4L6R,5EE7


Conserved Protein Domain Family
7tmB1_GCGR

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cd15267: 7tmB1_GCGR 
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glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
Glucagon receptor (GCGR) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon-like peptide-1 receptor (GLP1R) and GLP2R. GCGR is activated by glucagon, which is derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. 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 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: 320395
View PSSM: cd15267
Aligned: 6 rows
Threshold Bit Score: 351.816
Threshold Setting Gi: 1028910075
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 25 residues -Click on image for an interactive view with Cn3D
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.
  • Structure:5EE7: Human Glucagon Receptor binds solvent molecule in ligand binding pocket; contacts at 4A
    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           #     #   #                                     #   #  ##  #                 
4L6R_A       120 KMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSqkigddlsvstw 199
5EE7_A         1 KGYSSFQVMYTVGYSLSLAALLLALAILGGLSKLHCTANAIHANLFLSFVLKASAVLFIDGLLRTRYSqkieddlsvstw 80
gi 17224912  131 KTYERFKIVYTVGYSVSLGTLILAFAILVGFSKLHCMRNYIHMNLFASFILKSLSVLVQDILLKTRYTkkiedevh--sr 208
gi 47215413  119 PYYGHIQIMYTVGYSLSLVALVLALGILIFFRKLHCMRNNIHMNLFASFIMRALSVLIKDALLDATNKtshwst-----t 193
gi 1346144   136 KMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSqkigddlsvstw 215
gi 149193351 131 KTYGSFKVMYTVGYSVSLCALLLALAVLLGFSKLHCMRNYIHMNLFASFIVKGVSVLVIDALLKTHYSdkiddynv-riw 209
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 #     ##  #   #                                                        
4L6R_A       200 lsdgaVAGCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLA--------------------------------------- 240
5EE7_A        81 lsdgaVAACRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLNifemlrideglrlkiykdtegyytigighlltkspslna 160
gi 17224912  209 lsseaLAGCRAATVLMQYGMIANYYWLMVEGIYLYNLLVLT--------------------------------------- 249
gi 47215413  194 vnnetMICCRIAFVMMQYSIMANSYWLLVEGIYLHNLLVIT--------------------------------------- 234
gi 1346144   216 lsdgaVAGCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLA--------------------------------------- 256
gi 149193351 210 lsdeaAAGCRAATVFMQYGIVANYCWLLVEGIYLHNLLVVA--------------------------------------- 250
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
4L6R_A           --------------------------------------------------------------------------------
5EE7_A       161 akseldkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvfqmgetgvagftnslrml 240
gi 17224912      --------------------------------------------------------------------------------
gi 47215413      --------------------------------------------------------------------------------
gi 1346144       --------------------------------------------------------------------------------
gi 149193351     --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                    ##  
4L6R_A       241 --------------------------------------TLPERSFFSLYLGIGWGAPMLFVVPWAVVKclFENVQCWTSN 282
5EE7_A       241 qqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdAYPERSFFSLYLGIGWGAPALFVVPWAVVKclFENVQCWTSN 320
gi 17224912  250 --------------------------------------VFSERNYFALYLCIGWGTPALFIIPWVAVKytYENIDCWSAN 291
gi 47215413  235 --------------------------------------VFTERNYFKIYLCIGWGMPLLFLVPWVMAKywYENHMCWELN 276
gi 1346144   257 --------------------------------------TLPERSFFSLYLGIGWGAPMLFVVPWAVVKclFENVQCWTSN 298
gi 149193351 251 --------------------------------------VFSERSYFTLYLCIGWGAPVLFLIPWVVVKflYENIQCWSTN 292
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            ## ###                                                     #  #             
4L6R_A       283 dNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMhhTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEHAQGT-- 360
5EE7_A       321 dNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMhhTDYAFRLAKSTLTLIPLLGVHFVVFAFVTDEHAQGT-- 398
gi 17224912  292 nNMGFWWIIRSSVLLAIVINFVIFVRIIQILVSKMRAPQMwyTDYKFRLAKSTLTLIPLLGIHEVAFAFLADETTQGT-- 369
gi 47215413  277 tSMNIWWIIRSLILLAVVINFLIFIHIIKILVSKLRAHQMryTDYKFRLAKSTLTLIPLLGIHHMVFIFVTDESTLSTig 356
gi 1346144   299 dNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMhhTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEHAQGT-- 376
gi 149193351 293 hNMGFWWILRFPVFLAILINFFIFIRIIQILVSKLRAHQMryTDYKFRLAKSTLTLIPLLGIHEVIFAFITDEHAQGT-- 370
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|.
Feature 1             ##  #                               
4L6R_A       361 LRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 401
5EE7_A       399 LRSAKLFFDLALSSFQGLLVAVLYCFLNKEVQSELRRRWHR 439
gi 17224912  370 LRLVKLFFDLFFGSFQGMLVAVLYCFMNKEVQSELFKKWKR 410
gi 47215413  357 LRLTKLFIDLFFSSFQGLLVAILYCFVNKEVSELIHTFRPC 397
gi 1346144   377 LRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 417
gi 149193351 371 LRYVKLFFDLFLSSFQGMLVAILYCFVNKEVQAELLKRWQR 411

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