETPFYAES 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88517

cd05616

STKc_cPKC_beta

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

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

false

true

false

323

2e-15

80.82

57.28

8,29,20,5,34,27,37,71,65,24,95,92,9,106,101,59,166,160,11,177,175,7,188,182,23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   30 RLGRD--VALKFLQPALAQDEGRRERFLNEARAAAALNHPGIAT-IHSIEEDDGSLFIVMELIEGQTLR---QLSGGRPM 103
cd05616        21 RKGTDelYAIKILKKDVVIQDDDVECTMVEKRVLALSGKPPFLTqLHSCFQTMDRLYFVMEYVNGGDLMyqiQQVGRFKE 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  104 PlaRALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPE----QA 179
cd05616       101 P--HAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENMWDGVTTKT-FCGTPDYIAPEiiayQP 177

                         170       180       190
                  ....*....|....*....|....*....|..
gi 116620426  180 IGAAVdprcDLWSLGIVLYELLTGRLPFTGEN 211
cd05616       178 YGKSV----DWWAFGVLLYEMLAGQAPFEGED 205

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

2e-15

80.84

70.28

6,22,10,73,95,84,70,166,154,11,177,169,7,188,176,35,227,211,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGR 101
cd05595        11 VILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFfHLSRER 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPE---- 177
cd05595        91 VFTEERARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKT-FCGTPEYLAPEvled 169

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 116620426  178 QAIGAAVdprcDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEpepvSRYRGDVPATVHRILARALTKDRELR 253
cd05595       170 NDYGRAV----DWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEE----IRFPRTLSPEAKSLLAGLLKKDPKQR 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88514

cd05613

STKc_MSK1_N

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

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

false

true

false

290

2e-15

80.44

74.83

8,39,41,14,53,56,8,66,64,28,94,93,87,181,182,27,208,212,6,214,219,11,229,230,28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   40 LQPALAQDEGRRER-FLNEARAAaalnhPGIATIHSIEEDDGSLFIVMELIEGQTL-RQLSGGRPMPLARALQYCTAAAD 117
cd05613        42 VQKAKTTEHTRTERqVLEHIRQS-----PFLVTLHYAFQTDTKLHLILDYINGGELfTHLSQRERFKEQEVQIYSGEIVL 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  118 ALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPEQAIG--AAVDPRCDLWSLGI 195
cd05613       117 ALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFGLSKEFHEDEVERAYSFCGTIEYMAPDIVRGgdGGHDKAVDWWSMGV 196

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 116620426  196 VLYELLTGRLPFT---GENYRA-VLHGLLNTEPEpvsrYRGDVPATVHRILARALTKDRELRYASA 257
cd05613       197 LMYELLTGASPFTvdgEKNSQAeISRRILKSEPP----YPQEMSALAKDIIQRLLMKDPKKRLGCG 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132975

cd06644

STKc_STK10_LOK

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

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

false

true

false

292

2e-15

80.46

82.19

7,22,27,19,44,46,47,91,97,18,111,115,54,166,169,14,180,188,44,225,232,35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQpalAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEG----QTLRQLS 98
cd06644        28 VYKAKNKETGALAAAKVIE---TKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGgavdAIMLELD 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   99 GGRPMPLARALqyCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPEQ 178
cd06644       105 RGLTEPQIQVI--CRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSAKNVKTLQRRDS-FIGTPYWMAPEV 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  179 AI-----GAAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPePVSRYRGDVPATVHRILARALTKDRELR 253
cd06644       182 VMcetmkDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEP-PTLSQPSKWSMEFRDFLKTALDKHPETR 260


                  ....*..
gi 116620426  254 YASADLM 260
cd06644       261 PSAAQLL 267

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133164

cd05032

PTKc_InsR_like

Catalytic Domain of Insulin Receptor-like Protein Tyrosine Kinases

false

true

false

277

2e-15

80.07

75.81

8,22,21,3,25,26,7,32,36,16,49,52,3,53,55,42,95,108,59,154,168,48,202,217,14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYR--ARDIRLG---RDVALKFLQPALAQDEgRRErFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-- 95
cd05032        22 VYEglAKGVVKGepeTRVAIKTVNENASMRE-RIE-FLNEASVMKEFNCHHVVRLLGVVSTGQPTLVIMELMARGDLKsy 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   96 ---------QLSGGRPMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK-LPESSLVTQEN 165
cd05032       100 lrsrrpeaeNNPGLGPPTLQEFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMARdIYETDYYRKGG 179

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 116620426  166 ILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLT-GRLPFTGENYRAVL 216
cd05032       180 KGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATlAEQPYQGLSNEEVL 231

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132969

cd06638

STKc_myosinIIIA

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

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

false

true

false

286

3e-15

80.06

88.11

12,22,33,32,55,65,7,64,72,11,75,88,25,100,122,3,104,125,6,113,131,39,152,171,8,162,179,14,176,198,31,213,229,6,219,240,45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFlNEARAAAalNHPGIATIHSI-----EEDDGSLFIVMELIEGQTLRQL 97
cd06638        34 VFKVLNKKNGSKAAVKILDPIHDIDEEIEAEY-NILKALS--DHPNVVKFYGMyykkdVKNGDQLWLVLELCNGGSVTDL 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   98 SGG---------RPMpLARALQyctAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGL-AKLPESSLvtQENIL 167
cd06638       111 VKGflkrgermeEPI-IAYILH---EALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVsAQLTSTRL--RRNTS 184

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  168 MGTMAYMSP-----EQAIGAAVDPRCDLWSLGIVLYELLTGRLPFtgenyrAVLHGL-----LNTEPEPVSRYRGDVPAT 237
cd06638       185 VGTPFWMAPeviacEQQLDSTYDARCDVWSLGITAIELGDGDPPL------ADLHPMralfkIPRNPPPTLHQPELWSNE 258

                         250       260
                  ....*....|....*....|....*..
gi 116620426  238 VHRILARALTKDRELRYASADLMLSDL 264
cd06638       259 FNDFIRKCLTKDYEKRPTVSDLLQHVF 285

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133202

cd05071

PTKc_Src

Catalytic Domain of the Protein Tyrosine Kinase, Src

false

true

false

262

5e-15

79.32

82.06

7,34,32,15,53,47,26,80,73,9,89,83,10,99,95,103,202,199,26,231,225,22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   35 VALKFLQPALAQDEGrrerFLNEARAAAALNHPGIATIHSIEEDDgSLFIVMELI-EGQTLRQLSG--GRPMPLARALQY 111
cd05071        33 VAIKTLKPGTMSPEA----FLQEAQVMKKLRHEKLVQLYAVVSEE-PIYIVTEYMsKGSLLDFLKGemGKYLRLPQLVDM 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  112 CTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENILMGTMAYMSPEQAIGAAVDPRCDLW 191
cd05071       108 AAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVW 187

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116620426  192 SLGIVLYELLT-GRLPFTGENYRAVLHGLLNTEPEPVSryrGDVPATVHRILARALTKDRELR 253
cd05071       188 SFGILLTELTTkGRVPYPGMVNREVLDQVERGYRMPCP---PECPESLHDLMCQCWRKEPEER 247

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

5e-15

78.97

83.75

5,22,19,26,50,45,103,153,149,7,162,156,65,230,221,30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEgrRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGRP 102
cd06641        20 VFKGIDNRTQKVVAIKIIDLEEAEDE--IEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGSALDLLEPGP 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  103 MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLA-KLPESSLvtQENILMGTMAYMSPEQAIG 181
cd06641        98 LDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAgQLTDTQI--KRNTFVGTPFWMAPEVIKQ 175

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116620426  182 AAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPVsryRGDVPATVHRILARALTKDRELRYASADLM 260
cd06641       176 SAYDSKADIWSLGITAIELAKGEPPHSELHPMKVLFLIPKNNPPTL---EGNYSKPLKEFVEACLNKEPSFRPTAKELL 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133176

cd05044

PTKc_c-ros

Catalytic Domain of the Protein Tyrosine Kinase, C-ros

false

true

false

270

5e-15

79.08

73.70

8,32,26,11,44,37,8,53,45,43,96,89,6,102,102,42,144,150,10,154,161,48,202,210,15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   33 RDVALKFLQPAlAQDEGRRErFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQ-LSGGRP-------MP 104
cd05044        27 IRVAVKTLRKG-ATDQEKKE-FLKEAHLMSNFNHPNILKLLGVCLLNEPQYLILELMEGGDLLSyLRGARVtrfgpplLT 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  105 LARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDR------VKVLDFGLAK-LPESSLVTQENILMGTMAYMSPE 177
cd05044       105 LSELLDICLDVAKGCVYLERMHFIHRDLAARNCLVSEKTYsdadrvVKIGDFGLARdIYKNDYYRKEGEGLLPVRWMAPE 184

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 116620426  178 QAIGAAVDPRCDLWSLGIVLYELLT-GRLPFTGENYRAVLH 217
cd05044       185 SLLDGIFTTQSDVWAFGVLMWEILTlGQQPYPALNNQEVLQ 225

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

6e-15

79.08

80.78

6,22,30,79,101,110,52,158,162,23,181,188,47,230,235,29,263,264,14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   23 VYRARDIRLGRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQLSGGR- 101
cd06607        31 VYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIKEVRFLQQLRHPNTIEYKGCYLREHTAWLVMEYCLGSASDILEVHKk 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  102 PMPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAklpesSLVTQENILMGTMAYMSPEQAIG 181
cd06607       111 PLQEVEIAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFGSA-----SLVSPANSFVGTPYWMAPEVILA 185

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  182 ---AAVDPRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEPEPVSryRGDVPATVHRILARALTKDRELRYASAD 258
cd06607       186 mdeGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLS--SNDWSDYFRNFVDSCLQKIPQDRPSSEE 263

                         250
                  ....*....|....*....
gi 116620426  259 LmlsdLRNWHVMRPSSDAT 277
cd06607       264 L----LKHRFVLRERPPTV 278

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

6e-15

78.95

52.91

5,35,23,25,60,49,35,95,85,59,154,147,8,166,155,41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   36 ALKFLQPALAQDEGRRERFLNEARA-AAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLR-QLSGGRPMPLARALQYCT 113
cd05617        24 AMKVVKKELVHDDEDIDWVQTEKHVfEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMfHMQRQRKLPEEHARFYAA 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  114 AAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAK---LPESSLVTqeniLMGTMAYMSPEQAIGAAVDPRCDL 190
cd05617       104 EICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKeglGPGDTTST----FCGTPNYIAPEILRGEEYGFSVDW 179

                         170
                  ....*....|....*..
gi 116620426  191 WSLGIVLYELLTGRLPF 207
cd05617       180 WALGVLMFEMMAGRSPF 196

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132981

cd06650

PKc_MEK1

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

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

false

true

false

333

6e-15

78.92

46.55

4,50,46,47,97,96,28,126,124,35,164,159,42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   51 RERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SGGRPMPLARALQYCTAAADALRAAHHKgI 127
cd06650        47 RNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVlkkAGRIPEQILGKVSIAVIKGLTYLREKHK-I 125

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116620426  128 IHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVtqeNILMGTMAYMSPEQAIGAAVDPRCDLWSLGIVLYELLTGRLP 206
cd06650       126 MHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMA---NSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAIGRYP 201

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88525

cd05624

STKc_MRCK_beta

STKc_MRCK_beta: Serine/Threonine Kinases (STKs), DMPK-like subfamily, DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK) beta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCKbeta is expressed ubiquitously in many tissues.

STKc_MRCK_beta: Serine/Threonine Kinases (STKs), DMPK-like subfamily, DMPK-related cell...

false

true

false

331

8e-15

78.52

58.31

7,68,62,20,88,83,14,102,98,75,177,175,8,185,186,40,225,227,21,246,249,6

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   69 IATIHSIEEDDGSLFIVMEL-IEGQTLRQLSGGRP-MPLARALQYCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVK 146
cd05624        63 ITTLHYAFQDENYLYLVMDYyVGGDLLTLLSKFEDrLPEDMARFYIAEMVLAIHSIHQLHYVHRDIKPDNVLLDMNGHIR 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  147 VLDFGLAKLPESSLVTQENILMGTMAYMSPE--QAIGAAVD---PRCDLWSLGIVLYELLTGRLPFTGENYRAVLHGLLN 221
cd05624       143 LADFGSCLKMNQDGTVQSSVAVGTPDYISPEilQAMEDGMGkygPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMN 222

                         170       180       190
                  ....*....|....*....|....*....|...
gi 116620426  222 TEPE-PVSRYRGDVPATVHRILARAL-TKDREL 252
cd05624       223 HEERfQFPSHITDVSEEAKDLIQRLIcSRERRL 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133166

cd05034

PTKc_Src_like

Catalytic Domain of Src kinase-like Protein Tyrosine Kinases

false

true

false

261

1e-14

77.73

83.14

9,33,31,16,53,47,44,97,94,67,167,161,3,170,167,32,202,200,14,224,214,5,229,220,2,231,226,22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   34 DVALKFLQPALAQDEGrrerFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEGQTLRQL---SGGRPMPLARALQ 110
cd05034        32 KVAVKTLKPGTMSPEA----FLEEAQIMKKLRHDKLVQLYAVCSEEEPIYIVTEYMSKGSLLDFlksGEGKKLRLPQLVD 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQEnilMGT---MAYMSPEQAIGAAVDPR 187
cd05034       108 MAAQIAEGMAYLESRNYIHRDLAARNVLVGENLVCKVADFGLARLIEDDEYTAR---EGAkfpIKWTAPEAALYGRFTIK 184

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 116620426  188 CDLWSLGIVLYELLT-GRLPFTGENYRAVLhgllntepEPVSR-YR----GDVPATVHRILARALTKDRELR 253
cd05034       185 SDVWSFGILLTEIVTyGRVPYPGMTNREVL--------EQVERgYRmprpPNCPDELYDIMLQCWDKDPEER 248

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-14

77.03

67.08

4,31,19,60,91,80,74,166,154,57,227,211,26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426   32 GRDVALKFLQPALAQDEGRRERFLNEARAAAALNHPGIATIHSIEEDDGSLFIVMELIEG-QTLRQLSGGRPMPLARALQ 110
cd05593        20 GKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGgELFFHLSRERVFSEDRTRF 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116620426  111 YCTAAADALRAAHHKGIIHRDIKSSNIMVTAEDRVKVLDFGLAKLPESSLVTQENiLMGTMAYMSPEQAIGAAVDPRCDL 190
cd05593       100 YGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMKT-FCGTPEYLAPEVLEDNDYGRAVDW 178

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116620426  191 WSLGIVLYELLTGRLPFTGENYRAVLHGLLNTEpepvSRYRGDVPATVHRILARALTKDRELR 253
cd05593       179 WGLGVVMYEMMCGRLPFYNQDHEKLFELILMED----IKFPRTLSADAKSLLSGLLIKDPNKR 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

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

false

true

false

279

2e-14

77.00

69.53

9,22,19,5,27,28,16,45,44,35,80,81,16,96,98,6,102,105,57,159,165,14,174,179,28,202,208,5