Conserved Protein Domain Family
7tmA_PGE2_EP4

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cd15142: 7tmA_PGE2_EP4 
prostaglandin E2 receptor EP4 subtype, member of the class A family of seven-transmembrane G protein-coupled receptors
Prostaglandin E2 receptor EP4, also called prostanoid EP4 receptor, is one of four receptor subtypes whose endogenous physiological ligand is prostaglandin E2 (PGE2). Each of these subtypes (EP1-EP4) have unique but overlapping tissue distributions that activate different intracellular signaling pathways. Like the EP2 receptor, stimulation of the EP4 receptor by PGE2 causes cAMP accumulation through G(s) protein activation. Knockout studies in mice suggest that EP4 receptor may be involved in the maintenance of bone mass and fracture healing. Prostanoids are the cyclooxygenase (COX) metabolites of arachidonic acid, which include the prostaglandins (PGD2, PGE2, PGF2alpha), prostacyclin (PGI2), and thromboxane A2 (TxA2). These five major bioactive prostanoids acts as mediators or modulators in a wide range of physiological and pathophysiological processes within the kidney and play important roles in inflammation, platelet aggregation, and vasoconstriction/relaxation, among many others. They act locally by preferentially interacting with G protein-coupled receptors designated DP, EP. FP, IP, and TP, respectively. The phylogenetic tree suggests that the prostanoid receptors can be grouped into two major branches: G(s)-coupled (DP1, EP2, EP4, and IP) and G(i)- (EP3) or G(q)-coupled (EP1, FP, and TP), forming three clusters.
Statistics
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PSSM-Id: 320270
View PSSM: cd15142
Aligned: 6 rows
Threshold Bit Score: 416.901
Threshold Setting Gi: 47210150
Created: 15-Dec-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative ligand binding pocket [chemical binding site]
Evidence:
  • Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracelllular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                  #  ##           ######
gi 548476     18 NSPVTIPAVMFIFGVVGNLVAIVVLCKSRKEqkettFYTLVCGLAVTDLLGTLLVSPVTIATYmKGQWPGGqpLCEYSTF 97
gi 118341487   3 PTVPTIPAIMFIFGVISNLIAIVVLCKSRREqkettFYTLVCGLAVTDLLGTVLASPVTIATYvKGAWPDGdpLCQYFGF 82
gi 125630639  26 GKPATIPTVMFIFGVVGNLIAIVVLCKSRKEqkettFYTLVCGLAVTDLLGTCLVSPVTIATYlQNRWPGGpaLCEYSSF 105
gi 523496424  44 FRSLVTSATMFGVGVLGNLVAIVVLCISKKEqkettFYTLVCGMAITDLLGTCFTSPVVIATYiAGRWPGGalLCHFFSF 123
gi 187607854  24 STPPIIPAVMFLLGVVGNLIAIIVLCKSRKEqkettFYTLVCGLALTDLLGTCLISPVTIATYiQGEWPGGhaLCEYGSF 103
gi 47210150    9 AETMALPVFMFAGGAIGNLIAIIVLSVSRQErkssaFYTLVCGLAVTDLLGTCMASPITIANYlDQSVLKDqhVCNFLSF 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ##  #                                             # #####                      
gi 548476     98 ILLFFSLSGLSIICAMSVERYLAINHAyFYSHYV-DKRLAGLTLFAVYASNVLFCALPNMGlgssrlQYPDTWCFIDWtt 176
gi 118341487  83 VLLFFSLAGLSIICAMSIERYIAINHAyFYNDYV-DKRLAGVTLLAIYASNILFCALPSVGfgevkmQYPQTWCFIDWrt 161
gi 125630639 106 ILLFFGLSGLSIICAMSIERYLAINHAyFYNHYV-DKKLAGLTLFAIYASNVLFCALPSMGlskstlQYPDTWCFIDWra 184
gi 523496424 124 SMLFFGSAGMSILCAMSVERYLAINHAyFYSQHV-DRAMARFALMATYLANIVLCIMPSFGfgkhkrHFPGTWCFLDWra 202
gi 187607854 104 ILLFFGLAGLSIICAMSIERYLAINHAyFYNHYV-DKKLAGLTLFAIYVSNVLFCALPSMGlgkttfQYPKTWCFIDWrt 182
gi 47210150   89 LLLFFSLSGLSIICAMAAERYLAICCPyTYKRWGvDRRFAQTFLLFVYISHIFFCCLPVMGmvkselQESKTWCFIDWrt 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #  ### ### ##                                                                
gi 548476    177 nvtAHAAYSYMYAGFSSFLILATVLCNVLVCGALlrmhrqfmrrtslgteqhhaaaaasvasrghpaaspalprlsdfrr 256
gi 118341487 162 nvsAHAAFSYMYAGCSSLLILVTVVCNVLVCGALirmhrrfvrrtslgtdp---------------------qraadpgr 220
gi 125630639 185 ekaTHAAYSYMYAGFSSFLIMVTVICNILVCVALirmhrqfmrrtslgtdtt-------------------ssrlsdfrr 245
gi 523496424 203 mdsVGASYTFLYGGFMLLLIAVTVLCNFAVCRSLvgmskmsrmvraev--------------------------pghags 256
gi 187607854 183 nvsTYAAYSYMYAGFSSFLILATVLCNVLVCVALirmhrqfvrrtslgtd----------------------nrlsdfrr 240
gi 47210150  169 depVAAAYTLLYGLVSLLVILGTILLNLLVCGALllmrqrtvqrpvt----------------------------rasvr 220
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                    #  ## ##  #              ## ###  #  ##              
gi 548476    257 rrsfrriaGAEIQMVILLIATSLVVLICSIPLVVRVFVNqlyqps---lerevSKNPDLQAIRIASVNPILDPWIYILLR 333
gi 118341487 221 srsfsrlaGAEIQMVILLIATSAVVLICSIPLVVQVFLNqlyktp---vekrlDKNPDLLAIRFASTNPILDPWIYILLR 297
gi 125630639 246 rrsfrrmaGAEIQMVILLIATSLVVLICSIPLVVRVFVNqlyrpp---fvkdlRQNPDLQAIRIASVNPILDPWVYILLR 322
gi 523496424 257 rrgfrltsAAEIQMFWLLILMTIVFLICSIPLVVRIFVNqlydpayissgkspDYRSDLLAIRFASFNPILDPWVYILCR 336
gi 187607854 241 rrsfrrmaGAEIQMVIVLIGTSVVVVICSTPLVVRIFINqlyqpa---vvediSKNPDLQAIRMASVNPILDPWIYILLR 317
gi 47210150  221 erwralssAAETQMIAVLLMTSVVVLACSTPLVIQVFANhfk--------lthERDADLAAIRIASVNPILDPWIYILLR 292

                 ....*...
Feature 1                
gi 548476    334 KtVLSKAI 341
gi 118341487 298 KaVLSKVV 305
gi 125630639 323 KtVLRKAI 330
gi 523496424 337 KnLLTKGC 344
gi 187607854 318 KtVLSKLI 325
gi 47210150  293 RsLFRRLL 300

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