ID GLR_HUMAN Reviewed; 477 AA. AC P47871; Q2M3M5; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=Glucagon receptor; DE Short=GL-R; DE Flags: Precursor; GN Name=GCGR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Liver; RX PubMed=7507321; DOI=10.1006/bbrc.1994.1046; RA Macneil D.J., Occi J.L., Hey P.J., Strader C.D., Graziano M.P.; RT "Cloning and expression of a human glucagon receptor."; RL Biochem. Biophys. Res. Commun. 198:328-334(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8144028; DOI=10.1016/0378-1119(94)90545-2; RA Lok S., Kuijper J.L., Jelinek L.J., Kramer J.M., Whitmore T.E., RA Sprecher C.A., Mathewes S., Grant F.J., Biggs S.H., Rosenberg G.B.; RT "The human glucagon receptor encoding gene: structure, cDNA sequence and RT chromosomal localization."; RL Gene 140:203-209(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 21-54. RC TISSUE=Placenta; RX PubMed=8020989; DOI=10.1006/geno.1994.1179; RA Menzel S., Stoffel M., Espinosa R. III, Fernald A.A., Le Beau M.M., RA Bell G.I.; RT "Localization of the glucagon receptor gene to human chromosome band RT 17q25."; RL Genomics 20:327-328(1994). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=9287038; DOI=10.2337/diab.46.9.1400; RA Buggy J.J., Heurich R.O., MacDougall M., Kelley K.A., Livingston J.N., RA Yoo-Warren H., Rossomando A.J.; RT "Role of the glucagon receptor COOH-terminal domain in glucagon-mediated RT signaling and receptor internalization."; RL Diabetes 46:1400-1405(1997). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456 AND SER-459, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 412-420 IN COMPLEX WITH CLASS I RP MHC. RX PubMed=16221670; DOI=10.1074/jbc.m508528200; RA Ruckert C., Fiorillo M.T., Loll B., Moretti R., Biesiadka J., Saenger W., RA Ziegler A., Sorrentino R., Uchanska-Ziegler B.; RT "Conformational dimorphism of self-peptides and molecular mimicry in a RT disease-associated HLA-B27 subtype."; RL J. Biol. Chem. 281:2306-2316(2006). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 28-123, FUNCTION, MUTAGENESIS OF RP TYR-65 AND GLN-113, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-74 AND RP ASN-78. RX PubMed=22908259; DOI=10.1073/pnas.1206734109; RA Koth C.M., Murray J.M., Mukund S., Madjidi A., Minn A., Clarke H.J., RA Wong T., Chiang V., Luis E., Estevez A., Rondon J., Zhang Y., Hotzel I., RA Allan B.B.; RT "Molecular basis for negative regulation of the glucagon receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 109:14393-14398(2012). RN [9] RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 123-432, FUNCTION, SUBCELLULAR RP LOCATION, DISULFIDE BONDS, MEMBRANE TOPOLOGY, MUTAGENESIS OF TRP-36; RP ASP-63; ALA-135; TYR-145; TYR-149; LEU-198; ARG-201; TYR-202; ASP-208; RP TRP-215; GLN-232; TYR-233; LYS-286; GLU-290; CYS-294; TRP-295; TRP-304; RP LEU-382 AND LEU-386, AND CHARACTERIZATION OF VARIANT MVAH SER-86. RX PubMed=23863937; DOI=10.1038/nature12393; RA Siu F.Y., He M., de Graaf C., Han G.W., Yang D., Zhang Z., Zhou C., Xu Q., RA Wacker D., Joseph J.S., Liu W., Lau J., Cherezov V., Katritch V., RA Wang M.W., Stevens R.C.; RT "Structure of the human glucagon class B G-protein-coupled receptor."; RL Nature 499:444-449(2013). RN [10] {ECO:0007744|PDB:5EE7} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 136-254; 256-256 AND 259-417 IN RP COMPLEX WITH SYNTHETIC ANTAGONIST, FUNCTION, SUBCELLULAR LOCATION, AND RP DISULFIDE BONDS. RX PubMed=27111510; DOI=10.1038/nature17414; RA Jazayeri A., Dore A.S., Lamb D., Krishnamurthy H., Southall S.M., RA Baig A.H., Bortolato A., Koglin M., Robertson N.J., Errey J.C., RA Andrews S.P., Teobald I., Brown A.J., Cooke R.M., Weir M., Marshall F.H.; RT "Extra-helical binding site of a glucagon receptor antagonist."; RL Nature 533:274-277(2016). RN [11] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 27-432 IN COMPLEX WITH THE RP SYNTHETIC ANTAGONIST NNC0640, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, RP GLYCOSYLATION AT ASN-46; ASN-59; ASN-74 AND ASN-78, MUTAGENESIS OF GLN-113; RP VAL-130; ASP-209; LEU-210; SER-350 AND THR-353, AND DISULFIDE BONDS. RX PubMed=28514451; DOI=10.1038/nature22363; RA Zhang H., Qiao A., Yang D., Yang L., Dai A., de Graaf C., Reedtz-Runge S., RA Dharmarajan V., Zhang H., Han G.W., Grant T.D., Sierra R.G., Weierstall U., RA Nelson G., Liu W., Wu Y., Ma L., Cai X., Lin G., Wu X., Geng Z., Dong Y., RA Song G., Griffin P.R., Lau J., Cherezov V., Yang H., Hanson M.A., RA Stevens R.C., Zhao Q., Jiang H., Wang M.W., Wu B.; RT "Structure of the full-length glucagon class B G-protein-coupled RT receptor."; RL Nature 546:259-264(2017). RN [12] RP VARIANT SER-40. RX PubMed=7589886; DOI=10.1007/bf00400589; RA Fujisawa T., Ikegami H., Yamato E., Takekawa K., Nakagawa Y., Hamada Y., RA Ueda H., Fukuda M., Ogihara T.; RT "A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the RT association with diabetes mellitus."; RL Diabetologia 38:983-985(1995). RN [13] RP VARIANT MVAH SER-86, INVOLVEMENT IN MVAH, FUNCTION, SUBCELLULAR LOCATION, RP AND CHARACTERIZATION OF VARIANT MVAH SER-86. RX PubMed=19657311; DOI=10.1097/mpa.0b013e3181b2bb03; RA Zhou C., Dhall D., Nissen N.N., Chen C.R., Yu R.; RT "Homozygous P86S mutation of the human glucagon receptor is associated with RT hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor."; RL Pancreas 38:941-946(2009). RN [14] RP VARIANTS MVAH HIS-225 AND MET-368, AND INVOLVEMENT IN MVAH. RX PubMed=25695890; DOI=10.1210/jc.2014-4405; RA Sipos B., Sperveslage J., Anlauf M., Hoffmeister M., Henopp T., Buch S., RA Hampe J., Weber A., Hammel P., Couvelard A., Hoebling W., Lieb W., RA Boehm B.O., Kloeppel G.; RT "Glucagon cell hyperplasia and neoplasia with and without glucagon receptor RT mutations."; RL J. Clin. Endocrinol. Metab. 100:E783-E788(2015). RN [15] RP VARIANT MVAH ASN-63. RX PubMed=30032256; DOI=10.1210/jc.2018-01074; RA Gild M.L., Tsang V., Samra J., Clifton-Bligh R.J., Tacon L., Gill A.J.; RT "Hypercalcemia in glucagon cell hyperplasia and neoplasia (Mahvash RT syndrome): a new association."; RL J. Clin. Endocrinol. Metab. 103:3119-3123(2018). RN [16] RP VARIANT MVAH PHE-320 DEL, CHARACTERIZATION OF VARIANT MVAH PHE-320 DEL, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=30294546; DOI=10.1016/j.ymgmr.2018.09.006; RA Li H., Zhao L., Singh R., Ham J.N., Fadoju D.O., Bean L.J.H., Zhang Y., RA Xu Y., Xu H.E., Gambello M.J.; RT "The first pediatric case of glucagon receptor defect due to biallelic RT mutations in GCGR is identified by newborn screening of elevated RT arginine."; RL Mol. Genet. Metab. Rep. 17:46-52(2018). RN [17] RP CHARACTERIZATION OF VARIANTS MVAH HIS-225 AND MET-368, VARIANTS SER-40; RP MET-76; GLN-336; HIS-414; ARG-416; GLN-428; LEU-438; HIS-458; VAL-461 AND RP LEU-476, CHARACTERIZATION OF VARIANTS SER-40; MET-76; GLN-336; HIS-414; RP ARG-416; GLN-428; LEU-438; HIS-458; VAL-461 AND LEU-476, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=32677665; DOI=10.1042/bcj20200235; RA Lin G., Liu Q., Dai A., Cai X., Zhou Q., Wang X., Chen Y., Ye C., Li J., RA Yang D., Wang M.W.; RT "Characterization of a naturally occurring mutation V368M in the human RT glucagon receptor and its association with metabolic disorders."; RL Biochem. J. 477:2581-2594(2020). CC -!- FUNCTION: G-protein coupled receptor for glucagon that plays a central CC role in the regulation of blood glucose levels and glucose homeostasis. CC Regulates the rate of hepatic glucose production by promoting glycogen CC hydrolysis and gluconeogenesis. Plays an important role in mediating CC the responses to fasting. Ligand binding causes a conformation change CC that triggers signaling via guanine nucleotide-binding proteins (G CC proteins) and modulates the activity of down-stream effectors, such as CC adenylate cyclase. Promotes activation of adenylate cyclase. Besides, CC plays a role in signaling via a phosphatidylinositol-calcium second CC messenger system. {ECO:0000269|PubMed:19657311, CC ECO:0000269|PubMed:22908259, ECO:0000269|PubMed:23863937, CC ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451, CC ECO:0000269|PubMed:30294546, ECO:0000269|PubMed:32677665, CC ECO:0000269|PubMed:7507321, ECO:0000269|PubMed:9287038}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19657311, CC ECO:0000269|PubMed:23863937, ECO:0000269|PubMed:27111510, CC ECO:0000269|PubMed:28514451, ECO:0000269|PubMed:30294546, CC ECO:0000269|PubMed:32677665, ECO:0000269|PubMed:7507321, CC ECO:0000269|PubMed:9287038}; Multi-pass membrane protein CC {ECO:0000269|PubMed:19657311, ECO:0000269|PubMed:23863937, CC ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451, CC ECO:0000269|PubMed:7507321, ECO:0000269|PubMed:9287038}. Note=Is CC rapidly internalized after ligand-binding. CC {ECO:0000269|PubMed:9287038}. CC -!- PTM: Ligand-binding promotes phosphorylation of serine residues in the CC C-terminal cytoplasmic domain. Phosphorylation is important for CC receptor endocytosis after ligand-binding. CC {ECO:0000269|PubMed:9287038}. CC -!- DISEASE: Mahvash disease (MVAH) [MIM:619290]: An autosomal recessive CC disorder characterized by alpha-cell hyperplasia of the pancreas, CC hyperglucagonemia without glucagonoma syndrome, aminoacidemia, and CC occasional hypoglycemia. The disease may lead to glucagonomas and/or CC primitive neuroectodermal tumors. {ECO:0000269|PubMed:19657311, CC ECO:0000269|PubMed:23863937, ECO:0000269|PubMed:25695890, CC ECO:0000269|PubMed:30032256, ECO:0000269|PubMed:30294546, CC ECO:0000269|PubMed:32677665}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U03469; AAC52063.1; -; mRNA. DR EMBL; L20316; AAA53628.1; -; mRNA. DR EMBL; BC104854; AAI04855.1; -; mRNA. DR EMBL; BC112041; AAI12042.1; -; mRNA. DR EMBL; L24751; AAA35897.1; -; Genomic_DNA. DR CCDS; CCDS54177.1; -. DR PIR; JC2041; JC2041. DR RefSeq; NP_000151.1; NM_000160.4. DR RefSeq; XP_006722340.1; XM_006722277.1. DR PDB; 2A83; X-ray; 1.40 A; C=412-420. DR PDB; 3CZF; X-ray; 1.20 A; C=412-420. DR PDB; 4ERS; X-ray; 2.64 A; A=28-123. DR PDB; 4L6R; X-ray; 3.30 A; A=123-432. DR PDB; 4LF3; X-ray; 2.74 A; C/F=29-123. DR PDB; 5EE7; X-ray; 2.50 A; A=136-254, A=259-417. DR PDB; 5XEZ; X-ray; 3.00 A; A/B=27-432. DR PDB; 6LMK; EM; 3.70 A; R=27-432. DR PDB; 6LML; EM; 3.90 A; R=27-432. DR PDB; 6WHC; EM; 3.40 A; R=1-477. DR PDB; 6WPW; EM; 3.10 A; R=27-477. DR PDB; 7V35; EM; 3.40 A; R=27-432. DR PDB; 8FU6; EM; 2.90 A; R=27-477. DR PDB; 8JIQ; EM; 3.40 A; R=27-431. DR PDB; 8JIT; EM; 2.91 A; R=27-431. DR PDB; 8JIU; EM; 2.76 A; R=27-431. DR PDB; 8JRU; EM; 3.50 A; R=27-432. DR PDB; 8JRV; EM; 3.30 A; R=27-432. DR PDBsum; 2A83; -. DR PDBsum; 3CZF; -. DR PDBsum; 4ERS; -. DR PDBsum; 4L6R; -. DR PDBsum; 4LF3; -. DR PDBsum; 5EE7; -. DR PDBsum; 5XEZ; -. DR PDBsum; 6LMK; -. DR PDBsum; 6LML; -. DR PDBsum; 6WHC; -. DR PDBsum; 6WPW; -. DR PDBsum; 7V35; -. DR PDBsum; 8FU6; -. DR PDBsum; 8JIQ; -. DR PDBsum; 8JIT; -. DR PDBsum; 8JIU; -. DR PDBsum; 8JRU; -. DR PDBsum; 8JRV; -. DR AlphaFoldDB; P47871; -. DR EMDB; EMD-0917; -. DR EMDB; EMD-0918; -. DR EMDB; EMD-21671; -. DR EMDB; EMD-21866; -. DR EMDB; EMD-31676; -. DR EMDB; EMD-36324; -. DR EMDB; EMD-36327; -. DR EMDB; EMD-36328; -. DR SMR; P47871; -. DR BioGRID; 108912; 152. DR IntAct; P47871; 4. DR STRING; 9606.ENSP00000383558; -. DR BindingDB; P47871; -. DR ChEMBL; CHEMBL1985; -. DR DrugBank; DB15226; Dasiglucagon. DR DrugBank; DB00040; Glucagon. DR DrugCentral; P47871; -. DR GuidetoPHARMACOLOGY; 251; -. DR TCDB; 9.A.14.4.13; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P47871; 4 sites, No reported glycans. DR GlyGen; P47871; 4 sites. DR iPTMnet; P47871; -. DR PhosphoSitePlus; P47871; -. DR BioMuta; GCGR; -. DR DMDM; 1346144; -. DR MassIVE; P47871; -. DR PaxDb; 9606-ENSP00000383558; -. DR PeptideAtlas; P47871; -. DR ABCD; P47871; 109 sequenced antibodies. DR Antibodypedia; 4808; 578 antibodies from 36 providers. DR DNASU; 2642; -. DR Ensembl; ENST00000400723.8; ENSP00000383558.3; ENSG00000215644.10. DR Ensembl; ENST00000671794.1; ENSP00000500297.1; ENSG00000288269.1. DR GeneID; 2642; -. DR KEGG; hsa:2642; -. DR MANE-Select; ENST00000400723.8; ENSP00000383558.3; NM_000160.5; NP_000151.1. DR UCSC; uc010wuw.2; human. DR AGR; HGNC:4192; -. DR CTD; 2642; -. DR DisGeNET; 2642; -. DR GeneCards; GCGR; -. DR HGNC; HGNC:4192; GCGR. DR HPA; ENSG00000215644; Group enriched (kidney, liver). DR MalaCards; GCGR; -. DR MIM; 138033; gene. DR MIM; 619290; phenotype. DR neXtProt; NX_P47871; -. DR OpenTargets; ENSG00000215644; -. DR Orphanet; 438274; GCGR-related hyperglucagonemia. DR PharmGKB; PA28607; -. DR VEuPathDB; HostDB:ENSG00000215644; -. DR eggNOG; KOG4564; Eukaryota. DR GeneTree; ENSGT00940000157969; -. DR HOGENOM; CLU_002753_4_0_1; -. DR InParanoid; P47871; -. DR OMA; HWHRWRL; -. DR OrthoDB; 4209404at2759; -. DR PhylomeDB; P47871; -. DR TreeFam; TF315710; -. DR PathwayCommons; P47871; -. DR Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-420092; Glucagon-type ligand receptors. DR SignaLink; P47871; -. DR SIGNOR; P47871; -. DR BioGRID-ORCS; 2642; 16 hits in 1160 CRISPR screens. DR EvolutionaryTrace; P47871; -. DR GeneWiki; Glucagon_receptor; -. DR GenomeRNAi; 2642; -. DR Pharos; P47871; Tclin. DR PRO; PR:P47871; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P47871; Protein. DR Bgee; ENSG00000215644; Expressed in right lobe of liver and 73 other cell types or tissues. DR ExpressionAtlas; P47871; baseline and differential. DR GO; GO:0005768; C:endosome; IEA:Ensembl. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0004967; F:glucagon receptor activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro. DR GO; GO:0071377; P:cellular response to glucagon stimulus; IDA:UniProtKB. DR GO; GO:0009267; P:cellular response to starvation; ISS:ARUK-UCL. DR GO; GO:0006887; P:exocytosis; IEA:Ensembl. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL. DR GO; GO:0008217; P:regulation of blood pressure; TAS:ProtInc. DR GO; GO:0070873; P:regulation of glycogen metabolic process; ISS:UniProtKB. DR GO; GO:0007584; P:response to nutrient; TAS:ProtInc. DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB. DR CDD; cd15267; 7tmB1_GCGR; 1. DR Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR036445; GPCR_2_extracell_dom_sf. DR InterPro; IPR001879; GPCR_2_extracellular_dom. DR InterPro; IPR003290; GPCR_2_GLP1/glucagon_rcpt. DR InterPro; IPR003291; GPCR_2_glucagon_rcpt. DR InterPro; IPR000832; GPCR_2_secretin-like. DR InterPro; IPR017983; GPCR_2_secretin-like_CS. DR PANTHER; PTHR45620:SF29; GLUCAGON RECEPTOR; 1. DR PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF02793; HRM; 1. DR PRINTS; PR01353; GLUCAGNFAMLY. DR PRINTS; PR01354; GLUCAGONR. DR PRINTS; PR00249; GPCRSECRETIN. DR SMART; SM00008; HormR; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF111418; Hormone receptor domain; 1. DR PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1. DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1. DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR Genevisible; P47871; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Diabetes mellitus; Disease variant; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..477 FT /note="Glucagon receptor" FT /id="PRO_0000012832" FT TOPO_DOM 26..136 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 137..161 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 162..173 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 174..198 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 199..225 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 226..249 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 250..263 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 264..285 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 286..303 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 304..326 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 327..350 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 351..369 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 370..381 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TRANSMEM 382..402 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT TOPO_DOM 403..477 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451" FT REGION 350..353 FT /note="Important for allosteric inhibitor binding" FT /evidence="ECO:0000269|PubMed:27111510, FT ECO:0000269|PubMed:28514451" FT REGION 431..477 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 459 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28514451" FT CARBOHYD 59 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28514451" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:22908259, FT ECO:0000269|PubMed:28514451, ECO:0007744|PDB:4ERS" FT CARBOHYD 78 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:22908259, FT ECO:0000269|PubMed:28514451, ECO:0007744|PDB:4ERS" FT DISULFID 43..67 FT /evidence="ECO:0000269|PubMed:22908259, FT ECO:0000269|PubMed:28514451, ECO:0007744|PDB:4ERS, FT ECO:0007744|PDB:4LF3" FT DISULFID 58..100 FT /evidence="ECO:0000269|PubMed:22908259, FT ECO:0000269|PubMed:28514451, ECO:0007744|PDB:4ERS, FT ECO:0007744|PDB:4LF3" FT DISULFID 81..121 FT /evidence="ECO:0000269|PubMed:22908259, FT ECO:0000269|PubMed:28514451, ECO:0007744|PDB:4ERS, FT ECO:0007744|PDB:4LF3" FT DISULFID 224..294 FT /evidence="ECO:0000269|PubMed:23863937, FT ECO:0000269|PubMed:27111510, ECO:0000269|PubMed:28514451, FT ECO:0007744|PDB:4L6R, ECO:0007744|PDB:5EE7" FT VARIANT 40 FT /note="G -> S (no effect on glucagon-elicited cAMP FT production; dbSNP:rs1801483)" FT /evidence="ECO:0000269|PubMed:32677665, FT ECO:0000269|PubMed:7589886" FT /id="VAR_003581" FT VARIANT 63 FT /note="D -> N (in MVAH)" FT /evidence="ECO:0000269|PubMed:30032256" FT /id="VAR_085613" FT VARIANT 76 FT /note="T -> M (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085614" FT VARIANT 86 FT /note="P -> S (in MVAH; abolishes glucagon binding)" FT /evidence="ECO:0000269|PubMed:19657311, FT ECO:0000269|PubMed:23863937" FT /id="VAR_069815" FT VARIANT 114 FT /note="P -> A (in dbSNP:rs5385)" FT /id="VAR_014837" FT VARIANT 225 FT /note="R -> H (in MVAH; when associated in cis with M-368; FT decreased glucagon binding and decreased glucagon-elicited FT cAMP production; decreased localization to the cell FT membrane)" FT /evidence="ECO:0000269|PubMed:25695890, FT ECO:0000269|PubMed:32677665" FT /id="VAR_085615" FT VARIANT 303 FT /note="F -> C (in dbSNP:rs5387)" FT /id="VAR_033966" FT VARIANT 320 FT /note="Missing (in MVAH; loss of glucagon-elicited cAMP FT production; no effect on localization to the cell FT membrane)" FT /evidence="ECO:0000269|PubMed:30294546" FT /id="VAR_085616" FT VARIANT 336 FT /note="R -> Q (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085617" FT VARIANT 368 FT /note="V -> M (in MVAH; when associated in cis with H-225; FT decreased glucagon binding and decreased glucagon-elicited FT cAMP production; no effect on localization to the cell FT membrane)" FT /evidence="ECO:0000269|PubMed:25695890, FT ECO:0000269|PubMed:32677665" FT /id="VAR_085618" FT VARIANT 414 FT /note="R -> H (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085619" FT VARIANT 416 FT /note="H -> R (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085620" FT VARIANT 428 FT /note="R -> Q (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085621" FT VARIANT 438 FT /note="S -> L (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085622" FT VARIANT 458 FT /note="D -> H (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085623" FT VARIANT 461 FT /note="A -> V (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085624" FT VARIANT 476 FT /note="P -> L (no effect on glucagon-elicited cAMP FT production)" FT /evidence="ECO:0000269|PubMed:32677665" FT /id="VAR_085625" FT MUTAGEN 36 FT /note="W->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 63 FT /note="D->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 65 FT /note="Y->A: Strongly reduced affinity for glucagon. FT Increased constitutive signaling via G-proteins." FT /evidence="ECO:0000269|PubMed:22908259" FT MUTAGEN 113 FT /note="Q->A,N: No effect on affinity for glucagon." FT /evidence="ECO:0000269|PubMed:22908259" FT MUTAGEN 113 FT /note="Q->C: Causes the formation of an artifactual FT disulfide bond that abolishes glucagon binding; when FT associated with C-209." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 113 FT /note="Q->E: Strongly reduced affinity for glucagon." FT /evidence="ECO:0000269|PubMed:22908259" FT MUTAGEN 130 FT /note="V->C: Causes the formation of an artifactual FT disulfide bond that interferes with glucagon binding; when FT associated with C-210." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 135 FT /note="A->P: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 145 FT /note="Y->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 149 FT /note="Y->A: Abolishes expression at cell surface and FT glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 198 FT /note="L->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 201 FT /note="R->D: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 202 FT /note="Y->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 208 FT /note="D->Q: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 209 FT /note="D->C: Causes the formation of an artifactual FT disulfide bond that abolishes glucagon binding; when FT associated with C-113." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 210 FT /note="L->C: Causes the formation of an artifactual FT disulfide bond that interferes with glucagon binding; when FT associated with C-130." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 215 FT /note="W->L: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 232 FT /note="Q->L: Abolishes expression at cell surface and FT glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 233 FT /note="Y->A: Abolishes glucagon binding. Strongly reduces FT expression at the cell surface." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 286 FT /note="K->L: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 290 FT /note="E->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 294 FT /note="C->A,S: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 295 FT /note="W->A,H: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 304 FT /note="W->Q: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 350 FT /note="S->A: Strongly decreases affinity for synthetic FT antagonist." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 353 FT /note="T->A: Loss of synthetic antagonist binding." FT /evidence="ECO:0000269|PubMed:28514451" FT MUTAGEN 382 FT /note="L->A: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT MUTAGEN 386 FT /note="L->F: Abolishes glucagon binding." FT /evidence="ECO:0000269|PubMed:23863937" FT HELIX 31..49 FT /evidence="ECO:0007829|PDB:4ERS" FT STRAND 54..58 FT /evidence="ECO:0007829|PDB:4ERS" FT STRAND 64..68 FT /evidence="ECO:0007829|PDB:4LF3" FT STRAND 75..80 FT /evidence="ECO:0007829|PDB:4ERS" FT TURN 86..90 FT /evidence="ECO:0007829|PDB:4ERS" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:8FU6" FT STRAND 95..100 FT /evidence="ECO:0007829|PDB:4ERS" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:4LF3" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:6WPW" FT HELIX 119..121 FT /evidence="ECO:0007829|PDB:4ERS" FT STRAND 127..130 FT /evidence="ECO:0007829|PDB:5XEZ" FT TURN 131..133 FT /evidence="ECO:0007829|PDB:6WHC" FT HELIX 139..165 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 167..169 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 172..198 FT /evidence="ECO:0007829|PDB:5EE7" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:5XEZ" FT HELIX 209..211 FT /evidence="ECO:0007829|PDB:8FU6" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 218..253 FT /evidence="ECO:0007829|PDB:5EE7" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:8FU6" FT HELIX 264..271 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 273..289 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 293..295 FT /evidence="ECO:0007829|PDB:8FU6" FT HELIX 301..304 FT /evidence="ECO:0007829|PDB:8FU6" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 308..334 FT /evidence="ECO:0007829|PDB:5EE7" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:7V35" FT TURN 338..340 FT /evidence="ECO:0007829|PDB:6WPW" FT HELIX 343..369 FT /evidence="ECO:0007829|PDB:5EE7" FT STRAND 370..372 FT /evidence="ECO:0007829|PDB:8FU6" FT HELIX 379..389 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 392..400 FT /evidence="ECO:0007829|PDB:5EE7" FT TURN 401..403 FT /evidence="ECO:0007829|PDB:5EE7" FT HELIX 405..417 FT /evidence="ECO:0007829|PDB:5EE7" SQ SEQUENCE 477 AA; 54009 MW; ADBB477C6267AE6E CRC64; MPPCQPQRPL LLLLLLLACQ PQVPSAQVMD FLFEKWKLYG DQCHHNLSLL PPPTELVCNR TFDKYSCWPD TPANTTANIS CPWYLPWHHK VQHRFVFKRC GPDGQWVRGP RGQPWRDASQ CQMDGEEIEV QKEVAKMYSS FQVMYTVGYS LSLGALLLAL AILGGLSKLH CTRNAIHANL FASFVLKASS VLVIDGLLRT RYSQKIGDDL SVSTWLSDGA VAGCRVAAVF MQYGIVANYC WLLVEGLYLH NLLGLATLPE RSFFSLYLGI GWGAPMLFVV PWAVVKCLFE NVQCWTSNDN MGFWWILRFP VFLAILINFF IFVRIVQLLV AKLRARQMHH TDYKFRLAKS TLTLIPLLGV HEVVFAFVTD EHAQGTLRSA KLFFDLFLSS FQGLLVAVLY CFLNKEVQSE LRRRWHRWRL GKVLWEERNT SNHRASSSPG HGPPSKELQF GRGGGSQDSS AETPLAGGLP RLAESPF //