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P43220 (GLP1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glucagon-like peptide 1 receptor

Short name=GLP-1 receptor
Short name=GLP-1-R
Short name=GLP-1R
Gene names
Name:GLP1R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length463 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

Subunit structure

May form homodimers and heterodimers with GIPR. Ref.13

Subcellular location

Cell membrane; Multi-pass membrane protein.

Post-translational modification

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

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 463440Glucagon-like peptide 1 receptor
PRO_0000012835

Regions

Topological domain24 – 139116Extracellular By similarity
Transmembrane140 – 16425Helical; Name=1; By similarity
Topological domain165 – 17612Cytoplasmic By similarity
Transmembrane177 – 20125Helical; Name=2; By similarity
Topological domain202 – 22726Extracellular By similarity
Transmembrane228 – 25124Helical; Name=3; By similarity
Topological domain252 – 26514Cytoplasmic By similarity
Transmembrane266 – 28722Helical; Name=4; By similarity
Topological domain288 – 30518Extracellular By similarity
Transmembrane306 – 32823Helical; Name=5; By similarity
Topological domain329 – 35224Cytoplasmic By similarity
Transmembrane353 – 37119Helical; Name=6; By similarity
Topological domain372 – 38312Extracellular By similarity
Transmembrane384 – 40421Helical; Name=7; By similarity
Topological domain405 – 46359Cytoplasmic By similarity

Amino acid modifications

Modified residue3411ADP-ribosylcysteine
Modified residue3481ADP-ribosylarginine
Glycosylation631N-linked (GlcNAc...) Ref.13
Glycosylation821N-linked (GlcNAc...) Ref.13
Glycosylation1151N-linked (GlcNAc...) Ref.13
Disulfide bond46 ↔ 71 Ref.11 Ref.14
Disulfide bond62 ↔ 104 Ref.11 Ref.14
Disulfide bond85 ↔ 126 Ref.11 Ref.14
Disulfide bond226 ↔ 296 Ref.11 Ref.14

Natural variations

Natural variant71P → L. Ref.7
Corresponds to variant rs10305420 [ dbSNP | Ensembl ].
VAR_018924
Natural variant201R → K. Ref.7
Corresponds to variant rs10305421 [ dbSNP | Ensembl ].
VAR_018925
Natural variant441R → H. Ref.7
Corresponds to variant rs2295006 [ dbSNP | Ensembl ].
VAR_018926
Natural variant1311R → Q. Ref.7
Corresponds to variant rs3765467 [ dbSNP | Ensembl ].
VAR_018927
Natural variant1681G → S. Ref.7
Corresponds to variant rs6923761 [ dbSNP | Ensembl ].
VAR_018928
Natural variant2601L → F. Ref.1 Ref.2 Ref.3 Ref.5 Ref.7 Ref.9
Corresponds to variant rs1042044 [ dbSNP | Ensembl ].
VAR_015098
Natural variant3161A → T. Ref.7
Corresponds to variant rs10305492 [ dbSNP | Ensembl ].
VAR_018929
Natural variant3331S → C. Ref.7
Corresponds to variant rs10305493 [ dbSNP | Ensembl ].
VAR_018930
Natural variant4211R → Q. Ref.7
Corresponds to variant rs10305510 [ dbSNP | Ensembl ].
VAR_018931

Experimental info

Sequence conflict121L → V in AAA03614. Ref.1
Sequence conflict121L → V no nucleotide entry Ref.4
Sequence conflict121L → V in AAB64013. Ref.10
Sequence conflict136 – 1372SP → WG in AAA03614. Ref.1
Sequence conflict1371P → R no nucleotide entry Ref.4
Sequence conflict1511G → A in AAA03614. Ref.1
Sequence conflict2211Q → L in AAA63787. Ref.5
Sequence conflict2891Y → I in AAA03614. Ref.1
Sequence conflict3161A → G in AAA62471. Ref.2
Sequence conflict3161A → G in AAC50050. Ref.2

Secondary structure

................. 463
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P43220 [UniParc].

Last modified November 2, 2010. Version 2.
Checksum: EE7C0EAE29931F5D

FASTA46353,026
        10         20         30         40         50         60 
MAGAPGPLRL ALLLLGMVGR AGPRPQGATV SLWETVQKWR EYRRQCQRSL TEDPPPATDL 

        70         80         90        100        110        120 
FCNRTFDEYA CWPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW 

       130        140        150        160        170        180 
RDLSECEESK RGERSSPEEQ LLFLYIIYTV GYALSFSALV IASAILLGFR HLHCTRNYIH 

       190        200        210        220        230        240 
LNLFASFILR ALSVFIKDAA LKWMYSTAAQ QHQWDGLLSY QDSLSCRLVF LLMQYCVAAN 

       250        260        270        280        290        300 
YYWLLVEGVY LYTLLAFSVL SEQWIFRLYV SIGWGVPLLF VVPWGIVKYL YEDEGCWTRN 

       310        320        330        340        350        360 
SNMNYWLIIR LPILFAIGVN FLIFVRVICI VVSKLKANLM CKTDIKCRLA KSTLTLIPLL 

       370        380        390        400        410        420 
GTHEVIFAFV MDEHARGTLR FIKLFTELSF TSFQGLMVAI LYCFVNNEVQ LEFRKSWERW 

       430        440        450        460 
RLEHLHIQRD SSMKPLKCPT SSLSSGATAG SSMYTATCQA SCS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor."
Thorens B., Porret A., Buehler L., Deng S., Morel P., Widmann C.
Diabetes 42:1678-1682(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-260.
Tissue: Pancreatic islet.
[2]"Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor."
Dillon J.S., Tanizawa Y., Wheeler M.B., Leng X., Ligon B.B., Rabin D.U., Yoo-Warren H., Permutt M., Boyd A.E.
Endocrinology 133:1907-1910(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-260.
Tissue: Pancreas.
[3]"Cloning and functional expression of a human glucagon-like peptide-1 receptor."
Graziano M.P., Hey P.J., Borkowski D., Chicchi G.C., Strader C.D.
Biochem. Biophys. Res. Commun. 196:141-146(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-260.
Tissue: Gastric carcinoma.
[4]"Signal transduction of the GLP-1-receptor cloned from a human insulinoma."
van Eyll B., Lankat-Buttgereit B., Bode H.P., Goeke R., Goeke B.
FEBS Lett. 348:7-13(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Insulinoma.
[5]"Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences."
Wei Y., Mojsov S.
FEBS Lett. 358:219-224(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-260.
Tissue: Pancreas.
[6]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]NIEHS SNPs program
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-7; LYS-20; HIS-44; GLN-131; SER-168; PHE-260; THR-316; CYS-333 AND GLN-421.
[8]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PHE-260.
[10]"Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene."
Lankat-Buttgereit B., Goeke B.
Peptides 18:617-624(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
Tissue: Placenta.
[11]"Functional coupling of Cys-226 and Cys-296 in the glucagon-like peptide-1 (GLP-1) receptor indicates a disulfide bond that is close to the activation pocket."
Mann R.J., Al-Sabah S., de Maturana R.L., Sinfield J.K., Donnelly D.
Peptides 31:2289-2293(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BOND.
[12]"Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase."
Dezelak M., Bavec A.
Mol. Biol. Rep. 39:4375-4381(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ADP-RIBOSYLATION AT CYS-341 AND ARG-348.
[13]"Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation and receptor heteromerization."
Whitaker G.M., Lynn F.C., McIntosh C.H., Accili E.A.
PLoS ONE 7:E32675-E32675(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-63; ASN-82 AND ASN-115, SUBUNIT.
[14]"Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain."
Runge S., Thogersen H., Madsen K., Lau J., Rudolph R.
J. Biol. Chem. 283:11340-11347(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 24-145 IN COMPLEX WITH ANTAGONIST EXENDIN-4, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Glucagon-like peptide 1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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. Translation: CAB71177.1.
BC112126 mRNA. Translation: AAI12127.1.
BC113493 mRNA. Translation: AAI13494.1.
U66062 Genomic DNA. Translation: AAB64013.1.
CCDSCCDS4839.1.
PIRI84494.
S71624.
RefSeqNP_002053.3. NM_002062.3.
XP_006715128.1. XM_006715065.1.
UniGeneHs.389103.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3C59X-ray2.30A24-145[»]
3C5TX-ray2.10A24-145[»]
3IOLX-ray2.10A24-145[»]
ProteinModelPortalP43220.
SMRP43220. Positions 28-412.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109002. 43 interactions.
DIPDIP-29980N.
MINTMINT-1217566.
STRING9606.ENSP00000362353.

Chemistry

BindingDBP43220.
ChEMBLCHEMBL1784.
DrugBankDB01276. Exenatide.
DB00040. Glucagon recombinant.
GuidetoPHARMACOLOGY249.

Protein family/group databases

TCDB9.A.14.4.6. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteP43220.

Polymorphism databases

DMDM311033387.

Proteomic databases

PaxDbP43220.
PRIDEP43220.

Protocols and materials databases

DNASU2740.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373256; ENSP00000362353; ENSG00000112164.
GeneID2740.
KEGGhsa:2740.
UCSCuc003ooj.4. human.

Organism-specific databases

CTD2740.
GeneCardsGC06P039063.
H-InvDBHIX0095000.
HIX0200932.
HGNCHGNC:4324. GLP1R.
MIM138032. gene.
neXtProtNX_P43220.
PharmGKBPA28725.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263329.
HOGENOMHOG000008250.
HOVERGENHBG008318.
InParanoidP43220.
KOK04581.
OMACIVVSKL.
OrthoDBEOG7TF78W.
PhylomeDBP43220.
TreeFamTF315710.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.

Gene expression databases

BgeeP43220.
CleanExHS_GLP1R.
GenevestigatorP43220.

Family and domain databases

InterProIPR017981. GPCR_2-like.
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.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR01353. GLUCAGNFAMLY.
PR01355. GLUCAGNLIKER.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. 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.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP43220.
GeneWikiGlucagon-like_peptide_1_receptor.
GenomeRNAi2740.
NextBio10800.
PROP43220.
SOURCESearch...

Entry information

Entry nameGLP1R_HUMAN
AccessionPrimary (citable) accession number: P43220
Secondary accession number(s): Q2M229, Q99669
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries