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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)

Identity

Alias_namestrefoil factor 3 (intestinal)
Alias_symbol (synonym)HITF
ITF
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)

DNA/RNA

Description 3.3 kb gene, 3 exons
Transcription 600 bp

Protein

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

Note
  
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.
  

Bibliography

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
 

Citation

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 : http://AtlasGeneticsOncology.org/Genes/TFF3ID265.html


External links

Nomenclature
HGNC (Hugo)TFF3   11757
Cards
AtlasTFF3ID265
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]  chr21:42311667-42315596 [Contig_View]  TFF3 [Vega]
ICGC DataPortalENSG00000160180
TCGA cBioPortalTFF3
AceView (NCBI)TFF3
Genatlas (Paris)TFF3
WikiGenes7033
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)
EnsemblTFF3 - 21q22.3 [CytoView hg19]  TFF3 - 21q22.3 [CytoView hg38]
Mapping of homologs : NCBITFF3 [Mapview hg19]  TFF3 [Mapview hg38]
OMIM600633   
Gene and transcription
Genbank (Entrez)AF432265 BC017859 BQ016069 DQ891963 DQ895153
RefSeq transcript (Entrez)NM_003226
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TFF3
Cluster EST : UnigeneHs.82961 [ NCBI ]
CGAP (NCI)Hs.82961
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]
GenevestigatorExpression 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
Splice isoforms : SwissVarQ07654
PhosPhoSitePlusQ07654
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
DMDM Disease mutations7033
Blocks (Seattle)TFF3
PDB (SRS)1E9T    1PE3   
PDB (PDBSum)1E9T    1PE3   
PDB (IMB)1E9T    1PE3   
PDB (RSDB)1E9T    1PE3   
Structural Biology KnowledgeBase1E9T    1PE3   
SCOP (Structural Classification of Proteins)1E9T    1PE3   
CATH (Classification of proteins structures)1E9T    1PE3   
SuperfamilyQ07654
Human Protein Atlas [tissue]ENSG00000160180-TFF3 [tissue]
Peptide AtlasQ07654
HPRD02797
IPIIPI00018909   IPI00792724   
Protein Interaction databases
DIP (DOE-UCLA)Q07654
IntAct (EBI)Q07654
FunCoupENSG00000160180
BioGRIDTFF3
STRING (EMBL)TFF3
ZODIACTFF3
Ontologies - Pathways
QuickGOQ07654
Ontology : AmiGOmolecular_function  protein binding  extracellular region  proteinaceous extracellular matrix  extracellular space  cytoplasm  defense response  digestion  wound healing  extracellular exosome  
Ontology : EGO-EBImolecular_function  protein binding  extracellular region  proteinaceous extracellular matrix  extracellular space  cytoplasm  defense response  digestion  wound healing  extracellular exosome  
Pathways : BIOCARTATrefoil Factors Initiate Mucosal Healing [Genes]   
NDEx NetworkTFF3
Atlas of Cancer Signalling NetworkTFF3
Wikipedia pathwaysTFF3
Orthology - Evolution
OrthoDB7033
GeneTree (enSembl)ENSG00000160180
Phylogenetic Trees/Animal Genes : TreeFamTFF3
HOVERGENQ07654
HOGENOMQ07654
Homologs : HomoloGeneTFF3
Homology/Alignments : Family Browser (UCSC)TFF3
Gene fusions - Rearrangements
Fusion : MitelmanTSPAN1/TFF3 [1p34.1/21q22.3]  [t(1;21)(p34;q22)]  
Fusion: TCGA_MDACCTSPAN1 1p34.1 TFF3 21q22.3 PRAD
Tumor Fusion PortalTFF3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTFF3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TFF3
dbVarTFF3
ClinVarTFF3
1000_GenomesTFF3 
Exome Variant ServerTFF3
ExAC (Exome Aggregation Consortium)ENSG00000160180
GNOMAD BrowserENSG00000160180
Genetic variants : HAPMAP7033
Genomic Variants (DGV)TFF3 [DGVbeta]
DECIPHERTFF3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTFF3 
Mutations
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]  
Mutations and Diseases : HGMDTFF3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TFF3
DgiDB (Drug Gene Interaction Database)TFF3
DoCM (Curated mutations)TFF3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TFF3 (select a term)
intoGenTFF3
NCG5 (London)TFF3
Cancer3DTFF3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600633   
Orphanet
DisGeNETTFF3
MedgenTFF3
Genetic Testing Registry TFF3
NextProtQ07654 [Medical]
TSGene7033
GENETestsTFF3
Target ValidationTFF3
Huge Navigator TFF3 [HugePedia]
snp3D : Map Gene to Disease7033
BioCentury BCIQTFF3
ClinGenTFF3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7033
Chemical/Pharm GKB GenePA36472
Clinical trialTFF3
Miscellaneous
canSAR (ICR)TFF3 (select the gene name)
Probes
Litterature
PubMed119 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTFF3
EVEXTFF3
GoPubMedTFF3
iHOPTFF3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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