NCBI Conserved Domain Search

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Conserved domains on [gi\|94968787\|ref\|YP_590835.1\|]
serine/threonine protein kinase [Candidatus Koribacter versatilis Ellin345]

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List of domain hits		?

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

29142

cd00180

S_TKc

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

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

true

256

8e-46

179.63

95.70

6,3,0,73,78,73,19,97,93,50,147,150,52,201,202,18,219,221,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVR 83
cd00180       1 DYELLEKLGKGAFGKVYLARDKKTGELVAIKIIKKKKEKKKQVERILREIKILKRLNHPNIVKLYDVFEDEDK--LYLVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRS 155
cd00180      79 EYMSGGDLFDLLKKrGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFglakqldSGGRKLTT 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 156 FHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRgaSPVDWSAHRRALSIANNG-PLHISPEVDQLLAKA 234
cd00180     159 FVGTPWYMAPEVLLGKGYGKKVDIWSLGVILYELLTGKPPFPGD--NEEDLLEKILKGKGTPDElPPNISPEAKDLIKKL 236


                ....*....
gi 94968787 235 LAKNPADRF 243
cd00180     237 LVKDPEKRP 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

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

5e-35

143.69

94.40

6,10,0,46,56,47,20,78,67,19,97,87,50,147,144,68,219,212,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYDVGISNEKqmLYLVREYVAGV 89
cd05123       1 LGKGSFGKVYLVRKKDTGKLYAMKVLKKKKILKRNEVEHTLNERDIlSRVDHPFIVKLHYAFQTKEK--LYLVMEYVNGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFHGDNA 161
cd05123      79 DLFTHLSKeGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFglakegiDDGVRTTTFCGTPE 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 FFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIanngPLHISPEVDQLLAKALAKNPAD 241
cd05123     159 YLAPEVLQGKGYGKAVDWWSLGVLLYEMLTGRPPFYAEDEAETYQKILKDKLRF----PEFLSEEAKDLIKKLLTKDPTK 234


                ..
gi 94968787 242 RF 243
cd05123     235 RL 236

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

5e-34

140.38

92.66

9,10,7,35,50,42,3,53,50,23,77,73,20,97,94,55,152,158,43,205,201,9,214,214,5,219,224,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNplqffLDA-----RAVKRLTHPGIVELYDVGISNEKqMLYLVREY 85
cd06606       8 LGRGSFGSVYLALSKDTGELVAVKSVELSSDSEEE-----LESlereiRILSKLQHPNIVRYYGCEVTEEN-TLNIFMEY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL---------SRS 155
cd06606      82 VSGGSLASLLKKfGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRlasiaysggLKS 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 156 FHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPfhgrgaspvdWSAHRRALS----IANNG-----PLHISPE 226
cd06606     162 VRGTPYWMAPEVIRGEEYGRASDIWSLGCTVIEMLTGKPP----------WSELGNPMAllykIGSSGeppeiPEDLSEE 231

                       250
                ....*....|....*.
gi 94968787 227 VDQLLAKALAKNPADR 242
cd06606     232 AKDFLRKCLRRDPKKR 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132935

cd05122

PKc_STE

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

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

false

true

false

253

1e-33

138.83

95.26

8,4,1,44,50,45,26,78,71,30,108,102,42,150,145,4,154,155,43,204,198,16,220,220,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQffLDARAVKRLTHPGIVELYDVGISNEKqmLYLVRE 84
cd05122       2 FEKLEKIGKGAFGTVYKARHKKTGELVAVKVIKLESDEEQEQIL--NEIQILKKCKHPNIVKYYGSYLKKDE--LWIVME 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETILQSGSLSPETALQT-AKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-RLSR------SF 156
cd05122      78 YCDGGSLDDLLKSTGPLPESQIAYiCREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFGVSaQLSDtkakrnTF 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 157 HGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHgrgaspvDWSAHRRALSIANNGP------LHISPEVDQL 230
cd05122     158 VGTPYWMAPEVINGEPYGFKADIWSLGITAIEMAEGKPPYS-------ELNPMKALFKIATNPPpglpspEKWSPEFRDF 230

                       250
                ....*....|..
gi 94968787 231 LAKALAKNPADR 242
cd05122     231 LKKCLQKDPEKR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

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

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

false

true

false

279

1e-31

132.61

94.27

7,4,2,45,49,48,11,60,60,16,78,76,8,86,85,66,152,178,46,202,224,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQF-FLDARAVKRLT-HPGIVELYDVGISNEKqmLYLV 82
cd05581       3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKVLDKRHLIKEKKVKYvKREKEVLTRLNgHPGIVKLYYTFQDEEN--LYFV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYV-AGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL--------- 152
cd05581      81 LEYAeNGELLEYIKKFGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFGTAKVldpnsspes 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 153 ------------------SRSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGrgasPVDWSAHRRALS 214
cd05581     161 nkgkatnidsqieknrrrRASFVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRG----SNEYLTFQKIVK 236

                       250       260
                ....*....|....*....|....*....
gi 94968787 215 IANNGPLHISPEVDQLLAKALAKNPADRF 243
cd05581     237 LEYEFPPNFPPDAKDLIEKLLVLDPQDRL 265

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

7e-28

120.03

91.92

5,7,0,52,59,54,14,75,68,22,97,91,54,151,148,91

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRL--THPGIVELYDVGISneKQMLYLVREY 85
cd05611       1 LKPISKGAFGSVYLAKKRSTGDYFAIKVLKKSDMIAKNQVTNVKAERAIMMIqgESPYVAKLYYSFQS--KDYLYLVMEY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR---LSRSFHGDNA 161
cd05611      79 LNGGDCASLIKTlGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRnglENKKFVGTPD 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 FFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNGPLHISPEVDQLLAKALAKNPAD 241
cd05611     159 YLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPEAVDLINRLLCMDPAK 238


                .
gi 94968787 242 R 242
cd05611     239 R 239

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

2e-27

118.50

95.28

11,3,0,67,72,67,24,96,92,4,101,96,3,104,101,8,113,109,34,147,144,15,162,165,41,211,206,2,213,209,6,219,219,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTHPGIVELYDVgiSNEKQMLYLVR 83
cd06627       1 NYQLGDLIGKGAFGVVYKGLNLETGDFVAIKQISLEKIKEEALKSIMQEIDLLKNLNHPNIVKYIGS--VKTSDSLYIIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQ-SGSLsPET--ALQTAKELaEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-SGSRLSRSFHGD 159
cd06627      79 EYAENGSLRQIIKkFGKF-PESlvAVYVYQVL-QGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFgVATKLSDVSKDD 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NAF------FAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPvdwsahrrAL-SIANNG----PLHISPEVD 228
cd06627     157 ESVvgtpywMAPEVIEMSGASTASDIWSLGCTVIELLTGNPPYYDLNPMP--------ALfRIVQDDhpplPEGISPELK 228

                       250
                ....*....|....
gi 94968787 229 QLLAKALAKNPADR 242
cd06627     229 DFLMQCFQKDPNLR 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

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

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

false

true

false

258

1e-25

112.25

96.51

6,4,1,52,56,54,20,78,74,14,92,89,55,147,150,68,216,218,32

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYDVGISNEKqmLYLVR 83
cd05578       2 FEILRVIGKGSFGKVCIVQKRDTKKMFAMKYMNKQKCVEKGSVRNVLNELQIlQSLEHPFLVNLWYSFQDEED--MYLVV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLE-TILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------SGSRLSRSF 156
cd05578      80 DLLLGGDLRyHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFniatklTPDTLATST 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 157 HGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIaNNGPLHISPEVDQLLAKALA 236
cd05578     160 SGTPPYMAPEVFCRQGYSFAVDWWSLGVTAYEMLRGKRPYRGHSRTPREEILAKFETAD-VLYPAGWSSEAIDAINKLLE 238

                       250
                ....*....|..
gi 94968787 237 KNPADRFQVARQ 248
cd05578     239 RDPQKRLGDNLS 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

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

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

false

true

false

265

3e-25

111.43

92.45

6,10,0,46,56,47,20,78,67,19,97,87,50,147,152,52,201,204,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYDVGISNEKqmLYLVREYVAGV 89
cd05579       1 ISKGAYGRVFLAKKKSTGDIYAIKVIKKADMIRKNQVDQVLTERNIlSQAQNPFVVKLYYSFQGKKN--LYLVMEYLPGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF---------------SGSRLS 153
cd05579      79 DLASLLENvGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFglskvglvrrqinlnDDEKED 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 154 RSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRgaSPVDWSAHRRALSIANNGPLHISPEVDQLLAK 233
cd05579     159 KRIVGTPDYIAPEVILGQGHSKTVDWWSLGCILYEFLTGIPPFHGE--TPEEIFQNILNGKIEWPEDVEVSDEAKDLISK 236


                ....*....
gi 94968787 234 ALAKNPADR 242
cd05579     237 LLVPDPEKR 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

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

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

false

true

false

315

4e-23

104.18

88.57

6,3,1,53,56,55,12,70,67,27,97,97,50,147,182,73,222,255,25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYdvGISNEKQMLYLV 82
cd05574       2 DFKKIKLLGKGDVGRVYLVRLKGTGKLFALKVLDKKEMIKRNKVKRVLTEQEIlATLDHPFLPTLY--ASFQTETYLCLV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLETILQS---GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------------ 147
cd05574      80 MDYCPGGELFRLLQRqpgKCFPEEVARFYAAEVLLALEYLHLLGIVYRDLKPENILLHEDGHIMLSDFdlskqsdveptp 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 148 -----------------------SGSRLSRSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPV 204
cd05574     160 vskalrkgsrgsvnkittetfseEPSFRSNSFVGTEEYLAPEVISGDGHSSAVDWWTLGILLYEMLYGTTPFKGKNRDET 239

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 94968787 205 DWSAHRRALSIANNGPlhISPEVDQLLAKALAKNPADRFQVAR 247
cd05574     240 FSNILKKEVTFPGSPP--VSSSARDLIRKLLVKDPSKRLGSKR 280

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

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

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

false

true

false

333

2e-22

101.53

60.06

5,2,0,58,60,59,10,72,69,23,95,93,56,151,153,47

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   3 GRYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT-HPGIVELYDVgiSNEKQMLYL 81
cd05600       1 KDFQILTQVGQGGYGQVFLAKKKDTGEIVALKRMKKSLLFKLNEVRHVLTERDILTTTkSEWLVKLLYA--FQDDEYLYL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  82 VREYVAGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR----LSRSF 156
cd05600      79 AMEYVPGGDFRTLLnNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFGLSKgivtYANSV 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 94968787 157 HGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHG 198
cd05600     159 VGSPDYMAPEVLRGKGYDFTVDYWSLGCMLYEFLCGFPPFSG 200

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

6e-22

100.31

64.97

6,4,2,53,57,56,11,68,71,1,75,72,20,95,93,55,150,186,46

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVK-RLTHPGIVELY----DvgisneKQML 79
cd05573       3 FEKIKVIGRGAFGEVWLVRKKDTGKVYAMKILRKSDMLKRNQVAHVRAERDILaDADSPWIVKLYysfqD------EEYL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  80 YLVREYVAGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-------- 150
cd05573      77 YLVMEYMPGGDLMTLLiKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFGLCkkmkkagd 156

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94968787 151 ------------------------------RLSRSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPF 196
cd05573     157 seyylndshnlldsdrdnvlkrrrpkkqrrVRAYSTVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGYPPF 232

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88513

cd05612

STKc_PRKX_like

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

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

false

true

false

291

8e-22

99.93

81.79

8,4,2,52,56,55,14,72,69,24,96,94,55,151,151,6,157,159,39,198,198,5,205,203,37

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYDVgiSNEKQMLYLVR 83
cd05612       3 LERIETLGTGTFGRVYLVRHKASGAYYALKVLAIPEVIRLKQVEHVHNEKSIlSEISHPFIVNMYWT--FHDDKFLYMLM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR--LSRSFH--G 158
cd05612      81 EYVPGGELFSYLRkAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAKkvRDRTWTlcG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 159 DNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFhgRGASPvdWSAHRRALSIANNGPLHISPEVDQLLAKALAKN 238
cd05612     161 TPEYLAPEIIQSKGHGKAVDWWALGILIYEMLVGYPPF--FDDNP--FGIYEKILAGKLEFPRHFDLRAKDLIKKLLVVD 236


                ....
gi 94968787 239 PADR 242
cd05612     237 RTRR 240

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

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

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

false

true

false

290

8e-22

99.82

82.41

7,4,2,52,56,55,12,70,67,25,95,93,56,151,151,6,157,159,39,200,198,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYdvGISNEKQMLYLVR 83
cd05580       3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKILSKAKIVKLKQVEHVLNEKRIlQAVRHPFLVNLL--GSFKDNSNLYMVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR--LSRSFH--G 158
cd05580      81 EFVPGGELFSLLrRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAKrvKGRTYTlcG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 159 DNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFhgrgASPVDWSAHRRALSIANNGPLHISPEVDQLLAKALAKN 238
cd05580     161 TPEYLAPEIILSKGYGKAVDWWALGILIYEMLAGYPPF----FDDNPMKIYEKILSGKVRFPSFFSSDAKDLLRNLLQVD 236


                ....*
gi 94968787 239 PADRF 243
cd05580     237 LTKRL 241

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

1e-21

99.61

87.96

13,3,1,33,36,41,4,46,45,2,48,50,5,58,55,18,78,73,69,147,144,3,151,147,11,162,164,34,198,198,6,210,204,5,215,211,6,221,221,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAI-------PIAEfpesnpLQ---FFLDAravkrLTHPGIVELYDVGIS 73
cd06609       2 LFTLLECIGKGSFGEVYKAIDKRTNQVVAIKVIdleeaedEIED------IQqeiQFLSQ-----CRSPYITKYYGSFLK 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  74 NEKqmLYLVREYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF--SGSr 151
cd06609      71 GSK--LWIIMEYCGGGSCLDLLKPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFgvSGQ- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 152 LSRSFHGDNAF------FAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFhgRGASPVdwsahrRALSI--ANNGPL-- 221
cd06609     148 LTSTMSKRNTFvgtpfwMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPL--SDLHPM------RVLFLipKNNPPSle 219

                       250       260
                ....*....|....*....|...
gi 94968787 222 --HISPEVDQLLAKALAKNPADR 242
cd06609     220 gnKFSKPFKDFVSLCLNKDPKER 242

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

1e-21

99.33

78.79

6,3,0,73,78,73,30,108,104,39,147,144,7,154,161,22,176,186,22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVR 83
cd06626       1 RWQRGNKIGGGTFGKVYTAVNLDTGELMAVKEIRIQDNDPKTIKEIADEMKVLELLKHPNLVKYYGVEVHREK--VYIFM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQSGSLSPETALQT-AKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-SGSRLSR------- 154
cd06626      79 EYCSGGTLEELLEHGRILDEHVIRVyTLQLLEGLAYLHSHGIVHRDIKPANIFLDHNGVIKLGDFgCAVKLKNntttmge 158

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 ---SFHGDNAFFAPEQLNGGVADAQ---TDLFSLGALLYTMLTGHVPFHG 198
cd06626     159 evqSLAGTPAYMAPEVITGGKGKGHgraADIWSLGCVVLEMATGKRPWSE 208

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

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

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

false

true

false

262

2e-21

98.33

90.84

8,10,0,35,45,36,25,72,61,25,97,87,50,147,144,4,152,148,52,206,200,12,218,214,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESN-PLQFFLDARAVKRLTHPGIVELYDVgiSNEKQMLYLVREYVAGV 89
cd05572       1 LGVGGFGRVELVQYKSKNRTFALKCVKKRHIVETGqQEHIFSEKEILEECNSPFIVRLYRT--FKDKKYIYFLMEYCLGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRlSRSFHGDNA 161
cd05572      79 ELWTILRDrGLLDEYTARFYTACVVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFgfakklkSGQK-TYTFCGTPE 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 FFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwSAHRRALSIANN--GPLHISPEVDQLLAKALAKNP 239
cd05572     158 YVAPEIILNKGYDFSVDYWSLGILLYELLTGSPPFGEDDEDPM--KIYNLILKGIDKleFPKYIDKAAKDLIKQLLRRNP 235


                ...
gi 94968787 240 ADR 242
cd05572     236 EER 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

3e-21

97.97

95.40

12,9,1,14,23,18,14,38,32,30,70,62,26,96,97,51,148,148,1,151,149,11,162,172,29,191,202,7,203,209,11,217,220,2,219,227,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  10 EIGRGELGAVYQGH---DSENDRVVAIKAIPiAEFPESNPLQFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREYV 86
cd00192       2 KLGEGAFGEVYKGElkgKGGKKTPVAVKTLK-EDASDSEREDFLKEAKIMKKLGHPNIVRLL--GVCTEEEPLYLVLEYM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  87 AGVTLETILQ---------SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFsGsrLSRSFH 157
cd00192      79 EGGDLLDFLRksrpvfspeSSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADF-G--LSRDIY 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 158 GDNAF------------FAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGrgaspVDWSAHRRALSianNG----- 219
cd00192     156 DDDYYrkkgggklpirwMAPESLKDGKFTTKSDVWSFGVLLWEIFTlGGTPYPG-----LSNEEVLEYLR---KGyrlpk 227

                       250       260
                ....*....|....*....|...
gi 94968787 220 PLHISPEVDQLLAKALAKNPADR 242
cd00192     228 PENCPDELYELMLSCWQEDPEDR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88485

cd05584

STKc_p70S6K

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

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

false

true

false

323

6e-21

96.96

78.02

7,10,3,11,21,17,33,54,52,22,78,74,18,96,93,51,147,151,68,219,219,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQ---GHDSENDRVVAIKAIPIAEFPESNPLQFFLDAR--AVKRLTHPGIVELYDVGISNEKqmLYLVREY 85
cd05584       4 LGKGGYGKVFQvrkVTGADTGKIFAMKVLKKATIVRNQKDTAHTKAErnILEAVKHPFIVDLIYAFQTGGK--LYLILEY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFH 157
cd05584      82 LSGGELFMHLErEGIFMEDTACFYLSEISLALEHLHQQGIIYRDLKPENILLDAQGHVKLTDFglckesiHEGTVTHTFC 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 158 GDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIanngPLHISPEVDQLLAKALAK 237
cd05584     162 GTIEYMAPEILMRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLNL----PPYLTPEARDLLKKLLKR 237

                       250
                ....*....|....*...
gi 94968787 238 NPADRFQVARQMAYAIQK 255
cd05584     238 NPSSRLGAGPGDAAEVQS 255

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

7e-21

96.95

79.56

7,7,0,13,20,18,5,27,23,49,78,72,29,107,102,46,153,155,62,219,217,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVY-----QGHDSenDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLV 82
cd05582       1 LKVLGQGSFGKVFlvrkiTGPDA--GQLYAMKVLKKATLKVRDRVRTKMERDILAEVNHPFIVKLHYAFQTEGK--LYLI 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLETILQSGSLSPETALQ-TAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLS-------R 154
cd05582      77 LDFLRGGDLFTRLSKEVMFTEEDVKfYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESidhekkaY 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 SFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIanngPLHISPEVDQLLAKA 234
cd05582     157 SFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGM----PQFLSPEAQSLLRAL 232

                       250       260
                ....*....|....*....|.
gi 94968787 235 LAKNPADRFQVARQMAYAIQK 255
cd05582     233 FKRNPANRLGAGPDGVEEIKR 253

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

8e-21

96.51

92.42

9,5,3,38,44,41,31,77,72,31,108,104,14,122,119,31,153,157,49,204,206,9,216,215,5,221,226,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPEsNPLQFFLDARAVKRLTHPGIVELYDVGISNEkqMLYLVREY 85
cd06623       4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHVDGDEE-FRKQLLRELKTLRSCESPYVVKCYGAFYKEG--EISIVLEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQSGSLSPETALQT-AKELAEALDHAHRQ-GFIHGNVQPYNILITEEGHAKLAEFSGSRLS-------RSF 156
cd06623      81 MDGGSLADLLKKVGKIPEPVLAYiARQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISKVLentldqcNTF 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 157 HGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASpvDWSAHRRALsiaNNGPL------HISPEVDQL 230
cd06623     161 VGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPPGQP--SFFELMQAI---CDGPPpslpaeEFSPEFRDF 235

                       250
                ....*....|..
gi 94968787 231 LAKALAKNPADR 242
cd06623     236 ISACLQKDPKKR 247

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

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

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

false

true

false

318

1e-20

95.69

78.30

6,10,2,50,60,54,10,72,64,20,92,85,56,148,148,67,219,215,36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT--HPGIVELYDVgiSNEKQMLYLVREYVAG 88
cd05570       3 LGKGSFGKVLLAELKGTDELYAIKVLKKDVVLQDDDVECTMTEKRVLALAgkHPFLTQLHSC--FQTKDRLFFVMEYVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLE-TILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS-------GSRLSRSFHGDN 160
cd05570      81 GDLMyHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGmckegilGGVTTSTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIanngPLHISPEVDQLLAKALAKNPA 240
cd05570     161 DYIAPEILQGQPYGFSVDWWALGVLLYEMLAGQSPFDGDDEDELFQSILEDNVRY----PRWLSKEAKSILKGFLTKNPE 236

                       250
                ....*....|....*
gi 94968787 241 DRFQVARQMAYAIQK 255
cd05570     237 KRLGCGPTGEQDIKG 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88490

cd05589

STKc_PKN

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

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

false

true

false

324

2e-20

95.33

87.96

10,4,0,50,54,54,14,70,68,78,148,154,5,154,159,50,204,210,1,213,211,6,219,220,36,262,256,14,278,270,15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDAR----AVKRLTHPGIVELYdvGISNEKQMLY 80
cd05589       1 FRCLAVLGRGHFGKVLLAEYKKTGELYAIKALKKGDIIARDEVESLMCEKrifeTANSERHPFLVNLF--ACFQTEDHVC 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  81 LVREYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS--------GSRL 152
cd05589      79 FVMEYAAGGDLMMHIHTDVFSEPRAVFYAACVVLGLQYLHENKIVYRDLKLDNLLLDTEGYVKIADFGlckegmgfGDRT 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 153 SrSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPV-DwsahrralSIANNG---PLHISPEVD 228
cd05589     159 S-TFCGTPEFLAPEVLTETSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVfD--------SIVNDEvryPRFLSREAI 229

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94968787 229 QLLAKALAKNPADRFQVARQMAYAIQKvlepavpEPVLEDIAPESLVAipEQRPTPEVPAVGAPA 293
cd05589     230 SIMRRLLRRNPERRLGSGERDAEDVKK-------QPFFRDINWDALLA--RRIPPPFVPTIKGPE 285

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

5e-20

93.84

75.95

7,10,2,50,60,54,16,78,70,13,91,84,57,148,148,58,213,206,9,222,218,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT--HPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05592       3 LGKGSFGKVMLAELKGTNEYYAIKALKKDVVLEDDDVECTMVERRVLILAweHPFLTHLFCTFQTKEH--LFFVMEYLNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTL-ETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS-------GSRLSRSFHGDN 160
cd05592      81 GDLmFHIQSSGRFDEARARFYAAEIICGLQFLHKKGIIYRDLKLDNVLLDRDGHIKIADFGmckeninGEGKASTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWsahrralSIANNGPLH---ISPEVDQLLAKALAK 237
cd05592     161 DYIAPEILKGQKYNESVDWWSFGVLLYEMLIGQSPFHGEDEDELFD-------SILNDRPHFprwISKEAKDCLSKLFER 233


                ....*....
gi 94968787 238 NPADRFQVA 246
cd05592     234 EPTKRLGMD 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

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

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

false

true

false

277

2e-19

92.12

87.36

10,3,4,4,10,8,28,39,36,22,61,61,7,70,68,77,147,152,26,173,179,23,201,202,4,207,206,14,221,225,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEIlaeIGRGELGAVYQGHDSENDRVVAIKAIPIaEFPESNPLQFFLDARAVKRLTH---PGIVELYdvGISNEKQMLY 80
cd06917       5 RLEL---IGRGAYGAVYRGKHVPTGRVVALKIINL-DTPDDDVSDIQREVALLSQLRQsqpPNITKYY--GSYLKGPRLW 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  81 LVREYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLS 153
cd06917      79 IIMEYAEGGSVRTLMKAGPIAEKYISVIIREVLVALKYIHKVGVIHRDIKAANILVTNTGNVKLCDFgvaallnQNSSKR 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 154 RSFHGDNAFFAPEQLNGGVA-DAQTDLFSLGALLYTMLTGHVPFhgrgaSPVDwsAHRRALSIANNGPL-----HISPEV 227
cd06917     159 STFVGTPYWMAPEVITEGKYyDTKADIWSLGITIYEMATGNPPY-----SDVD--AFRAMMLIPKSKPPrlednGYSKLL 231

                       250
                ....*....|....*
gi 94968787 228 DQLLAKALAKNPADR 242
cd06917     232 REFVAACLDEEPKER 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

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

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

false

true

false

258

2e-19

91.72

92.64

8,10,7,37,47,47,21,70,68,27,97,96,53,150,155,20,170,176,27,204,203,15,219,223,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPL---QFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREYVA 87
cd06632       8 LGSGSFGSVYEGLNLDDGDFFAVKEVSLADDGQTGQEavkQLEQEIALLSKLQHPNIVQYL--GTEREEDNLYIFLELVP 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS------RLSRSFHGDN 160
cd06632      86 GGSLAKLLKKyGSFPEPVIRLYTRQILLGLEYLHDRNTVHRDIKGANILVDTNGVVKLADFGMAkqvvefSFAKSFKGSP 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNG-GVADAQTDLFSLGALLYTMLTGHVPFHgrgaspvDWSAHRRALSIANNG-----PLHISPEVDQLLAKA 234
cd06632     166 YWMAPEVIAQqGGYGLAADIWSLGCTVLEMATGKPPWS-------QLEGVAAVFKIGRSKelppiPDHLSDEAKDFILKC 238


                ....*...
gi 94968787 235 LAKNPADR 242
cd06632     239 LQRDPSLR 246

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

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

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

false

true

false

287

3e-19

91.51

84.32

11,4,20,36,42,56,33,77,89,14,91,104,17,108,122,39,147,167,7,154,175,45,201,220,3,210,223,3,213,227,10,223,243,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEfpESNPLQFFLDARAVKRLTHPGIVELYDVGISNEkqMLYLVRE 84
cd06614      21 YDNLEKIGEGASGEVYTATDRATGKEVAIKKMRLRK--QPKKELIINEILIMKECKHPNIVNYYDSYLVGD--ELWVVME 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTL-ETILQSGSLSPETALQT-AKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------SGSRLSR-S 155
cd06614      97 YMDGGSLtDIITQTFVRMNESQIAYvCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFgfaaqlTKEKSKRnS 176

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 156 FHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRgaSPVdwsahrRAL-SIANNGPLHI------SPEVD 228
cd06614     177 MVGTPYWMAPEVIKRKDYGPKVDIWSLGIMAIEMAEGEPPYLNE--PPL------RALfLITTKGIPPLknpekwSPEFK 248

                       250
                ....*....|....
gi 94968787 229 QLLAKALAKNPADR 242
cd06614     249 DFLNKCLVKDPEKR 262

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

3e-19

91.17

73.37

6,10,2,46,56,50,20,78,70,26,104,97,43,147,147,71,222,218,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV--KRLTHPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05575       3 IGKGSFGKVLLAKHKEDGKFYAVKVLQKKAILKKNEQKHIMAERNVllKNVKHPFLVGLHYSFQTKEK--LYFVLDYVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQSGSLSPET-ALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFHGDN 160
cd05575      81 GELFFHLQRERSFPEPrARFYAAEIASALGYLHSLNIIYRDLKPENILLDSKGHVVLTDFglckegiAGSKTTSTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNgplhISPEVDQLLAKALAKNPA 240
cd05575     161 EYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILNKPLRLRPN----ISVSARHLLEGLLQKDRT 236


                ...
gi 94968787 241 DRF 243
cd05575     237 KRL 239

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

3e-19

91.11

54.15

2,99,91,46,145,143,98

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 100 LSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLA------EFSGSRLSRSFHGDNAFFAPEQLNGGVA 173
cd05577      92 FDEARARFYAAEIICGLEHLHRRRIVYRDLKPENILLDDHGHIRISdlglavEFPEGKKIHGRVGTVGYMAPEVLQNEVY 171

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 174 DAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNGPLHISPEVDQLLAKALAKNPADRF 243
cd05577     172 DFSPDWFALGCLLYEMIAGHSPFRQRKEKVKKEEVDRRTLTDEVEYPDKFSEEAKSICEGLLQKDPEKRL 241

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

8e-19

89.73

86.52

13,4,44,57,61,102,9,72,111,75,148,186,10,158,200,3,161,208,14,175,226,25,200,253,19,221,272,12,233,291,8,243,299,8,251,315,12,263,338,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTH-PGIVELYDVgiSNEKQMLYLVR 83
cd05622      45 YEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANsPWVVQLFYA--FQDDRYLYMVM 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFsGSRLSRSFHG----D 159
cd05622     123 EYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADF-GTCMKMNKEGmvrcD 201

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NA-----FFAPEQLNGGVADA----QTDLFSLGALLYTMLTGHVPFHGRG--ASPVDWSAHRRALSIANNGplHISPEVD 228
cd05622     202 TAvgtpdYISPEVLKSQGGDGyygrECDWWSVGVFLYEMLVGDTPFYADSlvGTYSKIMNHKNSLTFPDDN--DISKEAK 279

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 229 QLLAK-------ALAKNPADrfQVARQMAY--------AIQKVLEPAVPE-----------PVLEDIAPESLVAIPEQRP 282
cd05622     280 NLICAfltdrevRLGRNGVE--EIKRHLFFkndqwaweTLRDTVAPVVPDlssdidtsnfdDIEEDKGEEETFPIPKAFV 357


                ....*...
gi 94968787 283 TPEVPAVG 290
cd05622     358 GNQLPFVG 365

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

1e-18

89.41

89.55

8,2,0,44,47,44,48,95,97,52,147,151,2,149,156,55,207,211,13,220,227,8,228,243,14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   3 GRYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPlQFFLDARAVKRLTHPGIVELYDVGISNEKQMLYLV 82
cd06621       1 EKIVELSRLGEGAGGSVTKCRLKNTGMIFALKTITTDPNPDLQK-QILRELEINKSCKSPYIVKYYGAFLDESSSSIGIA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLETIL-----QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF--SG---SRL 152
cd06621      80 MEYCEGGSLDSIYkkvkkRGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFgvSGelvNSL 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 153 SRSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwsAHRRALSIANNGP---LHISPEVD- 228
cd06621     160 AGTFTGTSFYMAPERIQGKPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPPL---GPIELLSYIVNMPnpeLKDEPGNGi 236

                       250       260
                ....*....|....*....|.
gi 94968787 229 -------QLLAKALAKNPADR 242
cd06621     237 kwseefkDFIKQCLEKDPTRR 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88486

cd05585

STKc_YPK1_like

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

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

false

true

false

312

1e-18

89.32

75.64

6,10,0,46,56,47,20,78,67,18,96,86,56,152,149,52,208,201,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVELYDVGISNEKqmLYLVREYVAGV 89
cd05585       1 IGKGSFGKVMQVRKKDTQRIYALKTIRKAHIVSRSEVTHTLAERTVlAQVNCPFIVPLKFSFQSPEK--LYFVLAFINGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL-------SRSFHGDNA 161
cd05585      79 ELFHHLQkEGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYQGHIALCDFGLCKLnmkdddrTNTFCGTPE 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 FFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwsaHRRALSIANNGPLHISPEVDQLLAKALAKNPAD 241
cd05585     159 YLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEM----YRKILQEPLRFPDGFDRDAKDLLTGLLNRDPTQ 234


                ..
gi 94968787 242 RF 243
cd05585     235 RL 236

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

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

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

false

true

false

265

2e-18

88.91

92.45

9,5,3,41,47,44,29,78,73,23,101,97,5,106,103,16,122,120,29,151,154,50,204,204,17,221,227,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPlQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVREY 85
cd06605       4 ETLGELGAGNSGVVSKVRHRPTGKIMAVKTIRLEINEAIQK-QILRELDILHKCNSPYIVGFYGAFYNNGD--ISICMEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQSGSLS-PETAL-QTAKELAEALDHAHRQ-GFIHGNVQPYNILITEEGHAKLAEFSGSR-----LSRSFH 157
cd06605      81 MDGGSLDKILKEVQGRiPERILgKIAVAVLKGLTYLHEKhKIIHRDVKPSNILVNSRGEIKLCDFGVSGqlvnsLAKTFV 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 158 GDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGAspvDWSAHRRALSIANNGPL------HISPEVDQLL 231
cd06605     161 GTSSYMAPERIQGNDYGVKSDVWSLGLSLIELATGRFPYPPEND---PPDGIFELLQYIVNEPPprlpsgRFSPDFQDFV 237

                       250
                ....*....|.
gi 94968787 232 AKALAKNPADR 242
cd06605     238 NLCLIKDPRER 248

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-18

87.76

94.74

14,4,2,40,44,43,5,51,48,17,71,65,2,73,68,25,98,96,11,109,108,41,150,158,4,154,163,12,166,178,4,172,182,32,210,214,10,220,225,3,223,235,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPES-NPLQFflDARAVKRLTHPGIVELYdvgIS-NEKQMLYLV 82
cd06610       3 YKLIEVIGSGATAVVQRAICLPNGEKVAIKRIDLEKCQTSmDELRK--EIQAMSLCHHPNVVKYY---TSfVVGDELWVV 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLETILQSG---SLSPETALQTA-KELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-------- 150
cd06610      78 MPLMSGGSCLDIMKYSypqGGLDEAIIATIlKEVLKGLEYLHKNGQIHRDIKAGNILLDSDGSVKLADFGVSasladggd 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 151 -RLSR-SFHGDNAFFAPE---QLNGgvADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwsahrRALSIANNGP-LHI- 223
cd06610     158 rTKVRkTFVGTPCWMAPEvmeQVHG--YDFKADIWSFGITAIELATGAAPYSKYPPMKV------LMLTLQNDPPsLETe 229

                       250       260
                ....*....|....*....|....*
gi 94968787 224 ------SPEVDQLLAKALAKNPADR 242
cd06610     230 adykkySKSFRKMISKCLQKDPAKR 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

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

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

false

true

false

370

5e-18

87.30

55.14

8,4,44,57,61,102,7,69,109,8,78,117,72,150,190,5,155,197,6,161,208,15,176,227,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTH-PGIVELYdVGISNEKQmLYLVR 83
cd05596      45 FDVIKVIGRGAFGEVQLVRHKSSKQVYAMKLLSKFEMIKRSDSAFFWEERDIMAHANsEWIVQLH-YAFQDDKY-LYMVM 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-RLSRS--FHGDN 160
cd05596     123 EYMPGGDLVNLMSNYDIPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCmKMDANgmVRCDT 202

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 94968787 161 A-----FFAPEQLNGGVADAQ----TDLFSLGALLYTMLTGHVPFH 197
cd05596     203 AvgtpdYISPEVLKSQGGDGYygreCDWWSVGVFLYEMLVGDTPFY 248

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-18

86.90

63.33

8,4,2,52,56,55,11,67,67,3,73,70,22,95,94,52,147,147,10,157,164,11,168,181,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV-KRLTHPGIVEL-YDVgisNEKQMLYLV 82
cd05601       3 FEVKSVIGRGHFGEVQVVREKATGDIYAMKVMKKSVLLAQETVSFFEEERDImAIANSPWIPQLqYAF---QDKDNLYLV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLETIL--QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-SGSRLSRSFH-- 157
cd05601      80 MEYHPGGDLLSLLnrYEDQFDESMAQFYLAELVLAIHSLHQMGYVHRDIKPENILIDRTGHIKLADFgSAAKLNANKMvn 159

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 94968787 158 -----GDNAFFAPEQL------NGGVADAQTDLFSLGALLYTMLTGHVPFHG 198
cd05601     160 sklpvGTPDYIAPEVLtslngdSKSTYGVECDWWSLGVIAYEMIYGRSPFSE 211

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

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

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

false

true

false

288

1e-17

86.14

88.19

9,4,1,16,20,22,5,27,27,9,36,37,25,61,64,15,78,79,17,95,97,57,152,162,21,173,185,70

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVY-----QGHDSenDRVVAIKAI-PIAEFPESNPLQFFLDARAVKRLTH--PGIVELYDVGISNEK 76
cd05583       2 FELLRVLGTGAYGKVFlvrkvGGHDA--GKLYAMKVLkKATIVQKAKTAEHTRTERQVLEAVRrcPFLVTLHYAFQTDTK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  77 qmLYLVREYVAGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL--- 152
cd05583      80 --LHLILDYVNGGELFTHLyQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFGLSKEfla 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 153 -----SRSFHGDNAFFAPEQLNGGVA--DAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNGPLHISP 225
cd05583     158 eeeerAYSFCGTIEYMAPEVIRGGSGghDKAVDWWSLGVLTFELLTGASPFTVDGEQNSQSEISRRILKSKPPFPKTMSA 237

                       250
                ....*....|....*...
gi 94968787 226 EVDQLLAKALAKNPADRF 243
cd05583     238 EARDFIQKLLEKDPKKRL 255

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

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

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

false

true

false

256

1e-17

85.78

93.75

9,4,4,34,40,38,8,50,46,25,77,71,20,107,91,8,115,111,35,150,153,47,204,200,14,218,220,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIaeFPESNPLQffLDARAVKRLTHPGIVELYDVGISNEkqMLYLVRE 84
cd06612       5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPV--EEDLQEII--KEISILKQCDSPYIVKYYGSYFKNT--DLWIVME 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETILQSgslspetalqTAKELAEA------------LDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-- 150
cd06612      79 YCGAGSVSDIMKI----------TNKTLTEEeiaailyqtlkgLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSgq 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 151 -----RLSRSFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHgrgaspvDWSAHRRALSIANN------G 219
cd06612     149 ltdtmAKRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYS-------DIHPMRAIFMIPNKppptlsD 221

                       250       260
                ....*....|....*....|...
gi 94968787 220 PLHISPEVDQLLAKALAKNPADR 242
cd06612     222 PEKWSPEFNDFVKKCLVKDPEER 244

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133190

cd05059

PTKc_Tec_like

Catalytic Domain of Tec-like Protein Tyrosine Kinases

false

true

false

256

1e-17

85.57

92.58

10,7,8,16,24,24,21,48,45,20,70,65,27,97,94,51,151,145,9,160,160,3,163,168,28,191,197,19,213,216,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHdSENDRVVAIKAIPIAEFPESNplqFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREYVA 87
cd05059       9 LKELGSGQFGVVRLGK-WRGKIDVAIKMIREGAMSEDD---FIEEAKVMMKLSHPNLVQLY--GVCTKQRPIFIVTEYMA 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQS--GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSgsrLSRSFHGDN----- 160
cd05059      83 NGCLLNFLRQrrGKFGTEWLLDMCSDVCEAMEYLESNSFIHRDLAARNCLVGEDNVVKVSDFG---LARYVLDDQytssq 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 -AFF-----APEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRGASPVDWSAHRralSIANNGPLHISPEVDQLLAK 233
cd05059     160 gTKFpvkwaPPEVFNYSRFSSKSDVWSFGVLMWEVFSeGKMPYERFTNSEVVESVHR---GYRLYRPKLASTEVYTIMCD 236


                ....*....
gi 94968787 234 ALAKNPADR 242
cd05059     237 CWQEKPEDR 245

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132944

cd06613

STKc_MAP4K3_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK).

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

false

true

false

261

2e-17

85.42

94.64

13,3,3,45,50,48,26,78,74,19,99,93,10,109,106,41,150,148,12,162,166,4,166,174,6,173,180,23,205,203,4,209,208,4,213,215,10,223,231,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQffLDARAVKRLTHPGIVELYDVGISNEKqmLYLVR 83
cd06613       4 DYELLQRIGSGTYGDVYKARDIATGELAAVKVIKLEPGDDFEIIQ--QEISMLKECRHPNIVAYFGSYLRRDK--LWIVM 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQSgsLSPETALQTA---KELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-RLSRSFHGD 159
cd06613      80 EYCGGGSLQDIYQV--TGPLSELQIAyvcRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFGVSaQLTATIAKR 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NAF------FAPE----QLNGGVaDAQTDLFSLGALLYTMLTGHVPFhgrgaspvdWSAH-RRAL---SIANNGPLHI-- 223
cd06613     158 KSFigtpywMAPEvaavERKGGY-DGKCDIWALGITAIELAELQPPM---------FDLHpMRALfliSKSNFQPPKLkd 227

                       250       260
                ....*....|....*....|...
gi 94968787 224 ----SPEVDQLLAKALAKNPADR 242
cd06613     228 kekwSPVFHDFIKKCLTKDPKKR 250

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88522

cd05621

STKc_ROCK2

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

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

false

true

false

370

2e-17

85.49

55.41

8,4,44,57,61,102,7,69,109,8,78,117,69,147,187,8,155,197,6,161,208,14,175,226,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTH-PGIVELYdVGISNEKQmLYLVR 83
cd05621      45 YDVVKVIGRGAFGEVQLVRHKSSQKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANsPWVVQLF-CAFQDDKY-LYMVM 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-SGSRLSRS--FHGDN 160
cd05621     123 EYMPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFgTCMKMDETgmVRCDT 202

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 94968787 161 A-----FFAPEQLNGGVADA----QTDLFSLGALLYTMLTGHVPFHG 198
cd05621     203 AvgtpdYISPEVLKSQGGDGyygrECDWWSVGVFLFEMLVGDTPFYA 249

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

3e-17

84.82

94.42

10,10,2,20,31,22,14,46,36,21,69,57,27,96,86,52,151,138,9,160,159,31,191,191,7,205,198,14,219,216,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVvAIKAIPIAEFPESNpLQFFLDARAVKRLTHPGIVELydVGISNEKQMLYLVREYVAGVT 90
cd05041       3 IGKGNFGDVYKGVLKGKTEV-AVKTCRSTLPPDLK-RKFLQEAEILKQYDHPNIVKL--IGVCVQKQPIYIVMELVPGGS 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  91 LETILQ--SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSgsrLSRSFHGDN-------- 160
cd05041      79 LLTFLRkkKNRLTVKKLLQMSLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFG---MSREEEGGIytvsdglk 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 ----AFFAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGrgaspvdWSAHRRALSIANNG----PLHISPEVDQLL 231
cd05041     156 qipiKWTAPEALNYGRYTSESDVWSYGILLWETFSlGDTPYPG-------MSNQQTRERIESGYrmpaPQLCPEEIYRLM 228

                       250
                ....*....|.
gi 94968787 232 AKALAKNPADR 242
cd05041     229 LQCWAYDPENR 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133171

cd05039

PTKc_Csk_like

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

false

true

false

256

3e-17

84.76

96.09

14,5,8,17,23,25,4,28,29,9,41,38,11,52,50,15,69,65,28,97,96,65,162,165,29,191,195,13,206,208,3,214,211,4,218,219,24,242,245,1,243,247,7

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGhDSENdRVVAIKAIPiaefPESNPLQFFLD-ARAVKRLTHPGIVELydVGISNEKQMLYLVRE 84
cd05039       9 KLGATIGKGEFGDVMLG-DYRG-QKVAVKCLK----DDSTAAQAFLAeASVMTTLRHPNLVQL--LGVVLQGNPLYIVTE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETILQS---GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLSRSFHGDNA 161
cd05039      81 YMAKGSLVDYLRSrgrAVITLAQQLGFALDVCEGMEYLEEKNFVHRDLAARNVLVSEDLVAKVSDFGLAKEASQGQDSGK 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 F----FAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRGASPVdwSAHrralsIANN----GPLHISPEVDQLLA 232
cd05039     161 LpvkwTAPEALREKKFSTKSDVWSFGILLWEIYSfGRVPYPRIPLKDV--VPH-----VEKGyrmeAPEGCPPEVYKVMK 233

                       250       260
                ....*....|....*....|.
gi 94968787 233 KALAKNPADR--F-QVARQMA 250
cd05039     234 DCWELDPAKRptFkQLREQLA 254

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133243

cd05112

PTKc_Itk

Catalytic Domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase

false

true

false

256

3e-17

84.62

93.75

10,9,10,14,24,24,21,48,45,20,70,65,25,95,92,58,153,155,7,160,165,31,191,197,13,204,212,10,219,222,28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  10 EIGRGELGAVYQGHdSENDRVVAIKAIPIAEFPESNplqFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREYVAGV 89
cd05112      11 EIGSGQFGLVWLGY-WLEKRKVAIKTIREGAMSEED---FIEEAQVMMKLSHPKLVQLY--GVCTERSPICLVFEFMEHG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETIL--QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLS-----RSFHGDN-- 160
cd05112      85 CLSDYLraQRGKFSQETLLGMCLDVCEGMAYLESSNVIHRDLAARNCLVGENQVVKVSDFGMTRFVlddqyTSSTGTKfp 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 -AFFAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRGASPV--DWSAHRRALSianngPLHISPEVDQLLAKALA 236
cd05112     165 vKWSSPEVFSFSKYSSKSDVWSFGVLMWEVFSeGKTPYENRSNSEVveTINAGFRLYK-----PRLASQSVYELMQHCWK 239

                       250
                ....*....|.
gi 94968787 237 KNPADRFQVAR 247
cd05112     240 ERPEDRPSFSL 250

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

4e-17

84.03

82.46

9,9,25,38,49,63,27,78,90,70,148,161,5,153,172,46,201,218,4,207,222,4,214,226,8,222,240,20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  10 EIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLqfFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVREYVAGV 89
cd06648      26 KIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELL--FNEVVIMRDYQHPNIVEMYSSYLVGDE--LWVVMEFLEGG 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS-GSRLS------RSFHGDNAF 162
cd06648     102 ALTDIVTHTRMNEEQIATVCLAVLKALSFLHAQGVIHRDIKSDSILLTSDGRVKLSDFGfCAQVSkevprrKSLVGTPYW 181

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 163 FAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRgaSPVDwsAHRRalsIANNGPLH------ISPEVDQLLAKALA 236
cd06648     182 MAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNE--PPLQ--AMKR---IRDNLPPKlknlhkVSPRLRSFLDRMLV 254


                ....*.
gi 94968787 237 KNPADR 242
cd06648     255 RDPAQR 260

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133215

cd05084

PTKc_Fes

Catalytic Domain of the Protein Tyrosine Kinase, Fes

false

true

false

252

5e-17

83.83

77.78

7,9,1,28,38,29,29,69,58,28,97,88,54,151,147,9,160,160,27,187,188,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  10 EIGRGELGAVYQGHDSENDRVVAIKAIPiAEFPESNPLQFFLDARAVKRLTHPGIVELydVGISNEKQMLYLVREYVAGV 89
cd05084       2 RIGRGNFGEVFSGRLRADNTPVAVKSCR-ETLPPELKAKFLMEARILKQYSHPNIVKL--IGVCTQKQPIYIVMELVQGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQS--GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-----LSRSFHGDN-- 160
cd05084      79 DFLTFLRTegPRLKVKELIRMAENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSReeedgVYSATGGMKqi 158

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 94968787 161 --AFFAPEQLNGGVADAQTDLFSLGALLY-TMLTGHVPF 196
cd05084     159 pvKWTAPEALNYGRYSSESDVWSFGILLWeTFSLGAVPY 197

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

9e-17

83.32

92.02

9,10,9,29,41,38,12,53,55,15,70,70,21,91,92,59,150,152,3,153,164,43,203,207,16,219,228,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAefPESNPLQFFLDA-----RAVKRLTHPGIVELYdvGISNEKQMLYLVREY 85
cd06625      10 LGQGAFGRVYLCYDVDTGRELAVKQVPFD--PDSPETKKEVNAleceiQLLKNLQHERIVQYY--GCLRDDETLSIFMEY 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTL-ETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-RLS---------R 154
cd06625      86 MPGGSVkDQLKAYGALTETVTRKYTRQILEGVEYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASkRLQticssgtgmK 165

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 SFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFhgrgaspVDWSAHRRALSIANNG-----PLHISPEVDQ 229
cd06625     166 SVTGTPYWMSPEVISGEGYGRKADVWSVGCTVVEMLTEKPPW-------AEFEAMAAIFKIATQPtnpqlPSHVSPDARN 238

                       250
                ....*....|...
gi 94968787 230 LLAKALAKNPADR 242
cd06625     239 FLRRTFVENAKKR 251

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132942

cd06611

STKc_SLK_like

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

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

false

true

false

280

1e-16

82.87

88.21

10,4,6,30,37,36,11,48,48,28,78,76,16,94,95,14,109,109,46,155,162,14,169,181,28,204,209,14,218,229,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKaipIAEFPESNPLQ-FFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVR 83
cd06611       7 WEIIGELGDGAFGKVYKAQHKETGLFAAAK---IIQIESEEELEdFMVEIDILSECKHPNIVGLYEAYFYENK--LWILI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETI---LQSGSLSPETALQTaKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLSRS----- 155
cd06611      82 EFCDGGALDSImleLERGLTEPQIRYVC-RQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKStlqkr 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 156 --FHGDNAFFAPEQLN-----GGVADAQTDLFSLGALLYTMLTGHVPFHgrgaspvDWSAHRRALSIANN------GPLH 222
cd06611     161 dtFIGTPYWMAPEVVAcetfkDNPYDYKADIWSLGITLIELAQMEPPHH-------ELNPMRVLLKILKSepptldQPSK 233

                       250       260
                ....*....|....*....|
gi 94968787 223 ISPEVDQLLAKALAKNPADR 242
cd06611     234 WSSSFNDFLKSCLVKDPDDR 253

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133245

cd05114

PTKc_Tec_Rlk

Catalytic Domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase

Catalytic Domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in...

false

true

false

256

1e-16

82.97

75.78

10,7,8,23,31,31,14,48,45,20,70,65,17,87,83,10,97,94,51,151,145,9,160,160,3,163,168,28,191,197,5

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHDSENDRVvAIKAIPIAEFPESNplqFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREYVA 87
cd05114       9 MKELGSGQFGVVHLGKWRAQIKV-AIKAINEGAMSEED---FIEEAKVMMKLSHPKLVQLY--GVCTQQKPLYIVTEFME 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 -GVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSgsrLSRSFHGDN----- 160
cd05114      83 nGCLLNYLRQRqGKLSKDMLLSMCQDVCEGMEYLERNSFIHRDLAARNCLVSSTGVVKVSDFG---MTRYVLDDEytsss 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 94968787 161 -AFF-----APEQLNGGVADAQTDLFSLGALLYTMLT-GHVPF 196
cd05114     160 gAKFpvkwsPPEVFNFSKYSSKSDVWSFGVLMWEVFTeGKMPF 202

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133198

cd05067

PTKc_Lck_Blk

Catalytic Domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk

false

true

false

260

1e-16

82.57

75.00

8,9,12,14,24,26,17,44,43,26,73,69,26,99,98,53,152,154,11,163,170,28,191,199,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  10 EIGRGELGAVYQGHdSENDRVVAIKAIPIAEFpesNPLQFFLDARAVKRLTHPGIVELYDVgisNEKQMLYLVREYVAGV 89
cd05067      13 KLGAGQFGEVWMGY-YNNHTKVAIKSLKEGTM---SPEAFLAEANLMKQLQHERLVRLYAV---VTQEPIYIVTEYMENG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  90 TLETILQSGS---LSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL---SRSFHGDNAFF 163
cd05067      86 SLVDFLKTPEgikLTINKLIDMAAQIAEGMAYIERKNYIHRDLRAANILVSETLCCKIADFGLARIiedNEYTAREGAKF 165

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 94968787 164 -----APEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGR 199
cd05067     166 pikwtAPEAINYGTFTIKSDVWSFGILLTEIVTyGRIPYPGM 207

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88511

cd05610

STKc_MASTL

STKc_MASTL: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST-like (MASTL) 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. 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. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. The human MASTL gene has also been labelled FLJ14813. A missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. To date, the function of MASTL is unknown.

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

false

true

false

669

3e-16

81.26

22.72

5,1,2,44,45,49,13,60,62,16,78,78,18,96,97,57

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   2 IGRYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESN---PLQFFLDARAVKRltHPGIVELYDVGISNEKqm 78
cd05610       3 IEEFVIVKPISRGAFGKVYLGRKKNNSKLYAVKVVKKADMINKNmvhQVQAERDALALSK--SPFIVHLYYSLQSANN-- 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94968787  79 LYLVREYVAGVTLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLS 153
cd05610      79 VYLVMEYLIGGDVKSLLHiYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVT 154

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132972

cd06641

STKc_MST3

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

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

false

true

false

277

6e-16

80.51

69.31

5,7,8,33,41,41,35,78,76,69,147,151,8,155,160,40

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEfPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVREYVA 87
cd06641       9 LEKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEE-AEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTK--LWIIMEYLG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------SGSRLSRS-FHGDN 160
cd06641      86 GGSALDLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFgvagqlTDTQIKRNtFVGTP 165

                       170       180       190
                ....*....|....*....|....*....|....*
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVP 195
cd06641     166 FWMAPEVIKQSAYDSKADIWSLGITAIELAKGEPP 200

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

6e-16

80.42

73.83

7,10,2,50,60,54,16,78,70,14,92,85,55,147,147,57,204,205,10,219,215,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT--HPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05591       3 LGKGSFGKVMLAELKGTDEVYAIKVLKKDVILQDDDVDCTMTEKRILALAakHPFLTALHCCFQTKDR--LFFVMEYVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLE-TILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFHGDN 160
cd05591      81 GDLMfQIQRSRKFDEPRSRFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFgmckegiLNGVTTTTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPV-DWSAHRRALSianngPLHISPEVDQLLAKALAKNP 239
cd05591     161 DYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLfESILHDDVLY-----PVWLSKEAVSILKAFMTKNP 235


                ....
gi 94968787 240 ADRF 243
cd05591     236 NKRL 239

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

7e-16

80.07

79.52

9,4,1,16,20,22,5,27,27,14,41,42,20,61,64,15,78,79,17,95,97,56,151,161,25,176,187,78

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVY-----QGHDSenDRVVAIKAIPIAEF-PESNPLQFFLDARAVKRLTH--PGIVELYDVGISNEK 76
cd05614       2 FELLKVLGTGAYGKVFlvrkvTGHDT--GKLYAMKVLQKAALvQKAKTVEHTRTERNVLEHVRqsPFLVTLHYAFQTEAK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  77 qmLYLVREYVAGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR---- 151
cd05614      80 --LHLILDYVSGGEMFTHLyQRDNFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKefls 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 152 ----LSRSFHGDNAFFAPEQLNGGVADAQ-TDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNGPLHISPE 226
cd05614     158 eekeRTYSFCGTIEYMAPEIIRGKGGHGKaVDWWSLGILIFELLTGASPFTLEGERNTQSEVSRRILKCDPPFPSFIGPE 237

                       250       260
                ....*....|....*....|....*...
gi 94968787 227 VDQLLAKALAKNPADRFQVARQMAYAIQ 254
cd05614     238 AQDLLHKLLRKDPKKRLGAGPQGASEIK 265

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

1e-15

79.58

75.00

6,4,1,57,61,60,15,78,75,14,92,90,56,148,153,67,219,220,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTH--PGIVELYDVGISNEKqmLYLV 82
cd05587       2 FNFLMVLGKGSFGKVMLAERKGTDELYAIKILKKDVIIQDDDVECTMVEKRVLALPGkpPFLTQLHSCFQTMDR--LYFV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVTLE-TILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS-------GSRLSR 154
cd05587      80 MEYVNGGDLMyHIQQVGKFKEPHAVFYAAEIAIGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGmckenifGGKTTR 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 SFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIanngPLHISPEVDQLLAKA 234
cd05587     160 TFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSY----PKSLSKEAVSICKGL 235


                ....*....
gi 94968787 235 LAKNPADRF 243
cd05587     236 LTKHPAKRL 244

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

1e-15

79.27

75.63

7,10,2,50,60,54,8,70,62,27,97,90,51,148,148,56,211,204,11,222,218,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT--HPGIVELYdvGISNEKQMLYLVREYVAG 88
cd05619       3 LGKGSFGKVFLAELKGTNQFFAIKALKKDVVLMDDDVECTMVEKRVLSLAweHPFLTHLY--CTFQTKENLFFVMEYLNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFS-------GSRLSRSFHGDN 160
cd05619      81 GDLMFHIQScHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDTDGHIKIADFGmckenmlGDAKTCTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwsahrrALSIANNGPLH---ISPEVDQLLAKALAK 237
cd05619     161 DYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGHDEEEL-------FQSIRMDNPCYprwLTREAKDILVKLFVR 233


                ....*...
gi 94968787 238 NPADRFQV 245
cd05619     234 EPERRLGV 241

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133203

cd05072

PTKc_Lyn

Catalytic Domain of the Protein Tyrosine Kinase, Lyn

false

true

false

261

1e-15

79.31

80.84

9,5,8,18,24,26,13,41,39,11,52,51,24,78,75,19,97,97,57,158,154,4,162,170,29,191,200,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGHdSENDRVVAIKAIPiaefPESNPLQFFLD-ARAVKRLTHPGIVELYDVGISNEKqmLYLVRE 84
cd05072       9 KMVKKLGAGQFGEVWMGF-YNNSTKVAVKTLK----PGTMSVQAFLEeANLMKTLQHDKLVRLYAVVTKEEP--IYIITE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETILQS---GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLSRsfhgDNA 161
cd05072      82 YMAKGSLLDFLKSdegSKVQLPKLIDFSAQIAEGMAYIEKKNYIHRDLRAANVLVSESLMCKIADFGLARVIE----DNE 157

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94968787 162 F------------FAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRGASPVDWSAHR 210
cd05072     158 YtaregakfpikwTAPEAINYGSFTIKSDVWSFGVLLYEIITyGKIPYPGMSNSDVMSALQR 219

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132971

cd06640

STKc_MST4

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

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

false

true

false

277

2e-15

78.94

69.31

5,7,8,33,41,41,35,78,76,69,147,151,7,154,159,41

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEfPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVREYVA 87
cd06640       9 LERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEE-AEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTK--LWIIMEYLG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------SGSRLSR-SFHGDN 160
cd06640      86 GGSALDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFgvagqlTDTQIKRnTFVGTP 165

                       170       180       190
                ....*....|....*....|....*....|....*
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVP 195
cd06640     166 FWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPP 200

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88489

cd05588

STKc_aPKC

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

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

false

true

false

329

2e-15

78.87

77.51

7,10,2,46,56,50,20,78,70,26,104,97,47,151,151,53,204,205,19,223,228,29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV--KRLTHPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05588       3 IGRGSYAKVLLVELKKTRRIYAMKVIKKELVNDDEDIDWVQTEKHVfeTASNHPFLVGLHSCFQTESR--LFFVIEFVSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQSGSLSPET-ALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-------LSRSFHGDN 160
cd05588      81 GDLMFHMQRQRKLPEEhARFYSAEISLALNFLHERGIIYRDLKLDNVLLDAEGHIKLTDYGMCKegirpgdTTSTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPV-DWSAHRRALSIANNGPLHI----SPEVDQLLAKAL 235
cd05588     161 NYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGMSDNpDQNTEDYLFQVILEKQIRIprslSVKASSVLKGFL 240

                       250
                ....*....|....*..
gi 94968787 236 AKNPADRFQVARQMAYA 252
cd05588     241 NKDPKERLGCHPQTGFR 257

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132973

cd06642

STKc_STK25_YSK1

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

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

false

true

false

277

2e-15

78.16

69.68

5,7,8,33,41,41,35,78,76,69,147,151,7,154,159,42

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   8 LAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEfPESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVREYVA 87
cd06642       9 LERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEE-AEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTK--LWIIMEYLG 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------SGSRLSR-SFHGDN 160
cd06642      86 GGSALDLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFgvagqlTDTQIKRnTFVGTP 165

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPF 196
cd06642     166 FWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPN 201

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

2e-15

78.43

85.25

8,4,2,43,47,46,21,70,67,27,97,95,55,152,167,24,176,196,23,201,219,15,216,235,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPL-QFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVR 83
cd05609       3 FETIKLISNGAYGAVYLVRHKETRQRFAMKKINKQNLILRNQIqQVFVERDILTFAENPFVVSMF--CSFETRRHLCMVM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  84 EYVAGVTLETILQS-GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL---------- 152
cd05609      81 EYVEGGDCATLLKNiGPLPVDMARMYFAETVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIglmslttnly 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 153 -------SRSFHGDNAFFAPEQLNGGVADAQ-----TDLFSLGALLYTMLTGHVPFHGRgaSPVDWSAHRRALSIA-NNG 219
cd05609     161 eghiekdTREFLDKQVCGTPEYIAPEVILRQgygkpVDWWAMGIILYEFLVGCVPFFGD--TPEELFGQVISDDIEwPEG 238

                       250       260
                ....*....|....*....|....
gi 94968787 220 PLHISPEVDQLLAKALAKNPADRF 243
cd05609     239 DEALPADAQDLISRLLRQNPLERL 262

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

3e-15

78.14

74.06

7,10,2,49,59,53,17,78,70,14,92,85,59,151,151,53,211,204,8,219,215,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRL--THPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05590       3 LGKGSFGKVMLARLKESGRLYAVKVLKKDVILQDDDVECTMTEKRILSLarNHPFLTQLYCCFQTPDR--LFFVMEFVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLE-TILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-------LSRSFHGDN 160
cd05590      81 GDLMfHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKegifngkTTSTFCGTP 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVdwsahrrALSIANNG---PLHISPEVDQLLAKALAK 237
cd05590     161 DYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDL-------FEAILNDEvvyPTWLSQDAVDILKAFMTK 233


                ....*.
gi 94968787 238 NPADRF 243
cd05590     234 NPTMRL 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88534

cd05633

STKc_GRK3

STKc_GRK3: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK3 isoform, 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. There are seven types of GRKs, named GRK1 to GRK7. GRK3 (also known as beta-adrenergic receptor kinase 2) is widely expressed in many tissues. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 is involved in modulating the cholinergic response of airway smooth muscles. It also plays a role in dopamine receptor regulation. GRK3 promoter polymorphisms may be associated with bipolar disorder.

STKc_GRK3: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK)...

false

true

false

279

3e-15

78.14

86.38

6,10,1,53,63,57,82,145,145,11,157,156,16,173,173,24,198,197,45

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTHPG---IVELYDVGISNEKQMLYLVREYVA 87
cd05633       2 IGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGdcpFIVCMTYAFHTPDKLCFILDLMNG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  88 GVTLETILQSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLA------EFSGSRLSRSFhGDNA 161
cd05633      82 GDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISdlglacDFSKKKPHASV-GTHG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 162 FFAPEQLNGGVA-DAQTDLFSLGALLYTMLTGHVPFHgRGASPVDWSAHRRALSIANNGPLHISPEVDQLLAKALAKNPA 240
cd05633     161 YMAPEVLQKGTAyDSSADWFSLGCMLFKLLRGHSPFR-QHKTKDKHEIDRMTLTVNVELPDSFSPELKSLLEGLLQRDVS 239


                ...
gi 94968787 241 DRF 243
cd05633     240 KRL 242

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

5e-15

77.19

91.39

9,8,5,41,49,48,6,55,59,26,83,85,25,108,111,39,147,162,7,154,170,42,203,212,16,219,232,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   9 AEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQF--FLDARA-----VKRLTHPGIVELYDVGISNEKQMLYL 81
cd06628       6 ALIGSGSFGSVYLGMNAHSGELMAVKQVEIPSNSIGVQDRKrkMLDALQreinlLKELHHENIVQYLGSSQDAGHLNIFL 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  82 vrEYVAGVTLETILQSGSLSPETALQT-AKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------------S 148
cd06628      86 --EYVPGGSVAALLNNYGAFEESLVRNfVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFgiskkleanslsT 163

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 149 GSRLSR-SFHGDNAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFhgrgaspVDWSAHRRALSIANNG----PLHI 223
cd06628     164 KTNGARpSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMFTGKHPF-------PDCTQMQAIFKIGTNAspeiPSNA 236

                       250
                ....*....|...
gi 94968787 224 SPEVDQLLAKALA 236
cd06628     237 SSEAKNFLRKTFE 249

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88507

cd05606

STKc_beta_ARK

STKc_beta_ARK: Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, beta-adrenergic receptor kinase (beta-ARK) group, 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. There are seven types of GRKs, named GRK1 to GRK7. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism.

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

false

true

false

278

6e-15

76.99

86.69

8,10,1,51,61,56,15,78,71,17,95,89,50,145,145,11,157,156,16,173,173,26,200,199,43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLTH----PGIVELYDVGISNEKqmLYLVREYV 86
cd05606       2 IGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVStgdcPFIVCMTYAFHTPDK--LCFILDLM 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  87 AGVTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLA------EFSGSRLSRSFhGD 159
cd05606      80 NGGDLHYHLsQHGVFSEAEMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISdlglacDFSKKKPHASV-GT 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NAFFAPEQLNGGVA-DAQTDLFSLGALLYTMLTGHVPFHGRgASPVDWSAHRRALSIANNGPLHISPEVDQLLAKALAKN 238
cd05606     159 HGYMAPEVLQKGVAyDSSADWFSLGCMLFKLLRGHSPFRQH-KTKDKHEIDRMTLTMNVELPDSFSPELRSLLEGLLQRD 237


                ....*
gi 94968787 239 PADRF 243
cd05606     238 VNKRL 242

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132955

cd06624

STKc_ASK

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

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

false

true

false

268

6e-15

76.77

74.63

9,10,15,38,50,53,17,69,70,28,97,100,5,102,107,34,136,142,14,150,157,4,154,167,19,173,188,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQffLDARAVKRLTHPGIVELydVGISNEKQMLYLVREYVAGVT 90
cd06624      16 LGKGTYGVVYAGRDLSTQVRIAIKEIPERDSRYSQPLH--EEIALHSRLKHKNIVQY--LGSDSENGYFKIFMEQVPGGS 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  91 LETILQS--GSLSP--ETALQTAKELAEALDHAHRQGFIHGNVQPYNILI-TEEGHAKLAEFSGS-RLSR------SFHG 158
cd06624      92 LSALLRSkwGPLKDneSTIIFYTKQILEGLKYLHDNQIVHRDIKGDNVLVnTYSGVLKISDFGTSkRLAGinpcteTFTG 171

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 94968787 159 DNAFFAPEQLNGGVA--DAQTDLFSLGALLYTMLTGHVPFHGRG 200
cd06624     172 TLQYMAPEIIDKGPRgyGAPADIWSLGCTIIEMATGKPPFHELG 215

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88487

cd05586

STKc_Sck1_like

STKc_Sck1_like: Serine/Threonine Kinases (STKs), Fission yeast Suppressor of loss of cAMP-dependent protein kinase (Sck1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Sck1-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 Schizosaccharomyces pombe STK Sck1. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes.

STKc_Sck1_like: Serine/Threonine Kinases (STKs), Fission yeast Suppressor of loss of...

false

true

false

330

9e-15

76.22

60.30

8,10,0,50,60,54,7,67,62,8,78,70,18,96,89,55,151,151,17,168,170,6,175,176,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAVKRLT----HPGIVEL-YDVGISNEkqmLYLVREY 85
cd05586       1 IGKGTFGQVYQVRKKDTRRIYAMKVLSKKEIVAKKEVAHTIGERNILVRTlldeSPFIVGLkFSFQTDSD---LYLVTDY 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-------LSRSFH 157
cd05586      78 MSGGELFWHLQkEGRFSEDRAKFYIAELVLALEHLHKYDIVYRDLKPENILLDATGHIALCDFGLSKanltdnkTTNTFC 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 94968787 158 GDNAFFAPEQL--NGGVADaQTDLFSLGALLYTMLTGHVPFHG 198
cd05586     158 GTTEYLAPEVLldEKGYTK-HVDFWSLGVLVFEMCCGWSPFYA 199

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88472

cd05571

STKc_PKB

STKc_PKB: Serine/Threonine Kinases (STKs), Protein Kinase B (PKB) or Akt subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of PI3K and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis.

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

false

true

false

323

1e-14

76.18

73.07

8,10,2,41,51,44,16,67,61,3,73,64,22,95,87,52,147,146,53,208,199,11,219,214,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFL-DARAVKRLTHPGIVEL-YDVgisNEKQMLYLVREYVAG 88
cd05571       3 LGKGTFGKVILVREKATGKYYAMKILKKEVIIAKDEVAHTLtESRVLQNTRHPFLTALkYSF---QTHDRLCFVMEYANG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETIL-QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFHGDN 160
cd05571      80 GELFFHLsRERVFSEDRARFYGAEIVSALGYLHSCDVVYRDLKLENLMLDKDGHIKITDFglckegiSDGATMKTFCGTP 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGaspvdwsaHRRALSIANNG----PLHISPEVDQLLAKALA 236
cd05571     160 EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQD--------HEKLFELILMEeirfPRTLSPEAKSLLAGLLK 231


                ....*..
gi 94968787 237 KNPADRF 243
cd05571     232 KDPKQRL 238

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88514

cd05613

STKc_MSK1_N

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

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

false

true

false

290

2e-14

75.82

99.66

13,4,1,16,20,22,5,27,27,16,43,44,13,58,57,3,61,64,15,78,79,30,108,110,40,151,150,10,161,171,12,173,185,82,262,267,14,278,281,9

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVY-----QGHDSenDRVVAIKAIPIAEFPE-SNPLQFFLDARAVkrLTH----PGIVELYDVGISN 74
cd05613       2 FELLKVLGTGAYGKVFlvrkvSGHDS--GKLYAMKVLKKATIVQkAKTTEHTRTERQV--LEHirqsPFLVTLHYAFQTD 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  75 EKqmLYLVREYVAGVTLETILQSGSLSPETALQT-AKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSgsrLS 153
cd05613      78 TK--LHLILDYINGGELFTHLSQRERFKEQEVQIySGEIVLALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFG---LS 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 154 RSFHGDNA-----------FFAPEQLNGGVA--DAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNGP 220
cd05613     153 KEFHEDEVeraysfcgtieYMAPDIVRGGDGghDKAVDWWSMGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYP 232

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94968787 221 LHISPEVDQLLAKALAKNPADRFQVARQMAYAIQKvlepavpEPVLEDIAPESLVAipEQRPTPEVP 287
cd05613     233 QEMSALAKDIIQRLLMKDPKKRLGCGPSDADEIKK-------HPFFQKINWDDLAA--KKVPAPFKP 290

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

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

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

false

true

false

275

2e-14

75.39

77.45

11,2,5,38,40,49,12,60,61,12,72,77,16,88,95,2,90,99,14,106,113,3,109,119,42,151,162,3,154,171,12,166,188,30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   3 GRYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAE------FPESNPLQFFLDaravkrltHPGIVELYDVGI---- 72
cd06608       6 GIFELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDIIEdeeeeiEEEYNILRKYSN--------HPNIATFYGAFIkkgp 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  73 SNEKQMLYLVREYVAG--VT--LETILQSGSLSPETalQTA---KELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLA 145
cd06608      78 PGSDDQLWLVMELCGGgsVTdlVKGLRKKGKRLKEE--WIAyilRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLV 155

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94968787 146 EFSGSR-LSR------SFHGDNAFFAPE-----QLNGGVADAQTDLFSLGALLYTMLTGHVPF 196
cd06608     156 DFGVSAqLDStngrrnTSIGTPYWMAPEviacdEQPDASYDYRCDVWSLGITAIELADGKPPL 218

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

3e-14

74.97

62.54

6,4,2,32,36,43,26,72,69,25,97,96,50,147,154,23,170,182,27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAI---------PIAEFPESNPLQFFLDARAVKRLTHPgivelydvgiSNE 75
cd05597       3 FEILKVIGRGAFGEVAVVKMKNTGQVYAMKILnkwemlkraETACFREERDVLVNGDRRWITNLHYA----------FQD 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  76 KQMLYLVREYVAGVTLETILQS--GSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF------ 147
cd05597      73 ENNLYLVMDYYVGGDLLTLLSKfeDRLPEDMARFYLAEMVLAIDSVHQLGYVHRDIKPDNVLLDKNGHIRLADFgsclrl 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 94968787 148 --SGSRLSRSFHGDNAFFAPEQLNG-----GVADAQTDLFSLGALLYTMLTGHVPFH 197
cd05597     153 laDGTVQSNVAVGTPDYISPEILQAmedgkGRYGPECDWWSLGVCMYEMLYGETPFY 209

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132938

cd06607

STKc_TAO

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

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

false

true

false

307

4e-14

74.46

60.59

7,3,15,48,51,64,17,70,81,20,90,103,22,113,125,39,152,167,14,166,184,17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   4 RYEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFL-DARAVKRLTHPGIVELYdvGISNEKQMLYLV 82
cd06607      16 LFTDLREIGHGSFGAVYFARDVRTNEVVAIKKMSYSGKQSNEKWQDIIkEVRFLQQLRHPNTIEYK--GCYLREHTAWLV 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  83 REYVAGVT--LETILQSGSLSPETALQTAKELaEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRL---SRSFH 157
cd06607      94 MEYCLGSAsdILEVHKKPLQEVEIAAICHGAL-QGLAYLHSHERIHRDIKAGNILLTEPGTVKLADFGSASLvspANSFV 172

                       170       180
                ....*....|....*....|....*....
gi 94968787 158 GDNAFFAPE---QLNGGVADAQTDLFSLG 183
cd06607     173 GTPYWMAPEvilAMDEGQYDGKVDVWSLG 201

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

4e-14

74.30

84.59

10,4,13,36,42,49,34,78,83,16,94,102,12,107,114,43,150,162,4,154,168,11,165,184,32,204,216,19,223,241,19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVVAIKAIPIAEfpESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVRE 84
cd06644      14 WEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKS--EEELEDYMVEIEILATCNHPYIVKLLGAFYWDGK--LWIMIE 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETI---LQSGSLSPETALqTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGS-----RLSR-- 154
cd06644      90 FCPGGAVDAImleLDRGLTEPQIQV-ICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSaknvkTLQRrd 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 SFHGDNAFFAP-----EQLNGGVADAQTDLFSLGALLYTMLTGHVPFHgrgaspvDWSAHRRALSIANNGPLHI------ 223
cd06644     169 SFIGTPYWMAPevvmcETMKDTPYDYKADIWSLGITLIEMAQIEPPHH-------ELNPMRVLLKIAKSEPPTLsqpskw 241

                       250
                ....*....|....*....
gi 94968787 224 SPEVDQLLAKALAKNPADR 242
cd06644     242 SMEFRDFLKTALDKHPETR 260

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

7e-14

73.34

87.41

11,5,3,33,39,36,29,70,65,31,101,99,5,106,112,11,123,123,24,147,149,2,149,154,26,175,186,21,201,207,18,219,230,23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGHDSENDRVVAIKAIPIaEFPESNPLQFFLDARAVKRLTHPGIVELYdvGISNEKQMLYLVREY 85
cd06622       4 EVLDELGKGNYGSVYKVLHRPTGVTMAMKEIRL-ELDESKFNQIIMELDILHKAVSPYIVDFY--GAFFIEGAVYMCMEY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  86 VAGVTLETILQSGSLS---PETAL--------QTAKELAEALDhahrqgFIHGNVQPYNILITEEGHAKLAEF--SG--- 149
cd06622      81 MDAGSLDKLYAGGVATegiPEDVLrrityavvKGLKFLKEEHN------IIHRDVKPTNVLVNGNGQVKLCDFgvSGnlv 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 150 SRLSRSFHGDNAFFAPEQLNGGVADA------QTDLFSLGALLYTMLTGHVPFhgrgaSPVDWSAHRRALSIANNG---- 219
cd06622     155 ASLAKTNIGCQSYMAPERIKSGGPNQnptytvQSDVWSLGLSILEMALGRYPY-----PPETYANIFAQLSAIVDGdppt 229

                       250       260
                ....*....|....*....|....
gi 94968787 220 -PLHISPEVDQLLAKALAKNPADR 242
cd06622     230 lPSGYSDDAQDFVAKCLNKIPNRR 253

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

7e-14

73.56

72.92

7,10,2,46,56,50,20,78,70,21,99,93,10,110,103,41,151,151,67,222,218,21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV--KRLTHPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05602       3 IGKGSFGKVLLARHKSDEKFYAVKVLQKKAILKKKEEKHIMSERNVllKNVKHPFLVGLHFSFQTTDK--LYFVLDYING 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQSGS--LSPETALQTAkELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-------LSRSFHGD 159
cd05602      81 GELFYHLQRERcfLEPRARFYAA-EIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKeniepngTTSTFCGT 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NAFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGASPVDWSAHRRALSIANNgplhISPEVDQLLAKALAKNP 239
cd05602     160 PEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKPN----ITNSARHLLEGLLQKDR 235


                ....
gi 94968787 240 ADRF 243
cd05602     236 TKRL 239

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88505

cd05604

STKc_SGK3

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

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

false

true

false

325

9e-14

73.15

60.62

5,10,2,46,56,50,20,78,70,26,104,97,43,147,147,52

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV--KRLTHPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05604       3 IGKGSFGKVLLAKRKLDGKCYAVKVLQKKIVLNRKEQKHIMAERNVllKNVKHPFLVGLHYSFQTTEK--LYFVLDFVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQSGSLSPET-ALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEF-------SGSRLSRSFHGDN 160
cd05604      81 GELFFHLQRERSFPEPrARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHVVLTDFglckegiAQSDTTTTFCGTP 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGR 199
cd05604     161 EYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYGLPPFYCR 199

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

9e-14

73.14

62.31

5,10,2,46,56,50,20,78,70,18,96,89,55,151,151,51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  11 IGRGELGAVYQGHDSENDRVVAIKAIPIAEFPESNPLQFFLDARAV--KRLTHPGIVELYDVGISNEKqmLYLVREYVAG 88
cd05603       3 IGKGSFGKVLLAKRKSDGSFYAVKVLQKKTILKKKEQNHIMAERNVllKNLKHPFLVGLHYSFQTAEK--LYFVLDYVNG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  89 VTLETILQ-SGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSR-------LSRSFHGDN 160
cd05603      81 GELFFHLQrERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCKegvepeeTTSTFCGTP 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 94968787 161 AFFAPEQLNGGVADAQTDLFSLGALLYTMLTGHVPFHGRGAS 202
cd05603     161 EYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVS 202

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133248

cd05148

PTKc_Srm_Brk

Catalytic Domain of the Protein Tyrosine Kinases, Srm and Brk

false

true

false

261

1e-13

72.85

92.34

10,4,7,26,31,33,9,42,42,34,78,76,20,98,99,57,155,158,6,161,169,30,191,200,8,206,208,12,218,224,24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   5 YEILAEIGRGELGAVYQGHDSENDRVvAIKAIPIAEfpESNPLQFFLDARAVKRLTHPGIVELYDVGISNEKqmLYLVRE 84
cd05148       8 FTLERKLGSGYFGEVWEGLWKNRVRV-AIKILKSDD--LLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEP--VYIITE 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  85 YVAGVTLETILQSG---SLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLSRS--FHGD 159
cd05148      83 LMEKGSLLAFLRSPegqVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEdvYLSS 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 160 NA-----FFAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRgaspvdwSAHRRALSIANN----GPLHISPEVDQ 229
cd05148     163 DKkipykWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGM-------NNHEVYDQITAGyrmpCPAKCPQEIYK 235

                       250
                ....*....|...
gi 94968787 230 LLAKALAKNPADR 242
cd05148     236 IMLECWAAEPEDR 248

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133183

cd05052

PTKc_Abl

Catalytic Domain of the Protein Tyrosine Kinase, Abelson kinase

false

true

false

263

1e-13

72.55

93.92

10,1,2,8,9,12,28,41,40,15,56,56,11,69,67,29,98,99,56,154,159,8,162,171,29,191,201,13,207,214,35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   2 IGRYEILA--EIGRGELGAVYQGHDSENDRVVAIKAIPiaefPESNPLQFFLDARAV-KRLTHPGIVELydVGISNEKQM 78
cd05052       3 MERTDITMkhKLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVmKEIKHPNLVQL--LGVCTREPP 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  79 LYLVREYVAGVTLETILQSG---SLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGHAKLAEFSGSRLSR- 154
cd05052      77 FYIITEFMTYGNLLDYLRECnrqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTg 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787 155 ---SFHGDNAF----FAPEQLNGGVADAQTDLFSLGALLYTMLT-GHVPFHGRGASPVdwsAHRRALSIANNGPLHISPE 226
cd05052     157 dtyTAHAGAKFpikwTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV---YELLEKGYRMERPEGCPPK 233

                       250
                ....*....|....*.
gi 94968787 227 VDQLLAKALAKNPADR 242
cd05052     234 VYELMRACWQWNPSDR 249

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133168

cd05036

PTKc_ALK_LTK

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

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

false

true

false

277

1e-13

72.86

78.34

11,5,8,20,25,30,5,30,38,15,46,53,21,69,74,26,95,108,46,141,157,10,151,168,6,157,177,4,161,186,30,191,217,8

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787   6 EILAEIGRGELGAVYQGHDS--ENDRV---VAIKAIPIAEFPESNpLQFFLDARAVKRLTHPGIVELydVGISNEKQMLY 80
cd05036       9 TLLRALGHGAFGEVYEGLYRgrDGDAVelqVAVKTLPESCSEQDE-SDFLMEALIMSKFNHQNIVRL--IGVSFERLPRF 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94968787  81 LVREYVAGVTLETIL--------QSGSLSPETALQTAKELAEALDHAHRQGFIHGNVQPYNILITEEGH---AKLAEFSG 149
cd05036      86 ILLELMA