Conserved Protein Domain Family
7tmA_GPBAR1

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cd15905: 7tmA_GPBAR1 
G protein-coupled bile acid receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors
The G-protein coupled bile acid receptor GPBAR1 is also known as BG37, TGR5 (Takeda G-protein-coupled receptor 5), M-BAR (membrane-type receptor for bile acids), and GPR131. GPBAR1 is highly expressed in the gastrointestinal tract, but also found at many other tissues including liver, colon, heart, skeletal muscle, and brown adipose tissue. GPBAR1 functions as a membrane-bound receptor specific for bile acids, which are the end products of cholesterol metabolism that facilitate digestion and absorption of lipids or fat-soluble vitamins. Bile acids act as liver-specific metabolic signaling molecules and stimulate liver regeneration by activating GPBAR1 and nuclear receptors such as the farnesoid X receptor (FXR). Upon bile acids binding, GPBAR1 activation causes release of the G-alpha(s) subunit and activation of adenylate cyclase. The increase in intracellular cAMP level then stimulates the expression of many genes via the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB). Thus, GPAR1-signalling exerts various biological effects in immune cells, liver, and metabolic tissues. For example, GPBAR1 activation leads to enhanced energy expenditure in brown adipose tissue and skeletal muscle; stimulation of glucagon-like peptide-1 (GLP-1) production in enteroendocrine L-cells; and inhibition of pro-inflammatory cytokine production in macrophages and attenuation of atherosclerosis development. GPBAR1 is a member of the class A rhodopsin-like family of GPCRs, which comprises receptors for hormones, neurotransmitters, sensory stimuli, and a variety of other ligands.
Statistics
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PSSM-Id: 320571
View PSSM: cd15905
Aligned: 5 rows
Threshold Bit Score: 324.784
Threshold Setting Gi: 74762624
Created: 21-Oct-2014
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 74762624   17 ALGLSLALASLIITANLLLALGIAWDRRLrsppAGCFFLSLLLAGLLTGLALPTLPGLWNQSrrgywSCLLVYLAPNFSF 96
gi 465979180  19 IFWVSGPLSLFIILANLFIILGILCNRKLhg-pTSWFFLSLLLADLLAGVALPFIPQMQFEDsrgyhTCFFIHVAPNFLF 97
gi 353523831  21 IVLLSSPLSVFIIFSNLFIIVGIVFNKKIhn-tANYFFLSLLFADLLTGVALPCIPHMRYDKkfgyhICMISYILPNFFF 99
gi 688572492  29 IFYLTVPLSSIIIFTNLFIIIGIACNRQLhn-tPNYFFLSLLVADLCTGITLPFIPRMSLDRqldfrHCLVMYIFPNFLF 107
gi 557015875  19 VFWICVPLSVLLFSLNVLMIIGILGNKKLht-tTNFFFLSLFFADCFTGAVLPSFPWMSNETnvgfkLCLFLYVYPNFFF 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                    # #####                             
gi 74762624   97 LSLLANLLLVHGERYMAVLRPLqp-----pgSIRLALLLTWAGPLLFASLPALGWNHWtpganc---------------- 155
gi 465979180  98 LAFLANLLVVHYEKYLSISYPLhyhrfwvhrWVPLCLLLTWALPLLFACLPVLGWNHWepssnc---------------- 161
gi 353523831 100 LSFLANLLMVHYEKYLCIVYPLryhsiwvhrCVPLSLLIAWTLPLLFACLPMMGWNNWdtesnc---------------- 163
gi 688572492 108 LSFLFNLVMVHYERYLCIVSPLhhsqfwvhrCFPLALLTVWLPPLLYASLPAFGWNNWieaasnksldsnetfwrsqtsh 187
gi 557015875  98 LSLLFNLVMVHYERYLFIMYPLqyrnfwvhrWAPLALTIVWVLPLTYACLPVFGWNNWnatsln---------------- 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                      #  ### ### ##                                                     
gi 74762624  156 ---------ssqaiFPAPYLYLEVYGLLLPAVGAAAFLSVRVLATAHRQLqdicrlerav-crdepsalarALTWRQARA 225
gi 465979180 162 ---------syhqvFPTAYLYLEIYGFLIPSILAMAFMSIQVLRVARHQLqeikkvlrsvnqgqgpseleqQLELRHAKC 232
gi 353523831 164 ---------sykyvFTNTYIYLETYGVVIPSILAIVFITVKVLSVARKQLknikklhrsv-qsqagielehQMDLRYARC 233
gi 688572492 188 naskedevcsykqvFPKAFIYVEVCGLVLPAMLCIVCMTGRVLWIARKQLqdicklhrav-drlqtsdqeqQLNLRYAKC 266
gi 557015875 162 --------cssksvFIPAYIYLEVYGLVVPSILAIIFMMVRVLTVARRQLknitkllrav-qrdgvseteqQMNLKYAKC 232
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                   #  ## ##  #           ## ###  #  ##              
gi 74762624  226 QAGAMLLFGLCWGPYVATLLLSVLayeq-rpplGPGTLLSLLSLGSASAAAVPVAMGLGD 284
gi 465979180 233 IASLSLVFLVCWVPYVAGLHVSVLaiqn-rnfiDKYTLLILTCVGSGSAAMVPITLGFGR 291
gi 353523831 234 IAIVSLTFLVCWVPYIAVLQVSVLaieh--yefSWWIILTLTCVGSGSAAVIPVILGLCH 291
gi 688572492 267 VAAVSLTFLVCWVPYIIYQLMSVTalqsgvslpSSSLYIIMSCTGIGSMAVIPLILGLAN 326
gi 557015875 233 IAFISLIFLVCWVPYIIYIQMSLLafd----dcIELNTQVMSCIGCGSAAALPIILGLCN 288

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