1L3R,2F2U,1O6K,2BCJ,1ZRZ,1VZO,1H1W,1MRY,2ACX,2R5T


Conserved Protein Domain Family
STKc_AGC

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cd05123: STKc_AGC (this model, PSSM-Id:173660 is obsolete and has been replaced by 270693)
Click on image for an interactive view with Cn3D
Catalytic domain of AGC family Protein Serine/Threonine Kinases
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.
Statistics
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PSSM-Id: 173660
View PSSM: cd05123
Aligned: 56 rows
Threshold Bit Score: 218.158
Threshold Setting Gi: 94717650
Created: 30-Jun-2006
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 31 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1L3R_E; Mouse PKA binds 20-aa peptide substrate and ADP-Mg-AlF3; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1O6K_A; Human PKB-beta binds GSK3 peptide substrate and AMP-PNP; defined at 4A contacts.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #####   #               # #                                  #               ## 
1L3R_E        49 LGTGSFGRVMLVKHke---sgNHYAMKILDKqkvvklkqiehtLNEKRILQAVn---FPFLVKLEFSFKDnsNLYMVMEY 122
2BCJ_A       197 IGRGGFGEVYGCRKad---tgKMYAMKCLDKkrikmkqgetlaLNERIMLSLVstgdCPFIVCMSYAFHTpdKLSFILDL 273
1H1W_A        18 LGEGSFSTVVLAREla---tsREYAIKILEKrhiikenkvpyvTRERDVMSRLd---HPFFVKLYFTFQDdeKLYFGLSY 91
2ACX_B       192 LGKGGFGEVCACQVra---tgKMYACKKLEKkrikkrkgeamaLNEKQILEKVn---SRFVVSLAYAYETkdALCLVLTL 265
gi 55583952  132 LGRGSFGVVYCASAihd--seRKFAIKMQEKreiiskravlqvKREASIQRLLp--sHPFIARTYSTWQTrtHLYSLLQY 207
gi 62360315   67 LGKGSFAYVVLVRRvg---tnNLYAMKVVNKqglldhnrcrdvFIERNVLSRIn---HPFLLKLYWTFQSehKLFFVMEY 140
gi 14517660  369 VGRGTFGKVMKVIFre---dgKVYAMKVLNKcvihkrrmieyiREEKNIMSSLp--sHPYIVTCHFAFQTdyHLFFVLDY 443
gi 68127519  648 IGRGTFGKVLKVQMra---trKVYAMKIMNKatvyrrcmtsymKEEKAILTSLh--pSPYIVRCHYAFQTeyYLVFLLDY 722
gi 19074666   25 TGFGPFWEEFLVFIevgerigGLYGLRVMKKkkivdygeqnmmHHEYYVRSRIr---HSFLINTICGFQDyeHLFLLSEQ 101
gi 93140693   29 IGKGSFGKVCIVQKnd---tkKMYAMKYMNKqkcvernevrnvFKELQIMQGLe---HPFLVNLWYSFQDeeDMFMVVDL 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #     # #                                      # # ## #         ##  #           
1L3R_E       123 Va--GGEMFSHLRRig--rFXEPHARFYAAQIVLTFEYLHsLDLIYRDLKPENLLIDqqGYIQVTDFGFAKRvkg----- 193
2BCJ_A       274 Mn--GGDLHYHLSQhg--vFSEADMRFYAAEIILGLEHMHnRFVVYRDLKPANILLDehGHVRISDLGLACDfskk---- 345
1H1W_A        92 Ak--NGELLKYIRKig--sFDETCTRFYTAEIVSALEYLHgKGIIHRDLKPENILLNedMHIQITDFGTAKVlspesk-- 165
2ACX_B       266 Mn--GGDLKFHIYHmgqagFPEARAVFYAAEICCGLEDLHrERIVYRDLKPENILLDdhGHIRISDLGLAVHvpeg---- 339
gi 55583952  208 PtgsTGDLFSVWRQrg--sLSEAAIRLIGAELASAIDFLHqNDVIYRDVKLENVVLDqwGHALLIDFGLAKKlkqg---- 281
gi 62360315  141 Ma--GGDLDKYMNSvpnkqLDLPTSKLYGAEILMAILTLHeQSVIYRDLKPENILLTgdGHCVLADFGLSKDfydakmge 218
gi 14517660  444 Lp--GGDMHSRVYPkl--kLTESDVRLYIAELVLALQHLHrHDIAHRDVKLENIVLGedGHLKLTDFGLARMnfsr---- 515
gi 68127519  723 Lp--GGELYDYIYPkl--cLSPGAARIYAAELVLALECLHrQDVVHRDLKPENVVLTadGHICLTDFGLARRafsr---- 794
gi 19074666  102 S---QNYLIKLINSeg--rFSAKVSRFYLAEILLAIQHLHsKGLSYGFLSPSNMMIGddGHIKLKYDFLNRIdcv----- 171
gi 93140693  103 Ll--GGDLRYHLQQnv--hFKEETVKLFICELVMALDYLQnQRIIHRDMKPDNILLDehGHVHITDFNIAAMlpre---- 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                   ######                             #     #  #                        
1L3R_E       194 -------rtwXLCGTPEYLAPEIILSkg---ynKAVDWWALGVLIYEMAAGYPPFFADqp----iQIYEKIvs--gKVRF 257
2BCJ_A       346 -------kphASVGTHGYMAPEVLQKgva--ydSSADWFSLGCMLFKLLRGHSPFRQHktk-dkhEIDRMTlt--mAVEL 413
1H1W_A       166 -----qaranXFVGTAQYVSPELLTEks---acKSSDLWALGCIIYQLVAGLPPFRAGne----yLIFQKIik--lEYDF 231
2ACX_B       340 ------qtikGRVGTVGYMAPEVVKNer---ytFSPDWWALGCLLYEMIAGQSPFQQRkkkikreEVERLVke--vPEEY 408
gi 55583952  282 ------sstgTICGTLQYMSPDVASGgt---ysHYVDWWSLGVLLHILLTGIYPYPNSe------ATHHANlk-fiDYST 345
gi 62360315  219 nasvtdmranSFVGSPFYVAPDVLKQre---ytNAVDFWSFGILLYRMLCGRTPFSGKnm----kEVFDNIly--sDLRF 289
gi 14517660  516 ------qrrrSFVGSPEYLPPETIQGky---qtKAVDWWSAGVMLYEMLSGKTPFYSAyn----cEIYNNVlkaelDLTA 582
gi 68127519  795 ------srrrSFVGSPEYVAPETIQGqv---qtAAVDWWSFGVMLYEMLAGSTPFHARnn----nTVYNNVlh--kELAL 859
gi 19074666  172 --------vgDPERNVEYASIDYKERge---isPVSDYWSMGIILYYMLVGVTPFAAPdt----aLVVARIkr--gRIEF 234
gi 93140693  175 ------tqitTMAGTKPYMAPEMFSSrkgagysFAVDWWSLGVTAYELLRGRRPYHIRsst-sskEIVHTFet--tVVTY 245
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
Feature 1                                                                            
1L3R_E       258 PShf---------------------------sSDLKDLLRNLLQvdLTKRFGnlkn-gvnDIKNHKWF 297
2BCJ_A       414 PDsf---------------------------sPELRSLLEGLLQrdVNRRLGclgr-gaqEVKESPFF 453
1H1W_A       232 PEkf---------------------------fPKARDLVEKLLVldATKRLGceemegygPLKAHPFF 272
2ACX_B       409 SErf---------------------------sPQARSLCSQLLCkdPAERLGcrgg-sarEVKEHPLF 448
gi 55583952  346 PIgc---------------------------sREFANLMDRMLAvsITHRLCsf-----tVLHAHPFF 381
gi 62360315  290 PStvs-------------------------ipSEAKDLISRLLVkdAAHRIKg------pEVKAHPFW 326
gi 14517660  583 PCf----------------------------tPEAASLIEQLLQshPKARLQda-----gAIKAHPYF 617
gi 68127519  860 PVlraddgagaaaasasqpgvaegaptfrgfsPEAVSLLTGLLArdPSMRLQda-----nVIKRHPFF 922
gi 19074666  235 PEfl---------------------------dENARDLISRLLAvsPRDRLGyaeg-daeTIRRHPFF 274
gi 93140693  246 PSaw---------------------------sQEMVSLLKKLLEpnPDQRFSql-----sDVQNFPYM 281

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