P43220 (GLP1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucagon-like peptide 1 receptor
Short name=GLP-1 receptor
Short name=GLP-1-R
Short name=GLP-1R

Gene names

Name:

GLP1R

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	463 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	ADP-ribosylation Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Traceable author statement Ref.1. Source: ProtInc cAMP-mediated signaling Inferred from direct assay PubMed 7589461. Source: UniProtKB cellular response to glucagon stimulus Inferred from electronic annotation. Source: GOC elevation of cytosolic calcium ion concentration Inferred from direct assay PubMed 7589461. Source: UniProtKB energy reserve metabolic process Traceable author statement. Source: Reactome regulation of insulin secretion Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Traceable author statement Ref.1. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	G-protein coupled peptide receptor activity Inferred from electronic annotation. Source: InterPro glucagon receptor activity Inferred from electronic annotation. Source: InterPro transmembrane signaling receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Chain

24 – 463

440

Glucagon-like peptide 1 receptor

PRO_0000012835

Regions

Topological domain

24 – 145

122

Extracellular Potential

Transmembrane

146 – 168

23

Helical; Name=1; Potential

Topological domain

169 – 176

8

Cytoplasmic Potential

Transmembrane

177 – 196

20

Helical; Name=2; Potential

Topological domain

197 – 227

31

Extracellular Potential

Transmembrane

228 – 252

25

Helical; Name=3; Potential

Topological domain

253 – 264

12

Cytoplasmic Potential

Transmembrane

265 – 288

24

Helical; Name=4; Potential

Topological domain

289 – 303

15

Extracellular Potential

Transmembrane

304 – 329

26

Helical; Name=5; Potential

Topological domain

330 – 351

22

Cytoplasmic Potential

Transmembrane

352 – 372

21

Helical; Name=6; Potential

Topological domain

373 – 387

15

Extracellular Potential

Transmembrane

388 – 408

21

Helical; Name=7; Potential

Topological domain

409 – 463

55

Cytoplasmic Potential

Amino acid modifications

Modified residue

341

1

ADP-ribosylcysteine

Modified residue

348

1

ADP-ribosylarginine

Glycosylation

63

1

N-linked (GlcNAc...) Ref.13

Glycosylation

82

1

N-linked (GlcNAc...) Ref.13

Glycosylation

115

1

N-linked (GlcNAc...) Ref.13

Disulfide bond

46 ↔ 71

Ref.11 Ref.14

Disulfide bond

62 ↔ 104

Ref.11 Ref.14

Disulfide bond

85 ↔ 126

Ref.11 Ref.14

Disulfide bond

226 ↔ 296

Ref.11 Ref.14

Natural variations

Natural variant

7

1

P → L. Ref.7
Corresponds to variant rs10305420 [ dbSNP | Ensembl ].

VAR_018924

Natural variant

20

1

R → K. Ref.7
Corresponds to variant rs10305421 [ dbSNP | Ensembl ].

VAR_018925

Natural variant

44

1

R → H. Ref.7
Corresponds to variant rs2295006 [ dbSNP | Ensembl ].

VAR_018926

Natural variant

131

1

R → Q. Ref.7
Corresponds to variant rs3765467 [ dbSNP | Ensembl ].

VAR_018927

Natural variant

168

1

G → S. Ref.7
Corresponds to variant rs6923761 [ dbSNP | Ensembl ].

VAR_018928

Natural variant

260

1

L → F. Ref.1 Ref.2 Ref.3 Ref.5 Ref.7 Ref.9
Corresponds to variant rs1042044 [ dbSNP | Ensembl ].

VAR_015098

Natural variant

316

1

A → T. Ref.7
Corresponds to variant rs10305492 [ dbSNP | Ensembl ].

VAR_018929

Natural variant

333

1

S → C. Ref.7
Corresponds to variant rs10305493 [ dbSNP | Ensembl ].

VAR_018930

Natural variant

421

1

R → Q. Ref.7
Corresponds to variant rs10305510 [ dbSNP | Ensembl ].

VAR_018931

Experimental info

Sequence conflict

12

1

L → V in AAA03614. Ref.1

Sequence conflict

12

1

L → V no nucleotide entry Ref.4

Sequence conflict

12

1

L → V in AAB64013. Ref.10

Sequence conflict

136 – 137

2

SP → WG in AAA03614. Ref.1

Sequence conflict

137

1

P → R no nucleotide entry Ref.4

Sequence conflict

151

1

G → A in AAA03614. Ref.1

Sequence conflict

221

1

Q → L in AAA63787. Ref.5

Sequence conflict

289

1

Y → I in AAA03614. Ref.1

Sequence conflict

316

1

A → G in AAA62471. Ref.2

Sequence conflict

316

1

A → G in AAC50050. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

463

Helix Strand Turn

Details...

Helix

32 – 52

21

Beta strand

57 – 59

3

Beta strand

79 – 84

6

Helix

92 – 94

3

Beta strand

99 – 104

6

Beta strand

108 – 110

3

Beta strand

114 – 117

4

Helix

124 – 126

3

Sequences

	Sequence		Length	Mass (Da)
	P43220 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: EE7C0EAE29931F5D	FASTA	463	53,026
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00300576.

PIR

I84494.
S71624.

RefSeq

NP_002053.3. NM_002062.3.

UniGene

Hs.389103.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C59	X-ray	2.30	A	24-145	[»]
3C5T	X-ray	2.10	A	24-145	[»]
3IOL	X-ray	2.10	A	24-145	[»]

ProteinModelPortal

P43220.

SMR

P43220. Positions 28-131.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29980N.

MINT

MINT-1217566.

STRING

9606.ENSP00000362353.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P43220.

Polymorphism databases

DMDM

311033387.

Proteomic databases

PaxDb

P43220.

PRIDE

P43220.

Protocols and materials databases

DNASU

2740.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373256; ENSP00000362353; ENSG00000112164.

GeneID

2740.

KEGG

hsa:2740.

UCSC

uc003ooj.4. human.

Organism-specific databases

CTD

2740.

GeneCards

GC06P039063.

H-InvDB

HIX0095000.
HIX0200932.

HGNC

HGNC:4324. GLP1R.

MIM

138032. gene.

neXtProt

NX_P43220.

PharmGKB

PA28725.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG263329.

HOGENOM

HOG000008250.

HOVERGEN

HBG008318.

InParanoid

P43220.

KO

K04581.

OMA

CIVVSKL.

OrthoDB

EOG46143W.

PhylomeDB

P43220.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.

Gene expression databases

Bgee

P43220.

CleanEx

HS_GLP1R.

Genevestigator

P43220.

GermOnline

ENSG00000112164. Homo sapiens.

Family and domain databases

InterPro

IPR017981. 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]

PANTHER

PTHR12011:SF20. PTHR12011:SF20. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR01353. GLUCAGNFAMLY.
PR01355. GLUCAGNLIKER.
PR00249. GPCRSECRETIN.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P43220.

ChEMBL

CHEMBL1784.

DrugBank

DB01276. Exenatide.
DB00040. Glucagon recombinant.

EvolutionaryTrace

P43220.

GenomeRNAi

2740.

NextBio

10800.

SOURCE

Search...

Entry information

Entry name

GLP1R_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.