Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

TFF3 trefoil factor 3 (intestinal)

Written2001-03Catherine Tomasetto
I.G.B.M.C., BP 163, 1 rue Laurent Fries, 67404 Illkirch, France

(Note : for Links provided by Atlas : click)


Alias_namestrefoil factor 3 (intestinal)
Alias_symbol (synonym)HITF
Other aliasITF (Intestinal Trefoil Factor)
HGNC (Hugo) TFF3
LocusID (NCBI) 7033
Atlas_Id 265
Location 21q22.3  [Link to chromosome band 21q22]
Location_base_pair Starts at 42311667 and ends at 42315596 bp from pter ( according to hg19-Feb_2009)  [Mapping TFF3.png]
Local_order Belongs to the TFF cluster
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
TFF3 (21q22.3) / TFF3 (21q22.3)TSPAN1 (1p34.1) / TFF3 (21q22.3)


Description 3.3 kb gene, 3 exons
Transcription 600 bp


Description precursor 74 amino acids, mature peptide 51 aminoacids, trefoil domain from aminoacids residues 24 to 67. The 74 aminoacids TFF3 protein precusor contains a signal peptide. The mature secreted peptide of 51 aminoacids contains one TFF (TreFoil Factor) domain and one acidic C-terminal domain. The acidic C-terminal domain contains a free cystein residue that promotes homodimerization and heterodimerization.
Expression Under normal conditions TFF3 is expressed by gobblet cell of the intesine and the colon. TFF3 expression was found in human respiratory tract, human conjunctival goblet cells and in human salivarygland. In addition TFF3 peptive was found in human hypothalamus.
Localisation In secreterory epithelia TFF3 is expressed by mucin-producing cells. In the brain TFF3 is expressed by a population of neurons of the human hypothamic paraventricular and supraoptic nuclei.
Function TFF3 promotes migration of epithelial cells in vitro and enhance mucosal healing and epithelial restitutions in vivo in the gastrointestinal mucosa. TFF3 deficient mice aresuceptible to colonic injury induced by standard agents and restitution is impaired. In addition TFF3 deficient mice have an increase in colonocyte apoptosis. The protective action of TFF3 involves activation of both EGF-R and PI3K-Akt pathways. The role of TFF3 in the brain is not clear yet.
Homology TFF3 belongs to the Trefoil peptide family (TFF) and possesse one TFF1 motif homologous to the TFF motif of TFF1 and TFF2. The TFF motif spans about 40 amino acids and is formed by 6 conserved cysteines residues involved in specific disulfites bridges.

Implicated in

Entity Inflamatory bowel diseases, TFF3 is expressed in cancer cells derived from the gastrointestinal tract, in hepatocellular carcinoma cells and in small cell lung carcinoma cells. Like TFF1, TFF3 is expressed in oestrogen-responsive breast cancer cell line and is expressed in breast cancer.


Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.
Babyatsky MW, deBeaumont M, Thim L, Podolsky DK
Gastroenterology. 1996 ; 110 (2) : 489-497.
PMID 8566596
Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers.
Chinery R, Bates PA, De A, Freemont PS
FEBS letters. 1995 ; 357 (1) : 50-54.
PMID 8001677
Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari A, Hattori T, Wright NA, Bodmer WF, Pignatelli M
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (6) : 3122-3127.
PMID 9501226
hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus.
Hauser F, Poulsom R, Chinery R, Rogers LA, Hanby AM, Wright NA, Hoffmann W
Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (15) : 6961-6965.
PMID 8346203
Co-localization of TFF3 peptide and oxytocin in the human hypothalamus.
Jagla W, Wiede A, Dietzmann K, Rutkowski K, Hoffmann W
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (9) : 1126-1131.
PMID 10834934
Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells.
Kanai M, Mullen C, Podolsky DK
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (1) : 178-182.
PMID 9419349
Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.
Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky DK
Gastroenterology. 1995 ; 109 (2) : 516-523.
PMID 7615201
Distinct pathways of cell migration and antiapoptotic response to epithelial injury: structure-function analysis of human intestinal trefoil factor.
Kinoshita K, Taupin DR, Itoh H, Podolsky DK
Molecular and cellular biology. 2000 ; 20 (13) : 4680-4690.
PMID 10848594
Secretory peptides TFF1 and TFF3 synthesized in human conjunctival goblet cells.
Langer G, Jagla W, Behrens-Baumann W, Walter S, Hoffmann W
Investigative ophthalmology & visual science. 1999 ; 40 (10) : 2220-2224.
PMID 10476786
Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor.
Mashimo H, Wu DC, Podolsky DK, Fishman MC
Science (New York, N.Y.). 1996 ; 274 (5285) : 262-265.
PMID 8824194
Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells.
May FE, Westley BR
The Journal of pathology. 1997 ; 182 (4) : 404-413.
PMID 9306961
Mechanisms of regulatory peptide action in the gastrointestinal tract: trefoil peptides.
Podolsky DK
Journal of gastroenterology. 2000 ; 35 Suppl 12 : 69-74.
PMID 10779222
Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.
Poulsom R, Hanby AM, Lalani EN, Hauser F, Hoffmann W, Stamp GW
The Journal of pathology. 1997 ; 183 (1) : 30-38.
PMID 9370944
The trefoil peptide family.
Sands BE, Podolsky DK
Annual review of physiology. 1996 ; 58 : 253-273.
PMID 8815795
The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3.
Seib T, Blin N, Hilgert K, Seifert M, Theisinger B, Engel M, Dooley S, Zang KD, Welter C
Genomics. 1997 ; 40 (1) : 200-202.
PMID 9070946
Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability.
Semenkovich CF, Coleman T, Goforth R
The Journal of biological chemistry. 1993 ; 268 (10) : 6961-6970.
PMID 8463228
Intestinal trefoil factor confers colonic epithelial resistance to apoptosis.
Taupin DR, Kinoshita K, Podolsky DK
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (2) : 799-804.
PMID 10639160
Trefoil peptides: from structure to function.
Thim L
Cellular and molecular life sciences : CMLS. 1997 ; 53 (11-12) : 888-903.
PMID 9447240
Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.
Wiede A, Jagla W, Welte T, Köhnlein T, Busk H, Hoffmann W
American journal of respiratory and critical care medicine. 1999 ; 159 (4 Pt 1) : 1330-1335.
PMID 10194185


This paper should be referenced as such :
Tomasetto, C
TFF3 (TreFoil Factor 3)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):114-115.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]

Solid Tumors TT_t0121p34q22ID104346

External links

HGNC (Hugo)TFF3   11757
Entrez_Gene (NCBI)TFF3  7033  trefoil factor 3
AliasesITF; P1B; TFI
GeneCards (Weizmann)TFF3
Ensembl hg19 (Hinxton)ENSG00000160180 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000160180 [Gene_View]  ENSG00000160180 [Sequence]  chr21:42311667-42315596 [Contig_View]  TFF3 [Vega]
ICGC DataPortalENSG00000160180
TCGA cBioPortalTFF3
AceView (NCBI)TFF3
Genatlas (Paris)TFF3
SOURCE (Princeton)TFF3
Genetics Home Reference (NIH)TFF3
Genomic and cartography
GoldenPath hg38 (UCSC)TFF3  -     chr21:42311667-42315596 -  21q22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TFF3  -     21q22.3   [Description]    (hg19-Feb_2009)
GoldenPathTFF3 - 21q22.3 [CytoView hg19]  TFF3 - 21q22.3 [CytoView hg38]
Mapping of homologs : NCBITFF3 [Mapview hg19]  TFF3 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF432265 BC017859 BQ016069 L08044 L15203
RefSeq transcript (Entrez)NM_003226
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TFF3
Alternative Splicing GalleryENSG00000160180
Gene ExpressionTFF3 [ NCBI-GEO ]   TFF3 [ EBI - ARRAY_EXPRESS ]   TFF3 [ SEEK ]   TFF3 [ MEM ]
Gene Expression Viewer (FireBrowse)TFF3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)7033
GTEX Portal (Tissue expression)TFF3
Human Protein AtlasENSG00000160180-TFF3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)TFF3
DMDM Disease mutations7033
Blocks (Seattle)TFF3
Human Protein Atlas [tissue]ENSG00000160180-TFF3 [tissue]
IPIIPI00018909   IPI00792724   
Protein Interaction databases
Ontologies - Pathways
Huge Navigator TFF3 [HugePedia]
snp3D : Map Gene to Disease7033
BioCentury BCIQTFF3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7033
Chemical/Pharm GKB GenePA36472
Clinical trialTFF3
canSAR (ICR)TFF3 (select the gene name)
DataMed IndexTFF3
PubMed146 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Feb 7 13:55:50 CET 2020

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us