GCGR glucagon receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: GCGRprovided by HGNC
Official Full Name: glucagon receptorprovided by HGNC
Primary source: HGNC:HGNC:4192
See related: Ensembl:ENSG00000215644 MIM:138033
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GGR; GL-R
Summary: The protein encoded by this gene is a glucagon receptor that is important in controlling blood glucose levels. Defects in this gene are a cause of non-insulin-dependent diabetes mellitus (NIDDM).[provided by RefSeq, Jan 2010]
Expression: Biased expression in liver (RPKM 10.3), kidney (RPKM 5.0) and 1 other tissue See more
Orthologs: mouse all

Genomic context

Location:: 17q25.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (81804078..81814008)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (79762010..79771889)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

3.0 A-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702
Title: Structure of the glucagon receptor in complex with a glucagon analogue.
work toward the mapping of interactions between the polypeptide hormone glucagon and the glucagon receptor
Title: Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by <sup>19</sup>F-NMR observation of 4-fluorophenylalanine.
3.0 A crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation
Title: Structure of the full-length glucagon class B G-protein-coupled receptor.
This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities.
Title: RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling.
Data suggest that GCGR activation proceeds via a mechanism in which transmembrane helix 6 (TM6) is held in an inactive conformation by a conserved polar core and a hydrophobic lock (involving intracellular loop 3, IC3); mutations in the corresponding polar core of GCGR disrupt these inhibitory elements, allow TM6 to swing outward, and induce constitutive G protein signaling.
Title: Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors.
The activation of the GCGR is characterized by the outward movement of the intracellular side of helix VI. In the active state of the GCGR, the Arg173(2.46)-Ser350(6.41) and Glu245(3.50)-Thr351(6.42) hydrogen bonds break, and the chi1 rotamer of Phe322(5.54) changes from perpendicular to parallel to helix VI.
Title: Activation and conformational dynamics of a class B G-protein-coupled glucagon receptor.
In the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the extracellular domain is required for signaling even when the hormone is covalently linked to the transmembrane domain.
Title: Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.
2.5 A crystal structure of human GCGR in complex with the antagonist MK-0893, which is found to bind to an allosteric site outside the seven transmembrane helical bundle in a position between TM6 and TM7 extending into the lipid bilayer
Title: Extra-helical binding site of a glucagon receptor antagonist.
Molecular dynamics and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. Glucagon binds to GCGR by a conformational selection mechanism.
Title: Conformational states of the full-length glucagon receptor.
glucagon cell adenomatosis with GCGR germline mutations seems to follow an autosomal-recessive trait.
Title: Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Diabetes mellitus type 2 MedGen: C0011860 OMIM: 125853 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class B Secretin-like, organism-specific biosystem (from WikiPathways)
GPCRs, Class B Secretin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
Glucagon signaling in metabolic regulation, organism-specific biosystem (from REACTOME)
Glucagon signaling in metabolic regulation, organism-specific biosystemGlucagon and insulin are peptide hormones released from the pancreas into the blood, that normally act in complementary fashion to stabilize blood glucose concentration. When blood glucose levels ris...
Glucagon signaling pathway, organism-specific biosystem (from KEGG)
Glucagon signaling pathway, organism-specific biosystemGlucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase ...
Glucagon signaling pathway, conserved biosystem (from KEGG)
Glucagon signaling pathway, conserved biosystemGlucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase ...
Glucagon-type ligand receptors, organism-specific biosystem (from REACTOME)
Glucagon-type ligand receptors, organism-specific biosystemThe glucagon hormone family regulates the activity of GPCRs from the secretin receptor subfamily in Class II/B (Mayo KE et al, 2003).
Integration of energy metabolism, organism-specific biosystem (from REACTOME)
Integration of energy metabolism, organism-specific biosystemMany hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insul...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH103588 (e-PCR)
- UniSTS:97913

NoName (e-PCR)
- UniSTS:483745

MARC_14771-14772:1010669884:1 (e-PCR)
- UniSTS:267730

Homology

Homologs of the GCGR gene: The GCGR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 232 organisms have orthologs with human gene GCGR
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G protein-coupled peptide receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
glucagon receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
glucagon receptor activity	IDA Inferred from Direct Assay more info	PubMed
guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
peptide hormone binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
cellular response to glucagon stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to glucagon stimulus	TAS Traceable Author Statement more info
exocytosis	IEA Inferred from Electronic Annotation more info
generation of precursor metabolites and energy	TAS Traceable Author Statement more info	PubMed
glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
hormone-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
regulation of blood pressure	TAS Traceable Author Statement more info	PubMed
regulation of glycogen metabolic process	ISS Inferred from Sequence or Structural Similarity more info
response to nutrient	TAS Traceable Author Statement more info	PubMed
response to starvation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
endosome	IEA Inferred from Electronic Annotation more info
integral component of membrane	TAS Traceable Author Statement more info	PubMed
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: glucagon receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016409.1 RefSeqGene

Range

2977..12835

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000160.5 → NP_000151.1 glucagon receptor precursor

See identical proteins and their annotated locations for NP_000151.1

Status: REVIEWED

Source sequence(s)

BC104854, DA639395, L20316, U03469

Consensus CDS

CCDS54177.1

UniProtKB/Swiss-Prot

P47871

Related

ENSP00000383558.3, ENST00000400723.8

Conserved Domains (2) summary

pfam02793
Location:55 → 122

HRM; Hormone receptor domain

cd15267
Location:136 → 410

7tmB1_GCGR; glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p13 Primary Assembly

Range

81804078..81814008

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017024446.1 → XP_016879935.1 glucagon receptor isoform X2
XM_011523539.1 → XP_011521841.1 glucagon receptor isoform X3

Conserved Domains (1) summary

pfam00002
Location:105 → 363

7tm_2; 7 transmembrane receptor (Secretin family)
XM_006722277.1 → XP_006722340.1 glucagon receptor isoform X1

See identical proteins and their annotated locations for XP_006722340.1

UniProtKB/Swiss-Prot

P47871

Conserved Domains (2) summary

pfam02793
Location:55 → 122

HRM; Hormone receptor domain

cd15267
Location:136 → 410

7tmB1_GCGR; glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
XM_017024447.1 → XP_016879936.1 glucagon receptor isoform X4

Conserved Domains (1) summary

pfam00002
Location:16 → 274

7tm_2; 7 transmembrane receptor (Secretin family)