GIPR_HUMAN
ID GIPR_HUMAN Reviewed; 466 AA.
AC P48546; B7WP14; B7ZKQ0; Q14401; Q16400; Q52M04; Q9UPI1;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Gastric inhibitory polypeptide receptor;
DE Short=GIP-R;
DE AltName: Full=Glucose-dependent insulinotropic polypeptide receptor;
DE Flags: Precursor;
GN Name=GIPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Usdin T.B., Gruber C., Modi W., Bonner T.I.;
RT "The human GIP receptor: gene structure, functional expression of its cDNA,
RT and chromosomal location.";
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7589426; DOI=10.1016/0014-5793(95)01006-z;
RA Volz A., Goke R., Lankat-Buttgereit B., Fehmann H.C., Bode H.P., Goke B.;
RT "Molecular cloning, functional expression, and signal transduction of the
RT GIP-receptor cloned from a human insulinoma.";
RL FEBS Lett. 373:23-29(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
RX PubMed=7556958; DOI=10.2337/diab.44.10.1202;
RA Gremlich S., Porret A., Hani E.H., Cherif D., Vionnet N., Froguel P.,
RA Thorens B.;
RT "Cloning, functional expression, and chromosomal localization of the human
RT pancreatic islet glucose-dependent insulinotropic polypeptide receptor.";
RL Diabetes 44:1202-1208(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8575774; DOI=10.1006/geno.1995.9937;
RA Yamada Y., Hayami T., Nakamura K., Kaisaki P.J., Someya Y., Wang C.Z.,
RA Seino S., Seino Y.;
RT "Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR)
RT and cDNA.";
RL Genomics 29:773-776(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Colon;
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 [7]
RP GLYCOSYLATION AT ASN-62 AND ASN-77, AND SUBUNIT.
RX PubMed=22412906; DOI=10.1371/journal.pone.0032675;
RA Whitaker G.M., Lynn F.C., McIntosh C.H., Accili E.A.;
RT "Regulation of GIP and GLP1 receptor cell surface expression by N-
RT glycosylation and receptor heteromerization.";
RL PLoS ONE 7:E32675-E32675(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-138 IN COMPLEX WITH GIP, AND
RP DISULFIDE BONDS.
RX PubMed=17715056; DOI=10.1073/pnas.0706404104;
RA Parthier C., Kleinschmidt M., Neumann P., Rudolph R., Manhart S.,
RA Schlenzig D., Fanghanel J., Rahfeld J.-U., Demuth H.-U., Stubbs M.T.;
RT "Crystal structure of the incretin-bound extracellular domain of a G
RT protein-coupled receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13942-13947(2007).
CC -!- FUNCTION: This is a receptor for GIP. The activity of this receptor is
CC mediated by G proteins which activate adenylyl cyclase.
CC -!- SUBUNIT: May form homodimers and heterodimers with GLP1R.
CC {ECO:0000269|PubMed:17715056, ECO:0000269|PubMed:22412906}.
CC -!- INTERACTION:
CC P48546; P01275: GCG; NbExp=2; IntAct=EBI-15653881, EBI-7629173;
CC P48546; P09681: GIP; NbExp=3; IntAct=EBI-15653881, EBI-8588553;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P48546-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48546-2; Sequence=VSP_053867, VSP_053868;
CC Name=3;
CC IsoId=P48546-3; Sequence=VSP_053866;
CC -!- PTM: N-glycosylation is required for cell surface expression and
CC lengthens receptor half-life by preventing degradation in the ER.
CC {ECO:0000269|PubMed:22412906}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA57426.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U39231; AAA84418.1; -; mRNA.
DR EMBL; S79852; AAB35419.2; -; mRNA.
DR EMBL; X81832; CAA57426.1; ALT_FRAME; mRNA.
DR EMBL; D49559; BAA08503.1; -; Genomic_DNA.
DR EMBL; AC006132; AAC97984.1; -; Genomic_DNA.
DR EMBL; AC007191; AAD22674.1; -; Genomic_DNA.
DR EMBL; BC093723; AAH93723.1; -; mRNA.
DR EMBL; BC101673; AAI01674.1; -; mRNA.
DR EMBL; BC143300; AAI43301.1; -; mRNA.
DR CCDS; CCDS12671.1; -. [P48546-1]
DR CCDS; CCDS82367.1; -. [P48546-3]
DR PIR; G02234; G02234.
DR PIR; I37411; I37411.
DR PIR; S66676; S66676.
DR RefSeq; NP_000155.1; NM_000164.3. [P48546-1]
DR RefSeq; NP_001295347.1; NM_001308418.1. [P48546-3]
DR PDB; 2QKH; X-ray; 1.90 A; A=24-138.
DR PDB; 4HJ0; X-ray; 3.00 A; A/B=24-138.
DR PDB; 6DKJ; X-ray; 1.95 A; C/D=22-138.
DR PDB; 7DTY; EM; 2.98 A; R=22-421.
DR PDB; 7FIN; EM; 3.10 A; R=22-421.
DR PDB; 7FIY; EM; 3.40 A; R=22-421.
DR PDB; 7RA3; EM; 3.24 A; R=22-466.
DR PDB; 7RBT; EM; 3.08 A; R=22-466.
DR PDB; 7VAB; EM; 3.20 A; R=22-421.
DR PDBsum; 2QKH; -.
DR PDBsum; 4HJ0; -.
DR PDBsum; 6DKJ; -.
DR PDBsum; 7DTY; -.
DR PDBsum; 7FIN; -.
DR PDBsum; 7FIY; -.
DR PDBsum; 7RA3; -.
DR PDBsum; 7RBT; -.
DR PDBsum; 7VAB; -.
DR AlphaFoldDB; P48546; -.
DR SMR; P48546; -.
DR BioGRID; 108963; 2.
DR DIP; DIP-46468N; -.
DR IntAct; P48546; 2.
DR STRING; 9606.ENSP00000467494; -.
DR BindingDB; P48546; -.
DR ChEMBL; CHEMBL4383; -.
DR GuidetoPHARMACOLOGY; 248; -.
DR TCDB; 9.A.14.4.5; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P48546; 2 sites.
DR iPTMnet; P48546; -.
DR PhosphoSitePlus; P48546; -.
DR BioMuta; GIPR; -.
DR DMDM; 1346133; -.
DR PaxDb; P48546; -.
DR PeptideAtlas; P48546; -.
DR PRIDE; P48546; -.
DR ABCD; P48546; 2 sequenced antibodies.
DR Antibodypedia; 17982; 610 antibodies from 32 providers.
DR DNASU; 2696; -.
DR Ensembl; ENST00000263281.7; ENSP00000263281.3; ENSG00000010310.9. [P48546-2]
DR Ensembl; ENST00000304207.12; ENSP00000305321.8; ENSG00000010310.9. [P48546-3]
DR Ensembl; ENST00000590918.6; ENSP00000467494.1; ENSG00000010310.9. [P48546-1]
DR GeneID; 2696; -.
DR KEGG; hsa:2696; -.
DR MANE-Select; ENST00000590918.6; ENSP00000467494.1; NM_000164.4; NP_000155.1.
DR UCSC; uc002pct.2; human. [P48546-1]
DR CTD; 2696; -.
DR DisGeNET; 2696; -.
DR GeneCards; GIPR; -.
DR HGNC; HGNC:4271; GIPR.
DR HPA; ENSG00000010310; Tissue enhanced (stomach).
DR MIM; 137241; gene.
DR neXtProt; NX_P48546; -.
DR OpenTargets; ENSG00000010310; -.
DR PharmGKB; PA28682; -.
DR VEuPathDB; HostDB:ENSG00000010310; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000161988; -.
DR HOGENOM; CLU_002753_4_0_1; -.
DR InParanoid; P48546; -.
DR OMA; LNCPPWR; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; P48546; -.
DR PathwayCommons; P48546; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P48546; -.
DR SIGNOR; P48546; -.
DR BioGRID-ORCS; 2696; 22 hits in 1076 CRISPR screens.
DR ChiTaRS; GIPR; human.
DR EvolutionaryTrace; P48546; -.
DR GeneWiki; Gastric_inhibitory_polypeptide_receptor; -.
DR GenomeRNAi; 2696; -.
DR Pharos; P48546; Tchem.
DR PRO; PR:P48546; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P48546; protein.
DR Bgee; ENSG00000010310; Expressed in right uterine tube and 116 other tissues.
DR ExpressionAtlas; P48546; baseline and differential.
DR Genevisible; P48546; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0016519; F:gastric inhibitory peptide receptor activity; IDA:BHF-UCL.
DR GO; GO:0120022; F:glucagon family peptide binding; IPI:BHF-UCL.
DR GO; GO:0017046; F:peptide hormone binding; IPI:BHF-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0031018; P:endocrine pancreas development; IEA:Ensembl.
DR GO; GO:0038192; P:gastric inhibitory peptide signaling pathway; IDA:BHF-UCL.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; TAS:ProtInc.
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; IPR001749; GPCR_2_GIP_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; PR01129; GIPRECEPTOR.
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 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..466
FT /note="Gastric inhibitory polypeptide receptor"
FT /id="PRO_0000012825"
FT TOPO_DOM 22..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..161
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..189
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..217
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..242
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..278
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..293
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..319
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..377
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..466
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 427..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22412906"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22412906"
FT DISULFID 46..70
FT /evidence="ECO:0000269|PubMed:17715056"
FT DISULFID 61..103
FT /evidence="ECO:0000269|PubMed:17715056"
FT DISULFID 84..118
FT /evidence="ECO:0000269|PubMed:17715056"
FT VAR_SEQ 58..93
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053866"
FT VAR_SEQ 400..419
FT /note="QSEIRRGWHHCRLRRSLGEE -> GRDPAAAPALWRQRGVRRRL (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:7556958"
FT /id="VSP_053867"
FT VAR_SEQ 420..466
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7556958"
FT /id="VSP_053868"
FT VARIANT 136
FT /note="R -> W (in dbSNP:rs13306402)"
FT /id="VAR_029333"
FT VARIANT 207
FT /note="A -> V (in dbSNP:rs1800436)"
FT /id="VAR_011808"
FT VARIANT 262
FT /note="L -> V (in dbSNP:rs5392)"
FT /id="VAR_011809"
FT VARIANT 354
FT /note="E -> Q (in dbSNP:rs1800437)"
FT /id="VAR_011810"
FT CONFLICT 12
FT /note="R -> G (in Ref. 2; AAB35419)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="G -> R (in Ref. 2; AAB35419)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="Missing (in Ref. 3; CAA57426)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="L -> V (in Ref. 2; AAB35419)"
FT /evidence="ECO:0000305"
FT CONFLICT 367..371
FT /note="GALRF -> APCV (in Ref. 3; CAA57426)"
FT /evidence="ECO:0000305"
FT HELIX 32..52
FT /evidence="ECO:0007829|PDB:2QKH"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:7DTY"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:2QKH"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4HJ0"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:2QKH"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:2QKH"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:4HJ0"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:6DKJ"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:2QKH"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:6DKJ"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 168..193
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 212..245
FT /evidence="ECO:0007829|PDB:7DTY"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 256..280
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 293..327
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 332..350
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 353..356
FT /evidence="ECO:0007829|PDB:7DTY"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 368..393
FT /evidence="ECO:0007829|PDB:7DTY"
FT HELIX 397..414
FT /evidence="ECO:0007829|PDB:7DTY"
SQ SEQUENCE 466 AA; 53157 MW; CA5CF86BA0E32383 CRC64;
MTTSPILQLL LRLSLCGLLL QRAETGSKGQ TAGELYQRWE RYRRECQETL AAAEPPSGLA
CNGSFDMYVC WDYAAPNATA RASCPWYLPW HHHVAAGFVL RQCGSDGQWG LWRDHTQCEN
PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF
MLRAAAILSR DRLLPRPGPY LGDQALALWN QALAACRTAQ IVTQYCVGAN YTWLLVEGVY
LHSLLVLVGG SEEGHFRYYL LLGWGAPALF VIPWVIVRYL YENTQCWERN EVKAIWWIIR
TPILMTILIN FLIFIRILGI LLSKLRTRQM RCRDYRLRLA RSTLTLVPLL GVHEVVFAPV
TEEQARGALR FAKLGFEIFL SSFQGFLVSV LYCFINKEVQ SEIRRGWHHC RLRRSLGEEQ
RQLPERAFRA LPSGSGPGEV PTSRGLSSGT LPGPGNEASR ELESYC
