TFF3_HUMAN
ID TFF3_HUMAN Reviewed; 80 AA.
AC Q07654; A0A0A6YYJ4; E9PBB5; Q96NX0; Q9UDA5;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Trefoil factor 3;
DE AltName: Full=Intestinal trefoil factor;
DE Short=hITF;
DE AltName: Full=Polypeptide P1.B;
DE Short=hP1.B;
DE Flags: Precursor;
GN Name=TFF3; Synonyms=ITF, TFI;
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=9070946; DOI=10.1006/geno.1996.4511;
RA Seib T., Blin N., Hilgert K., Seifert M., Theisinger B., Engel M.,
RA Dooley S., Zang K.D., Welter C.;
RT "The three human trefoil genes TFF1, TFF2, and TFF3 are located within a
RT region of 55 kb on chromosome 21q22.3.";
RL Genomics 40:200-202(1997).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-51.
RC TISSUE=Heart;
RX PubMed=14637006; DOI=10.1016/s0378-1119(03)00835-7;
RA Casadei R., Strippoli P., D'Addabbo P., Canaider S., Lenzi L., Vitale L.,
RA Giannone S., Frabetti F., Facchin F., Carinci P., Zannotti M.;
RT "mRNA 5' region sequence incompleteness: a potential source of systematic
RT errors in translation initiation codon assignment in human mRNAs.";
RL Gene 321:185-193(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Small intestine;
RX PubMed=8346203; DOI=10.1073/pnas.90.15.6961;
RA Hauser F., Poulsom R., Chinery R., Rogers L.A., Hanby A.M., Wright N.A.,
RA Hoffmann W.;
RT "hP1.B, a human P-domain peptide homologous with rat intestinal trefoil
RT factor, is expressed also in the ulcer-associated cell lineage and the
RT uterus.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6961-6965(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Colon;
RX PubMed=8454642; DOI=10.1016/s0021-9258(18)53305-6;
RA Podolsky D.K., Lynch-Devaney K., Stow J.L., Oates P., Murgue B.,
RA Debeaumont M., Sands B.E., Mahida Y.R.;
RT "Identification of human intestinal trefoil factor. Goblet cell-specific
RT expression of a peptide targeted for apical secretion.";
RL J. Biol. Chem. 268:6694-6702(1993).
RN [8]
RP ERRATUM OF PUBMED:8454642.
RA Podolsky D.K., Lynch-Devaney K., Stow J.L., Oates P., Murgue B.,
RA De-Beaumont M., Sands B.E., Mahida Y.R.;
RL J. Biol. Chem. 268:12230-12230(1993).
RN [9]
RP PROTEIN SEQUENCE OF 22-36.
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 [10]
RP PROTEIN SEQUENCE OF 22-37, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19670903; DOI=10.1021/pr9004426;
RA Casado-Vela J., Rodriguez-Suarez E., Iloro I., Ametzazurra A., Alkorta N.,
RA Garcia-Velasco J.A., Matorras R., Prieto B., Gonzalez S., Nagore D.,
RA Simon L., Elortza F.;
RT "Comprehensive proteomic analysis of human endometrial fluid aspirate.";
RL J. Proteome Res. 8:4622-4632(2009).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10824705; DOI=10.1055/s-2007-978604;
RA Griepentrog T., Bauer M., Hornstein C., Sauer H., Jirikowski G.F.;
RT "Coexistence of intestinal trefoil factor (hITF) and oxytocin in
RT magnocellular neurons in the human hypothalamus.";
RL Horm. Metab. Res. 32:121-124(2000).
RN [12]
RP FUNCTION.
RX PubMed=11694446; DOI=10.1165/ajrcmb.25.4.4429;
RA Oertel M., Graness A., Thim L., Buhling F., Kalbacher H., Hoffmann W.;
RT "Trefoil factor family-peptides promote migration of human bronchial
RT epithelial cells: synergistic effect with epidermal growth factor.";
RL Am. J. Respir. Cell Mol. Biol. 25:418-424(2001).
RN [13]
RP STRUCTURE BY NMR OF 22-80.
RX PubMed=18209; DOI=10.1016/0304-4165(77)90272-0;
RA De Luca S.;
RT "Incorporation of mannose and glucose into prenylphosphate sugars in
RT isolated human platelet membranes.";
RL Biochim. Biophys. Acta 498:341-348(1977).
RN [14]
RP STRUCTURE BY NMR OF 22-80, AND SUBUNIT.
RX PubMed=14690424; DOI=10.1021/bi030182k;
RA Muskett F.W., May F.E., Westley B.R., Feeney J.;
RT "Solution structure of the disulfide-linked dimer of human intestinal
RT trefoil factor (TFF3): the intermolecular orientation and interactions are
RT markedly different from those of other dimeric trefoil proteins.";
RL Biochemistry 42:15139-15147(2003).
CC -!- FUNCTION: Involved in the maintenance and repair of the intestinal
CC mucosa. Promotes the mobility of epithelial cells in healing processes
CC (motogen). {ECO:0000269|PubMed:11694446}.
CC -!- SUBUNIT: Monomer. Homodimer; disulfide-linked.
CC {ECO:0000269|PubMed:14690424}.
CC -!- INTERACTION:
CC Q07654; Q9Y6R7: FCGBP; NbExp=2; IntAct=EBI-10224676, EBI-2869882;
CC Q07654; P61457: PCBD1; NbExp=6; IntAct=EBI-10224676, EBI-740475;
CC Q07654; O43765: SGTA; NbExp=3; IntAct=EBI-10224676, EBI-347996;
CC Q07654; Q07654: TFF3; NbExp=2; IntAct=EBI-10224676, EBI-10224676;
CC Q07654; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-10224676, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:8454642}. Cytoplasm
CC {ECO:0000269|PubMed:10824705, ECO:0000269|PubMed:8454642}.
CC -!- TISSUE SPECIFICITY: Expressed in goblet cells of the intestines and
CC colon (at protein level). Expressed by goblet cells of small and large
CC intestinal epithelia and also by the uterus. Also expressed in the
CC hypothalamus where it is detected in paraventricular, periventricular
CC and supraoptic nuclei (at protein level). {ECO:0000269|PubMed:8346203,
CC ECO:0000269|PubMed:8454642}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36766.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH17859.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL28111.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA95531.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB13731.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TFF3ID265.html";
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DR EMBL; U25657; AAA83628.1; -; Genomic_DNA.
DR EMBL; U25654; AAA83628.1; JOINED; Genomic_DNA.
DR EMBL; U25656; AAA83628.1; JOINED; Genomic_DNA.
DR EMBL; AB038162; BAB13731.1; ALT_INIT; Genomic_DNA.
DR EMBL; AP001746; BAA95531.1; ALT_INIT; Genomic_DNA.
DR EMBL; AP001623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF432265; AAL28111.1; ALT_INIT; mRNA.
DR EMBL; L15203; AAA59981.1; -; mRNA.
DR EMBL; BC017859; AAH17859.1; ALT_INIT; mRNA.
DR EMBL; L08044; AAA36766.1; ALT_INIT; mRNA.
DR CCDS; CCDS33565.2; -.
DR PIR; A48284; A48284.
DR RefSeq; NP_003217.3; NM_003226.3.
DR PDB; 1E9T; NMR; -; A=22-80.
DR PDB; 1PE3; NMR; -; 1/2=22-80.
DR PDB; 6V1C; X-ray; 1.55 A; A=22-79.
DR PDBsum; 1E9T; -.
DR PDBsum; 1PE3; -.
DR PDBsum; 6V1C; -.
DR AlphaFoldDB; Q07654; -.
DR BioGRID; 112891; 6.
DR IntAct; Q07654; 4.
DR STRING; 9606.ENSP00000430690; -.
DR UniLectin; Q07654; -.
DR BioMuta; TFF3; -.
DR DMDM; 585328; -.
DR jPOST; Q07654; -.
DR MassIVE; Q07654; -.
DR PaxDb; Q07654; -.
DR PeptideAtlas; Q07654; -.
DR PRIDE; Q07654; -.
DR ProteomicsDB; 19187; -.
DR ProteomicsDB; 58522; -.
DR Antibodypedia; 23776; 460 antibodies from 32 providers.
DR DNASU; 7033; -.
DR Ensembl; ENST00000518498.3; ENSP00000430690.2; ENSG00000160180.17.
DR GeneID; 7033; -.
DR KEGG; hsa:7033; -.
DR MANE-Select; ENST00000518498.3; ENSP00000430690.2; NM_003226.4; NP_003217.4.
DR CTD; 7033; -.
DR DisGeNET; 7033; -.
DR GeneCards; TFF3; -.
DR HGNC; HGNC:11757; TFF3.
DR HPA; ENSG00000160180; Group enriched (cervix, intestine, salivary gland, thyroid gland).
DR MIM; 600633; gene.
DR neXtProt; NX_Q07654; -.
DR OpenTargets; ENSG00000160180; -.
DR PharmGKB; PA36472; -.
DR VEuPathDB; HostDB:ENSG00000160180; -.
DR eggNOG; ENOG502SV7V; Eukaryota.
DR GeneTree; ENSGT00940000162416; -.
DR InParanoid; Q07654; -.
DR OMA; QETECTF; -.
DR OrthoDB; 1563185at2759; -.
DR PhylomeDB; Q07654; -.
DR TreeFam; TF336092; -.
DR PathwayCommons; Q07654; -.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; Q07654; -.
DR SIGNOR; Q07654; -.
DR BioGRID-ORCS; 7033; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; TFF3; human.
DR EvolutionaryTrace; Q07654; -.
DR GeneWiki; Trefoil_factor_3; -.
DR GenomeRNAi; 7033; -.
DR Pharos; Q07654; Tbio.
DR PRO; PR:Q07654; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q07654; protein.
DR Bgee; ENSG00000160180; Expressed in mucosa of transverse colon and 121 other tissues.
DR ExpressionAtlas; Q07654; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IDA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IBA:GO_Central.
DR GO; GO:0010906; P:regulation of glucose metabolic process; 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; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Extracellular matrix; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:19670903"
FT CHAIN 22..80
FT /note="Trefoil factor 3"
FT /id="PRO_0000023465"
FT DOMAIN 30..73
FT /note="P-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DISULFID 32..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DISULFID 42..57
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DISULFID 52..69
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DISULFID 78
FT /note="Interchain"
FT CONFLICT 74..76
FT /note="QEA -> TRKT (in Ref. 7; AAA36766)"
FT /evidence="ECO:0000305"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6V1C"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:1PE3"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1E9T"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:6V1C"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:1E9T"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1E9T"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:6V1C"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:1PE3"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:1PE3"
SQ SEQUENCE 80 AA; 8641 MW; 8E117A58C0342013 CRC64;
MAARALCMLG LVLALLSSSS AEEYVGLSAN QCAVPAKDRV DCGYPHVTPK ECNNRGCCFD
SRIPGVPWCF KPLQEAECTF
