GAST_HUMAN
ID GAST_HUMAN Reviewed; 101 AA.
AC P01350; P78463; P78464;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-1986, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Gastrin;
DE Contains:
DE RecName: Full=Gastrin-71;
DE AltName: Full=Gastrin component I;
DE Contains:
DE RecName: Full=Gastrin-52;
DE Short=G52;
DE Contains:
DE RecName: Full=Big gastrin;
DE AltName: Full=Gastrin component II;
DE AltName: Full=Gastrin-34;
DE Short=G34;
DE Contains:
DE RecName: Full=Gastrin;
DE AltName: Full=Gastrin component III;
DE AltName: Full=Gastrin-17;
DE Short=G17;
DE Contains:
DE RecName: Full=Gastrin-14;
DE Short=G14;
DE Contains:
DE RecName: Full=Gastrin-6;
DE Short=G6;
DE Flags: Precursor;
GN Name=GAST; Synonyms=GAS;
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 [GENOMIC DNA].
RX PubMed=3034736; DOI=10.1016/0378-1119(86)90338-0;
RA Kariya Y., Kato K., Hayashizaki Y., Himeno S., Tarui S., Matsubara K.;
RT "Expression of human gastrin gene in normal and gastrinoma tissues.";
RL Gene 50:345-352(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6087340; DOI=10.1073/pnas.81.15.4662;
RA Ito R., Sato K., Helmer T., Jay G., Agarwal K.L.;
RT "Structural analysis of the gene encoding human gastrin: the large intron
RT contains an Alu sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4662-4666(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6324077; DOI=10.1093/nar/11.23.8197;
RA Kato K., Hayashizaki Y., Takahashi Y., Himeno S., Matsubara K.;
RT "Molecular cloning of the human gastrin gene.";
RL Nucleic Acids Res. 11:8197-8203(1983).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6574456; DOI=10.1073/pnas.80.10.2866;
RA Boel E., Vuust J., Norris F., Norris K., Wind A., Rehfeld J.F.,
RA Marcker K.A.;
RT "Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin
RT by gene duplication.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:2866-2869(1983).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6322186; DOI=10.1073/pnas.81.4.1067;
RA Wiborg O., Berglund L., Boel E., Norris F., Norris K., Rehfeld J.F.,
RA Marcker K.A., Vuust J.;
RT "Structure of a human gastrin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:1067-1069(1984).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6689486; DOI=10.1016/0378-1119(83)90035-5;
RA Kato K., Himeno S., Takahashi Y., Wakabayashi T., Tarui S., Matsubara K.;
RT "Molecular cloning of human gastrin precursor cDNA.";
RL Gene 26:53-57(1983).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP PROTEIN SEQUENCE OF 22-101, AND CHARACTERIZATION OF GASTRIN 71.
RC TISSUE=Gastric mucosa;
RX PubMed=8055952; DOI=10.1111/j.1432-1033.1994.tb19051.x;
RA Rehfeld J.F., Johnsen A.H.;
RT "Identification of gastrin component I as gastrin-71. The largest possible
RT bioactive progastrin product.";
RL Eur. J. Biochem. 223:765-773(1994).
RN [9]
RP PROTEIN SEQUENCE OF 76-92, PYROGLUTAMATE FORMATION AT GLN-76, AND AMIDATION
RP AT PHE-92.
RX PubMed=5921183; DOI=10.1038/209583b0;
RA Bentley P.H., Kenner G.W., Sheppard R.C.;
RT "Structures of human gastrins I and II.";
RL Nature 209:583-585(1966).
RN [10]
RP PROTEIN SEQUENCE OF 59-68, AND PYROGLUTAMATE FORMATION AT GLN-59.
RX PubMed=2730647; DOI=10.1016/s0006-291x(89)80154-8;
RA Higashimoto Y., Himeno S., Shinomura Y., Nagao K., Tamura T., Tarui S.;
RT "Purification and structural determination of urinary NH2-terminal big
RT gastrin fragments.";
RL Biochem. Biophys. Res. Commun. 160:1364-1370(1989).
RN [11]
RP PROTEIN SEQUENCE OF 76-92.
RX PubMed=5822140; DOI=10.1136/gut.10.8.603;
RA Gregory R.A., Tracy H.J., Agarwal K.L., Grossman M.I.;
RT "Aminoacid constitution of two gastrins isolated from Zollinger-Ellison
RT tumour tissue.";
RL Gut 10:603-608(1969).
RN [12]
RP PHOSPHORYLATION AT SER-96.
RX PubMed=3223964; DOI=10.1042/bj2560951;
RA Varro A., Desmond H., Pauwels S., Gregory H., Young J., Dockray G.J.;
RT "The human gastrin precursor. Characterization of phosphorylated forms and
RT fragments.";
RL Biochem. J. 256:951-957(1988).
RN [13]
RP PROTEOLYTIC PROCESSING, IDENTIFICATION BY MASS SPECTROMETRY, AND SULFATION
RP AT TYR-87.
RX PubMed=7530658; DOI=10.1002/j.1460-2075.1995.tb07013.x;
RA Rehfeld J.F., Hansen C.P., Johnsen A.H.;
RT "Post-poly(Glu) cleavage and degradation modified by O-sulfated tyrosine: a
RT novel post-translational processing mechanism.";
RL EMBO J. 14:389-396(1995).
RN [14]
RP SULFATION, MUTAGENESIS OF ALA-86 AND TYR-87, AND PROTEOLYTIC PROCESSING.
RX PubMed=7621822; DOI=10.1002/j.1460-2075.1995.tb07310.x;
RA Bundgaard J.R., Vuust J., Rehfeld J.F.;
RT "Tyrosine O-sulfation promotes proteolytic processing of progastrin.";
RL EMBO J. 14:3073-3079(1995).
RN [15]
RP PROTEOLYTIC PROCESSING, AND SULFATION AT TYR-87.
RX PubMed=11052986; DOI=10.1152/ajpgi.2000.279.5.g903;
RA Palnaes Hansen C., Stadil F., Rehfeld J.F.;
RT "Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6
RT in humans.";
RL Am. J. Physiol. 279:G903-G909(2000).
CC -!- FUNCTION: Gastrin stimulates the stomach mucosa to produce and secrete
CC hydrochloric acid and the pancreas to secrete its digestive enzymes. It
CC also stimulates smooth muscle contraction and increases blood
CC circulation and water secretion in the stomach and intestine.
CC -!- INTERACTION:
CC P01350; Q13520: AQP6; NbExp=3; IntAct=EBI-3436637, EBI-13059134;
CC P01350; O43315: AQP9; NbExp=3; IntAct=EBI-3436637, EBI-17444777;
CC P01350; Q12797-6: ASPH; NbExp=3; IntAct=EBI-3436637, EBI-12092171;
CC P01350; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-3436637, EBI-747430;
CC P01350; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-3436637, EBI-1045797;
CC P01350; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-3436637, EBI-6942903;
CC P01350; P00387: CYB5R3; NbExp=3; IntAct=EBI-3436637, EBI-1046040;
CC P01350; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-3436637, EBI-781551;
CC P01350; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-3436637, EBI-18304435;
CC P01350; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-3436637, EBI-712073;
CC P01350; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-3436637, EBI-13345167;
CC P01350; P43628: KIR2DL3; NbExp=3; IntAct=EBI-3436637, EBI-8632435;
CC P01350; O76011: KRT34; NbExp=3; IntAct=EBI-3436637, EBI-1047093;
CC P01350; Q6ZUX7: LHFPL2; NbExp=3; IntAct=EBI-3436637, EBI-17566767;
CC P01350; Q15546: MMD; NbExp=3; IntAct=EBI-3436637, EBI-17873222;
CC P01350; P15941-11: MUC1; NbExp=3; IntAct=EBI-3436637, EBI-17263240;
CC P01350; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-3436637, EBI-716063;
CC P01350; P60201-2: PLP1; NbExp=3; IntAct=EBI-3436637, EBI-12188331;
CC P01350; Q14973: SLC10A1; NbExp=3; IntAct=EBI-3436637, EBI-3923031;
CC P01350; P02787: TF; NbExp=5; IntAct=EBI-3436637, EBI-714319;
CC P01350; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-3436637, EBI-18178701;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Two different processing pathways probably exist in antral G-
CC cells. In the dominant pathway progastrin is cleaved at three sites
CC resulting in two major bioactive gastrins, gastrin-34 and gastrin-17.
CC In the putative alternative pathway, progastrin may be processed only
CC at the most C-terminal dibasic site resulting in the synthesis of
CC gastrin-71.
CC -!- PTM: Sulfation enhances proteolytic processing, and blocks peptide
CC degradation. Levels of sulfation differ between proteolytically-cleaved
CC gastrins. Thus, gastrin-6 is almost 73% sulfated, whereas the larger
CC gastrins are less than 50% sulfated. Sulfation levels are also tissue-
CC specific. {ECO:0000269|PubMed:11052986, ECO:0000269|PubMed:7530658,
CC ECO:0000269|PubMed:7621822}.
CC -!- SIMILARITY: Belongs to the gastrin/cholecystokinin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Gastrin entry;
CC URL="https://en.wikipedia.org/wiki/Gastrin";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GASTID44214ch17q21.html";
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; X00183; CAA25005.1; -; Genomic_DNA.
DR EMBL; X00183; CAA25006.1; -; Genomic_DNA.
DR EMBL; X00183; CAA25007.1; -; Genomic_DNA.
DR EMBL; V00511; CAA23769.1; -; mRNA.
DR EMBL; M15958; AAA52520.1; -; Genomic_DNA.
DR EMBL; K01254; AAB59533.1; -; Genomic_DNA.
DR EMBL; BC069724; AAH69724.1; -; mRNA.
DR EMBL; BC069762; AAH69762.1; -; mRNA.
DR CCDS; CCDS11404.1; -.
DR PIR; A93997; GMHUB.
DR RefSeq; NP_000796.1; NM_000805.4.
DR PDB; 5WRJ; X-ray; 2.31 A; F/H/J/L=81-92.
DR PDBsum; 5WRJ; -.
DR AlphaFoldDB; P01350; -.
DR BMRB; P01350; -.
DR SMR; P01350; -.
DR BioGRID; 108796; 37.
DR DIP; DIP-403N; -.
DR IntAct; P01350; 32.
DR MINT; P01350; -.
DR STRING; 9606.ENSP00000331358; -.
DR DrugBank; DB12532; Oxetacaine.
DR iPTMnet; P01350; -.
DR PhosphoSitePlus; P01350; -.
DR BioMuta; GAST; -.
DR DMDM; 120952; -.
DR MassIVE; P01350; -.
DR PaxDb; P01350; -.
DR PeptideAtlas; P01350; -.
DR PRIDE; P01350; -.
DR ProteomicsDB; 51377; -.
DR Antibodypedia; 3504; 426 antibodies from 35 providers.
DR DNASU; 2520; -.
DR Ensembl; ENST00000329402.4; ENSP00000331358.3; ENSG00000184502.4.
DR GeneID; 2520; -.
DR KEGG; hsa:2520; -.
DR MANE-Select; ENST00000329402.4; ENSP00000331358.3; NM_000805.5; NP_000796.1.
DR UCSC; uc002hxl.3; human.
DR CTD; 2520; -.
DR DisGeNET; 2520; -.
DR GeneCards; GAST; -.
DR HGNC; HGNC:4164; GAST.
DR HPA; ENSG00000184502; Tissue enriched (stomach).
DR MIM; 137250; gene.
DR neXtProt; NX_P01350; -.
DR OpenTargets; ENSG00000184502; -.
DR PharmGKB; PA28577; -.
DR VEuPathDB; HostDB:ENSG00000184502; -.
DR eggNOG; ENOG502SA9S; Eukaryota.
DR GeneTree; ENSGT00390000014792; -.
DR HOGENOM; CLU_2249245_0_0_1; -.
DR InParanoid; P01350; -.
DR OMA; KPRSQLQ; -.
DR OrthoDB; 1433918at2759; -.
DR PhylomeDB; P01350; -.
DR TreeFam; TF336994; -.
DR PathwayCommons; P01350; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR SignaLink; P01350; -.
DR SIGNOR; P01350; -.
DR BioGRID-ORCS; 2520; 16 hits in 1067 CRISPR screens.
DR ChiTaRS; GAST; human.
DR GeneWiki; Gastrin; -.
DR GenomeRNAi; 2520; -.
DR Pharos; P01350; Tbio.
DR PRO; PR:P01350; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P01350; protein.
DR Bgee; ENSG00000184502; Expressed in pylorus and 100 other tissues.
DR ExpressionAtlas; P01350; baseline and differential.
DR Genevisible; P01350; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0032094; P:response to food; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR InterPro; IPR039236; GAST.
DR InterPro; IPR001651; Gastrin/CCK.
DR InterPro; IPR013152; Gastrin/cholecystokinin_CS.
DR PANTHER; PTHR19309; PTHR19309; 1.
DR Pfam; PF00918; Gastrin; 1.
DR PROSITE; PS00259; GASTRIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Direct protein sequencing; Hormone; Phosphoprotein;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal;
KW Sulfation.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:8055952"
FT PEPTIDE 22..92
FT /note="Gastrin-71"
FT /id="PRO_0000010633"
FT PEPTIDE 41..92
FT /note="Gastrin-52"
FT /id="PRO_0000010634"
FT PEPTIDE 59..92
FT /note="Big gastrin"
FT /id="PRO_0000010635"
FT PEPTIDE 76..92
FT /note="Gastrin"
FT /id="PRO_0000010636"
FT PEPTIDE 79..92
FT /note="Gastrin-14"
FT /id="PRO_0000010637"
FT PEPTIDE 87..92
FT /note="Gastrin-6"
FT /id="PRO_0000010638"
FT PROPEP 96..101
FT /note="Removed in mature form"
FT /id="PRO_0000010639"
FT REGION 22..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 40..41
FT /note="Cleavage"
FT SITE 58..59
FT /note="Cleavage"
FT SITE 75..76
FT /note="Cleavage"
FT SITE 95..96
FT /note="Cleavage"
FT MOD_RES 59
FT /note="Pyrrolidone carboxylic acid; in form big gastrin"
FT /evidence="ECO:0000269|PubMed:2730647"
FT MOD_RES 76
FT /note="Pyrrolidone carboxylic acid; in form gastrin"
FT /evidence="ECO:0000269|PubMed:5921183"
FT MOD_RES 87
FT /note="Sulfotyrosine; partial"
FT /evidence="ECO:0000269|PubMed:11052986,
FT ECO:0000269|PubMed:7530658"
FT MOD_RES 92
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:5921183"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:3223964"
FT VARIANT 3
FT /note="R -> P (in dbSNP:rs34309618)"
FT /id="VAR_049127"
FT MUTAGEN 86
FT /note="A->D: Small increase in ratio of gastrin-17 versus
FT gastrin-34 production. No change in ratio of gastrin-17
FT versus gastrin-34 production; when associated with F-87."
FT /evidence="ECO:0000269|PubMed:7621822"
FT MUTAGEN 87
FT /note="Y->F: Small decrease in ratio of gastrin-17 versus
FT gastrin-34 production. No change in ratio of gastrin-17
FT versus gastrin-34 production; when associated with D-86."
FT /evidence="ECO:0000269|PubMed:7621822"
SQ SEQUENCE 101 AA; 11394 MW; A03C847FCFE7216C CRC64;
MQRLCVYVLI FALALAAFSE ASWKPRSQQP DAPLGTGANR DLELPWLEQQ GPASHHRRQL
GPQGPPHLVA DPSKKQGPWL EEEEEAYGWM DFGRRSAEDE N
