GIP_HUMAN
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 03-AUG-2022, entry version 178.
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}.
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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_004123.2.
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 PDBsum; 1T5Q; -.
DR PDBsum; 2B4N; -.
DR PDBsum; 2L70; -.
DR PDBsum; 2L71; -.
DR PDBsum; 2OBU; -.
DR PDBsum; 2QKH; -.
DR PDBsum; 7DTY; -.
DR PDBsum; 7RA3; -.
DR AlphaFoldDB; P09681; -.
DR BMRB; P09681; -.
DR SMR; P09681; -.
DR BioGRID; 108962; 46.
DR DIP; DIP-46469N; -.
DR IntAct; P09681; 11.
DR MINT; P09681; -.
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; P09681; -.
DR PeptideAtlas; P09681; -.
DR PRIDE; P09681; -.
DR ProteomicsDB; 52264; -.
DR Antibodypedia; 3388; 357 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 CTD; 2695; -.
DR DisGeNET; 2695; -.
DR GeneCards; GIP; -.
DR HGNC; HGNC:4270; GIP.
DR HPA; ENSG00000159224; Tissue enriched (intestine).
DR MIM; 137240; gene.
DR neXtProt; NX_P09681; -.
DR OpenTargets; ENSG00000159224; -.
DR PharmGKB; PA28681; -.
DR VEuPathDB; HostDB:ENSG00000159224; -.
DR eggNOG; ENOG502S7ZH; Eukaryota.
DR GeneTree; ENSGT00390000005121; -.
DR HOGENOM; CLU_146415_0_0_1; -.
DR InParanoid; P09681; -.
DR OMA; DQMEVCR; -.
DR OrthoDB; 1564478at2759; -.
DR PhylomeDB; P09681; -.
DR TreeFam; TF332333; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P09681; -.
DR BioGRID-ORCS; 2695; 8 hits in 1063 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 33 other tissues.
DR Genevisible; P09681; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
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:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0055123; P:digestive system development; IEA:Ensembl.
DR GO; GO:0031018; P:endocrine pancreas development; IEA:Ensembl.
DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0038192; P:gastric inhibitory peptide signaling pathway; IDA:BHF-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0070094; P:positive regulation of glucagon secretion; IEA:Ensembl.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
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:0010447; P:response to acidic pH; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0033993; P:response to lipid; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR InterPro; IPR039078; GIP.
DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR PANTHER; PTHR15211; PTHR15211; 1.
DR Pfam; PF00123; Hormone_2; 1.
DR SMART; SM00070; GLUCA; 1.
DR PROSITE; PS00260; GLUCAGON; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Hormone; 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
