P47871 (GLR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucagon receptor
Short name=GL-R

Gene names

Name:

GCGR

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	477 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 which plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and insulin secretion. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara adenylate cyclase-modulating G-protein coupled receptor signaling pathway Traceable author statement Ref.2. Source: ProtInc energy reserve metabolic process Traceable author statement. Source: Reactome exocytosis Inferred from electronic annotation. Source: Compara hormone-mediated signaling pathway Inferred from electronic annotation. Source: Compara regulation of blood pressure Traceable author statement PubMed 8563746. Source: ProtInc response to nutrient Traceable author statement PubMed 7773293. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	endosome Inferred from electronic annotation. Source: Compara integral to membrane Traceable author statement Ref.2. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	glucagon receptor activity Traceable author statement Ref.2. Source: ProtInc guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome peptide hormone binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 477

452

Glucagon receptor

PRO_0000012832

Regions

Topological domain

26 – 142

117

Extracellular Potential

Transmembrane

143 – 166

24

Helical; Name=1; Potential

Topological domain

167 – 173

7

Cytoplasmic Potential

Transmembrane

174 – 193

20

Helical; Name=2; Potential

Topological domain

194 – 225

32

Extracellular Potential

Transmembrane

226 – 249

24

Helical; Name=3; Potential

Topological domain

250 – 263

14

Cytoplasmic Potential

Transmembrane

264 – 285

22

Helical; Name=4; Potential

Topological domain

286 – 303

18

Extracellular Potential

Transmembrane

304 – 326

23

Helical; Name=5; Potential

Topological domain

327 – 350

24

Cytoplasmic Potential

Transmembrane

351 – 369

19

Helical; Name=6; Potential

Topological domain

370 – 381

12

Extracellular Potential

Transmembrane

382 – 404

23

Helical; Name=7; Potential

Topological domain

405 – 477

73

Cytoplasmic Potential

Amino acid modifications

Glycosylation

46

1

N-linked (GlcNAc...) Potential

Glycosylation

59

1

N-linked (GlcNAc...) Potential

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Glycosylation

78

1

N-linked (GlcNAc...) Potential

Disulfide bond

43 ↔ 67

By similarity

Disulfide bond

58 ↔ 100

By similarity

Disulfide bond

81 ↔ 121

By similarity

Natural variations

Natural variant

40

1

G → S. Ref.6
Corresponds to variant rs1801483 [ dbSNP | Ensembl ].

VAR_003581

Natural variant

114

1

P → A.
Corresponds to variant rs5385 [ dbSNP | Ensembl ].

VAR_014837

Natural variant

303

1

F → C.
Corresponds to variant rs5387 [ dbSNP | Ensembl ].

VAR_033966

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

477

Helix Strand Turn

Details...

Helix

31 – 49

19

Beta strand

54 – 58

5

Beta strand

75 – 80

6

Turn

86 – 90

5

Beta strand

95 – 100

6

Helix

119 – 121

3

Sequences

	Sequence		Length	Mass (Da)
	P47871 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: ADBB477C6267AE6E	FASTA	477	54,009
	10 20 30 40 50 60 MPPCQPQRPL LLLLLLLACQ PQVPSAQVMD FLFEKWKLYG DQCHHNLSLL PPPTELVCNR 70 80 90 100 110 120 TFDKYSCWPD TPANTTANIS CPWYLPWHHK VQHRFVFKRC GPDGQWVRGP RGQPWRDASQ 130 140 150 160 170 180 CQMDGEEIEV QKEVAKMYSS FQVMYTVGYS LSLGALLLAL AILGGLSKLH CTRNAIHANL 190 200 210 220 230 240 FASFVLKASS VLVIDGLLRT RYSQKIGDDL SVSTWLSDGA VAGCRVAAVF MQYGIVANYC 250 260 270 280 290 300 WLLVEGLYLH NLLGLATLPE RSFFSLYLGI GWGAPMLFVV PWAVVKCLFE NVQCWTSNDN 310 320 330 340 350 360 MGFWWILRFP VFLAILINFF IFVRIVQLLV AKLRARQMHH TDYKFRLAKS TLTLIPLLGV 370 380 390 400 410 420 HEVVFAFVTD EHAQGTLRSA KLFFDLFLSS FQGLLVAVLY CFLNKEVQSE LRRRWHRWRL 430 440 450 460 470 GKVLWEERNT SNHRASSSPG HGPPSKELQF GRGGGSQDSS AETPLAGGLP RLAESPF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a human glucagon receptor." Macneil D.J., Occi J.L., Hey P.J., Strader C.D., Graziano M.P. Biochem. Biophys. Res. Commun. 198:328-334(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization." Lok S., Kuijper J.L., Jelinek L.J., Kramer J.M., Whitmore T.E., Sprecher C.A., Mathewes S., Grant F.J., Biggs S.H., Rosenberg G.B. Gene 140:203-209(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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]. Tissue: Liver.
[4]	"Localization of the glucagon receptor gene to human chromosome band 17q25." Menzel S., Stoffel M., Espinosa R. III, Fernald A.A., Le Beau M.M., Bell G.I. Genomics 20:327-328(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 21-54. Tissue: Placenta.
[5]	"Conformational dimorphism of self-peptides and molecular mimicry in a disease-associated HLA-B27 subtype." Ruckert C., Fiorillo M.T., Loll B., Moretti R., Biesiadka J., Saenger W., Ziegler A., Sorrentino R., Uchanska-Ziegler B. J. Biol. Chem. 281:2306-2316(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 412-420 IN COMPLEX WITH CLASS I MHC.
[6]	"A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus." Fujisawa T., Ikegami H., Yamato E., Takekawa K., Nakagawa Y., Hamada Y., Ueda H., Fukuda M., Ogihara T. Diabetologia 38:983-985(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-40.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U03469 mRNA. Translation: AAC52063.1.
L20316 mRNA. Translation: AAA53628.1.
BC104854 mRNA. Translation: AAI04855.1.
BC112041 mRNA. Translation: AAI12042.1.
L24751 Genomic DNA. Translation: AAA35897.1.

IPI

IPI00412345.

PIR

JC2041.

RefSeq

NP_000151.1. NM_000160.3.

UniGene

Hs.208.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CZF	X-ray	1.20	C	412-420	[»]
4ERS	X-ray	2.64	A	28-123	[»]

ProteinModelPortal

P47871.

ModBase

Search...

Protein-protein interaction databases

IntAct

P47871. 2 interactions.

STRING

9606.ENSP00000383558.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P47871.

Polymorphism databases

DMDM

1346144.

Proteomic databases

PaxDb

P47871.

PRIDE

P47871.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400723; ENSP00000383558; ENSG00000215644.

GeneID

2642.

KEGG

hsa:2642.

UCSC

uc010wuw.2. human.

Organism-specific databases

CTD

2642.

GeneCards

GC17P079763.

HGNC

HGNC:4192. GCGR.

MIM

138033. gene.

neXtProt

NX_P47871.

PharmGKB

PA28607.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG263329.

HOGENOM

HOG000008250.

HOVERGEN

HBG008318.

InParanoid

P47871.

KO

K04583.

OMA

VAKMYSS.

OrthoDB

EOG473PRN.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P47871.

Bgee

P47871.

CleanEx

HS_GCGR.

Genevestigator

P47871.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR003290. GPCR_2_GLP1/glucagon_rcpt.
IPR003291. GPCR_2_glucagon_rcpt.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

PANTHER

PTHR12011:SF71. PTHR12011:SF71. 1 hit.

Pfam

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

PRINTS

PR01353. GLUCAGNFAMLY.
PR01354. GLUCAGONR.
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

P47871.

ChEMBL

CHEMBL1985.

DrugBank

DB00040. Glucagon recombinant.

EvolutionaryTrace

P47871.

GenomeRNAi

2642.

NextBio

10416.

SOURCE

Search...

Entry information

Entry name

GLR_HUMAN

Accession

Primary (citable) accession number: P47871
Secondary accession number(s): Q2M3M5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 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.