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Protein

Glucagon-like peptide 1 receptor

Gene

GLP1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:8405712, PubMed:8216285, PubMed:7517895, PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (PubMed:8405712, PubMed:8216285, PubMed:7517895, PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449). Plays a role in regulating insulin secretion in response to GLP-1 (By similarity).By similarity7 Publications

Enzyme regulationi

The allosteric modulators NNC0640, PF-06372222 and MK-0893 inhibit the increase of intracellular cAMP levels in response to GLP-1.1 Publication

GO - Molecular functioni

  • glucagon-like peptide 1 receptor activity Source: UniProtKB
  • glucagon receptor activity Source: InterPro
  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-418555 G alpha (s) signalling events
R-HSA-420092 Glucagon-type ligand receptors
SIGNORiP43220

Protein family/group databases

TCDBi9.A.14.4.6 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
Glucagon-like peptide 1 receptor
Short name:
GLP-1 receptor
Short name:
GLP-1-R
Short name:
GLP-1R
Gene namesi
Name:GLP1R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112164.5
HGNCiHGNC:4324 GLP1R
MIMi138032 gene
neXtProtiNX_P43220

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 139Extracellular1 PublicationAdd BLAST116
Transmembranei140 – 164Helical; Name=11 PublicationAdd BLAST25
Topological domaini165 – 175Cytoplasmic1 PublicationAdd BLAST11
Transmembranei176 – 201Helical; Name=21 PublicationAdd BLAST26
Topological domaini202 – 227Extracellular1 PublicationAdd BLAST26
Transmembranei228 – 251Helical; Name=31 PublicationAdd BLAST24
Topological domaini252 – 265Cytoplasmic1 PublicationAdd BLAST14
Transmembranei266 – 290Helical; Name=41 PublicationAdd BLAST25
Topological domaini291 – 305Extracellular1 PublicationAdd BLAST15
Transmembranei306 – 328Helical; Name=51 PublicationAdd BLAST23
Topological domaini329 – 348Cytoplasmic1 PublicationAdd BLAST20
Transmembranei349 – 370Helical; Name=61 PublicationAdd BLAST22
Topological domaini371 – 383Extracellular1 PublicationAdd BLAST13
Transmembranei384 – 404Helical; Name=71 PublicationAdd BLAST21
Topological domaini405 – 463Cytoplasmic1 PublicationAdd BLAST59

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32L → A: No effect on stimulation of cAMP accumulation and on GLP-1 binding. 1 Publication1
Mutagenesisi69Y → A: Abolishes stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi88Y → A: Abolishes stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi89L → A: Abolishes stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi90P → A: Strongly decreased stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi121R → A: Strongly decreased stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi127E → A: No effect on stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi128E → A: Slightly decreases stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi128E → Q: No effect on stimulation of cAMP accumulation in response to GLP-1. 1 Publication1
Mutagenesisi176R → Q: Decreases sensitivity to GLP-1. 1 Publication1
Mutagenesisi317I → C: Causes the formation of an artifactual disulfide bond that abolishes signaling in response to GLP-1 binding; when associated with C-361. 1 Publication1
Mutagenesisi352S → A: Abolishes inhibition by negative allosteric modulators. 1 Publication1
Mutagenesisi355T → A: Abolishes inhibition by the negative allosteric modulators NNC0640 and PF-06372222, but does not abolish inhibition by MK-0893. 1 Publication1
Mutagenesisi361G → C: Causes the formation of an artifactual disulfide bond that abolishes signaling in response to GLP-1 binding; when associated with C-317. 1 Publication1

Organism-specific databases

DisGeNETi2740
OpenTargetsiENSG00000112164
PharmGKBiPA28725

Chemistry databases

ChEMBLiCHEMBL1784
DrugBankiDB09043 Albiglutide
DB09045 Dulaglutide
DB01276 Exenatide
DB00040 Glucagon recombinant
DB05162 GSK716155
DB06655 Liraglutide
GuidetoPHARMACOLOGYi249

Polymorphism and mutation databases

BioMutaiGLP1R
DMDMi311033387

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001283524 – 463Glucagon-like peptide 1 receptorAdd BLAST440

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi46 ↔ 71Combined sources3 Publications
Disulfide bondi62 ↔ 104Combined sources3 Publications
Glycosylationi63N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi82N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi85 ↔ 126Combined sources3 Publications
Glycosylationi115N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi226 ↔ 296Combined sources4 Publications
Modified residuei341ADP-ribosylcysteine1 Publication1
Modified residuei348ADP-ribosylarginine1 Publication1

Post-translational modificationi

N-glycosylation enhances cell surface expression and lengthens receptor half-life by preventing degradation in the ER.1 Publication

Keywords - PTMi

ADP-ribosylation, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43220
PeptideAtlasiP43220
PRIDEiP43220
ProteomicsDBi55596

PTM databases

iPTMnetiP43220
PhosphoSitePlusiP43220

Expressioni

Gene expression databases

BgeeiENSG00000112164
CleanExiHS_GLP1R
GenevisibleiP43220 HS

Interactioni

Subunit structurei

May form homodimers and heterodimers with GIPR.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei121Interaction with the endogenous ligand GLP-11 Publication1
Sitei128Interaction with the endogenous ligand GLP-11 Publication1

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109002, 106 interactors
DIPiDIP-29980N
IntActiP43220, 10 interactors
MINTiP43220
STRINGi9606.ENSP00000362353

Chemistry databases

BindingDBiP43220

Structurei

Secondary structure

1463
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 52Combined sources21
Beta strandi57 – 59Combined sources3
Beta strandi68 – 71Combined sources4
Beta strandi79 – 84Combined sources6
Helixi92 – 94Combined sources3
Beta strandi99 – 104Combined sources6
Beta strandi108 – 110Combined sources3
Beta strandi116 – 119Combined sources4
Helixi124 – 126Combined sources3
Helixi137 – 142Combined sources6
Helixi170 – 172Combined sources3
Helixi175 – 199Combined sources25
Helixi206 – 210Combined sources5
Turni220 – 222Combined sources3
Helixi224 – 256Combined sources33
Helixi263 – 273Combined sources11
Helixi275 – 291Combined sources17
Turni295 – 298Combined sources4
Turni304 – 306Combined sources3
Helixi307 – 336Combined sources30
Helixi345 – 366Combined sources22
Turni367 – 369Combined sources3
Turni370 – 372Combined sources3
Helixi373 – 375Combined sources3
Helixi381 – 384Combined sources4
Helixi387 – 402Combined sources16
Turni403 – 405Combined sources3
Helixi407 – 421Combined sources15

3D structure databases

ProteinModelPortaliP43220
SMRiP43220
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43220

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni352 – 355Important for allosteric inhibitor binding1 Publication4

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564 Eukaryota
ENOG410XRS2 LUCA
GeneTreeiENSGT00760000118800
HOGENOMiHOG000008250
HOVERGENiHBG008318
InParanoidiP43220
KOiK04581
OMAiRNSNMNY
OrthoDBiEOG091G0NF8
PhylomeDBiP43220
TreeFamiTF315710

Family and domain databases

CDDicd15268 7tmB1_GLP1R, 1 hit
Gene3Di4.10.1240.10, 1 hit
InterProiView protein in InterPro
IPR017981 GPCR_2-like
IPR036445 GPCR_2_extracell_dom_sf
IPR001879 GPCR_2_extracellular_dom
IPR003290 GPCR_2_GLP1/glucagon_rcpt
IPR003292 GPCR_2_GLP1_rcpt
IPR000832 GPCR_2_secretin-like
IPR017983 GPCR_2_secretin-like_CS
PANTHERiPTHR12011:SF245 PTHR12011:SF245, 1 hit
PfamiView protein in Pfam
PF00002 7tm_2, 1 hit
PF02793 HRM, 1 hit
PRINTSiPR01353 GLUCAGNFAMLY
PR01355 GLUCAGNLIKER
PR00249 GPCRSECRETIN
SMARTiView protein in SMART
SM00008 HormR, 1 hit
SUPFAMiSSF111418 SSF111418, 1 hit
PROSITEiView protein in PROSITE
PS00649 G_PROTEIN_RECEP_F2_1, 1 hit
PS00650 G_PROTEIN_RECEP_F2_2, 1 hit
PS50227 G_PROTEIN_RECEP_F2_3, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43220-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGAPGPLRL ALLLLGMVGR AGPRPQGATV SLWETVQKWR EYRRQCQRSL
60 70 80 90 100
TEDPPPATDL FCNRTFDEYA CWPDGEPGSF VNVSCPWYLP WASSVPQGHV
110 120 130 140 150
YRFCTAEGLW LQKDNSSLPW RDLSECEESK RGERSSPEEQ LLFLYIIYTV
160 170 180 190 200
GYALSFSALV IASAILLGFR HLHCTRNYIH LNLFASFILR ALSVFIKDAA
210 220 230 240 250
LKWMYSTAAQ QHQWDGLLSY QDSLSCRLVF LLMQYCVAAN YYWLLVEGVY
260 270 280 290 300
LYTLLAFSVL SEQWIFRLYV SIGWGVPLLF VVPWGIVKYL YEDEGCWTRN
310 320 330 340 350
SNMNYWLIIR LPILFAIGVN FLIFVRVICI VVSKLKANLM CKTDIKCRLA
360 370 380 390 400
KSTLTLIPLL GTHEVIFAFV MDEHARGTLR FIKLFTELSF TSFQGLMVAI
410 420 430 440 450
LYCFVNNEVQ LEFRKSWERW RLEHLHIQRD SSMKPLKCPT SSLSSGATAG
460
SSMYTATCQA SCS
Length:463
Mass (Da):53,026
Last modified:November 2, 2010 - v2
Checksum:iEE7C0EAE29931F5D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12L → V in AAA03614 (PubMed:8405712).Curated1
Sequence conflicti12L → V no nucleotide entry (PubMed:7517895).Curated1
Sequence conflicti12L → V in AAB64013 (PubMed:9213353).Curated1
Sequence conflicti136 – 137SP → WG in AAA03614 (PubMed:8405712).Curated2
Sequence conflicti137P → R no nucleotide entry (PubMed:7517895).Curated1
Sequence conflicti151G → A in AAA03614 (PubMed:8405712).Curated1
Sequence conflicti221Q → L in AAA63787 (PubMed:7843404).Curated1
Sequence conflicti289Y → I in AAA03614 (PubMed:8405712).Curated1
Sequence conflicti316A → G in AAA62471 (PubMed:8404634).Curated1
Sequence conflicti316A → G in AAC50050 (PubMed:8404634).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0189247P → L1 PublicationCorresponds to variant dbSNP:rs10305420Ensembl.1
Natural variantiVAR_01892520R → K1 PublicationCorresponds to variant dbSNP:rs10305421Ensembl.1
Natural variantiVAR_01892644R → H1 PublicationCorresponds to variant dbSNP:rs2295006Ensembl.1
Natural variantiVAR_018927131R → Q1 PublicationCorresponds to variant dbSNP:rs3765467Ensembl.1
Natural variantiVAR_018928168G → S1 PublicationCorresponds to variant dbSNP:rs6923761Ensembl.1
Natural variantiVAR_015098260L → F6 PublicationsCorresponds to variant dbSNP:rs1042044Ensembl.1
Natural variantiVAR_018929316A → T1 PublicationCorresponds to variant dbSNP:rs10305492Ensembl.1
Natural variantiVAR_018930333S → C1 PublicationCorresponds to variant dbSNP:rs10305493Ensembl.1
Natural variantiVAR_018931421R → Q1 PublicationCorresponds to variant dbSNP:rs10305510Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U01104 mRNA Translation: AAA03614.1
U01157 mRNA Translation: AAA62471.1
U01156 mRNA Translation: AAC50050.1
L23503 mRNA Translation: AAA17021.1
U10037 mRNA Translation: AAA63787.1
AB065685 Genomic DNA Translation: BAC05908.1
AY439112 Genomic DNA Translation: AAR05444.1
AL035690 Genomic DNA No translation available.
BC112126 mRNA Translation: AAI12127.1
BC113493 mRNA Translation: AAI13494.1
U66062 Genomic DNA Translation: AAB64013.1
CCDSiCCDS4839.1
PIRiI84494
S71624
RefSeqiNP_002053.3, NM_002062.4
UniGeneiHs.351883
Hs.389103

Genome annotation databases

EnsembliENST00000373256; ENSP00000362353; ENSG00000112164
GeneIDi2740
KEGGihsa:2740
UCSCiuc003ooj.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGLP1R_HUMAN
AccessioniPrimary (citable) accession number: P43220
Secondary accession number(s): Q2M229, Q99669
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 2, 2010
Last modified: July 18, 2018
This is version 176 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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