NCBI Conserved Domain Search

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Conserved domains on [gi\|117927230\|ref\|YP_871781.1\|]
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

2e-55

211.99

98.83

6,17,0,44,62,44,29,95,73,72,170,145,62,233,207,38,272,245,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  18 RYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQtRFRREAQAAAALNHPSIVAVYDTGESMLDgvpvPY 97
cd00180        1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQVE-RILREIKILKRLNHPNIVKLYDVFEDEDK----LY 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTAT 177
cd00180       76 LVMEYMSGGDLFDLLKKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGL---AKQLDSG 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 178 VTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVPPSRLNPDVTPDIDA 257
cd00180      153 GRKLTTFVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGDNEEDL-LEKILKGKGTPDELPPNISPEAKD 231

                        250       260
                 ....*....|....*....|...
gi 117927230 258 IVMKALAKNPANRYqSAAEMRAD 280
cd00180      232 LIKKLLVKDPEKRP-TAEELLQH 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132935

cd05122

PKc_STE

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

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

false

true

false

253

3e-40

161.94

95.26

9,18,1,39,60,40,24,87,64,8,96,72,18,114,95,4,122,99,2,125,101,42,170,143,71,242,214,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDtsfQTRFRREAQAAAALNHPSIVAVYDtgeSMLDGVPVpYI 98
cd05122        2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEE---QEQILNEIQILKKCKHPNIVKYYG---SYLKKDEL-WI 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  99 VMEYVEGRTLRDILKS-----ESHIlprrALeIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQ 173
cd05122       75 VMEYCDGGSLDDLLKStgplpESQI----AY-ICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGV---SAQ 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 174 STATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPvPPSRLNPDVTP 253
cd05122      147 LSDTKAKRNTFVGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYSELNPMKALFKIATNPP-PGLPSPEKWSP 225

                        250
                 ....*....|....*..
gi 117927230 254 DIDAIVMKALAKNPANR 270
cd05122      226 EFRDFLKKCLQKDPEKR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132937

cd06606

STKc_MAPKKK

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

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

false

true

false

259

1e-39

159.63

97.30

8,17,0,32,51,32,12,63,45,30,96,75,70,167,145,59,226,205,18,246,223,25,272,248,4

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  18 RYELGEILGYGGMAEVRRGRDLRLGRDVAIKTlrVDLARDTSFQTR-FRREAQAAAALNHPSIVAVYDTGESMLDGVpvp 96
cd06606        1 EWTRGKLLGRGSFGSVYLALSKDTGELVAVKS--VELSSDSEEELEsLEREIRILSKLQHPNIVRYYGCEVTEENTL--- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiARAVAQSTA 176
cd06606       76 NIFMEYVSGGSLASLLKKFGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFG-CAKRLASIA 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTG-ESAVAVAYQHVREDPVPPsrLNPDVTPDI 255
cd06606      155 YSGGLKSVRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPPWSElGNPMALLYKIGSSGEPPE--IPEDLSEEA 232

                        250       260
                 ....*....|....*....|.
gi 117927230 256 DAIVMKALAKNPANRYqSAAE 276
cd06606      233 KDFLRKCLRRDPKKRP-TAEE 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

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

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

false

true

false

250

1e-35

146.39

94.00

6,24,0,59,83,62,6,96,68,71,170,139,62,233,201,9,245,210,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  25 LGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVY---DTGESMldgvpvpYIVME 101
cd05123        1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDILSRVDHPFIVKLHyafQTKEKL-------YLVME 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 102 YVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQT 181
cd05123       74 YVNGGDLFTHLSKEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGL---AKEGIDDGVRT 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 182 AAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVppsRLNPDVTPDIDAIVMK 261
cd05123      151 TTFCGTPEYLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAET-YQKILKDKL---RFPEFLSEEAKDLIKK 226


                 ....*....
gi 117927230 262 ALAKNPANR 270
cd05123      227 LLTKDPTKR 235

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

6e-35

143.93

97.64

11,17,0,31,50,31,7,57,39,27,84,69,5,96,74,17,114,91,12,126,104,41,170,145,67,238,212,6,246,218,24,271,242,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  18 RYELGEILGYGGMAEVRRGRDLRLGRDVAIKtlRVDLARD-TSFQTRFRREAQAAAALNHPSIVAVYD---TGESMldgv 93
cd06627        1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIK--QISLEKIkEEALKSIMQEIDLLKNLNHPNIVKYIGsvkTSDSL---- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  94 pvpYIVMEYVEGRTLRDILKsESHILPRRALEI-VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVA 172
cd06627       75 ---YIILEYAENGSLRQIIK-KFGKFPESLVAVyVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGV---AT 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 173 QSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVrEDPVPPsrLNPDVT 252
cd06627      148 KLSDVSKDDESVVGTPYWMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMPALFRIV-QDDHPP--LPEGIS 224

                        250       260
                 ....*....|....*....|....*
gi 117927230 253 PDIDAIVMKALAKNPANRyQSAAEM 277
cd06627      225 PELKDFLMQCFQKDPNLR-PTAKQL 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

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

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

false

true

false

265

2e-31

132.24

88.30

6,45,21,40,89,61,77,166,143,66,233,209,14,248,223,22,270,247,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDTgesmLDGVPVPYIVMEYVEGRTLRDILKSESHILPRRALE 125
cd05579       22 AIKVIKKADMIRKNQVDQVLTERNILSQAQNPFVVKLYYS----FQGKKNLYLVMEYLPGGDLASLLENVGSLDEDMARI 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 126 IVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFG-----IARAVAQSTATVTQTAAVIGTAQYLSPEQARGEP 200
cd05579       98 YIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFGlskvgLVRRQINLNDDEKEDKRIVGTPDYIAPEVILGQG 177

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 201 VDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVPPSRLnPDVTPDIDAIVMKALAKNPANR--YQSAAEMR 278
cd05579      178 HSKTVDWWSLGCILYEFLTGIPPFHGETPEEI-FQNILNGKIEWPED-VEVSDEAKDLISKLLVPDPEKRlgAKSIEEIK 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

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

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

false

true

false

279

3e-31

131.84

98.57

10,16,0,34,56,34,9,65,49,10,75,60,10,85,72,5,96,77,70,166,164,66,233,230,16,252,246,18,270,266,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLrvdlarDTSFQTRFR------REAQAAAALN-HPSIVAVYDT--GE 87
cd05581        1 DDFKFGKILGEGSFSTVYLAKEKETNKEYAIKVL------DKRHLIKEKkvkyvkREKEVLTRLNgHPGIVKLYYTfqDE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  88 SMLdgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFG- 166
cd05581       75 ENL------YFVLEYAENGELLEYIKKFGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGt 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 167 ----------------IARAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAV 230
cd05581      149 akvldpnsspesnkgkATNIDSQIEKNRRRRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEY 228

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 117927230 231 AVaYQHVREDPVPPSRLNPdvtPDIDAIVMKALAKNPANR--YQSAAEMRA 279
cd05581      229 LT-FQKIVKLEYEFPPNFP---PDAKDLIEKLLVLDPQDRlgVNGYDELKA 275

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

7e-30

127.32

84.85

12,45,29,8,55,37,25,80,66,8,96,74,22,119,96,9,128,106,12,140,119,27,170,146,54,224,202,20,246,222,4,250,227,20,271,247,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDlaRDTSFQTRFRREAQAAAALNHPSIV----AVYDTGESmldgvpvpYIVMEYVEGRTLRDILKSESHIlPR 121
cd06623       30 ALKKIHVD--GDEEFRKQLLRELKTLRSCESPYVVkcygAFYKEGEI--------SIVLEYMDGGSLADLLKKVGKI-PE 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 122 RALEIVA-DILAALEYSHRN-GIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGE 199
cd06623       99 PVLAYIArQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGI---SKVLENTLDQCNTFVGTVTYMSPERIQGE 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 200 PVDPRSDIYSTGCVLYELLTGTPPF--TGESAVAVAYQHVREDPVPPsrLNPD-VTPDIDAIVMKALAKNPANRyQSAAE 276
cd06623      176 SYSYAADIWSLGLTLLECALGKFPFlpPGQPSFFELMQAICDGPPPS--LPAEeFSPEFRDFISACLQKDPKKR-PSAAE 252


                 .
gi 117927230 277 M 277
cd06623      253 L 253

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

125.12

95.49

10,16,0,32,50,32,34,84,69,5,96,74,17,116,91,9,125,106,69,194,178,4,200,182,40,243,222,11,254,238,16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKtlRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYD---TGESMldgv 93
cd06610        1 SDYKLIEVIGSGATAVVQRAICLPNGEKVAIK--RIDLEKCQTSMDELRKEIQAMSLCHHPNVVKYYTsfvVGDEL---- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  94 pvpYIVMEYVEGRTLRDILKsesHILPRRALE------IVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI 167
cd06610       75 ---WVVMPLMSGGSCLDIMK---YSYPQGGLDeaiiatILKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGV 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 168 ARAVAQSTATVTQTAAVIGTAQYLSPE---QARGepVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDpvpP 244
cd06610      149 SASLADGGDRTKVRKTFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYSKYPPMKVLMLTLQND---P 223

                        250       260       270
                 ....*....|....*....|....*....|.
gi 117927230 245 SRLNPDVTPD-----IDAIVMKALAKNPANR 270
cd06610      224 PSLETEADYKkysksFRKMISKCLQKDPAKR 254

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

1e-27

119.63

86.41

12,18,20,30,50,50,15,66,65,19,85,86,5,96,91,17,113,114,6,124,120,43,170,163,65,236,228,10,247,238,3,250,242,20,271,262,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKtlRVDLARDTSFQTRFRrEAQAAAALNHPSIVAVYDT--GESMLdgvpvp 96
cd06614       21 YDNLEKIGEGASGEVYTATDRATGKEVAIK--KMRLRKQPKKELIIN-EILIMKECKHPNIVNYYDSylVGDEL------ 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILK------SESHILprralEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIara 170
cd06614       92 WVVMEYMDGGSLTDIITqtfvrmNESQIA-----YVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGF--- 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 171 VAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQhVREDPVPPSRlNPD 250
cd06614      164 AAQLTKEKSKRNSMVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNEPPLRALFL-ITTKGIPPLK-NPE 241

                        250       260
                 ....*....|....*....|....*...
gi 117927230 251 -VTPDIDAIVMKALAKNPANRyQSAAEM 277
cd06614      242 kWSPEFKDFLNKCLVKDPEKR-PSAEEL 268

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

4e-27

117.98

90.84

4,24,0,61,88,61,7,96,68,70,170,138,100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  25 LGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDTgesMLDGVPVpYIVMEYVE 104
cd05572        1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGQQEHIFSEKEILEECNSPFIVRLYRT---FKDKKYI-YFLMEYCL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 105 GRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiaraVAQSTATVTQTAAV 184
cd05572       77 GGELWTILRDRGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFG----FAKKLKSGQKTYTF 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 185 IGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTPDIDAIVMKALA 264
cd05572      153 CGTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGEDDEDPMKIYNLILKGIDKLEFPKYIDKAAKDLIKQLLR 232


                 ....*.
gi 117927230 265 KNPANR 270
cd05572      233 RNPEER 238

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

6e-26

114.25

88.32

8,16,0,33,51,33,32,86,65,9,96,74,18,114,96,5,124,101,43,170,144,70,242,214,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTlrVDLARDTSFQTRFRREAQAAAALNHPSIVAVYdtgESMLDGVPVp 96
cd06609        1 ELFTLLECIGKGSFGEVYKAIDKRTNQVVAIKV--IDLEEAEDEIEDIQQEIQFLSQCRSPYITKYY---GSFLKGSKL- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKS----ESHILprralEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVA 172
cd06609       75 WIIMEYCGGGSCLDLLKPgkldETYIA-----FILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFGV---SG 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 173 QSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDpvPPSRLNPDVT 252
cd06609      147 QLTSTMSKRNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRVLFLIPKNN--PPSLEGNKFS 224

                        250
                 ....*....|....*...
gi 117927230 253 PDIDAIVMKALAKNPANR 270
cd06609      225 KPFKDFVSLCLNKDPKER 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88512

cd05611

STKc_Rim15_like

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

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

false

true

false

260

3e-25

111.94

64.23

2,96,72,71,174,143,96

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravaqsTA 176
cd05611       73 YLVMEYLNGGDCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGL-------SR 145

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTPDID 256
cd05611      146 NGLENKKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPEAV 225

                        170
                 ....*....|....
gi 117927230 257 AIVMKALAKNPANR 270
cd05611      226 DLINRLLCMDPAKR 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

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

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

false

true

false

265

4e-25

111.64

82.64

10,45,29,9,56,38,24,80,66,8,96,74,28,124,103,16,140,120,27,172,147,61,233,213,6,242,219,9,251,229,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDLarDTSFQTRFRREAQAAAALNHPSIV----AVYDTGESmldgvpvpYIVMEYVEGRTLRDILKSESHILPR 121
cd06605       30 AVKTIRLEI--NEAIQKQILRELDILHKCNSPYIVgfygAFYNNGDI--------SICMEYMDGGSLDKILKEVQGRIPE 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 122 RAL-EIVADILAALEYSHRN-GIVHRDIKPGNIMLTHNGEVKVMDFGIaravaQSTATVTQTAAVIGTAQYLSPEQARGE 199
cd06605      100 RILgKIAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGEIKLCDFGV-----SGQLVNSLAKTFVGTSSYMAPERIQGN 174

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117927230 200 PVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVA-----YQHVREdpvPPSRLNPDV-TPDIDAIVMKALAKNPANR 270
cd06605      175 DYGVKSDVWSLGLSLIELATGRFPYPPENDPPDGifellQYIVNE---PPPRLPSGRfSPDFQDFVNLCLIKDPRER 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132957

cd06626

STKc_MEKK4

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

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

false

true

false

264

5e-24

107.81

88.26

13,45,28,16,62,44,21,91,65,5,96,74,17,114,91,12,126,104,41,167,146,37,204,186,22,226,209,8,235,217,2,237,221,10,249,231,22,272,253,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDLARDTSFQtRFRREAQAAAALNHPSIVAVYdtgesmldGVPVP----YIVMEYVEGRTLRDILKsESHILPR 121
cd06626       29 AVKEIRIQDNDPKTIK-EIADEMKVLELLKHPNLVKYY--------GVEVHrekvYIFMEYCSGGTLEELLE-HGRILDE 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 122 RALEI-VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI-ARAVAQSTATVTQTAAVIGTAQYLSPEQARGE 199
cd06626       99 HVIRVyTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFGCaVKLKNNTTTMGEEVQSLAGTPAYMAPEVITGG 178

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 200 PVDPR---SDIYSTGCVLYELLTGTPPFTG-ESAVAVAYqHV--REDPVPPSRLnpDVTPDIDAIVMKALAKNPANRYqS 273
cd06626      179 KGKGHgraADIWSLGCVVLEMATGKRPWSElDNEFQIMF-HVgaGHKPPIPDSL--QLSPEGKDFLDRCLESDPKKRP-T 254


                 ....*..
gi 117927230 274 AAEMRAD 280
cd06626      255 ASELLQH 261

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88474

cd05573

STKc_ROCK_NDR_like

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

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

false

true

false

354

1e-23

106.47

80.79

10,16,0,69,85,71,5,96,76,16,113,92,9,122,102,45,167,175,68,235,245,10,247,255,7,254,263,4,260,267,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDT--GESMLdgvp 94
cd05573        1 EDFEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILADADSPWIVKLYYSfqDEEYL---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 vpYIVMEYVEGRTLRDILkSESHILPRR-ALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI------ 167
cd05573       77 --YLVMEYMPGGDLMTLL-IKYDVFPEEtARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLckkmkk 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 168 ----------------------ARAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFT 225
cd05573      154 agdseyylndshnlldsdrdnvLKRRRPKKQRRVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPFY 233

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117927230 226 GESAVAVAYQ--HVREDPVPPSrlNPDVTPD-IDAIvmKALAKNPANRYQSAAEMRA 279
cd05573      234 SDTLQETYNKimNWKESLYFPA--DVKVSPEaIDLI--RRLLCDPEDRLGSFEEIKS 286

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

8e-23

104.06

67.37

7,75,74,9,87,83,8,96,91,16,113,107,54,170,161,61,232,222,39,272,261,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  76 HPSIVAVYDtgeSMLDGVPVpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLT 155
cd06648       75 HPNIVEMYS---SYLVGDEL-WVVMEFLEGGALTDIV-THTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLT 149

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 156 HNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAvAYQ 235
cd06648      150 SDGRVKLSDFGF---CAQVSKEVPRRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQ-AMK 225

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117927230 236 HVREDPVPPSRLNPDVTPDIDAIVMKALAKNPANRYqSAAEM 277
cd06648      226 RIRDNLPPKLKNLHKVSPRLRSFLDRMLVRDPAQRA-TAAEL 266

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

9e-23

103.52

97.32

11,16,2,44,63,46,22,85,70,5,96,75,17,113,97,5,122,102,2,125,104,42,170,146,26,196,175,55,251,231,19,271,250,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFqtrFRREAQAAAALNHPSIVAVYDT--GESMLdgvp 94
cd06613        3 EDYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLEPGDDFEI---IQQEISMLKECRHPNIVAYFGSylRRDKL---- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 vpYIVMEYVEGRTLRDILK-----SESHIlprrALeIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIar 169
cd06613       76 --WIVMEYCGGGSLQDIYQvtgplSELQI----AY-VCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGV-- 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 170 aVAQSTATVTQTAAVIGTAQYLSPEQA---RGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSR 246
cd06613      147 -SAQLTATIAKRKSFIGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLISKSNFQPPKL 225

                        250       260       270
                 ....*....|....*....|....*....|..
gi 117927230 247 LNPDV-TPDIDAIVMKALAKNPANRyQSAAEM 277
cd06613      226 KDKEKwSPVFHDFIKKCLTKDPKKR-PTAEKL 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

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

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

false

true

false

256

2e-22

102.73

93.75

10,18,4,35,57,39,5,63,44,23,86,69,4,96,73,29,125,103,42,170,145,65,236,210,5,242,215,7,249,223,21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDlardTSFQTrFRREAQAAAALNHPSIVAVYDTG--ESMLdgvpvp 96
cd06612        5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVE----EDLQE-IIKEISILKQCDSPYIVKYYGSYfkNTDL------ 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALE-IVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQST 175
cd06612       74 WIVMEYCGAGSVSDIMKITNKTLTEEEIAaILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGV---SGQLT 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 176 ATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQhVREDPvPPSRLNP-DVTPD 254
cd06612      151 DTMAKRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFM-IPNKP-PPTLSDPeKWSPE 228

                        250
                 ....*....|....*.
gi 117927230 255 IDAIVMKALAKNPANR 270
cd06612      229 FNDFVKKCLVKDPEER 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

3e-22

102.21

85.82

11,45,26,6,55,32,8,63,42,20,91,62,4,95,70,19,114,97,53,168,150,51,219,202,13,233,215,7,244,222,4,248,228,22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRvdlaRDTSFQTR--FRREAQAAAALNHPSIVAVYdtgesmldGVPV----PYIVMEYVEGRTLRDILKS----- 114
cd00192       27 AVKTLK----EDASDSERedFLKEAKIMKKLGHPNIVRLL--------GVCTeeepLYLVLEYMEGGDLLDFLRKsrpvf 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 115 ---ESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaRAVAQSTATVTQTAAVIGTAQYL 191
cd00192       95 speSSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGL-SRDIYDDDYYRKKGGGKLPIRWM 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 192 SPEQARGEPVDPRSDIYSTGCVLYELLT-GTPPFTGESAVAVaYQHVREDpvppSRLN--PDVTPDIDAIVMKALAKNPA 268
cd00192      174 APESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPGLSNEEV-LEYLRKG----YRLPkpENCPDELYELMLSCWQEDPE 248


                 ..
gi 117927230 269 NR 270
cd00192      249 DR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

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

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

false

true

false

258

3e-22

102.11

97.67

8,17,0,44,61,46,24,88,70,7,96,77,71,171,148,24,195,173,49,246,222,24,271,246,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  18 RYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQ--TRFRREAQAAAALNHPSIVAVYDTgesMLDGVPV 95
cd06632        1 RWRKGELLGSGSFGSVYEGLNLDDGDFFAVKEVSLADDGQTGQEavKQLEQEIALLSKLQHPNIVQYLGT---EREEDNL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  96 pYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravAQST 175
cd06632       78 -YIFLELVPGGSLAKLLKKYGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGM----AKQV 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 176 ATVTQTAAVIGTAQYLSPEQ-ARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPsrLNPDVTPD 254
cd06632      153 VEFSFAKSFKGSPYWMAPEViAQQGGYGLAADIWSLGCTVLEMATGKPPWSQLEGVAAVFKIGRSKELPP--IPDHLSDE 230

                        250       260
                 ....*....|....*....|...
gi 117927230 255 IDAIVMKALAKNPANRyQSAAEM 277
cd06632      231 AKDFILKCLQRDPSLR-PTAAEL 252

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

3e-22

101.58

85.76

10,25,7,26,51,34,31,82,68,7,96,75,71,170,146,24,194,174,7,205,181,28,239,209,9,248,220,48,296,271,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  26 GYGGMAEVRRGRDLRLGRDVAIKTLR-VDLARDTSFQTRFRREAQAAAALNHPSIVAV---YDTGESMldgvpvpYIVME 101
cd05584        8 GYGKVFQVRKVTGADTGKIFAMKVLKkATIVRNQKDTAHTKAERNILEAVKHPFIVDLiyaFQTGGKL-------YLILE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 102 YVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQT 181
cd05584       81 YLSGGELFMHLEREGIFMEDTACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFGL---CKESIHEGTVT 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 182 AAVIGTAQYLSPE----QARGEPVdprsDIYSTGCVLYELLTGTPPFTGESAVAVAyqhvreDPVPPSRLN--PDVTPDI 255
cd05584      158 HTFCGTIEYMAPEilmrSGHGKAV----DWWSLGALMYDMLTGAPPFTAENRKKTI------DKILKGKLNlpPYLTPEA 227

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 117927230 256 DAIVMKALAKNPANRYQSAAEMRADIERALLGKPVQATPLL---LDPTERLSAVTEE 309
cd05584      228 RDLLKKLLKRNPSSRLGAGPGDAAEVQSHPFFRHVNWDDLLarkVEPPFKPLLQSEE 284

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

4e-22

101.81

96.58

7,18,3,35,53,39,10,63,50,20,85,70,9,96,79,147,245,226,25,271,251,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVD-LARDTSFQTR-FRREAQAAAALNHPSIVAVYdtGESMLDGVPvp 96
cd06625        4 WRRGKLLGQGAFGRVYLCYDVDTGRELAVKQVPFDpDSPETKKEVNaLECEIQLLKNLQHERIVQYY--GCLRDDETL-- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVAQSTA 176
cd06625       80 SIFMEYMPGGSVKDQLKAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICS 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPpsRLNPDVTPDID 256
cd06625      160 SGTGMKSVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNP--QLPSHVSPDAR 237

                        250       260
                 ....*....|....*....|.
gi 117927230 257 AIVMKALAKNPANRyQSAAEM 277
cd06625      238 NFLRRTFVENAKKR-PSAEEL 257

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

5e-22

101.08

78.62

9,23,1,35,58,40,13,74,53,15,90,68,3,96,71,71,170,142,62,233,204,10,243,215,9,256,224,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  24 ILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDT----SFQTRFRREAQAAaalNHPSIVAVYDTGESMlDGVpvpYIV 99
cd05570        2 VLGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDddveCTMTEKRVLALAG---KHPFLTQLHSCFQTK-DRL---FFV 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 100 MEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVT 179
cd05570       75 MEYVNGGDLMYHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGM---CKEGILGGV 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 180 QTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDVTpdidAI 258
cd05570      152 TTSTFCGTPDYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDEL-FQSILEDNVRyPRWLSKEAK----SI 226

                        250       260
                 ....*....|....*....|....*
gi 117927230 259 VMKALAKNPANRYQSAAEMRADIER 283
cd05570      227 LKGFLTKNPEKRLGCGPTGEQDIKG 251

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

1e-21

100.04

94.18

11,15,4,47,66,51,8,74,60,9,85,69,11,96,84,18,115,102,10,125,117,42,170,159,24,194,188,45,242,233,9,251,244,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  16 ADRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTrfrrEAQAAAAL-NHPSIVAVYdtGESMLDGVP 94
cd06608        5 GGIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDIIEDEEEEIEE----EYNILRKYsNHPNIATFY--GAFIKKGPP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 VP----YIVMEYVEGRTLRDILKSeSHILPRRALE-----IVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDF 165
cd06608       79 GSddqlWLVMELCGGGSVTDLVKG-LRKKGKRLKEewiayILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDF 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 166 GIaraVAQSTATVTQTAAVIGTAQYLSPE-----QARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREd 240
cd06608      158 GV---SAQLDSTNGRRNTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPLCDMHPMRALFKIPRN- 233

                        250       260       270
                 ....*....|....*....|....*....|..
gi 117927230 241 pvPPSRLNPDV--TPDIDAIVMKALAKNPANR 270
cd06608      234 --PPPTLKSPTnwSKKFNDFISECLIKNYEQR 263

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

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

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

false

true

false

290

2e-21

99.05

86.55

7,16,0,69,85,71,5,96,76,70,172,146,60,233,206,10,243,217,9,256,226,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDT--GESMLdgvp 94
cd05580        1 DDFEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSfkDNSNL---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 vpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiaravaQS 174
cd05580       77 --YMVMEFVPGGELFSLLRRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFG------FA 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 175 TATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDVTp 253
cd05580      149 KRVKGRTYTLCGTPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPFFDDNPMKI-YEKILSGKVRfPSFFSSDAK- 226

                        250       260
                 ....*....|....*....|....*...
gi 117927230 254 didAIVMKALAKNPANRYQSAAEMRADI 281
cd05580      227 ---DLLRNLLQVDLTKRLGNLKNGVNDI 251

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

7e-21

97.25

88.89

6,16,0,74,94,74,22,116,97,10,126,108,41,167,174,78,247,252,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDTGESMLdgvpVP 96
cd05574        1 SDFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEILATLDHPFLPTLYASFQTET----YL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSES-HILPRRALEI-VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI------- 167
cd05574       77 CLVMDYCPGGELFRLLQRQPgKCFPEEVARFyAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFDLskqsdve 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 168 ------------------ARAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESA 229
cd05574      157 ptpvskalrkgsrgsvnkITTETFSEEPSFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNR 236

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 117927230 230 VAVAYQHVREDPVPPSrlNPDVTPDIDAIVMKALAKNPANRYQSAA 275
cd05574      237 DETFSNILKKEVTFPG--SPPVSSSARDLIRKLLVKDPSKRLGSKR 280

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-21

97.11

71.78

6,22,6,35,59,41,24,85,65,28,113,96,16,129,113,38,172,151,61

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDtsFQTRFRREAQAAAALNHPSIVAVYdtGESMLDGVPVPYIVMEY 102
cd06621        7 SRLGEGAGGSVTKCRLKNTGMIFALKTITTDPNPD--LQKQILRELEINKSCKSPYIVKYY--GAFLDESSSSIGIAMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 103 VEGRTLRDILK---SESHILPRRALEIVAD-ILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravaQSTATV 178
cd06621       83 CEGGSLDSIYKkvkKRGGRIGEKVLGKIAEsVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGV-----SGELVN 157

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 117927230 179 TQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVA 233
cd06621      158 SLAGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPPLG 212

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-20

96.18

60.37

6,73,52,9,82,64,7,96,71,71,170,142,58,229,200,13,245,213,34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  74 LNHPSIVAV---YDTGESMldgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPG 150
cd05575       53 VKHPFLVGLhysFQTKEKL-------YFVLDYVNGGELFFHLQRERSFPEPRARFYAAEIASALGYLHSLNIIYRDLKPE 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 151 NIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESaV 230
cd05575      126 NILLDSKGHVVLTDFGL---CKEGIAGSKTTSTFCGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRD-T 201

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 117927230 231 AVAYQHVREDPVppsRLNPDVTPDIDAIVMKALAKNPANRYQSAAEMRA 279
cd05575      202 AEMYDNILNKPL---RLRPNISVSARHLLEGLLQKDRTKRLGAKNDFLE 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

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

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

false

true

false

258

2e-20

96.07

76.36

7,64,47,21,85,71,4,96,75,71,171,146,62,233,209,13,247,222,11,259,233,11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  65 RREAQAAAALNHPSIVAVYDT---GESMldgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNG 141
cd05578       48 LNELQILQSLEHPFLVNLWYSfqdEEDM-------YLVVDLLLGGDLRYHLQQKVKFSEEQVKFYVCEIVLALEYLHSKG 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 142 IVHRDIKPGNIMLTHNGEVKVMDFGIaravAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGT 221
cd05578      121 IIHRDIKPDNILLDEQGHAHLTDFNI----ATKLTPDTLATSTSGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGK 196

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 117927230 222 PPFTGESAVAVA-YQHVREDPVPPSRlNPDVTPDIDAIvMKALAKNPANR 270
cd05578      197 RPYRGHSRTPREeILAKFETADVLYP-AGWSSEAIDAI-NKLLERDPQKR 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

3e-20

95.20

88.81

11,22,6,37,61,43,15,76,61,8,87,69,5,93,74,21,115,95,52,170,147,27,197,175,43,243,218,7,250,226,21,272,247,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSfqTRFRREAQAAAALNH---PSIVAVYDtgeSMLDGvPVPYIV 99
cd06917        7 ELIGRGAYGAVYRGKHVPTGRVVALKIINLDTPDDDV--SDIQREVALLSQLRQsqpPNITKYYG---SYLKG-PRLWII 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 100 MEYVEGRTLRDILKSeSHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVT 179
cd06917       81 MEYAEGGSVRTLMKA-GPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGV---AALLNQNSS 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 180 QTAAVIGTAQYLSPEQAR-GEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDpvpPSRLNPD-VTPDIDA 257
cd06917      157 KRSTFVGTPYWMAPEVITeGKYYDTKADIWSLGITIYEMATGNPPYSDVDAFRAMMLIPKSK---PPRLEDNgYSKLLRE 233

                        250       260
                 ....*....|....*....|
gi 117927230 258 IVMKALAKNPANRYqSAAEM 277
cd06917      234 FVAACLDEEPKERL-SAEEL 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

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

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

false

true

false

333

9e-20

93.82

54.05

5,96,76,71,173,147,59,232,211,10,242,223,13,259,236,20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravaqSTA 176
cd05600       77 YLAMEYVPGGDFRTLLNNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGL------SKG 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAV-----AYQHVREDPV--PPSRLNP 249
cd05600      151 IVTYANSVVGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSGSTPNETwenlkYWKETLQRPVydDPRFNLS 230

                        170       180       190
                 ....*....|....*....|....*....|
gi 117927230 250 DVTPDIdaivMKALAKNPANRYQSAAEMRA 279
cd05600      231 DEAWDL----ITKLINDPSRRFGSLEDIKN 256

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

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

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

false

true

false

305

6e-19

91.14

63.93

6,97,77,69,166,158,28,194,190,8,206,198,43,250,241,23,273,266,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFG----------- 166
cd05609       78 MVMEYVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGlskiglmsltt 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 167 -IARAVAQSTATVTQTAAVIGTAQYLSPE----QARGEPVDprsdIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDP 241
cd05609      158 nLYEGHIEKDTREFLDKQVCGTPEYIAPEvilrQGYGKPVD----WWAMGIILYEFLVGCVPFFGDTPEELFGQVISDDI 233

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 117927230 242 VPPSRLNPdVTPDIDAIVMKALAKNPANRYQS--AAEMRA 279
cd05609      234 EWPEGDEA-LPADAQDLISRLLRQNPLERLGTggAFEVKQ 272

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

7e-19

90.69

77.32

8,16,0,69,85,71,5,96,76,71,173,147,21,194,170,5,201,175,31,233,206,10,243,217,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYDT--GESMLdgvp 94
cd05612        1 SDLERIETLGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSILSEISHPFIVNMYWTfhDDKFL---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 vpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravaqS 174
cd05612       77 --YMLMEYVPGGELFSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGF------A 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 175 TATVTQTAAVIGTAQYLSPE--QARGEpvDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDV 251
cd05612      149 KKVRDRTWTLCGTPEYLAPEiiQSKGH--GKAVDWWALGILIYEMLVGYPPFFDDNPFGI-YEKILAGKLEfPRHFDLRA 225

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88493

cd05592

STKc_nPKC_theta_delta

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

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

false

true

false

316

8e-19

90.76

78.16

7,22,0,31,53,33,20,74,53,3,77,59,12,96,71,71,170,142,82,256,224,23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVD--LARDTSFQTRFRREAQAAAAlNHP---SIVAVYDTGESMldgvpvpY 97
cd05592        1 KVLGKGSFGKVMLAELKGTNEYYAIKALKKDvvLEDDDVECTMVERRVLILAW-EHPfltHLFCTFQTKEHL-------F 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTAT 177
cd05592       73 FVMEYLNGGDLMFHIQSSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGM---CKENING 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 178 VTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTpdidA 257
cd05592      150 EGKASTFCGTPDYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFDSILNDRPHFPRWISKEAK----D 225

                        250       260
                 ....*....|....*....|..
gi 117927230 258 IVMKALAKNPANRYQSAAEMRA 279
cd05592      226 CLSKLFEREPTKRLGMDGDIRQ 247

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

7e-18

87.39

72.60

9,74,74,10,87,84,8,96,92,16,113,108,54,170,162,61,232,223,6,239,229,9,248,239,22,271,261,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  75 NHPSIVAVYDtgeSMLDGVPVpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIML 154
cd06657       75 QHENVVEMYN---SYLVGDEL-WVVMEFLEGGALTDIV-THTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILL 149

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 155 THNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAvAY 234
cd06657      150 THDGRVKLSDFGF---CAQVSKEVPRRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLK-AM 225

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117927230 235 QHVReDPVPPSRLN-PDVTPDIDAIVMKALAKNPANRyQSAAEMRADIERALLGKPVQATPLL 296
cd06657      226 KMIR-DNLPPKLKNlHKVSPSLKGFLDRLLVRDPAQR-ATAAELLKHPFLAKAGPPSCIVPLM 286

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

8e-18

87.29

64.24

6,96,80,71,169,151,32,201,185,26,227,215,26,257,241,13,270,256,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIarAVAQSTA 176
cd05583       81 HLILDYVNGGELFTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGL--SKEFLAE 158

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPV--DPRSDIYSTGCVLYELLTGTPPFTGE----SAVAVAYQHVREDPVPPSRLNPD 250
cd05583      159 EEERAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDgeqnSQSEISRRILKSKPPFPKTMSAE 238

                        170       180       190
                 ....*....|....*....|....*....|.
gi 117927230 251 VTPdidaIVMKALAKNPANR--YQSAAEMRA 279
cd05583      239 ARD----FIQKLLEKDPKKRlgANGADEIKN 265

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

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

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

false

true

false

324

1e-17

86.86

77.47

8,23,5,30,53,37,11,64,49,16,80,68,9,96,77,25,122,102,45,170,147,82,256,229,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  24 ILGYGGMAEVRRGRDLRLGRDVAIKTLRVD--LARDTSFQTRF-RREAQAAAALNHPSIV---AVYDTGESMldgvpvpY 97
cd05589        6 VLGRGHFGKVLLAEYKKTGELYAIKALKKGdiIARDEVESLMCeKRIFETANSERHPFLVnlfACFQTEDHV-------C 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRrALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTAT 177
cd05589       79 FVMEYAAGGDLMMHIHTDVFSEPR-AVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGL---CKEGMGF 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 178 VTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTpdidA 257
cd05589      155 GDRTSTFCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSREAI----S 230

                        250       260
                 ....*....|....*....|....*.
gi 117927230 258 IVMKALAKNPANRYQSAAEMRADIER 283
cd05589      231 IMRRLLRRNPERRLGSGERDAEDVKK 256

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-17

85.86

87.55

7,18,3,36,54,40,9,63,50,20,83,74,8,97,82,138,236,220,8,245,228,7

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDL-ARDTSFQTR-FRREAQAAAALNHPSIVAVY----DTGESMLDg 92
cd06652        4 WRLGKLLGQGAFGRVYLCYDADTGRELAVKQVQFDPeSPETSKEVNaLECEIQLLKNLLHERIVQYYgclrDPMERTLS- 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  93 vpvpyIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVA 172
cd06652       83 -----IFMEHMPGGSIKDQLKSYGALTENVTRKYTRQILEGVSYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQ 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 173 QSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQhVREDPVPPsRLNPDVT 252
cd06652      158 TICLSGTGMKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFK-IATQPTNP-VLPPHVS 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88520

cd05619

STKc_nPKC_theta

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

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

false

true

false

316

2e-17

85.82

77.85

8,22,0,33,55,34,28,83,65,6,96,71,71,170,142,62,233,204,5,238,210,9,251,219,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLA-RDTSFQTRFRREAQAAAALNHPSIVAVY---DTGESMldgvpvpYI 98
cd05619        1 KMLGKGSFGKVFLAELKGTNQFFAIKALKKDVVlMDDDVECTMVEKRVLSLAWEHPFLTHLYctfQTKENL-------FF 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  99 VMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATV 178
cd05619       74 VMEYLNGGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGM---CKENMLGD 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 179 TQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVR-EDPVPPSRLnpdvTPDIDA 257
cd05619      151 AKTCTFCGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEEL-FQSIRmDNPCYPRWL----TREAKD 225

                        250       260
                 ....*....|....*....|.
gi 117927230 258 IVMKALAKNPANRYQSAAEMR 278
cd05619      226 ILVKLFVREPERRLGVKGDIR 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88492

cd05591

STKc_nPKC_epsilon

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

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

false

true

false

321

2e-17

85.81

74.14

5,22,0,31,53,32,30,87,62,80,170,142,82,256,224,14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVD-LARDTSFQTRFRREAQAAAALNHPSIVAVYdtgeSMLDGVPVPYIVME 101
cd05591        1 KVLGKGSFGKVMLAELKGTDEVYAIKVLKKDvILQDDDVDCTMTEKRILALAAKHPFLTALH----CCFQTKDRLFFVME 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 102 YVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQT 181
cd05591       77 YVNGGDLMFQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGM---CKEGILNGVTT 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 182 AAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTpdidAIVMK 261
cd05591      154 TTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAV----SILKA 229


                 ....*....
gi 117927230 262 ALAKNPANR 270
cd05591      230 FMTKNPNKR 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88504

cd05603

STKc_SGK2

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

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

false

true

false

321

3e-17

85.47

52.02

6,73,52,9,82,64,7,96,71,71,170,142,58,229,200,12,241,214,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  74 LNHPSIVAV---YDTGESMldgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPG 150
cd05603       53 LKHPFLVGLhysFQTAEKL-------YFVLDYVNGGELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPE 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 151 NIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESaV 230
cd05603      126 NILLDSQGHVVLTDFGL---CKEGVEPEETTSTFCGTPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRD-V 201

                        170
                 ....*....|....*...
gi 117927230 231 AVAYQHVREDP--VPPSR 246
cd05603      202 SQMYDNILHKPlqLPGGK 219

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

6e-17

84.30

79.38

7,22,0,31,53,32,30,83,65,6,96,71,71,170,142,82,256,224,22,281,246,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVD-LARDTSFQTRFRREAQAAAALNHPSIVAVY---DTGESMldgvpvpYI 98
cd05590        1 RVLGKGSFGKVMLARLKESGRLYAVKVLKKDvILQDDDVECTMTEKRILSLARNHPFLTQLYccfQTPDRL-------FF 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  99 VMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATV 178
cd05590       74 VMEFVNGGDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGM---CKEGIFNG 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 179 TQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLNPDVTpdidAI 258
cd05590      151 KTTSTFCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLSQDAV----DI 226

                        250       260       270
                 ....*....|....*....|....*....|.
gi 117927230 259 VMKALAKNPANRYQSAAEMRadiERALLGKP 289
cd05590      227 LKAFMTKNPTMRLGSLTLGG---EEAILRHP 254

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

6e-17

84.31

64.65

7,75,76,8,86,84,9,96,93,16,113,109,54,170,163,61,232,224,38,271,262,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  76 HPSIVAVYdtgESMLDGVPVpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLT 155
cd06659       77 HQNVVEMY---KSYLVGEEL-WVLMEFLQGGALTDIV-SQTRLNEEQIATVCESVLQALCYLHSQGVIHRDIKSDSILLT 151

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 156 HNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAvAYQ 235
cd06659      152 LDGRVKLSDFGF---CAQISKDVPKRKSLVGTPYWMAPEVISRTPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQ-AMK 227

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117927230 236 HVREDPVPPSRLNPDVTPDIDAIVMKALAKNPANRyQSAAEM 277
cd06659      228 RLRDSPPPKLKNAHKISPVLRDFLERMLTREPQER-ATAQEL 268

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

7e-17

84.35

83.83

5,21,6,33,54,40,7,61,48,22,83,74,8,97,82,147

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  22 GEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDL-ARDTSFQ-TRFRREAQAAAALNHPSIVAVY----DTGESMLDgvpv 95
cd06651        7 GKLLGQGAFGRVYLCYDVDTGRELAAKQVQFDPeSPETSKEvSALECEIQLLKNLQHERIVQYYgclrDRAEKTLT---- 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  96 pyIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVAQST 175
cd06651       83 --IFMEYMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTIC 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117927230 176 ATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPP 244
cd06651      161 MSGTGIRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPTNPQ 229

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132942

cd06611

STKc_SLK_like

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

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

false

true

false

280

7e-17

84.02

71.07

9,75,60,10,85,72,5,96,77,32,128,110,39,170,149,23,193,177,47,242,224,9,251,234,20,272,254,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  76 HPSIVAVYDT--GESMLdgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEIVA-DILAALEYSHRNGIVHRDIKPGNI 152
cd06611       61 HPNIVGLYEAyfYENKL------WILIEFCDGGALDSIMLELERGLTEPQIRYVCrQMLEALNFLHSHKVIHRDLKAGNI 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 153 MLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSP-----EQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGE 227
cd06611      135 LLTLDGDVKLADFGV---SAKNKSTLQKRDTFIGTPYWMAPevvacETFKDNPYDYKADIWSLGITLIELAQMEPPHHEL 211

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 117927230 228 SAVAVAYQHVREDpvPPSRLNPDV-TPDIDAIVMKALAKNPANRYqSAAEM 277
cd06611      212 NPMRVLLKILKSE--PPTLDQPSKwSSSFNDFLKSCLVKDPDDRP-TAAEL 259

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

7e-17

84.31

72.12

7,45,21,37,82,61,7,96,68,71,170,139,58,229,197,13,245,210,25,270,237,9

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAV---YDTGESMldgvpvpYIVMEYVEGRTLRDILKSESHILPRR 122
cd05585       22 ALKTIRKAHIVSRSEVTHTLAERTVLAQVNCPFIVPLkfsFQSPEKL-------YFVLAFINGGELFHHLQKEGRFDLSR 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 123 ALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVD 202
cd05585       95 ARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGL---CKLNMKDDDRTNTFCGTPEYLAPELLLGHGYT 171

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117927230 203 PRSDIYSTGCVLYELLTGTPPFTGESaVAVAYQHVREDPVppsRLNPDVTPDIDAIVMKALAKNPANR--YQSAAEMRA 279
cd05585      172 KAVDWWTLGVLLYEMLTGLPPFYDEN-TNEMYRKILQEPL---RFPDGFDRDAKDLLTGLLNRDPTQRlgYNGAQEIKN 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88488

cd05587

STKc_cPKC

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

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

false

true

false

324

7e-17

84.20

76.54

8,23,6,30,53,37,36,90,73,3,96,76,71,170,147,62,233,209,10,243,220,9,256,229,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  24 ILGYGGMAEVRRGRDLRLGRDVAIKTLRVD-LARDTSFQTRFRREAQAAAALNHPSIVAVYDTGESMlDGVpvpYIVMEY 102
cd05587        7 VLGKGSFGKVMLAERKGTDELYAIKILKKDvIIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTM-DRL---YFVMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 103 VEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTA 182
cd05587       83 VNGGDLMYHIQQVGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGM---CKENIFGGKTTR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 183 AVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDVTpdidAIVMK 261
cd05587      160 TFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDEL-FQSIMEHNVSyPKSLSKEAV----SICKG 234

                        250       260
                 ....*....|....*....|
gi 117927230 262 ALAKNPANRYQSAAEMRADI 281
cd05587      235 LLTKHPAKRLGCGPTGERDI 254

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-16

82.96

63.30

4,54,43,30,87,73,9,97,82,70,167,155,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  55 ARDTSFQTRFRREAQAAAALNHPSIVAVYDtgeSMLDGVPVPyIVMEYVEGRTLRDILKSESHILPRRALEIVADILAAL 134
cd06628       44 DRKRKMLDALQREINLLKELHHENIVQYLG---SSQDAGHLN-IFLEYVPGGSVAALLNNYGAFEESLVRNFVRQILKGL 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 135 EYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI---ARAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTG 211
cd06628      120 NYLHNRGIIHRDIKGANILVDNKGGIKISDFGIskkLEANSLSTKTNGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLG 199

                        170
                 ....*....|...
gi 117927230 212 CVLYELLTGTPPF 224
cd06628      200 CLVVEMFTGKHPF 212

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

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

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

false

true

false

272

2e-16

82.92

93.75

8,21,5,31,52,43,30,82,75,9,97,84,70,168,154,26,194,182,50,246,232,19,265,255,5

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  22 GEILGYGGMAEVRRGRDLRLGRDVAIKTLRV-------DLARDTSFQTRFRREAQAAAALNHPSIVAV--YDTGESMLDg 92
cd06629        6 GELIGKGTYGRVYLALNVTTGEMMAVKQVELpatiagrHDSRQKDMVKALRSEIETLKDLDHLNIVQYlgFETTEEYLS- 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  93 vpvpyIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaRAVA 172
cd06629       85 -----IFLEYVPGGSIGSCLRTYGRFEEQLVRFFTEQVLEGLAYLHSKGILHRDLKADNLLVDADGICKISDFGI-SKKS 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 173 QSTATVTQTAAVIGTAQYLSPE--QARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPsrLNPD 250
cd06629      159 DDIYDNDQNMSMQGSVFWMAPEviHSYSQGYSAKVDIWSLGCVVLEMFAGRRPWSDEEAIAAMFKLGNKRSAPP--IPPD 236

                        250       260
                 ....*....|....*....|....
gi 117927230 251 VTPDIDAIVMKALAK----NPANR 270
cd06629      237 VSMNLSPVALDFLNAcftiNPDNR 260

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

3e-16

82.38

85.23

6,18,3,36,54,40,9,63,50,20,83,74,8,97,82,138,236,220,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  19 YELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDL-ARDTSFQTR-FRREAQAAAALNHPSIVAVY----DTGESMLDg 92
cd06653        4 WRLGKLLGRGAFGEVYLCYDADTGRELAVKQVPFDPdSQETSKEVNaLECEIQLLKNLRHDRIVQYYgclrDPEEKKLS- 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  93 vpvpyIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVA 172
cd06653       83 -----IFVEYMPGGSIKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQ 157

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117927230 173 QSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQhVREDPVPP 244
cd06653      158 TICMSGTGIKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFK-IATQPTKP 228

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88505

cd05604

STKc_SGK3

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

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

false

true

false

325

5e-16

81.24

73.23

7,22,0,51,73,52,9,82,64,7,96,71,71,170,142,58,229,200,13,245,213,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAA-LNHPSIVAV---YDTGESMldgvpvpYI 98
cd05604        1 KVIGKGSFGKVLLAKRKLDGKCYAVKVLQKKIVLNRKEQKHIMAERNVLLKnVKHPFLVGLhysFQTTEKL-------YF 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  99 VMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATV 178
cd05604       74 VLDFVNGGELFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFGL---CKEGIAQS 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 179 TQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESaVAVAYQHVREDPVppsRLNPDVTPDIDAI 258
cd05604      151 DTTTTFCGTPEYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYGLPPFYCRD-VAEMYDNILHKPL---VLRPGASLTAWSI 226

                        250
                 ....*....|..
gi 117927230 259 VMKALAKNPANR 270
cd05604      227 LEELLEKDRQRR 238

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

5e-16

81.21

76.78

8,23,6,32,55,39,10,66,49,27,96,76,71,170,147,62,233,209,10,243,220,9,256,229,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  24 ILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLA-RDTSFQTRFRrEAQAAAALNHPSIVAVYDTGESMLDGVpvpYIVMEY 102
cd05615        7 VLGKGSFGKVMLAERKGTDELYAIKILKKDVViQDDDVECTMV-EKRVLALQDKPPFLTQLHSCFQTVDRL---YFVMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 103 VEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTA 182
cd05615       83 VNGGDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHRRGIIYRDLKLDNVMLDSEGHIKIADFGM---CKEHMVDGVTTR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 183 AVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDVTpdidAIVMK 261
cd05615      160 TFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDEL-FQSIMEHNVSyPKSLSKEAV----SICKG 234

                        250       260
                 ....*....|....*....|
gi 117927230 262 ALAKNPANRYQSAAEMRADI 281
cd05615      235 LMTKHPSKRLGCGPEGERDI 254

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

7e-16

80.72

84.91

8,21,4,10,32,14,21,53,39,8,62,47,23,88,70,8,97,78,70,167,151,59,226,211,18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  22 GEILGYGGMAeVRRGRDLRLGRDVAIKTLRVD----LARDTSFQtRFRREAQAAAALNHPSIVAVYDTgesMLDGVPVPy 97
cd06631        5 GEVLGKGAYG-TVYCGLTNQGQLIAVKQVELDtsnvLAAEKEYE-KLQEEVDLLKSLKHVNIVQYLGT---CLDDNTIS- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGI---ARAVAQS 174
cd06631       79 IFMEFVPGGSISSILNRFGPLPEPVFCKYTKQILDGVAYLHNNCVVHRDIKGNNVMLMPNGIIKLIDFGCarrLAWVGLH 158

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117927230 175 TATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTG-ESAVAVAYQHVREDPVPP 244
cd06631      159 GTHSNMLKSMHGTPYWMAPEVINESGYGRKSDIWSIGCTVFEMATGKPPLASmDRLAAMFYIGAHRGLMPR 229

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

8e-16

80.68

93.66

10,21,4,27,50,31,13,63,49,20,85,69,7,95,76,2,97,79,62,159,142,7,166,150,62,228,217,25,257,242,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  22 GEILGYGGMAEVRRGRDLRLGRDVAIKtlRVDLARDTSFQTR-----FRREAQAAAALNHPSIVAVYdtGESMLDGvpvP 96
cd06630        5 GQQLGTGAFSSCYQARDVKTGTLMAVK--QVTYVRNTSSEQEevveaLRKEIRLMARLNHPHIIRML--GATCEDS---H 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 Y-IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGE-VKVMDFG-IARAVAQ 173
cd06630       78 FnLFVEWMAGGSVSHLLSKYGAFKEAVIINYTEQLLRGLSYLHENQIIHRDVKGANLLIDSTGQrLRIADFGaAARLAAK 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 174 STATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGES-----AVAVAYQHVREDPVPPSRLN 248
cd06630      158 GTGAGEFQGQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKhsnhlALIFKIASATTAPSIPEHLS 237

                        250       260
                 ....*....|....*....|..
gi 117927230 249 PDVTPdidaIVMKALAKNPANR 270
cd06630      238 PGLRD----VTLRCLELQPEDR 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88503

cd05602

STKc_SGK1

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

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

false

true

false

325

8e-16

80.49

51.38

4,96,71,71,170,142,59,230,201,12,245,213,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTA 176
cd05602       72 YFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGL---CKENIE 148

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAvAVAYQHVREDPVppsRLNPDVTPDID 256
cd05602      149 PNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNT-AEMYDNILNKPL---QLKPNITNSAR 224

                        170
                 ....*....|....
gi 117927230 257 AIVMKALAKNPANR 270
cd05602      225 HLLEGLLQKDRTKR 238

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

9e-16

80.37

58.11

9,12,38,38,50,77,6,56,85,4,63,89,22,85,113,5,96,118,16,113,134,53,168,187,35,203,226,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  13 RILADRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTL-RVDLAR--DTSFqtrFRREAQAAAALNHPSIVAVYDT--GE 87
cd05596       39 RMKAEDFDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLsKFEMIKrsDSAF---FWEERDIMAHANSEWIVQLHYAfqDD 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  88 SMLdgvpvpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGi 167
cd05596      116 KYL------YMVMEYMPGGDLVNLM-SNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG- 187

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117927230 168 aRAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDP----RSDIYSTGCVLYELLTGTPPFTGESAV 230
cd05596      188 -TCMKMDANGMVRCDTAVGTPDYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSLV 253

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

9e-16

80.23

78.87

11,45,33,8,55,41,28,85,69,10,97,79,21,122,100,8,130,115,9,141,124,26,172,150,53,225,210,9,234,222,7,242,229,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDlaRDTSFQTRFRREAQAAAALNHPSIVAVYdtGESMLDGVPVpyIVMEYVEGRTLRDILKSESHIlprrALE 125
cd06620       34 AKKVVHIG--AKSSVRKQILRELQIMHECRSPYIVSFY--GAFLNENNIC--MCMEFMDCGSLDRIYKKGGPI----PVE 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 126 IVADI-------LAALEYSHRngIVHRDIKPGNIMLTHNGEVKVMDFGIaravaQSTATVTQTAAVIGTAQYLSPEQARG 198
cd06620      104 ILGKIavavvegLTYLYNVHR--IMHRDIKPSNILVNSRGQIKLCDFGV-----SGELINSIADTFVGTSTYMSPERIQG 176

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 199 EPVDPRSDIYSTGCVLYELLTGTPPFT-------GESAVAVAY---QHVREDPvPPSRLNPDVTPDIDAIVMKALAKNPA 268
cd06620      177 GKYTVKSDVWSLGISIIELALGKFPFAfsnidddGQDDPMGILdllQQIVQEP-PPRLPSSDFPEDLRDFVDACLLKDPT 255


                 ..
gi 117927230 269 NR 270
cd06620      256 ER 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132949

cd06618

PKc_MKK7

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

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

false

true

false

296

1e-15

80.11

59.12

10,96,89,7,104,96,20,124,117,12,136,130,31,171,161,23,196,184,7,203,197,23,226,221,14,240,236,8,250,244,20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVeGRTLRDILKSESHILPRRAL-EIVADILAALEY-SHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravAQS 174
cd06618       90 FICMELM-STCLDKLLKRIQGPIPEDILgKMTVAIVKALHYlKEKHGVIHRDVKPSNILLDASGNVKLCDFGI----SGR 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 175 TATVTQTAAVIGTAQYLSPEqaRGEPVDP------RSDIYSTGCVLYELLTGTPPFTG-ESAVAVAYQHVRED-PVPPSR 246
cd06618      165 LVDSKAKTRSAGCAAYMAPE--RIDPPDPnpkydiRADVWSLGISLVELATGQFPYKNcKTEFEVLTKILQEEpPSLPPN 242

                        170       180
                 ....*....|....*....|....
gi 117927230 247 LNpdVTPDIDAIVMKALAKNPANR 270
cd06618      243 EG--FSPDFCSFVDLCLTKDHRKR 264

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

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

false

true

false

279

2e-15

79.32

61.29

4,45,36,8,55,44,27,84,71,32,116,104,103

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDlaRDTSFQTRFRREAQAAAALNHPSIVAVydTGESMLDGVPVPYIVMEYVEGRTLRDILKSES-HILPRRAL 124
cd05038       37 AVKKLNTS--GVEAHRQDFEREIEIMRTLDHENIVKY--KGVSEEPGGRSLSLIMEYLPSGSLRDYLRRHRdQLNLKRLL 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 125 EIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPR 204
cd05038      113 LFALQIAKGMDYLGSKRLIHRDLAARNILVDSEDLVKISDFGLAKVLPEDKDYYYVKEPRESPIFWYAPECLRTGKFSSA 192

                        170
                 ....*....|....*
gi 117927230 205 SDIYSTGCVLYELLT 219
cd05038      193 SDVWSYGVTLYEMFT 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132938

cd06607

STKc_TAO

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

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

false

true

false

307

2e-15

79.47

70.36

11,96,90,9,106,99,6,114,105,14,128,122,38,173,160,21,194,183,5,199,189,41,242,230,28,271,258,6,280,264,13,294,277,29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGrTLRDILksESHILPRRALEIVA---DILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiaravaq 173
cd06607       91 WLVMEYCLG-SASDIL--EVHKKPLQEVEIAAichGALQGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFG------- 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 174 STATVTQTAAVIGTAQYLSPE--QARGE-PVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDpvPPSRLNPD 250
cd06607      161 SASLVSPANSFVGTPYWMAPEviLAMDEgQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQND--SPTLSSND 238

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117927230 251 VTPDIDAIVMKALAKNPANRyQSAAEMradIERALLGKPVQATpLLLDPTERLSAVTEEIRPAQPRTRRGLIY 323
cd06607      239 WSDYFRNFVDSCLQKIPQDR-PSSEEL---LKHRFVLRERPPT-VIIDLIQRTKDAVRELDNLQYRKMKKILF 306

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88517

cd05616

STKc_cPKC_beta

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

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

false

true

false

323

2e-15

79.28

77.09

8,23,6,32,55,39,34,90,73,3,96,76,71,170,147,62,233,209,10,243,220,9,256,229,26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  24 ILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLA-RDTSFQTRFRREAQAAAALNHPSIVAVYDTGESMlDGVpvpYIVMEY 102
cd05616        7 VLGKGSFGKVMLAERKGTDELYAIKILKKDVViQDDDVECTMVEKRVLALSGKPPFLTQLHSCFQTM-DRL---YFVMEY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 103 VEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTA 182
cd05616       83 VNGGDLMYQIQQVGRFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDSEGHIKIADFGM---CKENMWDGVTTK 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 183 AVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVP-PSRLNPDVTpdidAIVMK 261
cd05616      160 TFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDEL-FQSIMEHNVAyPKSMSKEAV----AICKG 234

                        250       260
                 ....*....|....*....|.
gi 117927230 262 ALAKNPANRYQSAAEMRADIE 282
cd05616      235 LMTKHPGKRLGCGPEGERDIK 255

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

3e-15

78.93

72.60

7,74,76,10,87,86,8,96,94,16,113,110,54,170,164,61,232,225,38,271,263,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  75 NHPSIVAVYDtgeSMLDGVPVpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIML 154
cd06658       77 HHENVVDMYN---SYLVGDEL-WVVMEFLEGGALTDIV-THTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILL 151

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 155 THNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAvAY 234
cd06658      152 TSDGRIKLSDFGF---CAQVSKEVPKRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQ-AM 227

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117927230 235 QHVREDPVPPSRLNPDVTPDIDAIVMKALAKNPANRyQSAAEMRADIERALLGKPVQATPLL 296
cd06658      228 RRIRDNLPPRVKDSHKVSSVLRGFLDLMLVREPSQR-ATAQELLQHPFLKLAGPPSCIVPLM 288

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

3e-15

78.85

68.55

7,48,35,4,55,39,2,60,41,25,85,68,5,96,73,71,170,144,77,251,221,32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  49 TLRVdlaRDtsfQTRFRREAQAAAALNHPSIVAVYDT--GESMLdgvpvpYIVMEYVEGRTLRDILKSESHILPRRALEI 126
cd05582       36 TLKV---RD---RVRTKMERDILAEVNHPFIVKLHYAfqTEGKL------YLILDFLRGGDLFTRLSKEVMFTEEDVKFY 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 127 VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSD 206
cd05582      104 LAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGL---SKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSAD 180

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117927230 207 IYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLnpdvTPDIDAIVMKALAKNPANRYQSAAEMRADIER 283
cd05582      181 WWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGMPQFL----SPEAQSLLRALFKRNPANRLGAGPDGVEEIKR 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133172

cd05040

PTKc_Ack_like

Catalytic Domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase

false

true

false

257

3e-15

78.58

85.21

9,45,26,8,55,34,29,84,66,6,98,72,17,115,91,104,219,196,21,244,217,3,247,221,6,253,228,17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDlaRDTSFQTRFRREAQAAAALNHPSIVAVYD---TGESMLdgvpvpyiVMEYVEGRTLRDILKSE--SHILP 120
cd05040       27 AVKCLKSD--KLSDIMDDFLKEAAIMHSLDHENLIRLYGvvlTHPLMM--------VTELAPLGSLLDRLRKDalGHFLI 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 121 RRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIARAVAQSTATVTQTAAVIGTAQYLSPEQARGEP 200
cd05040       97 STLCDYAVQIANGMRYLESKRFIHRDLAARNILLASDDKVKIGDFGLMRALPQNEDHYVMEEHLKVPFAWCAPESLRTRT 176

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 117927230 201 VDPRSDIYSTGCVLYELLT-GTPPFTGESAVAVAYQHVREDpvppSRL-NPDVTP-DIDAIVMKALAKNPANR 270
cd05040      177 FSHASDVWMFGVTLWEMFTyGEEPWAGLSGSQILKKIDKEG----ERLeRPEACPqDIYNVMLQCWAHNPADR 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88521

cd05620

STKc_nPKC_delta

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

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

false

true

false

316

4e-15

78.51

77.85

7,22,0,34,56,35,33,90,68,3,96,71,71,170,142,62,233,204,14,250,218,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLAR-DTSFQTRFRREAQAAAALNHPSIVAVYDTGESMlDGVpvpYIVME 101
cd05620        1 KVLGKGSFGKVLLAELKGKGEYFAVKALKKDVVLiDDDVECTMVEKRVLALAWENPFLTHLYCTFQTK-EHL---FFVME 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 102 YVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQT 181
cd05620       77 FLNGGDLMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGM---CKENVFGDNRA 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 182 AAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVaYQHVREDPVPPSRLnpdVTPDIDAIVMK 261
cd05620      154 STFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDEL-FESIRVDTPHYPRW---ITKESKDILEK 229

                        250
                 ....*....|....*..
gi 117927230 262 ALAKNPANRYQSAAEMR 278
cd05620      230 LFERDPTRRLGVVGNIR 246

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-15

77.79

84.84

9,22,9,37,61,46,23,87,69,8,96,77,19,119,96,7,126,106,41,170,147,64,235,211,9,246,220,24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSfqTRFRREAQAAAALNHPSIVAVYDtgeSMLDGVPVpYIVMEY 102
cd06640       10 ERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEI--EDIQQEITVLSQCDSPYVTKYYG---SYLKGTKL-WIIMEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 103 VEGRTLRDILKSEshilPRRALEI---VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVT 179
cd06640       84 LGGGSALDLLRAG----PFDEFQIatmLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGV---AGQLTDTQI 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 180 QTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYqHVREDPVPPsrLNPDVTPDIDAIV 259
cd06640      157 KRNTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLF-LIPKNNPPT--LTGEFSKPFKEFI 233

                        250
                 ....*....|.
gi 117927230 260 MKALAKNPANR 270
cd06640      234 DACLNKDPSFR 244

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

6e-15

77.66

66.97

7,16,0,67,86,67,9,96,76,30,126,107,40,168,147,37,205,190,23,229,213,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLARDTSFQTRFRREAQAAAALNHPSIVAVYdtgESMLDGVPVp 96
cd05601        1 KDFEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDIMAIANSPWIPQLQ---YAFQDKDNL- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEI-VADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiaRAVAQST 175
cd05601       77 YLVMEYHPGGDLLSLLNRYEDQFDESMAQFyLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFG--SAAKLNA 154

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117927230 176 ATVTQTAAVIGTAQYLSPEQARGEPVDPRS------DIYSTGCVLYELLTGTPPFTGESaVAVAYQHV 237
cd05601      155 NKMVNSKLPVGTPDYIAPEVLTSLNGDSKStygvecDWWSLGVIAYEMIYGRSPFSEGT-SAVTYSNI 221

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132946

cd06615

PKc_MEK

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

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

false

true

false

308

7e-15

77.48

61.04

8,65,47,15,80,66,9,97,75,21,119,96,5,124,102,12,136,115,31,172,146,68,240,222,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  66 REAQAAAALNHPSIV----AVYDTGESMldgvpvpyIVMEYVEGRTLRDILKSESHIlPRRAL-EIVADILAALEY-SHR 139
cd06615       48 RELKVLHECNSPYIVgfygAFYSDGEIS--------ICMEHMDGGSLDQVLKKAGRI-PENILgKISIAVLRGLTYlREK 118

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 140 NGIVHRDIKPGNIMLTHNGEVKVMDFGIaravaQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLT 219
cd06615      119 HKIMHRDVKPSNILVNSRGEIKLCDFGV-----SGQLIDSMANSFVGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAI 193

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 117927230 220 GTPPFTGESAVAVAYQHVRED--------PVPPSRLNPDVTP 253
cd06615      194 GRYPIPPPDAKELEAMFGRPVsegeakesHRPVSGHPPDSPR 235

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132948

cd06617

PKc_MKK3_6

Protein kinases (PKs), MAP kinase kinase 3 (MKK3) and MKK6 subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK3 and MKK6 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 plays roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma.

Protein kinases (PKs), MAP kinase kinase 3 (MKK3) and MKK6 subfamily, catalytic (c)...

false

true

false

280

8e-15

77.07

57.86

7,108,90,10,119,100,5,124,106,16,140,123,27,171,150,28,199,182,42,242,224,28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 109 RDILKSESHIlPRRAL-EIVADILAALEYSHRN-GIVHRDIKPGNIMLTHNGEVKVMDFGIaravAQSTATVTQTAAVIG 186
cd06617       91 KKVYKKGLTI-PEDILgKIAVSVVKALEYLHEKlSVIHRDVKPSNILINRNGQVKLCDFGI----SGYLVDSLAKTVDAG 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 187 TAQYLSPEQARGE----PVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPvPPSRLNPDVTPDIDAIVMKA 262
cd06617      166 CKPYMAPERIDPEgnqkGYDVRSDVWSLGITMIELATGRFPYDNWKTPFEQLKQVVEEP-SPQLPAEKFSPEFQDFVNKC 244


                 ....*...
gi 117927230 263 LAKNPANR 270
cd06617      245 LRKDYHER 252

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132947

cd06616

PKc_MKK4

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

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

false

true

false

288

8e-15

77.40

80.21

13,15,3,9,25,12,23,50,35,21,71,57,12,85,69,9,96,78,9,105,93,10,118,103,10,128,114,12,140,127,27,171,154,24,195,181,45,242,226,8

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  16 ADRYELGEIlGYGGMAEVRRGRDLRLGRDVAIKtlRVDLARDTSFQTRFRREAQAA-AALNHPSIVAVYdtGESMLDGVP 94
cd06616        4 EDLKDLGEI-GRGAFGTVNKMLHKPSGTIMAVK--RIRSTVDEKEQKRLLMDLDVVmRSSDCPYIVKFY--GALFREGDC 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  95 vpYIVMEYVEG------RTLRDILKSEshiLPRRALEIVA-DILAALEYSHRN-GIVHRDIKPGNIMLTHNGEVKVMDFG 166
cd06616       79 --WICMELMDIsldkfyKYVYEVLKSV---IPEEILGKIAvATVKALNYLKEElKIIHRDVKPSNILLDRNGNIKLCDFG 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 167 IaravAQSTATVTQTAAVIGTAQYLSPEQ---ARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDpvP 243
cd06616      154 I----SGQLVDSIAKTRDAGCRPYMAPERidpSARDGYDVRSDVWSLGITLYEVATGKFPYPKWNSVFDQLTQVVKG--D 227


                 ....*..
gi 117927230 244 PSRLNPD 250
cd06616      228 PPILSNS 234

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133173

cd05041

PTKc_Fes_like

Catalytic Domain of Fes-like Protein Tyrosine Kinases

false

true

false

251

8e-15

77.11

86.45

11,45,22,12,59,34,22,89,56,4,93,65,2,96,67,24,120,92,47,168,139,51,219,191,10,234,201,13,247,215,7,254,223,16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  46 AIKTLRVDLARDtsFQTRFRREAQAAAALNHPSIVAvydtgesmLDGV-----PVpYIVMEYVEGRTLRDILKSESHILP 120
cd05041       23 AVKTCRSTLPPD--LKRKFLQEAEILKQYDHPNIVK--------LIGVcvqkqPI-YIVMELVPGGSLLTFLRKKKNRLT 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 121 -RRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaRAVAQSTATVTQTAAVIGTAQYLSPEQARGE 199
cd05041       92 vKKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGM-SREEEGGIYTVSDGLKQIPIKWTAPEALNYG 170

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117927230 200 PVDPRSDIYSTGCVLYELLT-GTPPFTGESAvavayQHVREDPVPPSRL-NPDVTPD-IDAIVMKALAKNPANR 270
cd05041      171 RYTSESDVWSYGILLWETFSlGDTPYPGMSN-----QQTRERIESGYRMpAPQLCPEeIYRLMLQCWAYDPENR 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132953

cd06622

PKc_MAPKK_PBS2_like

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

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

false

true

false

286

1e-14

76.43

90.21

8,16,0,38,56,38,27,85,65,9,96,74,12,109,86,25,134,116,33,172,149,32,204,187,71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  17 DRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTLRVDLarDTSFQTRFRREAQAAAALNHPSIVAVYdtGESMLDGVPvp 96
cd06622        1 DEIEVLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLEL--DESKFNQIIMELDILHKAVSPYIVDFY--GAFFIEGAV-- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLrDILKSESHILPRRALEIVADILAAL-----EYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIarav 171
cd06622       75 YMCMEYMDAGSL-DKLYAGGVATEGIPEDVLRRITYAVvkglkFLKEEHNIIHRDVKPTNVLVNGNGQVKLCDFGV---- 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 172 aQSTATVTQTAAVIGTAQYLSPEQARGEPVDPR------SDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPS 245
cd06622      150 -SGNLVASLAKTNIGCQSYMAPERIKSGGPNQNptytvqSDVWSLGLSILEMALGRYPYPPETYANIFAQLSAIVDGDPP 228

                        250       260       270
                 ....*....|....*....|....*....|
gi 117927230 246 RLNPDVTPDIDAIVMKALAKNPANRYQSAA 275
cd06622      229 TLPSGYSDDAQDFVAKCLNKIPNRRPTYAQ 258

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88498

cd05597

STKc_DMPK_like

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

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

false

true

false

331

1e-14

76.51

41.69

5,96,76,16,112,93,54,168,147,26,194,175,5,199,183,31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDIL-KSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGiaRAVAQST 175
cd05597       77 YLVMDYYVGGDLLTLLsKFEDRLPEDMARFYLAEMVLAIDSVHQLGYVHRDIKPDNVLLDKNGHIRLADFG--SCLRLLA 154

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 176 ATVTQTAAVIGTAQYLSPE--QARGE---PVDPRSDIYSTGCVLYELLTGTPPFTGESAV 230
cd05597      155 DGTVQSNVAVGTPDYISPEilQAMEDgkgRYGPECDWWSLGVCMYEMLYGETPFYAESLV 214

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132978

cd06647

STKc_PAK_I

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

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

false

true

false

293

2e-14

76.10

51.54

5,75,74,10,85,87,4,96,91,16,113,107,54,170,161,64

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  76 HPSIVAVYDT---GESMldgvpvpYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNI 152
cd06647       75 HPNIVNYLDSylvGDEL-------WVVMEYLAGGSLTDVV-TETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNI 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 153 MLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAV 232
cd06647      147 LLGMDGSVKLTDFGF---CAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRA 223


                 ..
gi 117927230 233 AY 234
cd06647      224 LY 225

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

119328

cd06577

PASTA_pknB

PASTA domain of bacterial serine/threonine kinase pknB-like proteins. PknB is a member of a group of related transmembrane sensor kinases present in many gram positive bacteria, which has been shown to regulate cell shape in Mycobacterium tubercolosis. PknB is a receptor-like transmembrane protein with an extracellular signal sensor domain (containing multiple PASTA domains) and an intracellular, eukaryotic serine/threonine kinase-like domain. The PASTA domain is found at the C-termini of several Penicillin-binding proteins (PBPs) and bacterial serine/threonine kinases. The name PASTA is derived from PBP and Serine/Threonine kinase Associated domain.

PASTA domain of bacterial serine/threonine kinase pknB-like proteins. PknB is a member...

true

false

true

2e-14

76.03

100.00

2,421,0,30,451,31,31

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117927230 422 TVPDLTNKSLEDARAALRALGLTVGNVTQR-DSQQPAGTVLDQNPKPGSPAAAGSRVDLVVA 482
cd06577        1 TVPDVVGMTLDEAKAALEAAGLKVGVVTEEySDDVPKGTVISQSPAAGTKVKKGSTVTLTVS 62

cl02768

141692

PASTA

PASTA domain. This domain is found at the C-termini of several Penicillin-binding proteins (PBPs) and bacterial serine/threonine kinases. It is a small globular fold consisting of 3 beta-sheets and an alpha-helix. The name PASTA is derived from PBP and Serine/Threonine kinase Associated domain.

PASTA domain. This domain is found at the C-termini of several Penicillin-binding...

-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

3e-14

75.44

60.00

7,96,80,71,169,151,32,201,185,24,225,211,2,227,215,22,250,237,4,257,241,13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIarAVAQSTA 176
cd05613       81 HLILDYINGGELFTHLSQRERFKEQEVQIYSGEIVLALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFGL--SKEFHED 158

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPV--DPRSDIYSTGCVLYELLTGTPPFT--GE--SAVAVAYQHVREDPVPPSRLNPd 250
cd05613      159 EVERAYSFCGTIEYMAPDIVRGGDGghDKAVDWWSMGVLMYELLTGASPFTvdGEknSQAEISRRILKSEPPYPQEMSA- 237

                        170       180
                 ....*....|....*....|
gi 117927230 251 VTPDidaIVMKALAKNPANR 270
cd05613      238 LAKD---IIQRLLMKDPKKR 254

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-14

75.09

58.22

8,12,38,38,50,77,6,56,85,4,63,89,20,87,109,25,113,134,54,169,188,33,202,225,29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  13 RILADRYELGEILGYGGMAEVRRGRDLRLGRDVAIKTL-RVDLAR--DTSFqtrFRREAQAAAALNHPSIVAVYdtgeSM 89
cd05622       39 RMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLsKFEMIKrsDSAF---FWEERDIMAFANSPWVVQLF----YA 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  90 LDGVPVPYIVMEYVEGRTLRDILkSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIar 169
cd05622      112 FQDDRYLYMVMEYMPGGDLVNLM-SNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGT-- 188

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117927230 170 AVAQSTATVTQTAAVIGTAQYLSPEQARGEPVD----PRSDIYSTGCVLYELLTGTPPFTGESAVA 231
cd05622      189 CMKMNKEGMVRCDTAVGTPDYISPEVLKSQGGDgyygRECDWWSVGVFLYEMLVGDTPFYADSLVG 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

119328

cd06577

PASTA_pknB

PASTA domain of bacterial serine/threonine kinase pknB-like proteins. PknB is a member...

true

false

true

4e-14

74.87

100.00

2,354,0,25,379,26,36

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117927230 355 PVPNVINMTQSQAEQTLTSDGFKVK-VETQPNASVPQGIVFDQNPTAGTRLPKNSVVTITVS 415
cd06577        1 TVPDVVGMTLDEAKAALEAAGLKVGvVTEEYSDDVPKGTVISQSPAAGTKVKKGSTVTLTVS 62

cl02768

141692

PASTA

PASTA domain. This domain is found at the C-termini of several Penicillin-binding...

-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-14

75.03

77.71

7,22,0,29,51,31,12,65,43,17,82,63,8,97,71,70,170,141,77,251,218,33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  23 EILGYGGMAEVRRGRDLRLGRDVAIKTLR--VDLARDTSFQTRfrREAQAAAALNHPSIVAV---YDTGESMLdgvpvpy 97
cd05571        1 KLLGKGTFGKVILVREKATGKYYAMKILKkeVIIAKDEVAHTL--TESRVLQNTRHPFLTALkysFQTHDRLC------- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  98 IVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaraVAQSTAT 177
cd05571       72 FVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFGL---CKEGISD 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 178 VTQTAAVIGTAQYLSPEQARGEPVDPRSDIYSTGCVLYELLTGTPPFTGESAVAVAYQHVREDPVPPSRLnpdvTPDIDA 257
cd05571      149 GATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTL----SPEAKS 224

                        250       260
                 ....*....|....*....|....*..
gi 117927230 258 IVMKALAKNPANRYQSAAEMRADIERA 284
cd05571      225 LLAGLLKKDPKQRLGGGPEDAKEIMEH 251

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

4e-14

74.93

57.04

4,121,95,46,171,141,63,234,207,8,245,215,38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 122 RALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIaravAQSTATVTQTAAVIGTAQYLSPEQARGEPV 201
cd05577       96 RARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISDLGL----AVEFPEGKKIHGRVGTVGYMAPEVLQNEVY 171

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 202 DPRSDIYSTGCVLYELLTGTPPFTGESAVAVAY---QHVREDPVppsRLNPDVTPDIDAIVMKALAKNPANRYQSAAEMR 278
cd05577      172 DFSPDWFALGCLLYEMIAGHSPFRQRKEKVKKEevdRRTLTDEV---EYPDKFSEEAKSICEGLLQKDPEKRLGCRGEGA 248


                 ....*
gi 117927230 279 ADIER 283
cd05577      249 DEVKE 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88515

cd05614

STKc_MSK2_N

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK2, 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. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis.

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

332

5e-14

74.68

55.72

5,96,80,71,169,151,36,205,188,22,227,214,26,257,240,25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  97 YIVMEYVEGRTLRDILKSESHILPRRALEIVADILAALEYSHRNGIVHRDIKPGNIMLTHNGEVKVMDFGIarAVAQSTA 176
cd05614       81 HLILDYVSGGEMFTHLYQRDNFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGL--SKEFLSE 158

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 177 TVTQTAAVIGTAQYLSPEQARGEPVDPRS-DIYSTGCVLYELLTGTPPFTGE----SAVAVAYQHVREDPVPPSRLNPDV 251
cd05614      159 EKERTYSFCGTIEYMAPEIIRGKGGHGKAvDWWSLGILIFELLTGASPFTLEgernTQSEVSRRILKCDPPFPSFIGPEA 238

                        170       180       190
                 ....*....|....*....|....*....|.
gi 117927230 252 TPdidaIVMKALAKNPANRYQSAAEMRADIE 282
cd05614      239 QD----LLHKLLRKDPKKRLGAGPQGASEIK 265

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

1e-13

73.53

76.37

10,66,58,17,85,75,9,96,84,32,128,117,39,170,156,29,199,190,41,242,231,9,251,241,19,271,260,6,280,266,15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230  67 EAQAAAALNHPSIVAVYdtGESMLDGVPvpYIVMEYVEGRTLRDILKSESHILPRRALEIVA-DILAALEYSHRNGIVHR 145
cd06644       59 EIEILATCNHPYIVKLL--GAFYWDGKL--WIMIEFCPGGAVDAIMLELDRGLTEPQIQVICrQMLEALQYLHSMKIIHR 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117927230 146 DIKPGNIMLTHNGEVKVMDFGIaraVAQSTATVTQTAAVIGTAQYLSPEQARGE-----PVDPRSDIYSTGCVLYELLTG 220
cd06644      135 DLKAGNVLLTLDGDIKLADFGV---SAKNVKTLQRRDSFIGTPYWMAPEVVMCEtmkdtPYDYKADIWSLGITLIEMAQI 211

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117927230 221 TPPFTGESAVAVAYQHVREDpvPPSRLNPDV-TPDIDAIVMKALAKNPANRyQSAAEMradIERALLGK