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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 (NCBI)ITF (Intestinal Trefoil Factor)
HGNC (Hugo) TFF3
HGNC Alias symbHITF
HGNC Previous nametrefoil factor 3 (intestinal)
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 GRCh38/hg38-Dec_2013)  [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 ]

External links


HGNC (Hugo)TFF3   11757
Entrez_Gene (NCBI)TFF3    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]
Genome Data Viewer NCBITFF3 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF432265 BC017859 BQ016069 L08044 L15203
RefSeq transcript (Entrez)NM_003226
Consensus coding sequences : CCDS (NCBI)TFF3
Gene ExpressionTFF3 [ NCBI-GEO ]   TFF3 [ EBI - ARRAY_EXPRESS ]   TFF3 [ SEEK ]   TFF3 [ MEM ]
Gene Expression Viewer (FireBrowse)TFF3 [ Firebrowse - Broad ]
GenevisibleExpression of TFF3 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7033
GTEX Portal (Tissue expression)TFF3
Human Protein AtlasENSG00000160180-TFF3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ07654   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ07654  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ07654
Domaine pattern : Prosite (Expaxy)P_TREFOIL_1 (PS00025)    P_TREFOIL_2 (PS51448)   
Domains : Interpro (EBI)P_trefoil_chordata    P_trefoil_CS    P_trefoil_dom   
Domain families : Pfam (Sanger)Trefoil (PF00088)   
Domain families : Pfam (NCBI)pfam00088   
Domain families : Smart (EMBL)PD (SM00018)  
Conserved Domain (NCBI)TFF3
PDB (RSDB)1E9T    1PE3    6V1C   
PDB Europe1E9T    1PE3    6V1C   
PDB (PDBSum)1E9T    1PE3    6V1C   
PDB (IMB)1E9T    1PE3    6V1C   
Structural Biology KnowledgeBase1E9T    1PE3    6V1C   
SCOP (Structural Classification of Proteins)1E9T    1PE3    6V1C   
CATH (Classification of proteins structures)1E9T    1PE3    6V1C   
AlphaFold pdb e-kbQ07654   
Human Protein Atlas [tissue]ENSG00000160180-TFF3 [tissue]
Protein Interaction databases
IntAct (EBI)Q07654
Ontologies - Pathways
Ontology : AmiGOmolecular_function  protein binding  extracellular region  extracellular region  extracellular space  regulation of glucose metabolic process  secretory granule  maintenance of gastrointestinal epithelium  identical protein binding  
Ontology : EGO-EBImolecular_function  protein binding  extracellular region  extracellular region  extracellular space  regulation of glucose metabolic process  secretory granule  maintenance of gastrointestinal epithelium  identical protein binding  
Pathways : BIOCARTATrefoil Factors Initiate Mucosal Healing [Genes]   
REACTOMEQ07654 [protein]
REACTOME PathwaysR-HSA-9018519 [pathway]   
NDEx NetworkTFF3
Atlas of Cancer Signalling NetworkTFF3
Wikipedia pathwaysTFF3
Orthology - Evolution
GeneTree (enSembl)ENSG00000160180
Phylogenetic Trees/Animal Genes : TreeFamTFF3
Homologs : HomoloGeneTFF3
Homology/Alignments : Family Browser (UCSC)TFF3
Gene fusions - Rearrangements
Fusion : MitelmanTSPAN1::TFF3 [1p34.1/21q22.3]  
Fusion : QuiverTFF3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTFF3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TFF3
Exome Variant ServerTFF3
GNOMAD BrowserENSG00000160180
Varsome BrowserTFF3
ACMGTFF3 variants
Genomic Variants (DGV)TFF3 [DGVbeta]
DECIPHERTFF3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTFF3 
ICGC Data PortalTFF3 
TCGA Data PortalTFF3 
Broad Tumor PortalTFF3
OASIS PortalTFF3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTFF3  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTFF3
Mutations and Diseases : HGMDTFF3
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)TFF3
DoCM (Curated mutations)TFF3
CIViC (Clinical Interpretations of Variants in Cancer)TFF3
NCG (London)TFF3
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry TFF3
NextProtQ07654 [Medical]
Target ValidationTFF3
Huge Navigator TFF3 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDTFF3
Pharm GKB GenePA36472
Clinical trialTFF3
DataMed IndexTFF3
PubMed163 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:29:23 CEST 2021

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