GLR_MOUSE
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 03-AUG-2022, entry version 165.
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 -!- 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 -!- 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_008101.2.
DR RefSeq; XP_017169755.1; XM_017314266.1.
DR AlphaFoldDB; Q61606; -.
DR SMR; Q61606; -.
DR BioGRID; 199863; 1.
DR STRING; 10090.ENSMUSP00000026119; -.
DR BindingDB; Q61606; -.
DR ChEMBL; CHEMBL4773; -.
DR GuidetoPHARMACOLOGY; 251; -.
DR GlyGen; Q61606; 5 sites.
DR iPTMnet; Q61606; -.
DR PhosphoSitePlus; Q61606; -.
DR jPOST; Q61606; -.
DR MaxQB; Q61606; -.
DR PaxDb; Q61606; -.
DR PRIDE; Q61606; -.
DR ProteomicsDB; 267459; -.
DR ABCD; Q61606; 1 sequenced antibody.
DR Antibodypedia; 4808; 443 antibodies from 36 providers.
DR DNASU; 14527; -.
DR Ensembl; ENSMUST00000026119; ENSMUSP00000026119; ENSMUSG00000025127.
DR GeneID; 14527; -.
DR KEGG; mmu:14527; -.
DR UCSC; uc007mtc.2; mouse.
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; ARQMHYA; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; Q61606; -.
DR TreeFam; TF315710; -.
DR BioGRID-ORCS; 14527; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Gcgr; mouse.
DR PRO; PR:Q61606; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q61606; protein.
DR Bgee; ENSMUSG00000025127; Expressed in lobe of liver and 74 other tissues.
DR Genevisible; Q61606; MM.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004967; F:glucagon receptor activity; IDA:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
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:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0070873; P:regulation of glycogen metabolic process; IMP:UniProtKB.
DR GO; GO:0042594; P:response to starvation; IMP:UniProtKB.
DR Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
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 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; SSF111418; SSF111418; 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 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
