NCBI Conserved Domain Search

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Conserved domains on [gi\|117927604\|ref\|YP_872155.1\|]
serine/threonine protein kinase [Acidothermus cellulolyticus 11B]

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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

8e-54

206.21

97.66

4,16,0,91,107,92,65,173,157,56,229,217,33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  17 RYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd00180        1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDKLYLVMEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQT 175
cd00180       81 MSGGDLFDLLKkRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLDSGGRKLT-TF 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTR----PPRIDVGTPPGLRPMLAAMTAT 251
cd00180      160 VGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDLLEKILKgkgtPDELPPNISPEAKDLIKKLLVK 239

                        250
                 ....*....|.
gi 117927604 252 DPAARPSAVQV 262
cd00180      240 DPEKRPTAEEL 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

3e-47

184.29

94.98

6,22,6,63,85,70,21,106,92,57,163,150,53,216,205,6,222,213,39

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGF-RDHTTYLVLRWIDGQS 101
cd06606        7 LLGRGSFGSVYLALSKDTGELVAVKSVELSSDSEEELESLEREIRILSKLQHPNIVRYYGCEVtEENTLNIFMEYVSGGS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 102 LAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARF-ADATRLTATGQTIGTA 179
cd06606       87 LASLLkKFGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRlASIAYSGGLKSVRGTP 166

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 180 SYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYD--GTPVEA--AVARLTRPPRIDVGTPPGLRPMLAAMTATDPAA 255
cd06606      167 YWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSelGNPMALlyKIGSSGEPPEIPEDLSEEAKDFLRKCLRRDPKK 246


                 ....*.
gi 117927604 256 RPSAVQ 261
cd06606      247 RPTAEE 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

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

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

false

true

false

253

4e-45

177.35

97.23

8,17,1,40,59,41,48,107,90,53,165,143,9,174,156,41,215,198,7,222,207,9,231,217,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASaaERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWI 97
cd05122        2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEEQ--EQILNEIQILKKCKHPNIVKYYGSYLKKDELWIVMEYC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  98 DGQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIarfadATRLTATGQ-- 174
cd05122       80 DGGSLDDLLKsTGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGV-----SAQLSDTKAkr 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 --TIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA--AVARLTRPP-RIDVGTPPGLRPMLAAM 248
cd05122      155 ntFVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYsELNPMKAlfKIATNPPPGlPSPEKWSPEFRDFLKKC 234

                        250
                 ....*....|...
gi 117927604 249 TATDPAARPSAVQ 261
cd05122      235 LQKDPEKRPTAEE 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

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

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

false

true

false

250

3e-36

147.93

94.00

7,23,0,36,59,37,22,82,59,8,90,68,16,106,85,56,163,141,63,226,205,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAA-ERLRQEMRVLAQLDHPHIVDLLdAGFRDHTT-YLVLRWIDGQS 101
cd05123        1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEvEHTLNERDILSRVDHPFIVKLH-YAFQTKEKlYLVMEYVNGGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 102 LAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfADATRLTATGQTIGTAS 180
cd05123       80 LFTHLsKEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAK-EGIDDGVRTTTFCGTPE 158

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117927604 181 YLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVAR-LTRPPRIDVGTPPGLRPMLAAMTATDPAAR 256
cd05123      159 YLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKiLKDKLRFPEFLSEEAKDLIKKLLTKDPTKR 235

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-36

147.10

97.35

8,16,0,94,110,95,51,161,147,13,174,162,18,192,183,31,223,218,7,230,227,12,243,239,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  17 RYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd06626        1 RWQRGNKIGGGTFGKVYTAVNLDTGELMAVKEIRIQDNDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREKVYIFMEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVLTHGP-LDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIA-RFADATRLTATGQ 174
cd06626       81 CSGGTLEELLEHGRiLDEHVIRVYTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCAvKLKNNTTTMGEEV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 --TIGTASYLAPEQVRGGAV---GPAADVYALGLVILECLTGRREYDGTPVEAA----VARLTRP--PRIDVGTPPGLRp 243
cd06626      161 qsLAGTPAYMAPEVITGGKGkghGRAADIWSLGCVVLEMATGKRPWSELDNEFQimfhVGAGHKPpiPDSLQLSPEGKD- 239

                        250
                 ....*....|....*...
gi 117927604 244 MLAAMTATDPAARPSAVQ 261
cd06626      240 FLDRCLESDPKKRPTASE 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132958

cd06627

STKc_Cdc7_like

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

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

false

true

false

254

3e-35

144.70

97.24

9,16,0,67,84,67,6,90,74,16,106,91,54,165,145,10,175,159,40,215,200,7,222,209,9,232,218,29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  17 RYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAgFRDHTT-YLVLR 95
cd06627        1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQISLEKIKEEALKSIMQEIDLLKNLNHPNIVKYIGS-VKTSDSlYIILE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIarfadATRLTATGQ 174
cd06627       80 YAENGSLRQIIkKFGKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGV-----ATKLSDVSK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 T----IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA--AVARLTRPPrIDVGTPPGLRPMLAA 247
cd06627      155 DdesvVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYyDLNPMPAlfRIVQDDHPP-LPEGISPELKDFLMQ 233

                        250
                 ....*....|....
gi 117927604 248 MTATDPAARPSAVQ 261
cd06627      234 CFQKDPNLRPTAKQ 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

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

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

false

true

false

279

8e-32

133.38

95.70

10,15,0,34,49,35,24,73,60,10,84,70,6,90,77,18,108,96,67,175,182,44,219,230,7,226,238,7,237,245,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVL-RRDTTTASAAERLRQEMRVLAQLD-HPHIVDLLDAgFRDHTT-YL 92
cd05581        1 DDFKFGKILGEGSFSTVYLAKEKETNKEYAIKVLdKRHLIKEKKVKYVKREKEVLTRLNgHPGIVKLYYT-FQDEENlYF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  93 VLRWIDGQSLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTA 171
cd05581       80 VLEYAENGELLEYIKKfGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVLDPNSSPE 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 172 TGQT-------------------IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTP----VEAAVAR-L 227
cd05581      160 SNKGkatnidsqieknrrrrasfVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNeyltFQKIVKLeY 239

                        250       260       270
                 ....*....|....*....|....*....|..
gi 117927604 228 TRPPRIdvgtPPGLRPMLAAMTATDPAARPSA 259
cd05581      240 EFPPNF----PPDAKDLIEKLLVLDPQDRLGV 267

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

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

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

false

true

false

258

1e-31

132.28

94.19

8,17,1,32,49,34,34,84,68,6,90,75,18,108,94,64,174,158,43,217,204,8,225,213,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVL-RRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAgFRDHTT-YLVLR 95
cd05578        2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMnKQKCVEKGSVRNVLNELQILQSLEHPFLVNLWYS-FQDEEDmYLVVD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgq 174
cd05578       81 LLLGGDLRYHLQQkVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIATKLTPDTLATS-- 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 TIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG---TPVEAAVA-RLTRPPRIDVGTPPGLRPMLAAMTA 250
cd05578      159 TSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGhsrTPREEILAkFETADVLYPAGWSSEAIDAINKLLE 238


                 ....*.
gi 117927604 251 TDPAAR 256
cd05578      239 RDPQKR 244

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

2e-31

131.94

94.32

9,18,3,32,50,37,8,61,45,45,106,91,26,132,118,36,168,155,4,174,159,42,216,205,5,221,212,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  19 ELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLR--RDTTTASAaerLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd06623        4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHvdGDEEFRKQ---LLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHS-RGIVHRDVKPANILLDAADYAYLTDFGIARFADATR-LTATg 173
cd06623       81 MDGGSLADLLkKVGKIPEPVLAYIARQILKGLDYLHTkRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENTLdQCNT- 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 174 qTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYD----GTPVE--AAVARLTRPPRIDVGTPPGLRPMLAA 247
cd06623      160 -FVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLppgqPSFFElmQAICDGPPPSLPAEEFSPEFRDFISA 238

                        250
                 ....*....|....
gi 117927604 248 MTATDPAARPSAVQ 261
cd06623      239 CLQKDPKKRPSAAE 252

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

3e-31

131.18

92.33

11,9,9,8,17,20,31,48,53,7,59,60,55,114,117,46,165,163,10,175,177,54,229,233,5,236,238,2,238,244,26,264,272,2

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  10 ELVVLADR---YELRTLVGHGSMGEVYAAYDRRLDRVVAVKV--LRRDTTTasaaERLRQEMRVLAQLDHPHIVDLLDAG 84
cd06614       10 DIVSEGDPrelYDNLEKIGEGASGEVYTATDRATGKEVAIKKmrLRKQPKK----ELIINEILIMKECKHPNIVNYYDSY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  85 FRDHTTYLVLRWIDGQSLAEVLTHGPLDVT--RTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIar 162
cd06614       86 LVGDELWVVMEYMDGGSLTDIITQTFVRMNesQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGF-- 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 163 fadATRLTATGQT----IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTR--PPRIDvg 236
cd06614      164 ---AAQLTKEKSKrnsmVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFLITTkgIPPLK-- 238

                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 117927604 237 TP----PGLRPMLAAMTATDPAARPSAVQVAR--FL 266
cd06614      239 NPekwsPEFKDFLNKCLVKDPEKRPSAEELLQhpFL 274

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132961

cd06630

STKc_MEKK1

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

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

false

true

false

268

1e-30

129.21

95.15

6,22,6,39,61,49,46,107,96,45,156,141,16,172,165,50,222,221,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAER----LRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWID 98
cd06630        7 QLGTGAFSSCYQARDVKTGTLMAVKQVTYVRNTSSEQEEvveaLRKEIRLMARLNHPHIIRMLGATCEDSHFNLFVEWMA 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  99 GQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYayltDFGIARFADATRLTAT----- 172
cd06630       87 GGSVSHLLSkYGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQ----RLRIADFGAAARLAAKgtgag 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 173 ---GQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEA------AVARLTRPPRIDVGTPPGLRP 243
cd06630      163 efqGQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKHSNhlalifKIASATTAPSIPEHLSPGLRD 242

                        250
                 ....*....|....*....
gi 117927604 244 MLAAMTATDPAARPSAVQV 262
cd06630      243 VTLRCLELQPEDRPPSREL 261

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

3e-30

128.12

93.43

10,15,0,45,61,45,99,165,144,7,172,155,39,211,197,5,218,202,3,223,205,4,227,212,6,233,219,30,263,251,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAErLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06609        1 ELFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIDLEEAEDEIED-IQQEIQFLSQCRSPYITKYYGSFLKGSKLWIIME 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIarfadATRLTAT--- 172
cd06609       80 YCGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGV-----SGQLTSTmsk 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 173 -GQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTG---RREYDgtPVEaaVARL---TRPPRI-DVGTPPGLRPM 244
cd06609      155 rNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGeppLSDLH--PMR--VLFLipkNNPPSLeGNKFSKPFKDF 230

                        250       260
                 ....*....|....*....|....*.
gi 117927604 245 LAAMTATDPAARPSAVQVA--RFLRR 268
cd06609      231 VSLCLNKDPKERPSAKELLkhKFIKK 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

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

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

false

true

false

262

2e-29

125.30

72.14

6,23,0,38,61,39,20,82,59,7,89,67,17,106,85,66,174,151,38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAER-LRQEMRVLAQLDHPHIVDLLdAGFRDHT-TYLVLRWIDGQS 101
cd05572        1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEhIFSEKEILEECNSPFIVRLY-RTFKDKKyIYFLMEYCLGGE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 102 LAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgqTIGTAS 180
cd05572       80 LWTILrDRGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLKSGQKTYT--FCGTPE 157

                        170       180       190
                 ....*....|....*....|....*....|..
gi 117927604 181 YLAPEQVRGGAVGPAADVYALGLVILECLTGR 212
cd05572      158 YVAPEIILNKGYDFSVDYWSLGILLYELLTGS 189

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

3e-29

124.92

74.34

4,23,0,26,49,27,59,108,87,55,163,149,48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVL-RRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSL 102
cd05579        1 ISKGAYGRVFLAKKKSTGDIYAIKVIkKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 103 AEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARF-------ADATRLTATGQ 174
cd05579       81 ASLLENvGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGLSKVglvrrqiNLNDDEKEDKR 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 117927604 175 TIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTG 211
cd05579      161 IVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTG 197

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

3e-29

124.35

96.62

10,15,0,45,61,45,47,108,96,52,160,149,15,175,165,10,185,178,4,191,182,24,215,207,14,229,222,11,240,238,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAErLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06610        1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIKRIDLEKCQTSMDE-LRKEIQAMSLCHHPNVVKYYTSFVVGDELWVVMP 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGI-ARFADATRLT 170
cd06610       80 LMSGGSCLDIMKYsypqGGLDEAIIATILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVsASLADGGDRT 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 171 ATGQT-IGTASYLAPE---QVRGgaVGPAADVYALGLVILECLTGRREY-DGTPVEAAVARLTR-PPRIDVGTPPG---- 240
cd06610      160 KVRKTfVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYsKYPPMKVLMLTLQNdPPSLETEADYKkysk 237

                        250       260
                 ....*....|....*....|
gi 117927604 241 -LRPMLAAMTATDPAARPSA 259
cd06610      238 sFRKMISKCLQKDPAKRPTA 257

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

3e-28

121.27

94.34

11,18,1,5,23,8,33,57,41,49,106,92,26,132,119,29,166,148,6,172,155,3,175,159,40,215,201,14,229,220,8,237,229,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  19 ELRTL--VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTAsAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd06605        2 DLETLgeLGAGNSGVVSKVRHRPTGKIMAVKTIRLEINEA-IQKQILRELDILHKCNSPYIVGFYGAFYNNGDISICMEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVL--THGPLDVTRTAAIAAQAADALAYLHS-RGIVHRDVKPANILLDAADYAYLTDFGIArfadaTRLTAT- 172
cd06605       81 MDGGSLDKILkeVQGRIPERILGKIAVAVLKGLTYLHEkHKIIHRDVKPSNILVNSRGEIKLCDFGVS-----GQLVNSl 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 173 GQT-IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY--DGTPVEAAVARLTR-----PPRIDVGT-PPGLRP 243
cd06605      156 AKTfVGTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYppENDPPDGIFELLQYivnepPPRLPSGRfSPDFQD 235

                        250
                 ....*....|....*.
gi 117927604 244 MLAAMTATDPAARPSA 259
cd06605      236 FVNLCLIKDPRERPSY 251

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

5e-28

120.68

95.82

6,22,8,27,49,38,57,106,96,69,175,167,52,227,220,3,230,225,35

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVL---RRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDG 99
cd06625        9 LLGQGAFGRVYLCYDVDTGRELAVKQVpfdPDSPETKKEVNALECEIQLLKNLQHERIVQYYGCLRDDETLSIFMEYMPG 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATGQT--I 176
cd06625       89 GSVKDQLkAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICSSGTGMKsvT 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 177 GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARL-TRP--PRIDVGTPPGLRPMLAAMTATDP 253
cd06625      169 GTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIaTQPtnPQLPSHVSPDARNFLRRTFVENA 248

                        250
                 ....*....|..
gi 117927604 254 AARPSAVQVARF 265
cd06625      249 KKRPSAEELLRH 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

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

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

false

true

false

267

2e-27

118.40

95.51

7,22,6,39,61,52,46,107,99,69,176,173,39,215,213,7,222,222,18,241,240,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAER-------LRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06628        7 LIGSGSFGSVYLGMNAHSGELMAVKQVEIPSNSIGVQDRkrkmldaLQREINLLKELHHENIVQYLGSSQDAGHLNIFLE 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATGQ 174
cd06628       87 YVPGGSVAALLNnYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKTN 166

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 TI-----GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA--AVARLTRPPRIDVGTPPGlRPMLA 246
cd06628      167 GArpslqGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPFpDCTQMQAifKIGTNASPEIPSNASSEA-KNFLR 245

                        250
                 ....*....|....*.
gi 117927604 247 AMTATDPAARPSAVQV 262
cd06628      246 KTFEIDYNKRPTAAEL 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

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

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

false

true

false

290

4e-27

117.54

82.76

11,15,0,40,60,40,4,64,50,19,84,69,6,90,76,9,102,85,6,108,95,57,169,152,45,214,198,7,221,209,13,238,222,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTasaaeRLRQ------EMRVLAQLDHPHIVDLLDAgFRDHT 89
cd05580        1 DDFEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIV-----KLKQvehvlnEKRILQAVRHPFLVNLLGS-FKDNS 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  90 T-YLVLRWIDGqslAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFA 164
cd05580       75 NlYMVMEFVPG---GELFSLlrrsGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAKRV 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 165 DatrlTATGQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRRE-YDGTPVE----AAVARLTRPPRIDvgtpP 239
cd05580      152 K----GRTYTLCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPfFDDNPMKiyekILSGKVRFPSFFS----S 223

                        250
                 ....*....|....*..
gi 117927604 240 GLRPMLAAMTATDPAAR 256
cd05580      224 DAKDLLRNLLQVDLTKR 240

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

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

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

false

true

false

277

1e-26

115.95

87.00

5,23,11,32,56,43,116,173,159,39,212,201,14,227,215,37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTaSAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06641       12 IGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAE-DEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGSAL 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQTIGTASYLA 183
cd06641       91 DLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRN-TFVGTPFWMA 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 184 PEQVRGGAVGPAADVYALGLVILECLTGR---REYDGTPVEAAVARlTRPPRIDVGTPPGLRPMLAAMTATDPAARPSAV 260
cd06641      170 PEVIKQSAYDSKADIWSLGITAIELAKGEpphSELHPMKVLFLIPK-NNPPTLEGNYSKPLKEFVEACLNKEPSFRPTAK 248


                 ....
gi 117927604 261 QVAR 264
cd06641      249 ELLK 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

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

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

false

true

false

272

1e-26

115.66

94.12

11,22,7,27,49,42,32,83,74,9,92,85,14,106,100,56,162,157,34,196,193,31,227,228,4,231,233,5,236,241,14,251,255,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVL--------RRDTTTASAAERLRQEMRVLAQLDHPHIVDLLdaGFRDHTTYL-- 92
cd06629        8 LIGKGTYGRVYLALNVTTGEMMAVKQVelpatiagRHDSRQKDMVKALRSEIETLKDLDHLNIVQYL--GFETTEEYLsi 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  93 VLRWIDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIAR-FADATRLT 170
cd06629       86 FLEYVPGGSIGSCLrTYGRFEEQLVRFFTEQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGISKkSDDIYDND 165

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 171 ATGQTIGTASYLAPEQVRGGAVGPAA--DVYALGLVILECLTGRREYDGTPVEAAVARL----TRPP-RIDVG---TPPG 240
cd06629      166 QNMSMQGSVFWMAPEVIHSYSQGYSAkvDIWSLGCVVLEMFAGRRPWSDEEAIAAMFKLgnkrSAPPiPPDVSmnlSPVA 245

                        250
                 ....*....|....*....
gi 117927604 241 LRPMLAAMTAtDPAARPSA 259
cd06629      246 LDFLNACFTI-NPDNRPTA 263

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

5e-26

113.90

95.70

9,17,4,38,59,42,46,105,90,55,165,145,7,172,156,43,215,200,15,237,215,5,242,226,9,251,239,10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTasaaERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWI 97
cd06612        5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDL----QEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  98 DGQSLAEV--LTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIarfadATRLTAT--- 172
cd06612       81 GAGSVSDImkITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGV-----SGQLTDTmak 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 173 -GQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEAAVARLTRPpridvgtPPGLR------PM 244
cd06612      156 rNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYsDIHPMRAIFMIPNKP-------PPTLSdpekwsPE 228

                        250       260
                 ....*....|....*....|.
gi 117927604 245 LAAMTAT----DPAARPSAVQ 261
cd06612      229 FNDFVKKclvkDPEERPSAIQ 249

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-25

112.52

94.96

6,22,6,25,47,34,60,107,95,67,176,162,11,187,174,43,230,220,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVK---VLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDG 99
cd06632        7 LLGSGSFGSVYEGLNLDDGDFFAVKevsLADDGQTGQEAVKQLEQEIALLSKLQHPNIVQYLGTEREEDNLYIFLELVPG 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATGQtiGT 178
cd06632       87 GSLAKLLKkYGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAKQVVEFSFAKSFK--GS 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 179 ASYLAPEQV-RGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTRP---PRIDVGTPPGLRPMLAAMTATDPA 254
cd06632      165 PYWMAPEVIaQQGGYGLAADIWSLGCTVLEMATGKPPWSQLEGVAAVFKIGRSkelPPIPDHLSDEAKDFILKCLQRDPS 244


                 ....*..
gi 117927604 255 ARPSAVQ 261
cd06632      245 LRPTAAE 251

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

3e-25

111.56

91.92

6,23,3,28,51,32,18,69,51,37,106,89,62,173,151,56,229,212,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRR-DTTTASAAERLRQEMRVL-AQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQS 101
cd05611        4 ISKGAFGSVYLAKKRSTGDYFAIKVLKKsDMIAKNQVTNVKAERAIMmIQGESPYVAKLYYSFQSKDYLYLVMEYLNGGD 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 102 LAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRltatgQTIGTAS 180
cd05611       84 CASLIkTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLENK-----KFVGTPD 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 181 YLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTR-----PPRIDVGTPPGLRPMLAAMTATDPAA 255
cd05611      159 YLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSrrinwPEEVKEFCSPEAVDLINRLLCMDPAK 238


                 ....
gi 117927604 256 RPSA 259
cd05611      239 RLGA 242

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

6e-25

110.46

73.95

7,15,2,39,56,41,52,108,94,52,165,146,10,175,160,10,185,172,2,187,175,20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTtaSAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06613        3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLEPG--DDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVME 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIarfadATRLTATGQ 174
cd06613       81 YCGGGSLQDIYQVtGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGV-----SAQLTATIA 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 117927604 175 T----IGTASYLAPE--QV-RGGAVGPAADVYALGLVILE 207
cd06613      156 KrksfIGTPYWMAPEvaAVeRKGGYDGKCDIWALGITAIE 195

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

2e-24

108.68

90.25

9,16,4,4,23,8,37,61,45,13,74,61,87,163,148,12,175,161,15,190,177,37,227,216,6,233,223,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  17 RYELrtlVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAErLRQEMRVLAQLDH---PHIVDLLDAGFRDHTTYLV 93
cd06917        5 RLEL---IGRGAYGAVYRGKHVPTGRVVALKIINLDTPDDDVSD-IQREVALLSQLRQsqpPNITKYYGSYLKGPRLWII 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  94 LRWIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATRLTATG 173
cd06917       81 MEYAEGGSVRTLMKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA--ALLNQNSSKR 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 174 QT-IGTASYLAPEQVRGG-AVGPAADVYALGLVILECLTGRREYDGTPVEAAVARL--TRPPRI-DVGTPPGLRPMLAAM 248
cd06917      159 STfVGTPYWMAPEVITEGkYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIpkSKPPRLeDNGYSKLLREFVAAC 238

                        250
                 ....*....|....*.
gi 117927604 249 TATDPAARPSAVQVAR 264
cd06917      239 LDEEPKERLSAEELLK 254

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

2e-24

108.30

94.04

10,7,6,9,16,17,8,24,27,23,49,50,111,160,162,5,167,167,48,215,216,7,222,224,12,234,238,30,264,270,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604   8 AVELVVLAD--RYELRTLV--GHGSMGEVYAAYDRRLDRVVAVKvlRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDA 83
cd06648        7 ALQLVVDPGdpRSYLDNFVkiGEGSTGIVCIATDKSTGRQVAVK--KMDLRKQQRRELLFNEVVIMRDYQHPNIVEMYSS 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  84 GFRDHTTYLVLRWIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGI-AR 162
cd06648       85 YLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGFcAQ 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 163 FADatRLTATGQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA-AVARLTRPPRID--VGTP 238
cd06648      165 VSK--EVPRRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYfNEPPLQAmKRIRDNLPPKLKnlHKVS 242

                        250       260       270
                 ....*....|....*....|....*....|..
gi 117927604 239 PGLRPMLAAMTATDPAARPSAVQVAR--FLRR 268
cd06648      243 PRLRSFLDRMLVRDPAQRATAAELLNhpFLAK 274

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132973

cd06642

STKc_STK25_YSK1

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

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

false

true

false

277

3e-24

108.21

89.53

6,23,11,32,56,43,116,173,159,42,215,202,8,223,211,40,263,253,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTaSAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06642       12 IGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAE-DEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGSAL 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQTIGTASYLA 183
cd06642       91 DLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRN-TFVGTPFWMA 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 184 PEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEAA-VARLTRPPRIDVGTPPGLRPMLAAMTATDPAARPSAVQ 261
cd06642      170 PEVIKQSAYDFKADIWSLGITAIELAKGEPPNsDLHPMRVLfLIPKNSPPTLEGQYSKPFKEFVEACLNKDPRFRPTAKE 249

                        250
                 ....*....|
gi 117927604 262 VA--RFLRRW 269
cd06642      250 LLkhKFITRY 259

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

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

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

false

true

false

277

6e-24

107.06

87.00

5,23,11,32,56,43,116,173,159,39,212,199,25,237,225,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTaSAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06640       12 IGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAE-DEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGSAL 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQTIGTASYLA 183
cd06640       91 DLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRN-TFVGTPFWMA 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 184 PEQVRGGAVGPAADVYALGLVILECLTGR-REYDGTPVEAAVARLTRPPRIDVGT-PPGLRPMLAAMTATDPAARPSAVQ 261
cd06640      170 PEVIQQSAYDSKADIWSLGITAIELAKGEpPNSDMHPMRVLFLIPKNNPPTLTGEfSKPFKEFIDACLNKDPSFRPTAKE 249


                 ...
gi 117927604 262 VAR 264
cd06640      250 LLK 252

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

8e-24

106.48

70.45

7,15,0,35,50,36,49,102,85,6,108,95,54,167,149,9,176,159,38,214,198,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLR-RDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVL 94
cd05612        1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAiPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTFHDDKFLYMLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  95 RWIDGqslAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfadatRLT 170
cd05612       81 EYVPG---GELFSYlrkaGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAK-----KVR 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 117927604 171 ATGQTI-GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRRE-YDGTPVE 221
cd05612      153 DRTWTLcGTPEYLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPfFDDNPFG 205

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88486

cd05585

STKc_YPK1_like

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

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

false

true

false

312

1e-23

105.88

75.32

6,23,0,27,50,33,11,66,44,41,107,86,56,164,142,50,214,193,42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLR------RDTTTASAAERlrqemRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWI 97
cd05585        1 IGKGSFGKVMQVRKKDTQRIYALKTIRkahivsRSEVTHTLAER-----TVLAQVNCPFIVPLKFSFQSPEKLYFVLAFI 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  98 DGQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFaDATRLTATGQTI 176
cd05585       76 NGGELFHHLQkEGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKL-NMKDDDRTNTFC 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 177 GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRRE-YDGTPVEAAVARLTRPPRIDVGTPPGLRPMLAAMTATDPAA 255
cd05585      155 GTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPfYDENTNEMYRKILQEPLRFPDGFDRDAKDLLTGLLNRDPTQ 234


                 .
gi 117927604 256 R 256
cd05585      235 R 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88474

cd05573

STKc_ROCK_NDR_like

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

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

false

true

false

354

2e-23

105.32

67.51

9,15,0,46,61,47,22,84,69,3,87,73,20,107,94,54,161,149,5,166,176,8,174,191,40,214,232,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAER-LRQEMRVLAQLDHPHIVDLLDAgFRD-HTTYLV 93
cd05573        1 EDFEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAhVRAERDILADADSPWIVKLYYS-FQDeEYLYLV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  94 LRWIDGQSLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIA-RFADA----- 166
cd05573       80 MEYMPGGDLMTLLIkYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCkKMKKAgdsey 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 167 -----------------TRLTATGQ-------TIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRRE-YDGTPVE 221
cd05573      160 ylndshnlldsdrdnvlKRRRPKKQrrvraysTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPfYSDTLQE 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

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

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

false

true

false

315

1e-22

102.64

87.30

7,15,0,34,49,35,61,110,99,48,158,156,17,175,191,51,226,243,7,233,252,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVL-RRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVL 94
cd05574        1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLdKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTETYLCLVM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  95 RWIDGQSLAEVLTHGP---LDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDF---------GIAR 162
cd05574       81 DYCPGGELFRLLQRQPgkcFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFdlskqsdvePTPV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 163 FADATRLTATGQT------------------IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAV 224
cd05574      161 SKALRKGSRGSVNkittetfseepsfrsnsfVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDETF 240

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 117927604 225 AR-LTRPPRI--DVGTPPGLRPMLAAMTATDPAAR 256
cd05574      241 SNiLKKEVTFpgSPPVSSSARDLIRKLLVKDPSKR 275

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

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

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

false

true

false

318

2e-22

101.85

61.95

8,22,1,36,58,38,15,73,54,8,82,62,3,85,67,4,90,71,13,103,85,67,171,152,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLAQLD-HPHIVDLLdAGF--RDHTtYLVLRWID 98
cd05570        2 VLGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDDdVECTMTEKRVLALAGkHPFLTQLH-SCFqtKDRL-FFVMEYVN 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  99 GQSLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTaTGQTIG 177
cd05570       80 GGDLMyHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEGILGGVT-TSTFCG 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 117927604 178 TASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG 217
cd05570      159 TPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDG 198

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

3e-22

101.54

63.94

6,15,0,42,57,43,26,84,69,3,87,73,21,108,96,80,188,182,29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTAS-AAERLRQEMRVLAQLDHPHIVDLLDAgFRD-HTTYLV 93
cd05601        1 KDFEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQeTVSFFEEERDIMAIANSPWIPQLQYA-FQDkDNLYLV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  94 LRWIDGQSLAEVLTH--GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTA 171
cd05601       80 MEYHPGGDLLSLLNRyeDQFDESMAQFYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFGSAAKLNANKMVN 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 117927604 172 TGQTIGTASYLAPEQVR------GGAVGPAADVYALGLVILECLTGRREYDG 217
cd05601      160 SKLPVGTPDYIAPEVLTslngdsKSTYGVECDWWSLGVIAYEMIYGRSPFSE 211

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

4e-22

101.14

63.06

4,17,2,37,54,40,54,108,95,53,165,148,64

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTT-TASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd05600        3 FQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLfKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDDEYLYLAMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfadATRLTATGQT 175
cd05600       83 VPGGDFRTLLNNlGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLS----KGIVTYANSV 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTR 229
cd05600      159 VGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETWENLKY 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

4e-22

101.05

98.85

11,24,3,17,41,23,11,55,34,6,61,42,45,106,96,61,167,158,43,210,202,18,228,223,4,237,227,10,247,238,2,249,243,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  25 GHGSMGEVYAAYDRRLD---RVVAVKVLRRDtttASAAER--LRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDG 99
cd00192        4 GEGAFGEVYKGELKGKGgkkTPVAVKTLKED---ASDSERedFLKEAKIMKKLGHPNIVRLLGVCTEEEPLYLVLEYMEG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLAEVL---------THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADAT-RL 169
cd00192       81 GDLLDFLrksrpvfspESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSRDIYDDdYY 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 170 TATGQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLT-GRREYDGTPVEAAVARLT---RPPRidvgtPPGLRPML 245
cd00192      161 RKKGGGKLPIRWMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEVLEYLRkgyRLPK-----PENCPDEL 235

                        250       260
                 ....*....|....*....|....*.
gi 117927604 246 AA-MT---ATDPAARPSAVQVARFLR 267
cd00192      236 YElMLscwQEDPEDRPTFSELVERLE 261

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-22

99.81

88.85

11,18,4,5,24,9,39,64,48,26,90,76,12,102,92,7,113,99,15,128,119,36,165,155,7,174,162,41,215,205,4,219,220,39

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  19 ELRTLvGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRqEMRVLAQLDHPHIVDLLDAGFRDHTT--YLVLRW 96
cd06621        5 ELSRL-GEGAGGSVTKCRLKNTGMIFALKTITTDPNPDLQKQILR-ELEINKSCKSPYIVKYYGAFLDESSSsiGIAMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSL----AEVLTHGpldvTRTAAIAAQAADALA-----YLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAdAT 167
cd06621       83 CEGGSLdsiyKKVKKRG----GRIGEKVLGKIAESVlkglsYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGEL-VN 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 168 RLTATgqTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY--DGTP-----------VEAAVARLTRPPRID 234
cd06621      158 SLAGT--FTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFppEGEPplgpiellsyiVNMPNPELKDEPGNG 235

                        250       260
                 ....*....|....*....|....
gi 117927604 235 VGTPPGLRPMLAAMTATDPAARPS 258
cd06621      236 IKWSEEFKDFIKQCLEKDPTRRPT 259

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132986

cd06655

STKc_PAK2

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

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

false

true

false

296

2e-21

98.64

87.84

8,16,22,4,23,26,26,51,52,110,163,162,12,175,175,40,215,216,7,222,230,12,238,242,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  17 RYELrtlVGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd06655       23 RYEK---IGQGASGTVFTAIDVATGQEVAIKQI--NLQKQPKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEY 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATRLTATGQT- 175
cd06655       98 LAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFC--AQITPEQSKRSTm 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA-------AVARLTRPPRIDvgtpPGLRPMLAA 247
cd06655      176 VGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYlNENPLRAlyliatnGTPELQNPEKLS----PIFRDFLNR 251

                        250       260       270
                 ....*....|....*....|....*....|.
gi 117927604 248 MTATDPAARPSAVQVARFLRRWLGRPAVALT 278
cd06655      252 CLEMDVEKRGSAKELLQHPFLKLAKPLSSLT 282

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132950

cd06619

PKc_MKK5

Protein kinases (PKs), MAP kinase kinase 5 (MKK5) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK5, also referred to as MEK5, is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer.

Protein kinases (PKs), MAP kinase kinase 5 (MKK5) subfamily, catalytic (c) domain. PKs...

false

true

false

279

4e-21

97.64

67.38

6,20,5,35,56,40,46,103,86,11,116,97,46,166,143,9,175,153,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  21 RTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTaSAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd06619        6 QEILGHGNGGTVYKAYHLLTRRILAVKVIPLDITV-ELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGG 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLaEVLTHGPLDVTrtAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfadaTRLTATGQT-IGTA 179
cd06619       85 SL-DVYRKIPEHVL--GRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVST----QLVNSIAKTyVGTN 157

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 117927604 180 SYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY 215
cd06619      158 AYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

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

5e-21

97.28

87.37

9,23,26,26,51,52,109,160,162,12,174,174,41,215,216,14,235,230,3,238,242,26,264,270,3,269,273,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06647       27 IGQGASGTVYTAIDVATGQEVAIKQM--NLQQQPKKELIINEILVMRENKHPNIVNYLDSYLVGDELWVVMEYLAGGSLT 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGI-ARFADATRLTATgqTIGTASYL 182
cd06647      105 DVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQITPEQSKRST--MVGTPYWM 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 183 APEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEAAVARLTRppridvGTP---------PGLRPMLAAMTATD 252
cd06647      183 APEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYlNENPLRALYLIATN------GTPelqnpeklsAIFRDFLNRCLEMD 256

                        250       260
                 ....*....|....*....|....*...
gi 117927604 253 PAARPSAVQVAR--FLRrwLGRPAVALT 278
cd06647      257 VEKRGSAKELLQhpFLK--LAKPLSSLT 282

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

2e-20

95.30

90.91

10,15,0,47,63,47,46,109,99,4,113,104,19,134,123,33,168,156,4,174,160,21,195,187,20,218,207,25,243,240,20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLrQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06622        1 DEIEVLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLELDESKFNQII-MELDILHKAVSPYIVDFYGAFFIEGAVYMCME 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLTHG------PLDV-TRTAAIAAQAADALAYLHSrgIVHRDVKPANILLDAADYAYLTDFGIARFADATr 168
cd06622       80 YMDAGSLDKLYAGGvategiPEDVlRRITYAVVKGLKFLKEEHN--IIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVAS- 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 169 LTATgqTIGTASYLAPEQVRGGAVGPA------ADVYALGLVILECLTGRREYdgtPVEAAVARLTRPPRIDVGTPPGLR 242
cd06622      157 LAKT--NIGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPY---PPETYANIFAQLSAIVDGDPPTLP 231

                        250       260
                 ....*....|....*....|....*....
gi 117927604 243 P--------MLAAMTATDPAARPSAVQVA 263
cd06622      232 SgysddaqdFVAKCLNKIPNRRPTYAQLL 260

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

4e-20

94.49

61.56

8,23,22,24,49,46,14,63,63,38,101,103,7,109,110,59,173,169,16,189,188,18,208,206,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKvlRRDTTTASAAERLR---QEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd06607       23 IGHGSFGAVYFARDVRTNEVVAIK--KMSYSGKQSNEKWQdiiKEVRFLQQLRHPNTIEYKGCYLREHTAWLVMEYCLGS 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 S--LAEVLTHgPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRltatgQTIGT 178
cd06607      101 AsdILEVHKK-PLQEVEIAAICHGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFGSASLVSPAN-----SFVGT 174

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 117927604 179 ASYLAPEQVRG---GAVGPAADVYALGLVILEcLTGRR 213
cd06607      175 PYWMAPEVILAmdeGQYDGKVDVWSLGITCIE-LAERK 211

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

5e-20

93.83

61.11

6,21,5,37,58,43,29,87,73,16,103,90,59,162,152,5,171,157,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  22 TLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLAQLDHPHIVDLLDAGFRD-HTTYLVLRWIDG 99
cd05587        6 MVLGKGSFGKVMLAERKGTDELYAIKILKKDVIIQDDdVECTMVEKRVLALPGKPPFLTQLHSCFQTmDRLYFVMEYVNG 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIAR---FADATrltaTGQT 175
cd05587       86 GDLMyHIQQVGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKeniFGGKT----TRTF 161

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG 217
cd05587      162 CGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDG 203

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133171

cd05039

PTKc_Csk_like

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

false

true

false

256

1e-19

92.46

95.70

10,18,8,20,40,28,18,61,46,45,106,92,22,128,116,34,164,150,4,172,154,6,178,162,32,210,195,25,235,222,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  19 ELRTLVGHGSMGEVYAAYDRrlDRVVAVKVLRRDTTTASAaerLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWID 98
cd05039        9 KLGATIGKGEFGDVMLGDYR--GQKVAVKCLKDDSTAAQA---FLAEASVMTTLRHPNLVQLLGVVLQGNPLYIVTEYMA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  99 GQSLAEVL-THGPLDVTRTAAIAAQAADALA--YLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfaDATRltatGQT 175
cd05039       84 KGSLVDYLrSRGRAVITLAQQLGFALDVCEGmeYLEEKNFVHRDLAARNVLVSEDLVAKVSDFGLAK--EASQ----GQD 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 176 IGT--ASYLAPEQVRGGAVGPAADVYALGLVILECLT-GRREYDGTPVEAAVARLTRPPRIDV--GTPPGLRPMLAAMTA 250
cd05039      158 SGKlpVKWTAPEALREKKFSTKSDVWSFGILLWEIYSfGRVPYPRIPLKDVVPHVEKGYRMEApeGCPPEVYKVMKDCWE 237

                        250
                 ....*....|....*.
gi 117927604 251 TDPAARPSAVQVARFL 266
cd05039      238 LDPAKRPTFKQLREQL 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132983

cd06652

STKc_MEKK2

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

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

false

true

false

265

2e-19

92.41

96.98

8,17,3,36,53,42,30,84,72,3,87,78,19,106,98,67,173,167,58,236,225,14,250,246,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDT---TTASAAERLRQEMRVLAQLDHPHIVDLLDAgFRD---HTTY 91
cd06652        4 WRLGKLLGQGAFGRVYLCYDADTGRELAVKQVQFDPespETSKEVNALECEIQLLKNLLHERIVQYYGC-LRDpmeRTLS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  92 LVLRWIDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLT 170
cd06652       83 IFMEHMPGGSIKDQLkSYGALTENVTRKYTRQILEGVSYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLS 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 171 ATG--QTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTRPPridvgTPPGLRPMLAAM 248
cd06652      163 GTGmkSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQP-----TNPVLPPHVSDH 237

                        250       260
                 ....*....|....*....|...
gi 117927604 249 TA-------TDPAARPSAVQVAR 264
cd06652      238 CRdflkrifVEAKLRPSADELLR 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132982

cd06651

STKc_MEKK3

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

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

false

true

false

266

2e-19

92.06

81.58

6,22,8,31,53,42,30,84,72,4,88,79,18,106,98,67,173,167,58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDT---TTASAAERLRQEMRVLAQLDHPHIVDLLDAgFRDH---TTYLVLRW 96
cd06651        9 LLGQGAFGRVYLCYDVDTGRELAAKQVQFDPespETSKEVSALECEIQLLKNLQHERIVQYYGC-LRDRaekTLTIFMEY 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATG-- 173
cd06651       88 MPGGSVKDQLkAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICMSGTGir 167

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 117927604 174 QTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLTRPP 231
cd06651      168 SVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQP 225

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132985

cd06654

STKc_PAK1

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

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

false

true

false

296

2e-19

91.71

66.55

5,23,27,26,51,53,110,163,163,4,167,168,48,215,217,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06654       28 IGQGASGTVYTAMDVATGQEVAIRQM--NLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLT 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADAT-RLTATGQTIGTASYL 182
cd06654      106 DVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFC--AQITpEQSKRSTMVGTPYWM 183

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 117927604 183 APEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA 222
cd06654      184 APEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYlNENPLRA 224

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

2e-19

91.64

82.19

5,23,29,24,49,53,115,165,168,62,227,232,9,236,243,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKvlRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06658       30 IGEGSTGIVCIATEKHTGKQVAVK--KMDLRKQQRRELLFNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGALT 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAdATRLTATGQTIGTASYLA 183
cd06658      108 DIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQV-SKEVPKRKSLVGTPYWMA 186

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 184 PEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARL--TRPPRIDVG--TPPGLRPMLAAMTATDPAARPSA 259
cd06658      187 PEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIrdNLPPRVKDShkVSSVLRGFLDLMLVREPSQRATA 266


                 ...
gi 117927604 260 VQV 262
cd06658      267 QEL 269

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132984

cd06653

STKc_MEKK3_like_1

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

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

false

true

false

264

4e-19

91.24

97.35

9,17,3,35,52,41,31,84,72,6,90,81,16,106,98,67,173,167,54,227,222,3,230,227,22,253,249,11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRD---TTTASAAERLRQEMRVLAQLDHPHIVDLLDAgFRDHTT---Y 91
cd06653        4 WRLGKLLGRGAFGEVYLCYDADTGRELAVKQVPFDpdsQETSKEVNALECEIQLLKNLRHDRIVQYYGC-LRDPEEkklS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  92 LVLRWIDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLT 170
cd06653       83 IFVEYMPGGSIKDQLkAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMS 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 171 ATG--QTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARL-TRP--PRIDVGTPPGLRPML 245
cd06653      163 GTGikSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIaTQPtkPMLPDGVSDACRDFL 242

                        250
                 ....*....|....*....
gi 117927604 246 AAMTATDpAARPSAVQVAR 264
cd06653      243 KQIFVEE-KRRPTAEFLLR 260

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-19

90.94

86.20

7,23,26,26,51,52,110,163,162,12,175,175,40,215,216,7,222,230,13,239,243,39

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06656       27 IGQGASGTVYTAIDIATGQEVAIKQM--NLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLT 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATRLTATGQT-IGTASYL 182
cd06656      105 DVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFC--AQITPEQSKRSTmVGTPYWM 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 183 APEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEA-------AVARLTRPPRIDVgtppGLRPMLAAMTATDPA 254
cd06656      183 APEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYlNENPLRAlyliatnGTPELQNPERLSA----VFRDFLNRCLEMDVD 258

                        250       260
                 ....*....|....*....|....
gi 117927604 255 ARPSAVQVARFLRRWLGRPAVALT 278
cd06656      259 RRGSAKELLQHPFLKLAKPLSSLT 282

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

5e-19

90.76

87.85

10,17,1,18,37,19,3,40,27,13,53,42,21,74,64,25,102,89,6,108,99,85,193,186,22,215,211,11,226,224,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAydRRL-----DRVVAVKVLRRDT--TTASAAERLRQEMRVLAQLDH-PHIVDLLDAGFRDHT 89
cd05583        2 FELLRVLGTGAYGKVFLV--RKVgghdaGKLYAMKVLKKATivQKAKTAEHTRTERQVLEAVRRcPFLVTLHYAFQTDTK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  90 TYLVLRWIDGqslAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAD 165
cd05583       80 LHLILDYVNG---GELFTHlyqrEHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFL 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 166 ATRLTATGQTIGTASYLAPEQVRGGAVG--PAADVYALGLVILECLTGRREY---DGTPVEAAVAR--LTRPPRIDVGTP 238
cd05583      157 AEEEERAYSFCGTIEYMAPEVIRGGSGGhdKAVDWWSLGVLTFELLTGASPFtvdGEQNSQSEISRriLKSKPPFPKTMS 236

                        250
                 ....*....|....*...
gi 117927604 239 PGLRPMLAAMTATDPAAR 256
cd05583      237 AEARDFIQKLLEKDPKKR 254

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

9e-19

89.70

82.88

6,23,27,24,49,51,112,163,163,12,175,176,50,225,228,9,234,239,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKvlRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06657       28 IGEGSTGIVCIATVKSSGKLVAVK--KMDLRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALT 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATRLTATGQT-IGTASYL 182
cd06657      106 DIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFC--AQVSKEVPRRKSlVGTPYWM 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 183 APEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVA--RLTRPPRID--VGTPPGLRPMLAAMTATDPAARPS 258
cd06657      184 APELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKmiRDNLPPKLKnlHKVSPSLKGFLDRLLVRDPAQRAT 263


                 ....*.
gi 117927604 259 AVQVAR 264
cd06657      264 AAELLK 269

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88483

cd05582

STKc_RSK_N

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks.

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK)...

false

true

false

318

1e-18

89.64

75.79

7,22,2,11,33,16,78,111,98,3,117,101,47,165,148,62,230,210,13,243,227,16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVY---AAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDG 99
cd05582        3 VLGQGSFGKVFlvrKITGPDAGQLYAMKVLKKATLKVRDRVRTKMERDILAEVNHPFIVKLHYAFQTEGKLYLILDFLRG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLAEVLTHGPL----DVTrtaAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAdATRLTATGQT 175
cd05582       83 GDLFTRLSKEVMfteeDVK---FYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKES-IDHEKKAYSF 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAVARLtrpPRIDVGTPPGLRP----MLAAMTAT 251
cd05582      159 CGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMI---LKAKLGMPQFLSPeaqsLLRALFKR 235


                 ....*...
gi 117927604 252 DPAARPSA 259
cd05582      236 NPANRLGA 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

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

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

false

true

false

323

1e-18

89.26

74.92

8,20,0,15,35,18,25,60,45,39,102,84,6,108,94,54,163,148,61,224,214,10,238,224,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  21 RTLVGHGSMGEVYAA---YDRRLDRVVAVKVLRRDTTTASAAE--RLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd05584        1 LKVLGKGGYGKVFQVrkvTGADTGKIFAMKVLKKATIVRNQKDtaHTKAERNILEAVKHPFIVDLIYAFQTGGKLYLILE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGqslAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfADATRLTA 171
cd05584       81 YLSG---GELFMHlereGIFMEDTACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGLCK-ESIHEGTV 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 172 TGQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAV-----ARLTRPPRIDvgtpPGLRPMLA 246
cd05584      157 THTFCGTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIdkilkGKLNLPPYLT----PEARDLLK 232

                        250
                 ....*....|
gi 117927604 247 AMTATDPAAR 256
cd05584      233 KLLKRNPSSR 242

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

1e-18

89.25

73.68

7,21,0,33,54,34,17,71,52,28,102,80,6,108,90,54,163,144,51,214,196,42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  22 TLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTT-TASAAERLRQEMRVLAQ-LDHPHIVDLLDAGFRDHTTYLVLRWIDG 99
cd05575        1 KVIGKGSFGKVLLAKHKEDGKFYAVKVLQKKAIlKKNEQKHIMAERNVLLKnVKHPFLVGLHYSFQTKEKLYFVLDYVNG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 qslAEVLTH----GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfADATRLTATGQT 175
cd05575       81 ---GELFFHlqreRSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFGLCK-EGIAGSKTTSTF 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 176 IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRRE-YDGTPVEAAVARLTRPPRIDVGTPPGLRPMLAAMTATDPA 254
cd05575      157 CGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPfYSRDTAEMYDNILNKPLRLRPNISVSARHLLEGLLQKDRT 236


                 ..
gi 117927604 255 AR 256
cd05575      237 KR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

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

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

false

true

false

370

2e-18

88.57

54.59

3,14,41,37,51,79,138,189,221,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  15 ADRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRR-DTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLV 93
cd05621       42 AEDYDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLSKfEMIKRSDSAFFWEERDIMAFANSPWVVQLFCAFQDDKYLYMV 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  94 LRWIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATG 173
cd05621      122 MEYMPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFGTCMKMDETGMVRCD 201

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117927604 174 QTIGTASYLAPEQVRG----GAVGPAADVYALGLVILECLTG 211
cd05621      202 TAVGTPDYISPEVLKSqggdGYYGRECDWWSVGVFLFEMLVG 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133187

cd05056

PTKc_FAK

Catalytic Domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase

false

true

false

270

3e-18

88.25

91.85

9,15,5,20,35,27,8,43,36,11,55,47,28,84,75,26,110,103,100,210,204,17,227,224,7,235,231,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAA--YDRRLDRV-VAVKVLRRDTTtASAAERLRQEMRVLAQLDHPHIVDLLDAgFRDHTTYL 92
cd05056        6 EDITLGRCIGEGQFGDVYQGvyMSPENEKIaVAVKTCKNCTS-PSVREKFLQEAYIMRQFDHPHIVKLIGV-ITENPVWI 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  93 VLRWIDGQSLAEVLTHGP--LDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLT 170
cd05056       84 VMELAPLGELRSYLQVNKysLDLASLILYSYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYLEDESYY 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 171 ATGQTIGTASYLAPEQVRGGAVGPAADVYALGLVILECLT-GRREYDGTPVEAAVARL---TRPPRIDvGTPPGLRPMLA 246
cd05056      164 KASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMlGVKPFQGVKNNDVIGRIengERLPMPP-NCPPTLYSLMT 242

                        250
                 ....*....|.
gi 117927604 247 AMTATDPAARP 257
cd05056      243 KCWAYDPSKRP 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132966

cd06635

STKc_TAO1

Serine/threonine kinases (STKs), thousand-and-one amino acids 1 (TAO1) 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. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability.

Serine/threonine kinases (STKs), thousand-and-one amino acids 1 (TAO1) subfamily,...

false

true

false

317

3e-18

87.84

58.04

5,23,32,36,59,69,50,109,120,55,169,175,20,189,198,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAA-ERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSL 102
cd06635       33 IGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKwQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYCLGSAS 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 103 AEVLTHG-PLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAdatrlTATGQTIGTASY 181
cd06635      113 DLLEVHKkPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIA-----SPANSFVGTPYW 187

                        170       180
                 ....*....|....*....|....*....
gi 117927604 182 LAPEQVRG---GAVGPAADVYALGLVILE 207
cd06635      188 MAPEVILAmdeGQYDGKVDVWSLGITCIE 216

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88520

cd05619

STKc_nPKC_theta

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

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

false

true

false

316

3e-18

87.75

62.34

6,22,1,36,58,38,12,70,51,33,103,85,59,162,147,5,171,152,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLA-QLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd05619        2 MLGKGSFGKVFLAELKGTNQFFAIKALKKDVVLMDDdVECTMVEKRVLSlAWEHPFLTHLYCTFQTKENLFFVMEYLNGG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIAR---FADATrltaTGQTI 176
cd05619       82 DLMfHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGMCKenmLGDAK----TCTFC 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 117927604 177 GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG 217
cd05619      158 GTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHG 198

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132974

cd06643

STKc_SLK

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

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

false

true

false

282

4e-18

87.77

69.50

6,15,4,34,51,38,55,106,95,55,163,150,5,168,156,19,187,180,20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06643        5 EFWEIIGELGDGAFGKVYKAQNKETGVLAAAKVI--DTKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIE 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVL--THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATR-LTAT 172
cd06643       83 FCAGGAVDAVMleLERPLTEPQIRVVCKQTLEALNYLHENKIIHRDLKAGNILFTLDGDIKLADFGVS--AKNTRtIQRR 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 117927604 173 GQTIGTASYLAPEQV-----RGGAVGPAADVYALGLVILE 207
cd06643      161 DSFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGITLIE 200

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

4e-18

87.74

73.07

8,22,1,34,56,37,6,63,43,45,108,89,54,163,143,49,212,197,6,219,203,13,235,216,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTA--SAAERLrQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd05571        2 LLGKGTFGKVILVREKATGKYYAMKILKKEVIIAkdEVAHTL-TESRVLQNTRHPFLTALKYSFQTHDRLCFVMEYANGG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfADATRLTATGQTIGTA 179
cd05571       81 ELFFHLSReRVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGLCK-EGISDGATMKTFCGTP 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 180 SYLAPEQVRGGAVGPAADVYALGLVILECLTGR-----REYDGTpVEAAVARLTRPPRidvGTPPGLRPMLAAMTATDPA 254
cd05571      160 EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRlpfynQDHEKL-FELILMEEIRFPR---TLSPEAKSLLAGLLKKDPK 235


                 ..
gi 117927604 255 AR 256
cd05571      236 QR 237

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132976

cd06645

STKc_MAP4K3

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3 subfamily is part of a 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 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. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 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. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer.

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

false

true

false

267

4e-18

87.80

83.15

8,17,10,42,61,52,45,106,98,61,168,159,19,187,181,20,223,201,4,228,205,6,240,211,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAerLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWI 97
cd06645       11 FELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPGEDFAV--VQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFC 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  98 DGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATrLTATGQTI 176
cd06645       89 GGGSLQDIYhVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITAT-IAKRKSFI 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 177 GTASYLAPEQV---RGGAVGPAADVYALGLVILEcltgrreydgtpveaaVARLtRPPRIDvgtppgLRPMLAAMTATDP 253
cd06645      168 GTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIE----------------LAEL-QPPMFD------LHPMRALFLMTKS 224


                 ....*...
gi 117927604 254 AARPSAVQ 261
cd06645      225 NFQPPKLK 232

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132962

cd06631

STKc_YSK4

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

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

false

true

false

265

4e-18

87.66

96.23

6,22,6,17,40,23,21,61,48,47,108,96,68,176,169,48,224,221,40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRlDRVVAVKVLRRDTTTASAAER----LRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWID 98
cd06631        7 VLGKGAYGTVYCGLTNQ-GQLIAVKQVELDTSNVLAAEKeyekLQEEVDLLKSLKHVNIVQYLGTCLDDNTISIFMEFVP 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  99 GQSLAEVLTH-GPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATGQTI- 176
cd06631       86 GGSISSILNRfGPLPEPVFCKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMPNGIIKLIDFGCARRLAWVGLHGTHSNMl 165

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 177 ----GTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDGTPVEAAV----ARLTRPPRIDVGTPPGLRPMLAAM 248
cd06631      166 ksmhGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASMDRLAAMfyigAHRGLMPRLPDSFSAAAIDFVTSC 245

                        250
                 ....*....|....*.
gi 117927604 249 TATDPAARPSAVQVAR 264
cd06631      246 LTRDQHERPSALQLLR 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132965

cd06634

STKc_TAO2

Serine/threonine kinases (STKs), thousand-and-one amino acids 2 (TAO2) 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. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 activates both 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. TAO2 contains a long C-terminal extension with autoinhibitory segments. It is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor (TNF), interleukin 1 (IL-1), and Toll-like receptor (TLR).

Serine/threonine kinases (STKs), thousand-and-one amino acids 2 (TAO2) subfamily,...

false

true

false

308

5e-18

87.41

59.74

5,23,22,29,52,52,57,109,110,50,164,160,25,189,188,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRD-TTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSL 102
cd06634       23 IGHGSFGAVYFARDVRNSEVVAIKKMSYSgKQSNEKWQDIIKEVRFLQKLRHPNTIQYRGCYLREHTAWLVMEYCLGSAS 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 103 AEVLTHG-PLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGiarfaDATRLTATGQTIGTASY 181
cd06634      103 DLLEVHKkPLQEVEIAAVTHGALQGLAYLHSHNMIHRDVKAGNILLSEPGLVKLGDFG-----SASIMAPANXFVGTPYW 177

                        170       180
                 ....*....|....*....|....*....
gi 117927604 182 LAPEQVRG---GAVGPAADVYALGLVILE 207
cd06634      178 MAPEVILAmdeGQYDGKVDVWSLGITCIE 206

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132964

cd06633

STKc_TAO3

Serine/threonine kinases (STKs), thousand-and-one amino acids 3 (TAO3) 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. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. TAO3 is also known as JIK (JNK inhibitory kinase) or KFC (kinase from chicken). It specifically activates c-Jun N-terminal kinase (JNK), presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis.

Serine/threonine kinases (STKs), thousand-and-one amino acids 3 (TAO3) subfamily,...

false

true

false

313

6e-18

87.00

58.79

5,23,28,29,52,58,57,109,116,50,164,166,25,189,194,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRD-TTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSL 102
cd06633       29 IGHGSFGAVYFATNSHTNEVVAVKKMSYSgKQTNEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKEHTAWLVMEYCLGSAS 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 103 AEVLTHG-PLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGiarfaDATRLTATGQTIGTASY 181
cd06633      109 DLLEVHKkPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFG-----SASKSSPANSFVGTPYW 183

                        170       180
                 ....*....|....*....|....*....
gi 117927604 182 LAPEQVRG---GAVGPAADVYALGLVILE 207
cd06633      184 MAPEVILAmdeGQYDGKVDVWSLGITCIE 212

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

8e-18

86.62

87.33

9,15,11,34,51,45,54,105,102,4,110,106,52,163,158,32,195,195,15,210,213,16,227,229,10,237,241,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLR 95
cd06644       12 EVWEIIGELGDGAFGKVYKAKNKETGALAAAKVI--ETKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIE 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEV---LTHGpLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfADATRLTAT 172
cd06644       90 FCPGGAVDAImleLDRG-LTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSA-KNVKTLQRR 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 173 GQTIGTASYLAPEQVRGGAVGPA-----ADVYALGLVILECLT---GRREYDGTPVEAAVARlTRPPRIDVGT--PPGLR 242
cd06644      168 DSFIGTPYWMAPEVVMCETMKDTpydykADIWSLGITLIEMAQiepPHHELNPMRVLLKIAK-SEPPTLSQPSkwSMEFR 246

                        250       260
                 ....*....|....*....|
gi 117927604 243 PMLAAMTATDPAARPSAVQV 262
cd06644      247 DFLKTALDKHPETRPSAAQL 266

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

8e-18

86.60

61.30

5,21,5,37,58,43,29,87,73,16,103,90,67,171,157,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  22 TLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLAQLDHPHIVDLLDAGFRD-HTTYLVLRWIDG 99
cd05615        6 MVLGKGSFGKVMLAERKGTDELYAIKILKKDVVIQDDdVECTMVEKRVLALQDKPPFLTQLHSCFQTvDRLYFVMEYVNG 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTaTGQTIGT 178
cd05615       86 GDLMyHIQQVGKFKEPQAVFYAAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVDGVT-TRTFCGT 164

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 117927604 179 ASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG 217
cd05615      165 PDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDG 203

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88519

cd05618

STKc_aPKC_iota

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

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

false

true

false

329

1e-17

86.27

59.57

6,22,1,36,58,38,14,72,53,31,103,85,59,164,144,5,169,150,47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLAQL-DHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd05618        2 VIGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEdIDWVQTEKHVFEQAsNHPFLVGLHSCFQTESRLFFVIEYVNGG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARfaDATRL-TATGQTIGT 178
cd05618       82 DLMfHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCK--EGLRPgDTTSTFCGT 159

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 117927604 179 ASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYD 216
cd05618      160 PNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFD 197

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

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

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

false

true

false

370

1e-17

86.14

55.95

3,9,36,58,67,95,118,185,217,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  10 ELVVLADRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRQEMR-VLAQLDHPHIVDLLDAGFRDH 88
cd05596       37 KLRMKAEDFDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLSKFEMIKRSDSAFFWEERdIMAHANSEWIVQLHYAFQDDK 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  89 TTYLVLRWIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATR 168
cd05596      117 YLYMVMEYMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMDANG 196

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 117927604 169 LTATGQTIGTASYLAPE----QVRGGAVGPAADVYALGLVILECLTG 211
cd05596      197 MVRCDTAVGTPDYISPEvlksQGGDGYYGRECDWWSVGVFLYEMLVG 243

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88492

cd05591

STKc_nPKC_epsilon

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

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

false

true

false

321

1e-17

85.81

61.06

5,22,1,36,58,38,12,70,51,33,103,85,69,173,154,43

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLA-QLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd05591        2 VLGKGSFGKVMLAELKGTDEVYAIKVLKKDVILQDDdVDCTMTEKRILAlAAKHPFLTALHCCFQTKDRLFFVMEYVNGG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQTIGTA 179
cd05591       82 DLMfQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGILNGVTTT-TFCGTP 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 117927604 180 SYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYD 216
cd05591      161 DYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFE 197

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132951

cd06620

PKc_MAPKK_Byr1_like

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

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

false

true

false

284

1e-17

86.00

91.55

10,18,5,5,23,12,40,64,52,42,106,95,27,133,123,28,165,151,10,175,162,40,215,209,14,229,229,8,237,238,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  19 ELRTL--VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLRqEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRW 96
cd06620        6 DLETIsdLGAGNGGSVSKVKHIPTGTVMAKKVVHIGAKSSVRKQILR-ELQIMHECRSPYIVSFYGAFLNENNICMCMEF 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  97 IDGQSLAEVL-THGPLDVTRTAAIAAQAADALAYLHSR-GIVHRDVKPANILLDAADYAYLTDFGIArfadATRLTATGQ 174
cd06620       85 MDCGSLDRIYkKGGPIPVEILGKIAVAVVEGLTYLYNVhRIMHRDIKPSNILVNSRGQIKLCDFGVS----GELINSIAD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 175 T-IGTASYLAPEQVRGGAVGPAADVYALGLVILECLTGRREY-------DGTPVEAAVARLTR------PPRIDVGT-PP 239
cd06620      161 TfVGTSTYMSPERIQGGKYTVKSDVWSLGISIIELALGKFPFafsniddDGQDDPMGILDLLQqivqepPPRLPSSDfPE 240

                        250       260
                 ....*....|....*....|....*
gi 117927604 240 GLRPMLAAMTATDPAARPSAVQVAR 264
cd06620      241 DLRDFVDACLLKDPTERPTPQQLCA 265

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

2e-17

85.47

79.80

6,23,28,26,51,54,110,163,164,5,168,170,47,215,218,16,231,237,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLrrDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSLA 103
cd06659       29 IGEGSTGIVCIAREKHSGRQVAVKMM--DLRKQQRRELLFNEVVIMRDYQHQNVVEMYKSYLVGEELWVLMEFLQGGALT 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 104 EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIArfADATR-LTATGQTIGTASYL 182
cd06659      107 DIVSQTRLNEEQIATVCESVLQALCYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFC--AQISKdVPKRKSLVGTPYWM 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 183 APEQVRGGAVGPAADVYALGLVILECLTGRREY-DGTPVEAAVARLTRPP---RIDVGTPPGLRPMLAAMTATDPAARPS 258
cd06659      185 APEVISRTPYGTEVDIWSLGIMVIEMVDGEPPYfSDSPVQAMKRLRDSPPpklKNAHKISPVLRDFLERMLTREPQERAT 264


                 .
gi 117927604 259 A 259
cd06659      265 A 265

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-17

85.07

78.97

9,17,1,18,37,19,4,41,28,14,55,44,19,74,64,25,102,89,11,113,104,80,193,186,36,231,222,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  18 YELRTLVGHGSMGEVYAAydRRLD-----RVVAVKVLRRDTTT--ASAAERLRQEMRVLAQLDH-PHIVDLLDAGFRDHT 89
cd05613        2 FELLKVLGTGAYGKVFLV--RKVSghdsgKLYAMKVLKKATIVqkAKTTEHTRTERQVLEHIRQsPFLVTLHYAFQTDTK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  90 TYLVLRWIDGqslAEVLTHGPLDV----TRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFAD 165
cd05613       80 LHLILDYING---GELFTHLSQRErfkeQEVQIYSGEIVLALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFGLSKEFH 156

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117927604 166 ATRLTATGQTIGTASYLAPEQVRGGAVG--PAADVYALGLVILECLTGRREYDGTPVEAAVARLTRppRIDVGTPP 239
cd05613      157 EDEVERAYSFCGTIEYMAPDIVRGGDGGhdKAVDWWSMGVLMYELLTGASPFTVDGEKNSQAEISR--RILKSEPP 230

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133191

cd05060

PTKc_Syk_like

Catalytic Domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases

false

true

false

257

3e-17

84.71

98.05

9,23,2,20,43,25,20,64,45,23,88,68,19,107,88,56,163,146,47,210,194,15,225,215,6,235,221,33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRV---VAVKVLRRDTTTASAAERLRqEMRVLAQLDHPHIVDLLDAGFRDhTTYLVLRWIDGQ 100
cd05060        3 LGHGNFGSVVKGVYLMKSGKeveVAVKTLKQEHIAAGKKEFLR-EASVMAQLDHPCIVRLIGVCKGE-PLMLVMELAPLG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLAEVLT-HGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARF--ADATRLTATGQTIG 177
cd05060       81 PLLKYLKkRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRAlgAGSDYYRATTAGRW 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 178 TASYLAPEQVRGGAVGPAADVYALGLVILECLT-GRREYDGTPVEAAVA------RLTRPPridvGTPPGLRPMLAAMTA 250
cd05060      161 PLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSyGAKPYGEMKGAEVIAmlesgeRLPRPE----ECPQEIYSIMLSCWK 236

                        250
                 ....*....|....*...
gi 117927604 251 TDPAARPSAVQVARFLRR 268
cd05060      237 YRPEDRPTFSELESTFRR 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

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

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

false

true

false

275

3e-17

84.64

65.09

7,14,4,35,52,39,20,72,60,13,85,74,5,90,84,16,106,105,63,170,168,15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  15 ADRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLrrdTTTASAAERLRQEMRVLAQL-DHPHIVDLLDAGF-RDHTT-- 90
cd06608        5 GGIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIM---DIIEDEEEEIEEEYNILRKYsNHPNIATFYGAFIkKGPPGsd 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  91 ---YLVLRWIDGQSLAEVL-----THGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIAR 162
cd06608       82 dqlWLVMELCGGGSVTDLVkglrkKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFGVSA 161

                        170       180
                 ....*....|....*....|...
gi 117927604 163 FADATRLtATGQTIGTASYLAPE 185
cd06608      162 QLDSTNG-RRNTSIGTPYWMAPE 183

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

3e-17

84.72

55.80

3,9,36,42,51,79,138,189,221,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  10 ELVVLADRYELRTLVGHGSMGEVYAAYDRRLDRVVAVKVLRR-DTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDH 88
cd05622       37 DLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKfEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDR 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  89 TTYLVLRWIDGQSLAEVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATR 168
cd05622      117 YLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEG 196

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 117927604 169 LTATGQTIGTASYLAPEQVRG----GAVGPAADVYALGLVILECLTG 211
cd05622      197 MVRCDTAVGTPDYISPEVLKSqggdGYYGRECDWWSVGVFLYEMLVG 243

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

5e-17

84.32

83.51

10,23,11,13,36,28,24,61,52,20,81,76,8,91,84,16,107,101,3,110,105,68,178,175,32,210,208,14,224,237,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAY----DRRLDRVVAVKVLRRDTTTASAAErLRQEMRVLAQLDHPHIVDLL----DAGFRDHTtyLVLR 95
cd05038       12 LGEGHFGTVYLGTydppDDNTGEIVAVKKLNTSGVEAHRQD-FEREIEIMRTLDHENIVKYKgvseEPGGRSLS--LIME 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  96 WIDGQSLAEVLT-HGP-LDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATG 173
cd05038       89 YLPSGSLRDYLRrHRDqLNLKRLLLFALQIAKGMDYLGSKRLIHRDLAARNILVDSEDLVKISDFGLAKVLPEDKDYYYV 168

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117927604 174 QTIGT--ASYLAPEQVRGGAVGPAADVYALGLVILECLT-GRREYDGTPVEAAV---------------ARLTRPP 231
cd05038      169 KEPREspIFWYAPECLRTGKFSSASDVWSYGVTLYEMFTyGEEPSLSPPAEFLVmqmivtrllellesgERLPRPP 244

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

5e-17

83.96

73.99

11,22,21,29,54,50,13,67,66,23,95,89,11,106,106,27,133,134,28,161,163,5,169,168,26,195,198,29,226,227,3,229,235,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRdttTASAAERLRQEMR---VLAQLDHPHIVDLLDAGFRDHTTylvlrWIDG 99
cd06618       22 EIGSGTCGQVYKMRFKKTGHVMAVKQMRR---TGNKEENKRILMDldvVLKSHDCPYIVKCYGYFITDSDV-----FICM 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 100 QSLAEVL------THGPLDVTRTAAIAAQAADALAYLHSR-GIVHRDVKPANILLDAADYAYLTDFGIA-RFADAtrlTA 171
cd06618       94 ELMSTCLdkllkrIQGPIPEDILGKMTVAIVKALHYLKEKhGVIHRDVKPSNILLDASGNVKLCDFGISgRLVDS---KA 170

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117927604 172 TGQTIGTASYLAPEQVRGGAVGPA----ADVYALGLVILECLTGRREYDGTPVEAAVarLTR-----PPRID 234
cd06618      171 KTRSAGCAAYMAPERIDPPDPNPKydirADVWSLGISLVELATGQFPYKNCKTEFEV--LTKilqeePPSLP 240

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

5e-17

83.91

61.56

5,22,1,36,58,38,12,70,51,33,103,85,67,171,152,46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASA-AERLRQEMRVLA-QLDHPHIVDLLDAGFRDHTTYLVLRWIDGQ 100
cd05590        2 VLGKGSFGKVMLARLKESGRLYAVKVLKKDVILQDDdVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEFVNGG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 SLA-EVLTHGPLDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTaTGQTIGTA 179
cd05590       82 DLMfHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKT-TSTFCGTP 160

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 117927604 180 SYLAPEQVRGGAVGPAADVYALGLVILECLTGRREYDG 217
cd05590      161 DYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEA 198

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

9e-17

83.41

86.64

8,23,0,40,63,41,40,103,82,7,110,91,51,161,143,10,174,153,38,212,194,14,226,210,30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  24 VGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAERLR-QEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGQSL 102
cd05577        1 LGKGGFGEVCACQVRATGKMYACKKLDKKRIKKRKGETMAlNEKIILEKVSSPFIVSLAYAFETKDALCLVLTLMNGGDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 103 A-EVLTHGP--LDVTRTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIA-RFADATRLTAtgqTIGT 178
cd05577       81 KfHIYNVGNpgFDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGLAvEFPEGKKIHG---RVGT 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 179 ASYLAPEQVRGGAVGPAADVYALGLVILECLTGR---REYDGTPVEAAVAR--LTRPPRIDVGTPPGLRPMLAAMTATDP 253
cd05577      158 VGYMAPEVLQNEVYDFSPDWFALGCLLYEMIAGHspfRQRKEKVKKEEVDRrtLTDEVEYPDKFSEEAKSICEGLLQKDP 237


                 ...
gi 117927604 254 AAR 256
cd05577      238 EKR 240

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

1e-16

83.16

58.77

5,22,1,39,61,42,38,102,80,12,114,96,58,173,154,38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  23 LVGHGSMGEVYAAYDRRLDRVVAVKVLRRDTTTASAAER--LRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVLRWIDGq 100
cd05604        2 VIGKGSFGKVLLAKRKLDGKCYAVKVLQKKIVLNRKEQKhiMAERNVLLKNVKHPFLVGLHYSFQTTEKLYFVLDFVNG- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604 101 slAEVLTHGPLDVT----RTAAIAAQAADALAYLHSRGIVHRDVKPANILLDAADYAYLTDFGIARFADATRLTATgQTI 176
cd05604       81 --GELFFHLQRERSfpepRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGLCKEGIAQSDTTT-TFC 157

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 117927604 177 GTASYLAPEQVRGGAVGPAADVYALGLVILECLTG 211
cd05604      158 GTPEYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYG 192

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

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

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

false

true

false

305

1e-16

83.05

85.57

5,15,0,24,39,25,69,108,95,55,163,164,67,230,235,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927604  16 DRYELRTLVGHGSMGEVYAAYDRR-LDRVVAVKVLRRDTTTASAAERLRQEMRVLAQLDHPHIVDLLDAGFRDHTTYLVL 94
cd05609        1 EDFETIKLISNGAYGAVYLVRHKEtRQRFAMKKINKQNLILRNQIQQVFVE