Conserved Protein Domain Family
7tmA_PGE2_EP3

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cd15146: 7tmA_PGE2_EP3 
prostaglandin E2 receptor EP3 subtype, member of the class A family of seven-transmembrane G protein-coupled receptors
Prostaglandin E2 receptor EP3, also called prostanoid EP3 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. Stimulation of the EP3 receptor by PGE2 preferentially couples to G(i) protein. This leads to a decrease in adenylate cyclase activity, thereby decreasing cAMP levels, which subsequently produces smooth muscle contraction. Knockout mice studies suggest that the EP3 receptor may act as a systemic vasopressor. 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: 320274
View PSSM: cd15146
Aligned: 4 rows
Threshold Bit Score: 517.894
Threshold Setting Gi: 1172071
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 1172071    49 SVSVAFPITMLLTGFVGNALAMLLVSRSYRrreskrkkSFLLCIGWLALTDLVGQLLTTPVVIVVYlskqrWEHIDPSGr 128
gi 94957759   33 AVSVAFPLTMMITGIVGNALAMLLVSRSYRakenrrkrSFLLCIGSLALTDLSGQLLTSPIVIAVYlsdrvWTNVDPSGr 112
gi 148886734  41 AVSVAFPLSMMITGLVGNALAMLLVYKSYKnkegarkhSFLLCIGSLALTDFIGQLLTSPIVISVYlsnrqWAKVDTSGh 120
gi 47214880   41 SVSVGFPITMMITGMVGNTLALILAYVSYRkkenkrkrSFLLCIGSLALADLFGQLLTSPIVISVYradlkWERVDSSGf 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ###### ##  #                                            # #####                
gi 1172071   129 LCTFFGLTMTVFGLSSLFIASAMAVERALAIRAPHwYASHMkTRATRAVLLGVWLAVLAFALLPVLGVGQYtvQWPGTWC 208
gi 94957759  113 LCAFFGFSMTVFGLCPLFIASAMAAERTLAIRAPHcYASHMkTRVTKAVLLGIWLAVPAFALLPLAGLGRYalQWPGTWC 192
gi 148886734 121 LCPFFGLCMTMFGLCPLFIASAMAIERTLAIRTPHwYSCHMkPRATNTVLLCIWLGVLAFALLPILGVGQYtlQWPGTWC 200
gi 47214880  121 LCPFFGVCMTTFGLCALFLASAMAIERAMAVTNPHwYSNHMkTSVTKQTLVVIWCLVLLFALLPIAGVGKYtpQWPGTWC 200
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                         #  ### ### ##                                                  
gi 1172071   209 FISTgrggngtssshnwGNLFFASAFAFLGLLALTVTFSCNLATIKALvsrcrakatasqssaqWGRITTETAIQLMGIM 288
gi 94957759  193 FISTegq--------rpGSVLFASAFAGLGLFSLLVTMACNLATMEALvsrcrskaaasrsskqWGRIATETLIQLLGIM 264
gi 148886734 201 FISTgds-------eapGNIFFASTFACLGLVSLFTTFSCNLSTIVALvsrckrrsstshanrhWERITLETLIQLMGIM 273
gi 47214880  201 FISTgdg--------evLGNVFATTFASLGIFSLCVTVSCNVMTIRGLiircktktgksvsskqWERLTTETVVQLLGIM 272
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
Feature 1              #  ## ##  #                           ## ###  #  ##                      
gi 1172071   289 CVLSVCWSPLLIMMLKMifnqtsveh---------ckthtekqkECNFFLIAVRLASLNQILDPWVYLLLRkiLLRKFC 358
gi 94957759  265 CVLSACWSPLLVTMLKMifnrtsfesckg---fsaetqsselykECNFFLTAVRLASLNQILDPWVYLLLRkiLLQKFC 340
gi 148886734 274 CVLFACWSPLLVIMLKMisnhtslehckp----kgseqstelqkDCNFFLTAVRLASLNQILDPWVYLLLRqiLLRKFC 348
gi 47214880  273 CVLLICWSPLLGLMLRMisthvssqqcnstalatappathdvplDCNFFLFAIRMASLNQILDPWVYLLLReiLLRKFC 351

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