Conserved Protein Domain Family
7tmB1_GLP2R

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cd15266: 7tmB1_GLP2R 
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.
Statistics
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PSSM-Id: 320394
View PSSM: cd15266
Aligned: 7 rows
Threshold Bit Score: 448.04
Threshold Setting Gi: 573895354
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on mutagenesis of human glucagon receptor (GCGR), and modeling studies of GCGR and other related class B GPCRs, and on the structure of Oryctolagus cuniculus Glucagon-like Peptide-1 Receptor (GLP1R) with bound GLP1
  • Comment:Residues in the globular N-terminal extracellular domain and the extracellular loops of the 7TM domain may also be involved in ligand binding.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #     #   #                                     #   #  ##  #                   
gi 4758438   175 LSTLQLMYTVGYSFSLISLFLALTLLLFLRKLHCTRNYIHMNLFASFILRTLAVLVKDVVFYNSYSKRPDNENGWMSYLS 254
gi 253735892 149 LTTLQLLYTIGYCFSLISLVLALLILSLLRKLHCTRNYIHMNLFASFILRATAILIKDTVLHKIYSKRPNDETGWILYLS 228
gi 512880137 143 LSALQIIYTIGYSISLGALLLALVILLLFRKLHCTRNYIHMNLFASFIMRALAVLIKDIVYKNTYFKKNDEMGWMSHLTS 222
gi 410896236 596 QTALRLISIIGYSLSLFSLTVATLVMAMLRKLHCTRNYIHMNLFVSFILRAMAVILKEIIFYIKHFNLPKDDPGWKSYAD 675
gi 632943593 171 LNTLQLIYTVGYSFSLCSLSLAMAILLWLRKLHCTRNYIHMNLFVSFMLRALAVLIKDILLHSTYSKRPDDESGWISFFN 250
gi 488537244 175 LLILQRIYTVGHSLSLASLSLAIGLLLFLRKLHCTRNYIHVNVFAAFILKAVVVLIKDINLHSSYSKKPNSEDEWIAYQS 254
gi 573895354 139 QLVLRIVYTIGYSLSLSSLSLAVIILLLLRKLHCTRNFIHINLFTSFILRAVVILAKEIILYETYSKRPKDETGWIYILN 218
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #     ##  #   #                                                       ##
gi 4758438   255 ems--tsCRSVQVLLHYFVGANYLWLLVEGLYLHTLLEptvlPERRLWPRYLLLGWAFPVLFVVPWGFARAHLENtGCWT 332
gi 253735892 229 pei-liiCRAAQFFMHYFVGANYFWLLVEGIYLHTLLItavlSERRLLQTYIVIGWAVPILFVAPWGISRSKLENtGCWG 307
gi 512880137 223 eis--tsCRVAQVFMHFFVGANYCWLFVEGLYLHTILVtvilSEKGLLLKYLFIGWFFPLLFVVPWVIAKLYYENnGCWG 300
gi 410896236 676 sai-vlsCRVSAVCMQYFVACNYFWLLVEAVFLHTLLFsavlTKRRLLKRYMLLGWGTPVLFVTPWTVVKILHENtGCWS 754
gi 632943593 251 vei-sngCKVAQVFMHYFVGANFFWLLVEGIYLHKLIVlavlSEKNLLKQYILIGWVCPVLFVVPWIITKITSENeGCWG 329
gi 488537244 255 evsgstsCRLAHALLHYFVVANQSWLLVEGLYLYTLLKptvlSERRLWPKFMLVGWGYPVLFVVPWCVARVQLENkGCWM 334
gi 573895354 219 sen-spfCRAVQVFMHYLIGANAFWLLVEGIFLHTLLVtpvlSEKRLLKKYMVIGWGTPIMFVVPWAVTKALYENeGCWR 297
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              ## ###                                                     #  #           
gi 4758438   333 TNgNKKIWWIIRGPMMLCVTVNFFIFLKILKLLISKLKAHQmcFRDYKYRLAKSTLVLIPLLGVHEILFSFITDDQveGF 412
gi 253735892 308 TNeHMGIWWIIRGPMLFSITVNFGIFLKILRMLISKLKAQQmsFHDYKYRLARSTLVLIPLLGIHEFIFSFITDEQveGF 387
gi 512880137 301 VNeSPGIWWIIRGPMLLGILINFLIFIKVLKLLYSKLKAQQmrYTDCKYRLARATLALIPLLGMHHVVFTFITDELveGA 380
gi 410896236 755 IM-NKWIWWIIRGPITLTFVVIFCIFIKILMLLLSKLKADQlkFTDYRYSLVRATLVLIPLLGIHEVVFMVLTDECmeGR 833
gi 632943593 330 RNvNMWIWWIIRGPVSIAIIMNFYFFLKIMKMLLSKLQAQQmrFGDYKYRLARSTLVLIPLLGIHELVFIFLMDEHveGL 409
gi 488537244 335 KNkNMKIWWIIRGPILLCVTVNFVIFLYTVKLLISKLKAHQmcFRDYKYRLAKSTFFLISLLGVHDLVYYFITDEQvkGY 414
gi 573895354 298 RNtNMGIWWIIRGPIRFSIAVNFYLFIKILKLLLWKLKAEKmtFNDYKFRLARATLVLIPLMGIHEIVFAFMPDEQ--IK 375
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
Feature 1             ##  #                               
gi 4758438   413 AKLIRLFIQLTLSSFHGFLVALQYGFANGEVKAELRKYWVR 453
gi 253735892 388 LRHVRLFIQLTMSSFHGFFVAVLYCFANGEVKAELHKQWSR 428
gi 512880137 381 TRHFWLLIQLAFESFQGFVVAIFYCFTNGEVRAELRKQWNL 421
gi 410896236 834 SLYAKNFVNLTLNSFQGFLVAVLYCFANGEVQAELKKRWQL 874
gi 632943593 410 LRHIRLFLQLVISSFQGFLVAVLYCFTNGEVQAELKMRWRC 450
gi 488537244 415 SKHIRLYIQMSVGSFHGLLVAYHYCFANGEVKAELRRHWPH 455
gi 573895354 376 GRYTRSFIQLTLTSFQGFLVAVLYCFANREVKTELKKRWQL 416

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