ID   GIP_HUMAN               Reviewed;         153 AA.
AC   P09681; Q4VB42; Q6NTD3;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   02-SEP-2026, entry version 196.
DE   RecName: Full=Gastric inhibitory polypeptide;
DE            Short=GIP;
DE   AltName: Full=Glucose-dependent insulinotropic polypeptide;
DE   AltName: Full=Incretin hormone;
DE   Flags: Precursor;
GN   Name=GIP;
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].
RX   PubMed=2890159; DOI=10.1073/pnas.84.20.7005;
RA   Takeda J., Seino Y., Tanaka K., Fukumoto H., Kayano T., Takahashi H.,
RA   Mitani T., Kurono M., Suzuki T., Tobe T., Imura H.;
RT   "Sequence of an intestinal cDNA encoding human gastric inhibitory
RT   polypeptide precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:7005-7008(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2739653; DOI=10.1210/mend-3-6-1014;
RA   Inagaki N., Seino Y., Takeda J., Yano H., Yamada Y., Bell G.I.,
RA   Eddy R.L. Jr., Fukushima Y., Byers M.G., Shows T.B., Imura H.;
RT   "Gastric inhibitory polypeptide: structure and chromosomal localization of
RT   the human gene.";
RL   Mol. Endocrinol. 3:1014-1021(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-103.
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   [4]
RP   PROTEIN SEQUENCE OF 52-93.
RX   PubMed=6745415; DOI=10.1016/0014-5793(84)81114-x;
RA   Moody A.J., Thim L., Valverde I.;
RT   "The isolation and sequencing of human gastric inhibitory peptide (GIP).";
RL   FEBS Lett. 172:142-148(1984).
RN   [5]
RP   STRUCTURE BY NMR OF 52-81.
RX   PubMed=15522230; DOI=10.1016/j.bbrc.2004.10.033;
RA   Alana I., Hewage C.M., Malthouse J.P., Parker J.C., Gault V.A.,
RA   O'Harte F.P.;
RT   "NMR structure of the glucose-dependent insulinotropic polypeptide
RT   fragment, GIP(1-30)amide.";
RL   Biochem. Biophys. Res. Commun. 325:281-286(2004).
CC   -!- FUNCTION: Potent stimulator of insulin secretion and relatively poor
CC       inhibitor of gastric acid secretion.
CC   -!- INTERACTION:
CC       P09681; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-8588553, EBI-10173507;
CC       P09681; P48546: GIPR; NbExp=3; IntAct=EBI-8588553, EBI-15653881;
CC       P09681; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-8588553, EBI-945833;
CC       P09681; O43765: SGTA; NbExp=6; IntAct=EBI-8588553, EBI-347996;
CC       P09681; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-8588553, EBI-744081;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M18185; AAA88043.1; -; mRNA.
DR   EMBL; M31679; AAA53192.1; -; Genomic_DNA.
DR   EMBL; M31675; AAA53192.1; JOINED; Genomic_DNA.
DR   EMBL; M31676; AAA53192.1; JOINED; Genomic_DNA.
DR   EMBL; M31677; AAA53192.1; JOINED; Genomic_DNA.
DR   EMBL; M31678; AAA53192.1; JOINED; Genomic_DNA.
DR   EMBL; BC069100; AAH69100.1; -; mRNA.
DR   EMBL; BC069663; AAH69663.1; -; mRNA.
DR   EMBL; BC069686; AAH69686.1; -; mRNA.
DR   EMBL; BC069746; AAH69746.1; -; mRNA.
DR   EMBL; BC096146; AAH96146.1; -; mRNA.
DR   EMBL; BC096147; AAH96147.1; -; mRNA.
DR   EMBL; BC096148; AAH96148.1; -; mRNA.
DR   EMBL; BC096149; AAH96149.1; -; mRNA.
DR   CCDS; CCDS11542.1; -.
DR   PIR; A28406; A28406.
DR   RefSeq; NP_004114.1; NM_004123.3.
DR   PDB; 1T5Q; NMR; -; A=52-81.
DR   PDB; 2B4N; NMR; -; A=52-93.
DR   PDB; 2L70; NMR; -; A=52-93.
DR   PDB; 2L71; NMR; -; A=52-93.
DR   PDB; 2OBU; NMR; -; A=52-93.
DR   PDB; 2QKH; X-ray; 1.90 A; B=52-93.
DR   PDB; 7DTY; EM; 2.98 A; P=52-93.
DR   PDB; 7RA3; EM; 3.24 A; P=52-93.
DR   AlphaFoldDB; P09681; -.
DR   BMRB; P09681; -.
DR   EMDB; EMD-24334; -.
DR   EMDB; EMD-30860; -.
DR   SMR; P09681; -.
DR   BioGRID; 108962; 46.
DR   DIP; DIP-46469N; -.
DR   FunCoup; P09681; 571.
DR   IntAct; P09681; 43.
DR   MINT; P09681; -.
DR   NDEx; IQUERY-CP-GIP; 2 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000350005; -.
DR   BindingDB; P09681; -.
DR   iPTMnet; P09681; -.
DR   PhosphoSitePlus; P09681; -.
DR   BioMuta; GIP; -.
DR   DMDM; 121194; -.
DR   jPOST; P09681; -.
DR   MassIVE; P09681; -.
DR   PaxDb; 9606-ENSP00000350005; -.
DR   PeptideAtlas; P09681; -.
DR   ProteomicsDB; 52264; -.
DR   Antibodypedia; 3388; 372 antibodies from 29 providers.
DR   DNASU; 2695; -.
DR   Ensembl; ENST00000357424.2; ENSP00000350005.2; ENSG00000159224.4.
DR   GeneID; 2695; -.
DR   KEGG; hsa:2695; -.
DR   MANE-Select; ENST00000357424.2; ENSP00000350005.2; NM_004123.3; NP_004114.1.
DR   UCSC; uc002iol.2; human.
DR   AGR; HGNC:4270; -.
DR   ClinPGx; PA28681; -.
DR   CTD; 2695; -.
DR   DisGeNET; 2695; -.
DR   GeneCards; GIP; -.
DR   HGNC; HGNC:4270; GIP.
DR   HPA; ENSG00000159224; Tissue enriched (intestine).
DR   MIM; 137240; gene.
DR   OpenTargets; ENSG00000159224; -.
DR   VEuPathDB; HostDB:ENSG00000159224; -.
DR   eggNOG; ENOG502S7ZH; Eukaryota.
DR   GeneTree; ENSGT00390000005121; -.
DR   HOGENOM; CLU_146415_0_0_1; -.
DR   InParanoid; P09681; -.
DR   OMA; GHSRFHT; -.
DR   OrthoDB; 8874823at2759; -.
DR   PAN-GO; P09681; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P09681; -.
DR   PathwayCommons; P09681; -.
DR   Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   SignaLink; P09681; -.
DR   SIGNOR; P09681; -.
DR   Agora; ENSG00000159224; -.
DR   BioGRID-ORCS; 2695; 9 hits in 1141 CRISPR screens.
DR   ChiTaRS; GIP; human.
DR   EvolutionaryTrace; P09681; -.
DR   GenomeRNAi; 2695; -.
DR   Pharos; P09681; Tbio.
DR   PRO; PR:P09681; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P09681; protein.
DR   Bgee; ENSG00000159224; Expressed in jejunal mucosa and 34 other cell types or tissues.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR   GO; GO:0031767; F:gastric inhibitory polypeptide receptor binding; IPI:BHF-UCL.
DR   GO; GO:0031769; F:glucagon receptor binding; IBA:GO_Central.
DR   GO; GO:0005179; F:hormone activity; TAS:ProtInc.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0038192; P:gastric inhibitory peptide signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IEA:InterPro.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0009749; P:response to glucose; IEA:InterPro.
DR   GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   Gene3D; 6.10.250.590; -; 1.
DR   InterPro; IPR039078; GIP.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   PANTHER; PTHR15211:SF0; GASTRIC INHIBITORY POLYPEPTIDE; 1.
DR   PANTHER; PTHR15211; GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE; 1.
DR   Pfam; PF00123; Hormone_2; 1.
DR   SMART; SM00070; GLUCA; 1.
DR   PROSITE; PS00260; GLUCAGON; 1.
DR   PDBsum; 1T5Q; -.
DR   PDBsum; 2B4N; -.
DR   PDBsum; 2L70; -.
DR   PDBsum; 2L71; -.
DR   PDBsum; 2OBU; -.
DR   PDBsum; 2QKH; -.
DR   PDBsum; 7DTY; -.
DR   PDBsum; 7RA3; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Hormone; Proteomics identification;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..50
FT                   /id="PRO_0000011214"
FT   PEPTIDE         52..93
FT                   /note="Gastric inhibitory polypeptide"
FT                   /id="PRO_0000011215"
FT   PROPEP          95..153
FT                   /id="PRO_0000011216"
FT   REGION          102..125
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         103
FT                   /note="S -> G (in dbSNP:rs2291725)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_021897"
FT   VARIANT         146
FT                   /note="N -> S (in dbSNP:rs35703924)"
FT                   /id="VAR_033973"
FT   HELIX           57..79
FT                   /evidence="ECO:0007829|PDB:2QKH"
FT   TURN            80..82
FT                   /evidence="ECO:0007829|PDB:2QKH"
FT   STRAND          86..88
FT                   /evidence="ECO:0007829|PDB:2L70"
SQ   SEQUENCE   153 AA;  17108 MW;  51F5FC388A8897EC CRC64;
     MVATKTFALL LLSLFLAVGL GEKKEGHFSA LPSLPVGSHA KVSSPQPRGP RYAEGTFISD
     YSIAMDKIHQ QDFVNWLLAQ KGKKNDWKHN ITQREARALE LASQANRKEE EAVEPQSSPA
     KNPSDEDLLR DLLIQELLAC LLDQTNLCRL RSR
//