ID   GLR_MOUSE               Reviewed;         485 AA.
AC   Q61606; Q63960; Q8K0B5;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   04-NOV-2026, entry version 185.
DE   RecName: Full=Glucagon receptor;
DE            Short=GL-R;
DE   Flags: Precursor;
GN   Name=Gcgr;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=7590348; DOI=10.1016/0378-1119(95)00472-i;
RA   Burcelin R., Li J., Charron M.J.;
RT   "Cloning and sequence analysis of the murine glucagon receptor-encoding
RT   gene.";
RL   Gene 164:305-310(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 324-458.
RC   TISSUE=Brain;
RX   PubMed=8156917; DOI=10.1210/endo.134.5.8156917;
RA   Campos R.V., Lee Y.C., Drucker D.J.;
RT   "Divergent tissue-specific and developmental expression of receptors for
RT   glucagon and glucagon-like peptide-1 in the mouse.";
RL   Endocrinology 134:2156-2164(1994).
RN   [6]
RP   DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=12552113; DOI=10.1073/pnas.0237106100;
RA   Gelling R.W., Du X.Q., Dichmann D.S., Romer J., Huang H., Cui L., Obici S.,
RA   Tang B., Holst J.J., Fledelius C., Johansen P.B., Rossetti L.,
RA   Jelicks L.A., Serup P., Nishimura E., Charron M.J.;
RT   "Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell
RT   hyperplasia in glucagon receptor knockout mice.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:1438-1443(2003).
RN   [7]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=16627579; DOI=10.1210/en.2005-1410;
RA   Vuguin P.M., Kedees M.H., Cui L., Guz Y., Gelling R.W., Nejathaim M.,
RA   Charron M.J., Teitelman G.;
RT   "Ablation of the glucagon receptor gene increases fetal lethality and
RT   produces alterations in islet development and maturation.";
RL   Endocrinology 147:3995-4006(2006).
RN   [8]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=19046568; DOI=10.1016/j.cmet.2008.09.008;
RA   Longuet C., Sinclair E.M., Maida A., Baggio L.L., Maziarz M., Charron M.J.,
RA   Drucker D.J.;
RT   "The glucagon receptor is required for the adaptive metabolic response to
RT   fasting.";
RL   Cell Metab. 8:359-371(2008).
RN   [9]
RP   MUTAGENESIS OF VAL-369, AND FUNCTION.
RX   PubMed=32677665; DOI=10.1042/bcj20200235;
RA   Lin G., Liu Q., Dai A., Cai X., Zhou Q., Wang X., Chen Y., Ye C., Li J.,
RA   Yang D., Wang M.W.;
RT   "Characterization of a naturally occurring mutation V368M in the human
RT   glucagon receptor and its association with metabolic disorders.";
RL   Biochem. J. 477:2581-2594(2020).
CC   -!- FUNCTION: G protein-coupled receptor for glucagon that plays a central
CC       role in the regulation of blood glucose levels and glucose homeostasis.
CC       Regulates the rate of hepatic glucose production by promoting glycogen
CC       hydrolysis and gluconeogenesis. Plays an important role in mediating
CC       the responses to fasting. Ligand binding causes a conformation change
CC       that triggers signaling via guanine nucleotide-binding proteins (G
CC       proteins) and modulates the activity of down-stream effectors, such as
CC       adenylate cyclase. Promotes activation of adenylate cyclase. Besides,
CC       plays a role in signaling via a phosphatidylinositol-calcium second
CC       messenger system. {ECO:0000269|PubMed:12552113,
CC       ECO:0000269|PubMed:19046568, ECO:0000269|PubMed:32677665}.
CC   -!- SUBUNIT: Interacts with glucagon. Interacts with GNAS. Interacts with
CC       GNAI1. {ECO:0000250|UniProtKB:P47871}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12552113};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:12552113}. Note=Is
CC       rapidly internalized after ligand-binding.
CC       {ECO:0000250|UniProtKB:P47871}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in liver, kidney, adrenal,
CC       lung and stomach, while lower levels of expression are detected in
CC       brown and white adipose tissue, cerebellum, duodenum and heart.
CC       {ECO:0000269|PubMed:7590348}.
CC   -!- PTM: Ligand-binding promotes phosphorylation of serine residues in the
CC       C-terminal cytoplasmic domain. Phosphorylation is important for
CC       receptor endocytosis after ligand-binding (By similarity).
CC       {ECO:0000250|UniProtKB:P47871}.
CC   -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate.
CC       They display pancreas islet and alpha-cell hyperplasia and increased
CC       glucagon levels, but normal insulin levels. Mice display low blood
CC       glucose levels combined with increased hepatic glycogen levels. They
CC       develop severe hypoglycemia after prolonged fasting. Mutant mice are
CC       fertile, but the females produce only few pups; half of the embryos die
CC       before birth, and liveborn pups do not survive more than one day. These
CC       pups are much smaller than their littermates and exhibit severe
CC       hypoglycemia. {ECO:0000269|PubMed:12552113,
CC       ECO:0000269|PubMed:16627579, ECO:0000269|PubMed:19046568}.
CC   -!- MISCELLANEOUS: Selective recognition of glucagon over glucagon-like
CC       peptide is determined by residues located at the N-terminal end of the
CC       glucagon peptide. {ECO:0000250|UniProtKB:A0A2Z2U4G9}.
CC   -!- SIMILARITY: Belongs to the G protein-coupled receptor 2 family.
CC       {ECO:0000305}.
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DR   EMBL; L38613; AAA88244.1; -; mRNA.
DR   EMBL; AL669855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466558; EDL34761.1; -; Genomic_DNA.
DR   EMBL; BC031885; AAH31885.1; -; mRNA.
DR   EMBL; BC057988; AAH57988.1; -; mRNA.
DR   EMBL; S69384; AAB30529.2; -; mRNA.
DR   CCDS; CCDS25739.1; -.
DR   PIR; JC4363; JC4363.
DR   RefSeq; NP_032127.2; NM_008101.3.
DR   RefSeq; XP_017169755.1; XM_017314266.1.
DR   AlphaFoldDB; Q61606; -.
DR   SMR; Q61606; -.
DR   BioGRID; 199863; 1.
DR   FunCoup; Q61606; 743.
DR   STRING; 10090.ENSMUSP00000026119; -.
DR   BindingDB; Q61606; -.
DR   ChEMBL; CHEMBL4773; -.
DR   GuidetoPHARMACOLOGY; 251; -.
DR   GlyCosmos; Q61606; 5 sites, No reported glycans.
DR   GlyGen; Q61606; 5 sites.
DR   iPTMnet; Q61606; -.
DR   PhosphoSitePlus; Q61606; -.
DR   jPOST; Q61606; -.
DR   PaxDb; 10090-ENSMUSP00000026119; -.
DR   ProteomicsDB; 267459; -.
DR   ABCD; Q61606; 1 sequenced antibody.
DR   Antibodypedia; 4808; 575 antibodies from 40 providers.
DR   DNASU; 14527; -.
DR   Ensembl; ENSMPUT00000011448; ENSMPUP00000011260; ENSMPUG00000011352.
DR   Ensembl; ENSMUST00000026119.8; ENSMUSP00000026119.8; ENSMUSG00000025127.16.
DR   GeneID; 14527; -.
DR   KEGG; mmu:14527; -.
DR   UCSC; uc007mtc.2; mouse.
DR   AGR; MGI:99572; -.
DR   CTD; 2642; -.
DR   MGI; MGI:99572; Gcgr.
DR   VEuPathDB; HostDB:ENSMUSG00000025127; -.
DR   eggNOG; KOG4564; Eukaryota.
DR   GeneTree; ENSGT00940000157969; -.
DR   HOGENOM; CLU_002753_4_0_1; -.
DR   InParanoid; Q61606; -.
DR   OMA; AAGGNWH; -.
DR   OrthoDB; 5967113at2759; -.
DR   PhylomeDB; Q61606; -.
DR   Reactome; R-MMU-163359; Glucagon signaling in metabolic regulation.
DR   Reactome; R-MMU-416476; G alpha (q) signalling events.
DR   Reactome; R-MMU-418555; G alpha (s) signalling events.
DR   Reactome; R-MMU-420092; Glucagon-type ligand receptors.
DR   BioGRID-ORCS; 14527; 2 hits in 77 CRISPR screens.
DR   PRO; PR:Q61606; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q61606; protein.
DR   Bgee; ENSMUSG00000025127; Expressed in lobe of liver and 76 other cell types or tissues.
DR   GO; GO:0005768; C:endosome; ISO:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0004967; F:glucagon receptor activity; IDA:UniProtKB.
DR   GO; GO:0017046; F:peptide hormone binding; ISO:GO_Central.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR   GO; GO:0071377; P:cellular response to glucagon stimulus; IDA:UniProtKB.
DR   GO; GO:0009267; P:cellular response to starvation; IMP:ARUK-UCL.
DR   GO; GO:0006887; P:exocytosis; ISO:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:GO_Central.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR   GO; GO:0042594; P:response to starvation; IMP:UniProtKB.
DR   CDD; cd15267; 7tmB1_GCGR; 1.
DR   FunFam; 4.10.1240.10:FF:000009; Glucagon receptor; 1.
DR   FunFam; 1.20.1070.10:FF:000133; Glucagon receptor a; 1.
DR   Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR050332; GPCR_2.
DR   InterPro; IPR017981; GPCR_2-like_7TM.
DR   InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR   InterPro; IPR001879; GPCR_2_extracellular_dom.
DR   InterPro; IPR003290; GPCR_2_GLP1/glucagon_rcpt.
DR   InterPro; IPR003291; GPCR_2_glucagon_rcpt.
DR   InterPro; IPR000832; GPCR_2_secretin-like.
DR   InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR   PANTHER; PTHR45620:SF29; GLUCAGON RECEPTOR; 1.
DR   PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1.
DR   Pfam; PF00002; 7tm_2; 1.
DR   Pfam; PF02793; HRM; 1.
DR   PRINTS; PR01353; GLUCAGNFAMLY.
DR   PRINTS; PR01354; GLUCAGONR.
DR   PRINTS; PR00249; GPCRSECRETIN.
DR   SMART; SM00008; HormR; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   SUPFAM; SSF111418; Hormone receptor domain; 1.
DR   PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1.
DR   PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR   PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR   PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; G protein-coupled receptor; Glycoprotein;
KW   Membrane; Phosphoprotein; Receptor; Reference proteome; Signal; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..485
FT                   /note="Glucagon receptor"
FT                   /id="PRO_0000012833"
FT   TOPO_DOM        27..137
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        138..162
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        163..174
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        175..199
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        200..226
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        227..250
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        251..264
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        265..286
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        287..304
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        305..327
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        328..351
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        352..370
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        371..382
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TRANSMEM        383..403
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   TOPO_DOM        404..485
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   REGION          351..354
FT                   /note="Important for allosteric inhibitor binding"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   REGION          457..485
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        457..475
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         460
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   MOD_RES         476
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30082"
FT   CARBOHYD        47
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        60
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        75
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        118
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        44..68
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   DISULFID        59..101
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   DISULFID        82..122
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   DISULFID        225..295
FT                   /evidence="ECO:0000250|UniProtKB:P47871"
FT   MUTAGEN         369
FT                   /note="V->M: Results in impaired glucagon binding and
FT                   glucagon-mediated signaling. Homozygous mice show
FT                   hyperglucagonemia with alpha-cell hyperplasia and
FT                   enlargement of the pancreas."
FT                   /evidence="ECO:0000269|PubMed:32677665"
FT   CONFLICT        65
FT                   /note="K -> N (in Ref. 1; AAA88244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        89
FT                   /note="Y -> C (in Ref. 1; AAA88244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        238
FT                   /note="A -> P (in Ref. 1; AAA88244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        325
FT                   /note="H -> R (in Ref. 3; AAB30529)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        328
FT                   /note="H -> Q (in Ref. 1; AAA88244)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   485 AA;  54929 MW;  578EB30BF281E67A CRC64;
     MPLTQLHCPH LLLLLLVLSC LPEAPSAQVM DFLFEKWKLY SDQCHHNLSL LPPPTELVCN
     RTFDKYSCWP DTPPNTTANI SCPWYLPWYH KVQHRLVFKR CGPDGQWVRG PRGQPWRNAS
     QCQLDDEEIE VQKGVAKMYS SQQVMYTVGY SLSLGALLLA LVILLGLRKL HCTRNYIHGN
     LFASFVLKAG SVLVIDWLLK TRYSQKIGDD LSVSVWLSDG AMAGCRVATV IMQYGIIANY
     CWLLVEGVYL YSLLSLATFS ERSFFSLYLG IGWGAPLLFV IPWVVVKCLF ENVQCWTSND
     NMGFWWILRI PVFLALLINF FIFVHIIHLL VAKLRAHQMH YADYKFRLAR STLTLIPLLG
     VHEVVFAFVT DEHAQGTLRS TKLFFDLFLS SFQGLLVAVL YCFLNKEVQA ELMRRWRQWQ
     EGKALQEERL ASSHGSHMAP AGPCHGDPCE KLQLMSAGSS SGTGCVPSME TSLASSLPRL
     ADSPT
//