TFF1_HUMAN
ID TFF1_HUMAN Reviewed; 84 AA.
AC P04155;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Trefoil factor 1;
DE AltName: Full=Breast cancer estrogen-inducible protein;
DE AltName: Full=PNR-2;
DE AltName: Full=Polypeptide P1.A;
DE Short=hP1.A;
DE AltName: Full=Protein pS2;
DE Flags: Precursor;
GN Name=TFF1; Synonyms=BCEI, PS2;
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=6324130; DOI=10.1093/nar/12.6.2861;
RA Jakowlew S.B., Breathnach R., Jeltsch J.-M., Masiakowski P., Chambon P.;
RT "Sequence of the pS2 mRNA induced by estrogen in the human breast cancer
RT cell line MCF-7.";
RL Nucleic Acids Res. 12:2861-2878(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Mammary cancer;
RX PubMed=3838275; DOI=10.1089/dna.1985.4.11;
RA Prud'Homme J.-F., Fridlansky F., le Cunff M., Atger M., Mercier-Bodart C.,
RA Pichon M.-F., Milgrom E.;
RT "Cloning of a gene expressed in human breast cancer and regulated by
RT estrogen in MCF-7 cells.";
RL DNA 4:11-21(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3822834; DOI=10.1093/nar/15.4.1401;
RA Jeltsch J.-M., Roberts M., Schatz C., Garnier J.-M., Brown A.M.C.,
RA Chambon P.;
RT "Structure of the human oestrogen-responsive gene pS2.";
RL Nucleic Acids Res. 15:1401-1414(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Gastric carcinoma;
RX PubMed=2311759; DOI=10.1016/0014-5793(90)80572-z;
RA Takahashi H., Kida N., Fujii R., Tanaka K., Ohta M., Mori K., Hayashi K.;
RT "Expression of the pS2 gene in human gastric cancer cells derived from
RT poorly differentiated adenocarcinoma.";
RL FEBS Lett. 261:283-286(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2185238; DOI=10.1093/oxfordjournals.jbchem.a123014;
RA Mori K., Fujii R., Kida N., Takahashi H., Ohkubo S., Fujino M., Ohta M.,
RA Hayashi K.;
RT "Complete primary structure of the human estrogen-responsive gene (pS2)
RT product.";
RL J. Biochem. 107:73-76(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10950923; DOI=10.1006/geno.2000.6253;
RA Berry A., Scott H.S., Kudoh J., Talior I., Korostishevsky M.,
RA Wattenhofer M., Guipponi M., Barras C., Rossier C., Shibuya K., Wang J.,
RA Kawasaki K., Asakawa S., Minoshima S., Shimizu N., Antonarakis S.E.,
RA Bonne-Tamir B.;
RT "Refined localization of autosomal recessive nonsyndromic deafness DFNB10
RT locus using 34 novel microsatellite markers, genomic structure, and
RT exclusion of six known genes in the region.";
RL Genomics 68:22-29(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Kidney, and Stomach;
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 [9]
RP PROTEIN SEQUENCE OF 25-84.
RX PubMed=3146413;
RA Rio M.-C., Lepage P., Diemunsch P., Roitsch C., Chambon P.;
RT "Primary structure of human protein pS2.";
RL C. R. Acad. Sci. III, Sci. Vie 307:825-831(1988).
RN [10]
RP PROTEIN SEQUENCE OF 25-84, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH GKN2.
RC TISSUE=Stomach;
RX PubMed=15924415; DOI=10.1021/bi047287n;
RA Westley B.R., Griffin S.M., May F.E.B.;
RT "Interaction between TFF1, a gastric tumor suppressor trefoil protein, and
RT TFIZ1, a Brichos domain-containing protein with homology to SP-C.";
RL Biochemistry 44:7967-7975(2005).
RN [11]
RP PROTEIN SEQUENCE OF 25-63, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16308573; DOI=10.1172/jci25342;
RA Chutipongtanate S., Nakagawa Y., Sritippayawan S., Pittayamateekul J.,
RA Parichatikanond P., Westley B.R., May F.E., Malasit P., Thongboonkerd V.;
RT "Identification of human urinary trefoil factor 1 as a novel calcium
RT oxalate crystal growth inhibitor.";
RL J. Clin. Invest. 115:3613-3622(2005).
RN [12]
RP PROTEIN SEQUENCE OF 25-60.
RX PubMed=3261981; DOI=10.1016/s0006-291x(88)81094-5;
RA Mori K., Fujii R., Kida N., Ohta M., Hayashi K.;
RT "Identification of a polypeptide secreted by human breast cancer cells
RT (MCF-7) as the human estrogen-responsive gene (pS2) product.";
RL Biochem. Biophys. Res. Commun. 155:366-372(1988).
RN [13]
RP PROTEIN SEQUENCE OF 25-39.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [14]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=3041593; DOI=10.1126/science.3041593;
RA Rio M.C., Bellocq J.-P., Daniel J.Y., Tomasetto C., Lathe R., Chenard M.P.,
RA Batzenschlager A., Chambon P.;
RT "Breast cancer-associated pS2 protein: synthesis and secretion by normal
RT stomach mucosa.";
RL Science 241:705-708(1988).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=16718800; DOI=10.3748/wjg.v12.i19.3119;
RA Shi S.-Q., Cai J.-T., Yang J.-M.;
RT "Expression of trefoil factors 1 and 2 in precancerous condition and
RT gastric cancer.";
RL World J. Gastroenterol. 12:3119-3122(2006).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=17143957; DOI=10.3748/wjg.v12.i45.7361;
RA Ren J.L., Luo J.-Y., Lu Y.-P., Wang L., Shi H.-X.;
RT "Molecular forms of trefoil factor 1 in normal gastric mucosa and its
RT expression in normal and abnormal gastric tissues.";
RL World J. Gastroenterol. 12:7361-7364(2006).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=17242463; DOI=10.1369/jhc.6a7100.2007;
RA Madsen J., Nielsen O., Tornoe I., Thim L., Holmskov U.;
RT "Tissue localization of human trefoil factors 1, 2, and 3.";
RL J. Histochem. Cytochem. 55:505-513(2007).
RN [18]
RP STRUCTURE BY NMR.
RX PubMed=8521850; DOI=10.1111/j.1432-1033.1995.847_3.x;
RA Polshakov V.I., Frenkiel T.A., Westley B.R., Chadwick M.P., May F.E.B.,
RA Carr M.D., Feeney J.;
RT "NMR-based structural studies of the pNR-2/pS2 single domain trefoil
RT peptide. Similarities to porcine spasmolytic peptide and evidence for a
RT monomeric structure.";
RL Eur. J. Biochem. 233:847-855(1995).
RN [19]
RP STRUCTURE BY NMR.
RX PubMed=9096235; DOI=10.1006/jmbi.1997.0896;
RA Polshakov V.I., Williams M.A., Gargaro A.R., Frenkiel T.A., Westley B.R.,
RA Chadwick M.P., May F.E.B., Feeney J.;
RT "High-resolution solution structure of human pNR-2/pS2: a single trefoil
RT motif protein.";
RL J. Mol. Biol. 267:418-432(1997).
RN [20]
RP VARIANTS ILE-32; LYS-32; ASP-34; LYS-37; ILE-46 AND VAL-55.
RX PubMed=10982763; DOI=10.1053/gast.2000.16483;
RA Park W.-S., Oh R.-R., Park J.-Y., Lee J.-H., Shin M.-S., Kim H.-S.,
RA Lee H.-K., Kim Y.-S., Kim S.-Y., Lee S.-H., Yoo N.-J., Lee J.-Y.;
RT "Somatic mutations of the trefoil factor family 1 gene in gastric cancer.";
RL Gastroenterology 119:691-698(2000).
RN [21]
RP VARIANTS ASP-34 AND LYS-37, AND MUTAGENESIS OF CYS-82.
RX PubMed=16697734; DOI=10.1053/j.gastro.2006.01.040;
RA Yio X., Diamond M., Zhang J.-Y., Weinstein H., Wang L.-H., Werther L.,
RA Itzkowitz S.;
RT "Trefoil factor family-1 mutations enhance gastric cancer cell invasion
RT through distinct signaling pathways.";
RL Gastroenterology 130:1696-1706(2006).
CC -!- FUNCTION: Stabilizer of the mucous gel overlying the gastrointestinal
CC mucosa that provides a physical barrier against various noxious agents.
CC May inhibit the growth of calcium oxalate crystals in urine.
CC {ECO:0000269|PubMed:16308573}.
CC -!- SUBUNIT: Heterodimer with GKN2; disulfide linked.
CC -!- INTERACTION:
CC P04155; O00481: BTN3A1; NbExp=3; IntAct=EBI-743871, EBI-2809309;
CC P04155; Q6UX41: BTNL8; NbExp=3; IntAct=EBI-743871, EBI-4314379;
CC P04155; Q6UXZ3: CD300LD; NbExp=3; IntAct=EBI-743871, EBI-4314468;
CC P04155; Q96PJ5: FCRL4; NbExp=3; IntAct=EBI-743871, EBI-4314687;
CC P04155; Q92508: PIEZO1; NbExp=5; IntAct=EBI-743871, EBI-10986212;
CC P04155; Q96EQ0: SGTB; NbExp=5; IntAct=EBI-743871, EBI-744081;
CC P04155; Q9NYZ4: SIGLEC8; NbExp=3; IntAct=EBI-743871, EBI-4314991;
CC P04155; Q9UMX0: UBQLN1; NbExp=6; IntAct=EBI-743871, EBI-741480;
CC P04155; P62760: VSNL1; NbExp=3; IntAct=EBI-743871, EBI-740943;
CC P04155; P15622-3: ZNF250; NbExp=3; IntAct=EBI-743871, EBI-10177272;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15924415,
CC ECO:0000269|PubMed:3041593}.
CC -!- TISSUE SPECIFICITY: Found in stomach, with highest levels in the upper
CC gastric mucosal cells (at protein level). Detected in goblet cells of
CC the small and large intestine and rectum, small submucosal glands in
CC the esophagus, mucous acini of the sublingual gland, submucosal glands
CC of the trachea, and epithelial cells lining the exocrine pancreatic
CC ducts but not in the remainder of the pancreas (at protein level).
CC Scattered expression is detected in the epithelial cells of the
CC gallbladder and submucosal glands of the vagina, and weak expression is
CC observed in the bronchial goblet cells of the pseudostratified
CC epithelia in the respiratory system (at protein level). Detected in
CC urine (at protein level). Strongly expressed in breast cancer but at
CC low levels in normal mammary tissue. It is regulated by estrogen in
CC MCF-7 cells. Strong expression found in normal gastric mucosa and in
CC the regenerative tissues surrounding ulcerous lesions of
CC gastrointestinal tract, but lower expression found in gastric cancer
CC (at protein level). {ECO:0000269|PubMed:15924415,
CC ECO:0000269|PubMed:16308573, ECO:0000269|PubMed:16718800,
CC ECO:0000269|PubMed:17143957, ECO:0000269|PubMed:17242463,
CC ECO:0000269|PubMed:3041593, ECO:0000269|PubMed:3838275}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TFF1ID201.html";
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DR EMBL; X00474; CAA25155.1; -; mRNA.
DR EMBL; M12075; AAA52402.1; -; mRNA.
DR EMBL; X05030; CAA28695.1; -; Genomic_DNA.
DR EMBL; X05321; CAA28695.1; JOINED; Genomic_DNA.
DR EMBL; X05322; CAA28695.1; JOINED; Genomic_DNA.
DR EMBL; X52003; CAA36254.1; -; mRNA.
DR EMBL; AB038162; BAB13729.1; -; Genomic_DNA.
DR EMBL; AP001746; BAA95532.1; -; Genomic_DNA.
DR EMBL; BC032811; AAH32811.1; -; mRNA.
DR CCDS; CCDS13685.1; -.
DR PIR; A26667; A26667.
DR RefSeq; NP_003216.1; NM_003225.2.
DR PDB; 1HI7; NMR; -; A/B=25-84.
DR PDB; 1PS2; NMR; -; A=25-84.
DR PDB; 6V1D; X-ray; 2.40 A; A/B/C=27-74.
DR PDBsum; 1HI7; -.
DR PDBsum; 1PS2; -.
DR PDBsum; 6V1D; -.
DR AlphaFoldDB; P04155; -.
DR BMRB; P04155; -.
DR SMR; P04155; -.
DR BioGRID; 112889; 23.
DR IntAct; P04155; 19.
DR MINT; P04155; -.
DR STRING; 9606.ENSP00000291527; -.
DR DrugBank; DB04468; Afimoxifene.
DR DrugBank; DB00481; Raloxifene.
DR UniLectin; P04155; -.
DR BioMuta; TFF1; -.
DR DMDM; 131127; -.
DR jPOST; P04155; -.
DR MassIVE; P04155; -.
DR MaxQB; P04155; -.
DR PaxDb; P04155; -.
DR PeptideAtlas; P04155; -.
DR PRIDE; P04155; -.
DR ProteomicsDB; 51666; -.
DR Antibodypedia; 1095; 938 antibodies from 39 providers.
DR DNASU; 7031; -.
DR Ensembl; ENST00000291527.3; ENSP00000291527.2; ENSG00000160182.3.
DR GeneID; 7031; -.
DR KEGG; hsa:7031; -.
DR MANE-Select; ENST00000291527.3; ENSP00000291527.2; NM_003225.3; NP_003216.1.
DR UCSC; uc002zax.2; human.
DR CTD; 7031; -.
DR DisGeNET; 7031; -.
DR GeneCards; TFF1; -.
DR HGNC; HGNC:11755; TFF1.
DR HPA; ENSG00000160182; Tissue enriched (stomach).
DR MIM; 113710; gene.
DR neXtProt; NX_P04155; -.
DR OpenTargets; ENSG00000160182; -.
DR PharmGKB; PA36470; -.
DR VEuPathDB; HostDB:ENSG00000160182; -.
DR eggNOG; ENOG502S00P; Eukaryota.
DR GeneTree; ENSGT00940000162623; -.
DR HOGENOM; CLU_179440_1_0_1; -.
DR InParanoid; P04155; -.
DR OMA; RGFPWCF; -.
DR OrthoDB; 1563185at2759; -.
DR PhylomeDB; P04155; -.
DR TreeFam; TF336092; -.
DR PathwayCommons; P04155; -.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; P04155; -.
DR SIGNOR; P04155; -.
DR BioGRID-ORCS; 7031; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; TFF1; human.
DR EvolutionaryTrace; P04155; -.
DR GeneWiki; Trefoil_factor_1; -.
DR GenomeRNAi; 7031; -.
DR Pharos; P04155; Tbio.
DR PRO; PR:P04155; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P04155; protein.
DR Bgee; ENSG00000160182; Expressed in pancreatic ductal cell and 129 other tissues.
DR Genevisible; P04155; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR CDD; cd00111; Trefoil; 1.
DR Gene3D; 4.10.110.10; -; 1.
DR InterPro; IPR017994; P_trefoil_chordata.
DR InterPro; IPR017957; P_trefoil_CS.
DR InterPro; IPR000519; P_trefoil_dom.
DR InterPro; IPR044913; P_trefoil_dom_sf.
DR PANTHER; PTHR13826; PTHR13826; 1.
DR Pfam; PF00088; Trefoil; 1.
DR PRINTS; PR00680; PTREFOIL.
DR SMART; SM00018; PD; 1.
DR SUPFAM; SSF57492; SSF57492; 1.
DR PROSITE; PS00025; P_TREFOIL_1; 1.
DR PROSITE; PS51448; P_TREFOIL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:15924415, ECO:0000269|PubMed:16308573,
FT ECO:0000269|PubMed:3146413, ECO:0000269|PubMed:3261981"
FT CHAIN 25..84
FT /note="Trefoil factor 1"
FT /id="PRO_0000023456"
FT DOMAIN 29..72
FT /note="P-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DISULFID 31..57
FT DISULFID 41..56
FT DISULFID 51..68
FT VARIANT 22
FT /note="T -> I (in dbSNP:rs34795821)"
FT /id="VAR_053563"
FT VARIANT 32
FT /note="T -> I (in a gastric carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:10982763"
FT /id="VAR_015281"
FT VARIANT 32
FT /note="T -> K (in a gastric carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:10982763"
FT /id="VAR_015282"
FT VARIANT 34
FT /note="A -> D (in a gastric carcinoma sample; somatic
FT mutation; abolishes inhibition of gastric cancer cell
FT growth; abolishes inhibition of apoptosis in
FT gasterointestinal epithelial cells; increases invasive
FT activity in epithelial cells; dbSNP:rs961505229)"
FT /evidence="ECO:0000269|PubMed:10982763,
FT ECO:0000269|PubMed:16697734"
FT /id="VAR_015283"
FT VARIANT 37
FT /note="E -> K (in a gastric carcinoma sample; somatic
FT mutation; abolishes inhibition of gastric cancer cell
FT growth; abolishes inhibition of apoptosis in
FT gasterointestinal epithelial cells; increases invasive
FT activity in epithelial cells)"
FT /evidence="ECO:0000269|PubMed:10982763,
FT ECO:0000269|PubMed:16697734"
FT /id="VAR_015284"
FT VARIANT 46
FT /note="V -> I (in a gastric adenoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:10982763"
FT /id="VAR_015285"
FT VARIANT 55
FT /note="G -> V (in a gastric carcinoma sample; somatic
FT mutation; dbSNP:rs1203145163)"
FT /evidence="ECO:0000269|PubMed:10982763"
FT /id="VAR_015286"
FT MUTAGEN 82
FT /note="C->S: Abolishes inhibition of gastric cancer cell
FT growth."
FT /evidence="ECO:0000269|PubMed:16697734"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:6V1D"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:6V1D"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:1HI7"
FT HELIX 48..53
FT /evidence="ECO:0007829|PDB:6V1D"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:1HI7"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:6V1D"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1HI7"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1HI7"
SQ SEQUENCE 84 AA; 9150 MW; 65198523BAD6EBC7 CRC64;
MATMENKVIC ALVLVSMLAL GTLAEAQTET CTVAPRERQN CGFPGVTPSQ CANKGCCFDD
TVRGVPWCFY PNTIDVPPEE ECEF
