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Protein

Glucagon receptor

Gene

GCGR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.5 Publications

GO - Molecular functioni

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
  • 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
  • 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
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:G66-33884-MONOMER.
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

HGNCiHGNC:4192. GCGR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 136Extracellular1 PublicationAdd BLAST111
Transmembranei137 – 161Helical; Name=11 PublicationAdd BLAST25
Topological domaini162 – 173Cytoplasmic1 PublicationAdd BLAST12
Transmembranei174 – 198Helical; Name=21 PublicationAdd BLAST25
Topological domaini199 – 225Extracellular1 PublicationAdd BLAST27
Transmembranei226 – 249Helical; Name=31 PublicationAdd BLAST24
Topological domaini250 – 263Cytoplasmic1 PublicationAdd BLAST14
Transmembranei264 – 285Helical; Name=41 PublicationAdd BLAST22
Topological domaini286 – 303Extracellular1 PublicationAdd BLAST18
Transmembranei304 – 326Helical; Name=51 PublicationAdd BLAST23
Topological domaini327 – 350Cytoplasmic1 PublicationAdd BLAST24
Transmembranei351 – 369Helical; Name=61 PublicationAdd BLAST19
Topological domaini370 – 381Extracellular1 PublicationAdd BLAST12
Transmembranei382 – 402Helical; Name=71 PublicationAdd BLAST21
Topological domaini403 – 477Cytoplasmic1 PublicationAdd BLAST75

GO - Cellular componenti

  • endosome Source: Ensembl
  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

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 → E: Strongly reduced affinity for glucagon. 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
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
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 sources1 Publication
Glycosylationi46N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi58 ↔ 100Combined sources1 Publication
Glycosylationi59N-linked (GlcNAc...)Sequence analysis1
Glycosylationi74N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi78N-linked (GlcNAc...)Combined sources1 Publication1
Disulfide bondi81 ↔ 121Combined sources1 Publication
Disulfide bondi224 ↔ 294Combined sources1 Publication
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.

PTM databases

iPTMnetiP47871.
PhosphoSitePlusiP47871.

Expressioni

Gene expression databases

BgeeiENSG00000215644.
CleanExiHS_GCGR.
ExpressionAtlasiP47871. baseline and differential.
GenevisibleiP47871. HS.

Interactioni

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
Helixi139 – 165Combined sources27
Helixi167 – 169Combined sources3
Helixi172 – 198Combined sources27
Helixi213 – 215Combined sources3
Helixi218 – 253Combined sources36
Helixi264 – 271Combined sources8
Helixi273 – 289Combined sources17
Beta strandi293 – 295Combined sources3
Beta strandi303 – 305Combined sources3
Helixi308 – 326Combined sources19
Helixi331 – 334Combined sources4
Helixi341 – 348Combined sources8
Turni352 – 354Combined sources3
Helixi357 – 370Combined sources14
Helixi373 – 378Combined sources6
Helixi382 – 389Combined sources8
Helixi392 – 401Combined sources10
Helixi408 – 421Combined sources14
Helixi425 – 434Combined sources10
Helixi436 – 440Combined sources5
Helixi442 – 454Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2A83X-ray1.40C412-420[»]
3CZFX-ray1.20C412-420[»]
4ERSX-ray2.64A28-123[»]
4L6RX-ray3.30A123-432[»]
4LF3X-ray2.74C/F29-123[»]
5EE7X-ray2.50A136-254[»]
A259-417[»]
ProteinModelPortaliP47871.
SMRiP47871.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP47871.

Family & Domainsi

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

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01353. GLUCAGNFAMLY.
PR01354. GLUCAGONR.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]

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 → S.1 PublicationCorresponds to variant rs1801483dbSNPEnsembl.1
Natural variantiVAR_06981586P → S Abolishes glucagon binding. 2 Publications1
Natural variantiVAR_014837114P → A.Corresponds to variant rs5385dbSNPEnsembl.1
Natural variantiVAR_033966303F → C.Corresponds to variant rs5387dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2A83X-ray1.40C412-420[»]
3CZFX-ray1.20C412-420[»]
4ERSX-ray2.64A28-123[»]
4L6RX-ray3.30A123-432[»]
4LF3X-ray2.74C/F29-123[»]
5EE7X-ray2.50A136-254[»]
A259-417[»]
ProteinModelPortaliP47871.
SMRiP47871.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108912. 3 interactors.
IntActiP47871. 4 interactors.
STRINGi9606.ENSP00000383558.

Chemistry databases

BindingDBiP47871.
ChEMBLiCHEMBL1985.
DrugBankiDB00040. Glucagon recombinant.
GuidetoPHARMACOLOGYi251.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP47871.
PhosphoSitePlusiP47871.

Polymorphism and mutation databases

BioMutaiGCGR.
DMDMi1346144.

Proteomic databases

PaxDbiP47871.
PeptideAtlasiP47871.
PRIDEiP47871.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2642.
DisGeNETi2642.
GeneCardsiGCGR.
HGNCiHGNC:4192. GCGR.
MalaCardsiGCGR.
MIMi138033. gene.
neXtProtiNX_P47871.
OpenTargetsiENSG00000215644.
PharmGKBiPA28607.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000008250.
HOVERGENiHBG008318.
InParanoidiP47871.
KOiK04583.
PhylomeDBiP47871.
TreeFamiTF315710.

Enzyme and pathway databases

BioCyciZFISH:G66-33884-MONOMER.
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.

Miscellaneous databases

EvolutionaryTraceiP47871.
GeneWikiiGlucagon_receptor.
GenomeRNAii2642.
PROiP47871.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000215644.
CleanExiHS_GCGR.
ExpressionAtlasiP47871. baseline and differential.
GenevisibleiP47871. HS.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01353. GLUCAGNFAMLY.
PR01354. GLUCAGONR.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiGLR_HUMAN
AccessioniPrimary (citable) accession number: P47871
Secondary accession number(s): Q2M3M5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 147 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.