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TFF3 trefoil factor 3 (intestinal)

Identity

Other namesITF (Intestinal Trefoil Factor)
HGNC (Hugo) TFF3
LocusID (NCBI) 7033
Location 21q22.3
Location_base_pair Starts at 43731777 and ends at 43735706 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Belongs to the TFF cluster

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

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.
  

External links

Nomenclature
HGNC (Hugo)TFF3   11757
Entrez_Gene (NCBI)TFF3  7033  trefoil factor 3 (intestinal)
Cards
AtlasTFF3ID265
GeneCards (Weizmann)TFF3
Ensembl (Hinxton)ENSG00000160180 [Gene_View]  chr21:43731777-43735706 [Contig_View]  TFF3 [Vega]
AceView (NCBI)TFF3
Genatlas (Paris)TFF3
euGene (Indiana)7033
SOURCE (Stanford)NM_003226
Genomic and cartography
GoldenPath (UCSC)TFF3  -  21q22.3   chr21:43731777-43735706 -  21q22.3   [Description]    (hg19-Feb_2009)
EnsemblTFF3 - 21q22.3 [CytoView]
Mapping of homologs : NCBITFF3 [Mapview]
OMIM600633   
Gene and transcription
Genbank (Entrez)AF432265 BC017859 BQ016069 DQ891963 DQ895153
RefSeq transcript (SRS)NM_003226
RefSeq transcript (Entrez)NM_003226
RefSeq genomic (SRS)AC_000153 NC_000021 NT_011515 NW_001838714
RefSeq genomic (Entrez)AC_000153 NC_000021 NT_011515 NW_001838714
Consensus coding sequences : CCDS (NCBI)TFF3
Cluster EST : UnigeneHs.82961 [ SRS ] Hs.82961 [ NCBI ]
Alternative Splicing : Fast-db (Paris)3395
Alternative Splicing GalleryENSG00000160180
Gene ExpressionTFF3 [ NCBI-GEO ]   TFF3 [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ07654 (SRS) Q07654 (Uniprot)
With graphics : InterProQ07654
Splice isoforms : SwissVarQ07654(Swissvar)
Domaine pattern : Prosite (SRS)P_TREFOIL_1 (PS00025)    P_TREFOIL_2 (PS51448)   
Domaine pattern : Prosite (Expaxy)P_TREFOIL_1 (PS00025)    P_TREFOIL_2 (PS51448)   
Domains : Interpro (SRS)P_trefoil    P_trefoil_chordata    P_trefoil_CS   
Domains : Interpro (EBI)P_trefoil    P_trefoil_chordata    P_trefoil_CS   
Related proteins : CluSTrQ07654
Domain families : Pfam (SRS)Trefoil (PF00088)   
Domain families : Pfam (Sanger)Trefoil (PF00088)   
Domain families : Pfam (NCBI)pfam00088   
Domain families : Smart (EMBL)PD (SM00018)  
Blocks (Seattle)Q07654
PDB (SRS)1E9T    1PE3   
PDB (PDBSum)1E9T    1PE3   
PDB (IMB)1E9T    1PE3   
PDB (RSDB)1E9T    1PE3   
Human Protein AtlasENSG00000160180
HPRD02797
IPIIPI00018909   IPI00792724   
Protein Interaction databases
DIP (DOE-UCLA)Q07654
IntAct (EBI)Q07654
FunCoupENSG00000160180
REACTOMETFF3
BioGRIDTFF3
InParanoidQ07654
Interologous Interaction database Q07654
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TFF3
SNP (GeneSNP Utah)TFF3
SNP : HGBaseTFF3
Genetic variants : HAPMAPTFF3
Somatic Mutations in Cancer : COSMICTFF3 
CONAN: Copy Number AnalysisTFF3 
Mutations and Diseases : HGMDTFF3
OMIM600633   
GENETests600633   
Disease Genetic AssociationTFF3
Huge Navigator TFF3 [HugePedia]  TFF3 [HugeCancerGEM]
Genomic VariantsTFF3
snp3D : Map Gene to Disease7033
General knowledge
Homologs : HomoloGeneTFF3
Homology/Alignments : Family Browser (UCSC)TFF3
Phylogenetic Trees/Animal Genes : TreeFamTFF3
Chemical/Protein Interactions : CTD7033
Chemical/Pharm GKB GenePA36472
Clinical trialTFF3
Cancer Resource (Charite)ENSG00000160180
Ontology : AmiGOmolecular_function  extracellular region  proteinaceous extracellular matrix  defense response  digestion  apical lamina of hyaline layer  
Ontology : EGO-EBImolecular_function  extracellular region  proteinaceous extracellular matrix  defense response  digestion  apical lamina of hyaline layer  
Pathways : BIOCARTATrefoil Factors Initiate Mucosal Healing [Genes]   
Other databases
Probes
Probes : ImagenesTFF3 Related clones (RZPD - Berlin)
Litterature
PubMed72 Pubmed reference(s) in Entrez
PubGeneTFF3
iHOPTFF3

Bibliography

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.
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PMID 8001677
 
Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.
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PMID 7615201
 
Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.
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The trefoil peptide family.
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Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells.
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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.
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The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3.
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Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
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PMID 9501226
 
Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells.
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Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (1) : 178-182.
PMID 9419349
 
Secretory peptides TFF1 and TFF3 synthesized in human conjunctival goblet cells.
Langer G, Jagla W, Behrens-Baumann W, Walter S, Hoffmann W
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PMID 10476786
 
Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.
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PMID 10194185
 
Co-localization of TFF3 peptide and oxytocin in the human hypothalamus.
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Distinct pathways of cell migration and antiapoptotic response to epithelial injury: structure-function analysis of human intestinal trefoil factor.
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Mechanisms of regulatory peptide action in the gastrointestinal tract: trefoil peptides.
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Intestinal trefoil factor confers colonic epithelial resistance to apoptosis.
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PMID 10639160
 
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Contributor(s)

Written03-2001Catherine Tomasetto

Citation

This paper should be referenced as such :
Tomasetto C . TFF3 trefoil factor 3 (intestinal). Atlas Genet Cytogenet Oncol Haematol. March 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/TFF3ID265.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37730/1/03-2001-TFF3ID265.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 14:58:40 CEST 2012

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