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Database: UniProt
Entry: P43220
LinkDB: P43220
Original site: P43220 
ID   GLP1R_HUMAN             Reviewed;         463 AA.
AC   P43220; Q2M229; Q99669;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 2.
DT   02-JUN-2021, entry version 198.
DE   RecName: Full=Glucagon-like peptide 1 receptor;
DE            Short=GLP-1 receptor;
DE            Short=GLP-1-R;
DE            Short=GLP-1R;
DE   Flags: Precursor;
GN   Name=GLP1R;
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, SUBCELLULAR LOCATION, AND VARIANT
RP   PHE-260.
RC   TISSUE=Pancreatic islet;
RX   PubMed=8405712; DOI=10.2337/diab.42.11.1678;
RA   Thorens B., Porret A., Buehler L., Deng S., Morel P., Widmann C.;
RT   "Cloning and functional expression of the human islet GLP-1 receptor.
RT   Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist
RT   of the receptor.";
RL   Diabetes 42:1678-1682(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-260.
RC   TISSUE=Pancreas;
RX   PubMed=8404634; DOI=10.1210/endo.133.4.8404634;
RA   Dillon J.S., Tanizawa Y., Wheeler M.B., Leng X., Ligon B.B., Rabin D.U.,
RA   Yoo-Warren H., Permutt M., Boyd A.E.;
RT   "Cloning and functional expression of the human glucagon-like peptide-1
RT   (GLP-1) receptor.";
RL   Endocrinology 133:1907-1910(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND VARIANT
RP   PHE-260.
RC   TISSUE=Gastric carcinoma;
RX   PubMed=8216285; DOI=10.1006/bbrc.1993.2226;
RA   Graziano M.P., Hey P.J., Borkowski D., Chicchi G.C., Strader C.D.;
RT   "Cloning and functional expression of a human glucagon-like peptide-1
RT   receptor.";
RL   Biochem. Biophys. Res. Commun. 196:141-146(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Insulinoma;
RX   PubMed=7517895; DOI=10.1016/0014-5793(94)00553-2;
RA   van Eyll B., Lankat-Buttgereit B., Bode H.P., Goeke R., Goeke B.;
RT   "Signal transduction of the GLP-1-receptor cloned from a human
RT   insulinoma.";
RL   FEBS Lett. 348:7-13(1994).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-260.
RC   TISSUE=Pancreas;
RX   PubMed=7843404; DOI=10.1016/0014-5793(94)01430-9;
RA   Wei Y., Mojsov S.;
RT   "Tissue-specific expression of the human receptor for glucagon-like
RT   peptide-I: brain, heart and pancreatic forms have the same deduced amino
RT   acid sequences.";
RL   FEBS Lett. 358:219-224(1995).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA   Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT   "Genome-wide discovery and analysis of human seven transmembrane helix
RT   receptor genes.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-7; LYS-20; HIS-44;
RP   GLN-131; SER-168; PHE-260; THR-316; CYS-333 AND GLN-421.
RG   NIEHS SNPs program;
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-260.
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   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
RC   TISSUE=Placenta;
RX   PubMed=9213353; DOI=10.1016/s0196-9781(97)00001-6;
RA   Lankat-Buttgereit B., Goeke B.;
RT   "Cloning and characterization of the 5' flanking sequences (promoter
RT   region) of the human GLP-1 receptor gene.";
RL   Peptides 18:617-624(1997).
RN   [11]
RP   DISULFIDE BOND.
RX   PubMed=20869417; DOI=10.1016/j.peptides.2010.09.015;
RA   Mann R.J., Al-Sabah S., de Maturana R.L., Sinfield J.K., Donnelly D.;
RT   "Functional coupling of Cys-226 and Cys-296 in the glucagon-like peptide-1
RT   (GLP-1) receptor indicates a disulfide bond that is close to the activation
RT   pocket.";
RL   Peptides 31:2289-2293(2010).
RN   [12]
RP   ADP-RIBOSYLATION AT CYS-341 AND ARG-348.
RX   PubMed=21901419; DOI=10.1007/s11033-011-1225-0;
RA   Dezelak M., Bavec A.;
RT   "Glucagon like-peptide-1 receptor is covalently modified by endogenous
RT   mono-ADP-ribosyltransferase.";
RL   Mol. Biol. Rep. 39:4375-4381(2012).
RN   [13]
RP   GLYCOSYLATION AT ASN-63; ASN-82 AND ASN-115, AND SUBUNIT.
RX   PubMed=22412906; DOI=10.1371/journal.pone.0032675;
RA   Whitaker G.M., Lynn F.C., McIntosh C.H., Accili E.A.;
RT   "Regulation of GIP and GLP1 receptor cell surface expression by N-
RT   glycosylation and receptor heteromerization.";
RL   PLoS ONE 7:E32675-E32675(2012).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 24-145 IN COMPLEX WITH ANTAGONIST
RP   EXENDIN-4, AND DISULFIDE BONDS.
RX   PubMed=18287102; DOI=10.1074/jbc.m708740200;
RA   Runge S., Thogersen H., Madsen K., Lau J., Rudolph R.;
RT   "Crystal structure of the ligand-bound glucagon-like peptide-1 receptor
RT   extracellular domain.";
RL   J. Biol. Chem. 283:11340-11347(2008).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 24-145 IN COMPLEX WITH
RP   GLUCAGON-LIKE PEPTIDE-1, FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BONDS,
RP   AND MUTAGENESIS OF LEU-32; TYR-69; TYR-88; LEU-89; PRO-90; ARG-121; GLU-127
RP   AND GLU-128.
RX   PubMed=19861722; DOI=10.1074/jbc.m109.033829;
RA   Underwood C.R., Garibay P., Knudsen L.B., Hastrup S., Peters G.H.,
RA   Rudolph R., Reedtz-Runge S.;
RT   "Crystal structure of glucagon-like peptide-1 in complex with the
RT   extracellular domain of the glucagon-like peptide-1 receptor.";
RL   J. Biol. Chem. 285:723-730(2010).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 24-145, FUNCTION, SUBCELLULAR
RP   LOCATION, AND DISULFIDE BONDS.
RX   PubMed=26308095; DOI=10.1021/acs.jmedchem.5b00726;
RA   Lau J., Bloch P., Schaeffer L., Pettersson I., Spetzler J., Kofoed J.,
RA   Madsen K., Knudsen L.B., McGuire J., Steensgaard D.B., Strauss H.M.,
RA   Gram D.X., Knudsen S.M., Nielsen F.S., Thygesen P., Reedtz-Runge S.,
RA   Kruse T.;
RT   "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue
RT   Semaglutide.";
RL   J. Med. Chem. 58:7370-7380(2015).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 24-145, FUNCTION, SUBCELLULAR
RP   LOCATION, AND DISULFIDE BONDS.
RX   PubMed=27196125; DOI=10.1038/srep26236;
RA   Hennen S., Kodra J.T., Soroka V., Krogh B.O., Wu X., Kaastrup P.,
RA   Oerskov C., Roenn S.G., Schluckebier G., Barbateskovic S., Gandhi P.S.,
RA   Reedtz-Runge S.;
RT   "Structural insight into antibody-mediated antagonism of the Glucagon-like
RT   peptide-1 Receptor.";
RL   Sci. Rep. 6:26236-26236(2016).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 128-431 IN COMPLEXES WITH
RP   ALLOSTERIC MODULATORS, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP   TOPOLOGY, DISULFIDE BOND, AND MUTAGENESIS OF ARG-176; ILE-317; SER-352;
RP   THR-355 AND GLY-361.
RX   PubMed=28514449; DOI=10.1038/nature22378;
RA   Song G., Yang D., Wang Y., de Graaf C., Zhou Q., Jiang S., Liu K., Cai X.,
RA   Dai A., Lin G., Liu D., Wu F., Wu Y., Zhao S., Ye L., Han G.W., Lau J.,
RA   Wu B., Hanson M.A., Liu Z.J., Wang M.W., Stevens R.C.;
RT   "Human GLP-1 receptor transmembrane domain structure in complex with
RT   allosteric modulators.";
RL   Nature 546:312-315(2017).
CC   -!- FUNCTION: G-protein coupled receptor for glucagon-like peptide 1 (GLP-
CC       1) (PubMed:8405712, PubMed:8216285, PubMed:7517895, PubMed:19861722,
CC       PubMed:26308095, PubMed:27196125, PubMed:28514449). Ligand binding
CC       triggers activation of a signaling cascade that leads to the activation
CC       of adenylyl cyclase and increased intracellular cAMP levels
CC       (PubMed:8405712, PubMed:8216285, PubMed:7517895, PubMed:19861722,
CC       PubMed:26308095, PubMed:27196125, PubMed:28514449). Plays a role in
CC       regulating insulin secretion in response to GLP-1 (By similarity).
CC       {ECO:0000250|UniProtKB:O35659, ECO:0000269|PubMed:19861722,
CC       ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
CC       ECO:0000269|PubMed:28514449, ECO:0000269|PubMed:7517895,
CC       ECO:0000269|PubMed:8216285, ECO:0000269|PubMed:8405712}.
CC   -!- ACTIVITY REGULATION: The allosteric modulators NNC0640, PF-06372222 and
CC       MK-0893 inhibit the increase of intracellular cAMP levels in response
CC       to GLP-1. {ECO:0000269|PubMed:28514449}.
CC   -!- SUBUNIT: May form homodimers and heterodimers with GIPR.
CC       {ECO:0000269|PubMed:18287102, ECO:0000269|PubMed:22412906}.
CC   -!- INTERACTION:
CC       P43220; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7466542, EBI-3867333;
CC       P43220; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-7466542, EBI-11959885;
CC       P43220; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-7466542, EBI-10172290;
CC       P43220; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-7466542, EBI-10171774;
CC       P43220; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-7466542, EBI-10172052;
CC       P43220; Q9BYP8: KRTAP17-1; NbExp=3; IntAct=EBI-7466542, EBI-11988175;
CC       P43220; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-7466542, EBI-3958099;
CC       P43220; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-7466542, EBI-945833;
CC       P43220; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-7466542, EBI-22310682;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19861722,
CC       ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
CC       ECO:0000269|PubMed:28514449, ECO:0000269|PubMed:7517895,
CC       ECO:0000269|PubMed:8216285, ECO:0000269|PubMed:8405712}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:28514449}.
CC   -!- PTM: N-glycosylation enhances cell surface expression and lengthens
CC       receptor half-life by preventing degradation in the ER.
CC       {ECO:0000269|PubMed:22412906}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/glp1r/";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Glucagon-like peptide 1 entry;
CC       URL="https://en.wikipedia.org/wiki/Glucagon-like_peptide-1";
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DR   EMBL; U01104; AAA03614.1; -; mRNA.
DR   EMBL; U01157; AAA62471.1; -; mRNA.
DR   EMBL; U01156; AAC50050.1; -; mRNA.
DR   EMBL; L23503; AAA17021.1; -; mRNA.
DR   EMBL; U10037; AAA63787.1; -; mRNA.
DR   EMBL; AB065685; BAC05908.1; -; Genomic_DNA.
DR   EMBL; AY439112; AAR05444.1; -; Genomic_DNA.
DR   EMBL; AL035690; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC112126; AAI12127.1; -; mRNA.
DR   EMBL; BC113493; AAI13494.1; -; mRNA.
DR   EMBL; U66062; AAB64013.1; -; Genomic_DNA.
DR   CCDS; CCDS4839.1; -.
DR   PIR; I84494; I84494.
DR   PIR; S71624; S71624.
DR   RefSeq; NP_002053.3; NM_002062.4.
DR   PDB; 3C59; X-ray; 2.30 A; A=24-145.
DR   PDB; 3C5T; X-ray; 2.10 A; A=24-145.
DR   PDB; 3IOL; X-ray; 2.10 A; A=24-145.
DR   PDB; 4ZGM; X-ray; 1.80 A; A=24-145.
DR   PDB; 5E94; X-ray; 2.00 A; G/H=24-145.
DR   PDB; 5NX2; X-ray; 3.70 A; A=24-432.
DR   PDB; 5OTT; X-ray; 1.92 A; A=24-139.
DR   PDB; 5OTU; X-ray; 1.80 A; A/C=24-139.
DR   PDB; 5OTV; X-ray; 2.00 A; A/C=24-139.
DR   PDB; 5OTW; X-ray; 2.10 A; A/C=24-139.
DR   PDB; 5OTX; X-ray; 2.00 A; A/C=24-139.
DR   PDB; 5VEW; X-ray; 2.70 A; A/B=128-257, A/B=261-431.
DR   PDB; 5VEX; X-ray; 3.00 A; A/B=128-257, A/B=261-431.
DR   PDB; 6B3J; EM; 3.30 A; R=24-463.
DR   PDB; 6GB1; X-ray; 2.73 A; A=21-145.
DR   PDB; 6ORV; EM; 3.00 A; RP=24-463.
DR   PDB; 6VCB; EM; 3.30 A; R=24-422.
DR   PDB; 6X18; EM; 2.10 A; R=24-463.
DR   PDB; 6X19; EM; 2.10 A; R=24-463.
DR   PDB; 6X1A; EM; 2.50 A; R=24-463.
DR   PDB; 6XOX; EM; 3.10 A; R=24-422.
DR   PDB; 7C2E; EM; 4.20 A; R=24-463.
DR   PDB; 7LCI; EM; 2.90 A; R=24-463.
DR   PDB; 7LCJ; EM; 2.82 A; R=24-463.
DR   PDB; 7LCK; EM; 3.24 A; R=24-463.
DR   PDBsum; 3C59; -.
DR   PDBsum; 3C5T; -.
DR   PDBsum; 3IOL; -.
DR   PDBsum; 4ZGM; -.
DR   PDBsum; 5E94; -.
DR   PDBsum; 5NX2; -.
DR   PDBsum; 5OTT; -.
DR   PDBsum; 5OTU; -.
DR   PDBsum; 5OTV; -.
DR   PDBsum; 5OTW; -.
DR   PDBsum; 5OTX; -.
DR   PDBsum; 5VEW; -.
DR   PDBsum; 5VEX; -.
DR   PDBsum; 6B3J; -.
DR   PDBsum; 6GB1; -.
DR   PDBsum; 6ORV; -.
DR   PDBsum; 6VCB; -.
DR   PDBsum; 6X18; -.
DR   PDBsum; 6X19; -.
DR   PDBsum; 6X1A; -.
DR   PDBsum; 6XOX; -.
DR   PDBsum; 7C2E; -.
DR   PDBsum; 7LCI; -.
DR   PDBsum; 7LCJ; -.
DR   PDBsum; 7LCK; -.
DR   SMR; P43220; -.
DR   BioGRID; 109002; 261.
DR   DIP; DIP-29980N; -.
DR   IntAct; P43220; 11.
DR   MINT; P43220; -.
DR   STRING; 9606.ENSP00000362353; -.
DR   BindingDB; P43220; -.
DR   ChEMBL; CHEMBL1784; -.
DR   DrugBank; DB09043; Albiglutide.
DR   DrugBank; DB09045; Dulaglutide.
DR   DrugBank; DB01276; Exenatide.
DR   DrugBank; DB00040; Glucagon.
DR   DrugBank; DB06655; Liraglutide.
DR   DrugBank; DB09265; Lixisenatide.
DR   DrugBank; DB13928; Semaglutide.
DR   DrugCentral; P43220; -.
DR   GuidetoPHARMACOLOGY; 249; -.
DR   TCDB; 9.A.14.4.6; the g-protein-coupled receptor (gpcr) family.
DR   GlyGen; P43220; 3 sites.
DR   iPTMnet; P43220; -.
DR   PhosphoSitePlus; P43220; -.
DR   BioMuta; GLP1R; -.
DR   DMDM; 311033387; -.
DR   MassIVE; P43220; -.
DR   PaxDb; P43220; -.
DR   PeptideAtlas; P43220; -.
DR   PRIDE; P43220; -.
DR   ProteomicsDB; 55596; -.
DR   ABCD; P43220; 1 sequenced antibody.
DR   Antibodypedia; 15682; 544 antibodies.
DR   DNASU; 2740; -.
DR   Ensembl; ENST00000373256; ENSP00000362353; ENSG00000112164.
DR   GeneID; 2740; -.
DR   KEGG; hsa:2740; -.
DR   UCSC; uc003ooj.5; human.
DR   CTD; 2740; -.
DR   DisGeNET; 2740; -.
DR   GeneCards; GLP1R; -.
DR   HGNC; HGNC:4324; GLP1R.
DR   HPA; ENSG00000112164; Tissue enhanced (pancreas).
DR   MIM; 138032; gene.
DR   neXtProt; NX_P43220; -.
DR   OpenTargets; ENSG00000112164; -.
DR   PharmGKB; PA28725; -.
DR   VEuPathDB; HostDB:ENSG00000112164.5; -.
DR   eggNOG; KOG4564; Eukaryota.
DR   GeneTree; ENSGT00940000161009; -.
DR   HOGENOM; CLU_002753_4_0_1; -.
DR   InParanoid; P43220; -.
DR   OMA; CRLVFVM; -.
DR   OrthoDB; 651627at2759; -.
DR   PhylomeDB; P43220; -.
DR   TreeFam; TF315710; -.
DR   PathwayCommons; P43220; -.
DR   Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR   SIGNOR; P43220; -.
DR   BioGRID-ORCS; 2740; 5 hits in 987 CRISPR screens.
DR   EvolutionaryTrace; P43220; -.
DR   GeneWiki; Glucagon-like_peptide_1_receptor; -.
DR   GenomeRNAi; 2740; -.
DR   Pharos; P43220; Tclin.
DR   PRO; PR:P43220; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P43220; protein.
DR   Bgee; ENSG00000112164; Expressed in myocardium and 172 other tissues.
DR   Genevisible; P43220; HS.
DR   GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR   GO; GO:0004967; F:glucagon receptor activity; IEA:InterPro.
DR   GO; GO:0044508; F:glucagon-like peptide 1 receptor activity; IDA:UniProtKB.
DR   GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc.
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; IBA:GO_Central.
DR   GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
DR   GO; GO:0045777; P:positive regulation of blood pressure; IBA:GO_Central.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR   Gene3D; 4.10.1240.10; -; 1.
DR   InterPro; IPR017981; GPCR_2-like.
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; IPR003292; GPCR_2_GLP1_rcpt.
DR   InterPro; IPR000832; GPCR_2_secretin-like.
DR   InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR   PANTHER; PTHR45620:SF25; PTHR45620:SF25; 1.
DR   Pfam; PF00002; 7tm_2; 1.
DR   Pfam; PF02793; HRM; 1.
DR   PRINTS; PR01353; GLUCAGNFAMLY.
DR   PRINTS; PR01355; GLUCAGNLIKER.
DR   PRINTS; PR00249; GPCRSECRETIN.
DR   SMART; SM00008; HormR; 1.
DR   SUPFAM; SSF111418; SSF111418; 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.
PE   1: Evidence at protein level;
KW   3D-structure; ADP-ribosylation; Cell membrane; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW   Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..463
FT                   /note="Glucagon-like peptide 1 receptor"
FT                   /id="PRO_0000012835"
FT   TOPO_DOM        24..139
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        140..164
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        165..175
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        176..201
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        202..227
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        228..251
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        252..265
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        266..290
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        291..305
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        306..328
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        329..348
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        349..370
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        371..383
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TRANSMEM        384..404
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   TOPO_DOM        405..463
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   REGION          352..355
FT                   /note="Important for allosteric inhibitor binding"
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   SITE            121
FT                   /note="Interaction with the endogenous ligand GLP-1"
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   SITE            128
FT                   /note="Interaction with the endogenous ligand GLP-1"
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MOD_RES         341
FT                   /note="ADP-ribosylcysteine"
FT                   /evidence="ECO:0000269|PubMed:21901419"
FT   MOD_RES         348
FT                   /note="ADP-ribosylarginine"
FT                   /evidence="ECO:0000269|PubMed:21901419"
FT   CARBOHYD        63
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:22412906"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:22412906"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:22412906"
FT   DISULFID        46..71
FT                   /evidence="ECO:0000269|PubMed:19861722,
FT                   ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
FT                   ECO:0007744|PDB:3C59, ECO:0007744|PDB:3C5T,
FT                   ECO:0007744|PDB:3IOL, ECO:0007744|PDB:4ZGM,
FT                   ECO:0007744|PDB:5E94"
FT   DISULFID        62..104
FT                   /evidence="ECO:0000269|PubMed:19861722,
FT                   ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
FT                   ECO:0007744|PDB:3C59, ECO:0007744|PDB:3C5T,
FT                   ECO:0007744|PDB:3IOL, ECO:0007744|PDB:4ZGM,
FT                   ECO:0007744|PDB:5E94"
FT   DISULFID        85..126
FT                   /evidence="ECO:0000269|PubMed:19861722,
FT                   ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
FT                   ECO:0007744|PDB:3C59, ECO:0007744|PDB:3C5T,
FT                   ECO:0007744|PDB:3IOL, ECO:0007744|PDB:4ZGM,
FT                   ECO:0007744|PDB:5E94"
FT   DISULFID        226..296
FT                   /evidence="ECO:0000269|PubMed:19861722,
FT                   ECO:0000269|PubMed:26308095, ECO:0000269|PubMed:27196125,
FT                   ECO:0000269|PubMed:28514449, ECO:0007744|PDB:3C59,
FT                   ECO:0007744|PDB:3C5T, ECO:0007744|PDB:3IOL,
FT                   ECO:0007744|PDB:4ZGM, ECO:0007744|PDB:5E94,
FT                   ECO:0007744|PDB:5VEW, ECO:0007744|PDB:5VEX"
FT   VARIANT         7
FT                   /note="P -> L (in dbSNP:rs10305420)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018924"
FT   VARIANT         20
FT                   /note="R -> K (in dbSNP:rs10305421)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018925"
FT   VARIANT         44
FT                   /note="R -> H (in dbSNP:rs2295006)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018926"
FT   VARIANT         131
FT                   /note="R -> Q (in dbSNP:rs3765467)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018927"
FT   VARIANT         168
FT                   /note="G -> S (in dbSNP:rs6923761)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018928"
FT   VARIANT         260
FT                   /note="L -> F (in dbSNP:rs1042044)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:7843404, ECO:0000269|PubMed:8216285,
FT                   ECO:0000269|PubMed:8404634, ECO:0000269|PubMed:8405712,
FT                   ECO:0000269|Ref.7"
FT                   /id="VAR_015098"
FT   VARIANT         316
FT                   /note="A -> T (in dbSNP:rs10305492)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018929"
FT   VARIANT         333
FT                   /note="S -> C (in dbSNP:rs10305493)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018930"
FT   VARIANT         421
FT                   /note="R -> Q (in dbSNP:rs10305510)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_018931"
FT   MUTAGEN         32
FT                   /note="L->A: No effect on stimulation of cAMP accumulation
FT                   and on GLP-1 binding."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         69
FT                   /note="Y->A: Abolishes stimulation of cAMP accumulation in
FT                   response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         88
FT                   /note="Y->A: Abolishes stimulation of cAMP accumulation in
FT                   response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         89
FT                   /note="L->A: Abolishes stimulation of cAMP accumulation in
FT                   response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         90
FT                   /note="P->A: Strongly decreased stimulation of cAMP
FT                   accumulation in response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         121
FT                   /note="R->A: Strongly decreased stimulation of cAMP
FT                   accumulation in response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         127
FT                   /note="E->A: No effect on stimulation of cAMP accumulation
FT                   in response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         128
FT                   /note="E->A: Slightly decreases stimulation of cAMP
FT                   accumulation in response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         128
FT                   /note="E->Q: No effect on stimulation of cAMP accumulation
FT                   in response to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:19861722"
FT   MUTAGEN         176
FT                   /note="R->Q: Decreases sensitivity to GLP-1."
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   MUTAGEN         317
FT                   /note="I->C: Causes the formation of an artifactual
FT                   disulfide bond that abolishes signaling in response to GLP-
FT                   1 binding; when associated with C-361."
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   MUTAGEN         352
FT                   /note="S->A: Abolishes inhibition by negative allosteric
FT                   modulators."
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   MUTAGEN         355
FT                   /note="T->A: Abolishes inhibition by the negative
FT                   allosteric modulators NNC0640 and PF-06372222, but does not
FT                   abolish inhibition by MK-0893."
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   MUTAGEN         361
FT                   /note="G->C: Causes the formation of an artifactual
FT                   disulfide bond that abolishes signaling in response to GLP-
FT                   1 binding; when associated with C-317."
FT                   /evidence="ECO:0000269|PubMed:28514449"
FT   CONFLICT        12
FT                   /note="L -> V (in Ref. 1; AAA03614, 4; no nucleotide entry
FT                   and 10; AAB64013)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        136..137
FT                   /note="SP -> WG (in Ref. 1; AAA03614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        137
FT                   /note="P -> R (in Ref. 4; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        151
FT                   /note="G -> A (in Ref. 1; AAA03614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        221
FT                   /note="Q -> L (in Ref. 5; AAA63787)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        289
FT                   /note="Y -> I (in Ref. 1; AAA03614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        316
FT                   /note="A -> G (in Ref. 2; AAA62471/AAC50050)"
FT                   /evidence="ECO:0000305"
FT   HELIX           32..52
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   STRAND          57..59
FT                   /evidence="ECO:0007829|PDB:5E94"
FT   STRAND          68..70
FT                   /evidence="ECO:0007829|PDB:6XOX"
FT   STRAND          79..84
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   HELIX           92..94
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   STRAND          95..97
FT                   /evidence="ECO:0007829|PDB:6X19"
FT   STRAND          99..104
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   STRAND          108..110
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   STRAND          113..115
FT                   /evidence="ECO:0007829|PDB:6VCB"
FT   STRAND          116..119
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   HELIX           124..126
FT                   /evidence="ECO:0007829|PDB:4ZGM"
FT   HELIX           137..142
FT                   /evidence="ECO:0007829|PDB:5E94"
FT   HELIX           170..172
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           175..204
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           207..215
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            220..222
FT                   /evidence="ECO:0007829|PDB:5VEW"
FT   HELIX           224..255
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           264..291
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            294..298
FT                   /evidence="ECO:0007829|PDB:6X19"
FT   HELIX           303..337
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           345..360
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           362..365
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            366..369
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            372..374
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           378..392
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   HELIX           394..402
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            403..405
FT                   /evidence="ECO:0007829|PDB:5VEW"
FT   HELIX           407..418
FT                   /evidence="ECO:0007829|PDB:6X18"
FT   TURN            419..422
FT                   /evidence="ECO:0007829|PDB:6X18"
SQ   SEQUENCE   463 AA;  53026 MW;  EE7C0EAE29931F5D CRC64;
     MAGAPGPLRL ALLLLGMVGR AGPRPQGATV SLWETVQKWR EYRRQCQRSL TEDPPPATDL
     FCNRTFDEYA CWPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW
     RDLSECEESK RGERSSPEEQ LLFLYIIYTV GYALSFSALV IASAILLGFR HLHCTRNYIH
     LNLFASFILR ALSVFIKDAA LKWMYSTAAQ QHQWDGLLSY QDSLSCRLVF LLMQYCVAAN
     YYWLLVEGVY LYTLLAFSVL SEQWIFRLYV SIGWGVPLLF VVPWGIVKYL YEDEGCWTRN
     SNMNYWLIIR LPILFAIGVN FLIFVRVICI VVSKLKANLM CKTDIKCRLA KSTLTLIPLL
     GTHEVIFAFV MDEHARGTLR FIKLFTELSF TSFQGLMVAI LYCFVNNEVQ LEFRKSWERW
     RLEHLHIQRD SSMKPLKCPT SSLSSGATAG SSMYTATCQA SCS
//
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