GLP1R_HUMAN
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 03-AUG-2022, entry version 202.
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; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-7466542, EBI-11749135;
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; 7DUQ; EM; 2.50 A; R=24-463.
DR PDB; 7DUR; EM; 3.30 A; R=24-463.
DR PDB; 7E14; EM; 2.90 A; R=24-463.
DR PDB; 7EVM; EM; 2.50 A; R=24-463.
DR PDB; 7FIM; EM; 3.40 A; R=24-463.
DR PDB; 7KI0; EM; 2.50 A; R=24-463.
DR PDB; 7KI1; EM; 2.50 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 PDB; 7LLL; EM; 3.70 A; R=24-463.
DR PDB; 7LLY; EM; 3.30 A; R=24-463.
DR PDB; 7RG9; EM; 3.20 A; R=24-422.
DR PDB; 7RGP; EM; 2.90 A; R=24-422.
DR PDB; 7RTB; EM; 2.14 A; R=22-463.
DR PDB; 7S1M; EM; 2.41 A; R=24-463.
DR PDB; 7S3I; EM; 2.51 A; R=24-463.
DR PDB; 7VBH; EM; 3.00 A; R=24-463.
DR PDB; 7VBI; EM; 3.00 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; 7DUQ; -.
DR PDBsum; 7DUR; -.
DR PDBsum; 7E14; -.
DR PDBsum; 7EVM; -.
DR PDBsum; 7FIM; -.
DR PDBsum; 7KI0; -.
DR PDBsum; 7KI1; -.
DR PDBsum; 7LCI; -.
DR PDBsum; 7LCJ; -.
DR PDBsum; 7LCK; -.
DR PDBsum; 7LLL; -.
DR PDBsum; 7LLY; -.
DR PDBsum; 7RG9; -.
DR PDBsum; 7RGP; -.
DR PDBsum; 7RTB; -.
DR PDBsum; 7S1M; -.
DR PDBsum; 7S3I; -.
DR PDBsum; 7VBH; -.
DR PDBsum; 7VBI; -.
DR AlphaFoldDB; P43220; -.
DR SMR; P43220; -.
DR BioGRID; 109002; 261.
DR DIP; DIP-29980N; -.
DR IntAct; P43220; 12.
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; DB16697; Glutazumab.
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; 543 antibodies from 35 providers.
DR DNASU; 2740; -.
DR Ensembl; ENST00000373256.5; ENSP00000362353.4; ENSG00000112164.6.
DR GeneID; 2740; -.
DR KEGG; hsa:2740; -.
DR MANE-Select; ENST00000373256.5; ENSP00000362353.4; NM_002062.5; NP_002053.3.
DR UCSC; uc003ooj.5; human.
DR CTD; 2740; -.
DR DisGeNET; 2740; -.
DR GeneCards; GLP1R; -.
DR HGNC; HGNC:4324; GLP1R.
DR HPA; ENSG00000112164; Tissue enhanced (brain, heart muscle, pancreas).
DR MIM; 138032; gene.
DR neXtProt; NX_P43220; -.
DR OpenTargets; ENSG00000112164; -.
DR PharmGKB; PA28725; -.
DR VEuPathDB; HostDB:ENSG00000112164; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000161009; -.
DR HOGENOM; CLU_002753_4_0_1; -.
DR InParanoid; P43220; -.
DR OMA; CFVNNEK; -.
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 SignaLink; P43220; -.
DR SIGNOR; P43220; -.
DR BioGRID-ORCS; 2740; 10 hits in 1074 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 islet of Langerhans and 106 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:0046879; P:hormone secretion; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
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:0031204; P:post-translational protein targeting to membrane, translocation; IEA:Ensembl.
DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl.
DR GO; GO:1990911; P:response to psychosocial stress; IEA:Ensembl.
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 53..56
FT /evidence="ECO:0007829|PDB:7RTB"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:5E94"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:7RTB"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:4ZGM"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:7DUR"
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 TURN 105..107
FT /evidence="ECO:0007829|PDB:7KI0"
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 145..168
FT /evidence="ECO:0007829|PDB:7EVM"
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:7S1M"
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:7KI0"
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
