Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glucagon receptor

Gene

GCGR

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

Functioni

G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system.7 Publications

GO - Molecular functioni

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: UniProtKB
  • cell surface receptor signaling pathway Source: InterPro
  • cellular response to glucagon stimulus Source: UniProtKB
  • exocytosis Source: Ensembl
  • generation of precursor metabolites and energy Source: ProtInc
  • glucose homeostasis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: Reactome
  • hormone-mediated signaling pathway Source: Ensembl
  • regulation of blood pressure Source: ProtInc
  • regulation of glycogen metabolic process Source: UniProtKB
  • response to nutrient Source: ProtInc
  • response to starvation Source: UniProtKB

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-416476 G alpha (q) signalling events
R-HSA-418555 G alpha (s) signalling events
R-HSA-420092 Glucagon-type ligand receptors
SIGNORiP47871

Names & Taxonomyi

Protein namesi
Recommended name:
Glucagon receptor
Short name:
GL-R
Gene namesi
Name:GCGR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000215644.9
HGNCiHGNC:4192 GCGR
MIMi138033 gene
neXtProtiNX_P47871

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 domaini26 – 136Extracellular3 PublicationsAdd BLAST111
Transmembranei137 – 161Helical; Name=13 PublicationsAdd BLAST25
Topological domaini162 – 173Cytoplasmic3 PublicationsAdd BLAST12
Transmembranei174 – 198Helical; Name=23 PublicationsAdd BLAST25
Topological domaini199 – 225Extracellular3 PublicationsAdd BLAST27
Transmembranei226 – 249Helical; Name=33 PublicationsAdd BLAST24
Topological domaini250 – 263Cytoplasmic3 PublicationsAdd BLAST14
Transmembranei264 – 285Helical; Name=43 PublicationsAdd BLAST22
Topological domaini286 – 303Extracellular3 PublicationsAdd BLAST18
Transmembranei304 – 326Helical; Name=53 PublicationsAdd BLAST23
Topological domaini327 – 350Cytoplasmic3 PublicationsAdd BLAST24
Transmembranei351 – 369Helical; Name=63 PublicationsAdd BLAST19
Topological domaini370 – 381Extracellular3 PublicationsAdd BLAST12
Transmembranei382 – 402Helical; Name=73 PublicationsAdd BLAST21
Topological domaini403 – 477Cytoplasmic3 PublicationsAdd BLAST75

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi36W → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi63D → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi65Y → A: Strongly reduced affinity for glucagon. Increased constitutive signaling via G-proteins. 1 Publication1
Mutagenesisi113Q → A or N: No effect on affinity for glucagon. 1 Publication1
Mutagenesisi113Q → C: Causes the formation of an artifactual disulfide bond that abolishes glucagon binding; when associated with C-209. 1 Publication1
Mutagenesisi113Q → E: Strongly reduced affinity for glucagon. 1 Publication1
Mutagenesisi130V → C: Causes the formation of an artifactual disulfide bond that interferes with glucagon binding; when associated with C-210. 1 Publication1
Mutagenesisi135A → P: Abolishes glucagon binding. 1 Publication1
Mutagenesisi145Y → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi149Y → A: Abolishes expression at cell surface and glucagon binding. 1 Publication1
Mutagenesisi198L → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi201R → D: Abolishes glucagon binding. 1 Publication1
Mutagenesisi202Y → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi208D → Q: Abolishes glucagon binding. 1 Publication1
Mutagenesisi209D → C: Causes the formation of an artifactual disulfide bond that abolishes glucagon binding; when associated with C-113. 1 Publication1
Mutagenesisi210L → C: Causes the formation of an artifactual disulfide bond that interferes with glucagon binding; when associated with C-130. 1 Publication1
Mutagenesisi215W → L: Abolishes glucagon binding. 1 Publication1
Mutagenesisi232Q → L: Abolishes expression at cell surface and glucagon binding. 1 Publication1
Mutagenesisi233Y → A: Abolishes glucagon binding. Strongly reduces expression at the cell surface. 1 Publication1
Mutagenesisi286K → L: Abolishes glucagon binding. 1 Publication1
Mutagenesisi290E → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi294C → A or S: Abolishes glucagon binding. 1 Publication1
Mutagenesisi295W → A or H: Abolishes glucagon binding. 1 Publication1
Mutagenesisi304W → Q: Abolishes glucagon binding. 1 Publication1
Mutagenesisi350S → A: Strongly decreases affinity for synthetic antagonist. 1 Publication1
Mutagenesisi353T → A: Loss of synthetic antagonist binding. 1 Publication1
Mutagenesisi382L → A: Abolishes glucagon binding. 1 Publication1
Mutagenesisi386L → F: Abolishes glucagon binding. 1 Publication1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi2642
MalaCardsiGCGR
OpenTargetsiENSG00000215644
PharmGKBiPA28607

Chemistry databases

ChEMBLiCHEMBL1985
DrugBankiDB00040 Glucagon recombinant
GuidetoPHARMACOLOGYi251

Polymorphism and mutation databases

BioMutaiGCGR
DMDMi1346144

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000001283226 – 477Glucagon receptorAdd BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi43 ↔ 67Combined sources2 Publications
Glycosylationi46N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi58 ↔ 100Combined sources2 Publications
Glycosylationi59N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi74N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Glycosylationi78N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Disulfide bondi81 ↔ 121Combined sources2 Publications
Disulfide bondi224 ↔ 294Combined sources3 Publications
Modified residuei456PhosphoserineCombined sources1
Modified residuei459PhosphoserineCombined sources1

Post-translational modificationi

Ligand-binding promotes phosphorylation of serine residues in the C-terminal cytoplasmic domain. Phosphorylation is important for receptor endocytosis after ligand-binding.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP47871
PeptideAtlasiP47871
PRIDEiP47871
ProteomicsDBi55805

PTM databases

iPTMnetiP47871
PhosphoSitePlusiP47871

Expressioni

Gene expression databases

BgeeiENSG00000215644
CleanExiHS_GCGR
ExpressionAtlasiP47871 baseline and differential
GenevisibleiP47871 HS

Organism-specific databases

HPAiHPA071228

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108912, 3 interactors
IntActiP47871, 4 interactors
STRINGi9606.ENSP00000383558

Chemistry databases

BindingDBiP47871

Structurei

Secondary structure

1477
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 49Combined sources19
Beta strandi54 – 58Combined sources5
Beta strandi64 – 68Combined sources5
Beta strandi75 – 80Combined sources6
Turni86 – 90Combined sources5
Beta strandi95 – 100Combined sources6
Beta strandi104 – 106Combined sources3
Helixi119 – 121Combined sources3
Beta strandi127 – 130Combined sources4
Helixi139 – 165Combined sources27
Helixi167 – 169Combined sources3
Helixi172 – 198Combined sources27
Beta strandi203 – 206Combined sources4
Helixi213 – 215Combined sources3
Helixi218 – 253Combined sources36
Helixi264 – 271Combined sources8
Helixi273 – 289Combined sources17
Beta strandi293 – 295Combined sources3
Helixi305 – 307Combined sources3
Helixi308 – 334Combined sources27
Helixi343 – 369Combined sources27
Helixi379 – 389Combined sources11
Helixi392 – 400Combined sources9
Turni401 – 403Combined sources3
Helixi405 – 417Combined sources13

3D structure databases

ProteinModelPortaliP47871
SMRiP47871
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP47871

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni350 – 353Allosteric inhibitor binding2 Publications4

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564 Eukaryota
ENOG410XRS2 LUCA
GeneTreeiENSGT00760000118800
HOGENOMiHOG000008250
HOVERGENiHBG008318
InParanoidiP47871
KOiK04583
PhylomeDBiP47871
TreeFamiTF315710

Family and domain databases

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
IPR003291 GPCR_2_glucagon_rcpt
IPR000832 GPCR_2_secretin-like
IPR017983 GPCR_2_secretin-like_CS
PfamiView protein in Pfam
PF00002 7tm_2, 1 hit
PF02793 HRM, 1 hit
PRINTSiPR01353 GLUCAGNFAMLY
PR01354 GLUCAGONR
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.

P47871-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPCQPQRPL LLLLLLLACQ PQVPSAQVMD FLFEKWKLYG DQCHHNLSLL
60 70 80 90 100
PPPTELVCNR TFDKYSCWPD TPANTTANIS CPWYLPWHHK VQHRFVFKRC
110 120 130 140 150
GPDGQWVRGP RGQPWRDASQ CQMDGEEIEV QKEVAKMYSS FQVMYTVGYS
160 170 180 190 200
LSLGALLLAL AILGGLSKLH CTRNAIHANL FASFVLKASS VLVIDGLLRT
210 220 230 240 250
RYSQKIGDDL SVSTWLSDGA VAGCRVAAVF MQYGIVANYC WLLVEGLYLH
260 270 280 290 300
NLLGLATLPE RSFFSLYLGI GWGAPMLFVV PWAVVKCLFE NVQCWTSNDN
310 320 330 340 350
MGFWWILRFP VFLAILINFF IFVRIVQLLV AKLRARQMHH TDYKFRLAKS
360 370 380 390 400
TLTLIPLLGV HEVVFAFVTD EHAQGTLRSA KLFFDLFLSS FQGLLVAVLY
410 420 430 440 450
CFLNKEVQSE LRRRWHRWRL GKVLWEERNT SNHRASSSPG HGPPSKELQF
460 470
GRGGGSQDSS AETPLAGGLP RLAESPF
Length:477
Mass (Da):54,009
Last modified:February 1, 1996 - v1
Checksum:iADBB477C6267AE6E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00358140G → S1 PublicationCorresponds to variant dbSNP:rs1801483EnsemblClinVar.1
Natural variantiVAR_06981586P → S Abolishes glucagon binding. 2 Publications1
Natural variantiVAR_014837114P → A. Corresponds to variant dbSNP:rs5385Ensembl.1
Natural variantiVAR_033966303F → C. Corresponds to variant dbSNP:rs5387Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS54177.1
PIRiJC2041
RefSeqiNP_000151.1, NM_000160.4
XP_006722340.1, XM_006722277.1
UniGeneiHs.208

Genome annotation databases

EnsembliENST00000400723; ENSP00000383558; ENSG00000215644
GeneIDi2642
KEGGihsa:2642
UCSCiuc010wuw.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGLR_HUMAN
AccessioniPrimary (citable) accession number: P47871
Secondary accession number(s): Q2M3M5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: June 20, 2018
This is version 158 of the entry and version 1 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 17
    Human chromosome 17: 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health