Trefoil factor 1

Trefoil factor 1 is a protein that in humans is encoded by the TFF1 gene[5][6] (also called pS2 gene[7]).

TFF1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTFF1, BCEI, D21S21, HP1.A, HPS2, pNR-2, pS2, trefoil factor 1
External IDsOMIM: 113710 MGI: 88135 HomoloGene: 2426 GeneCards: TFF1
Orthologs
SpeciesHumanMouse
Entrez

7031

21784

Ensembl

ENSG00000160182

ENSMUSG00000024032

UniProt

P04155

Q08423

RefSeq (mRNA)

NM_003225

NM_009362

RefSeq (protein)

NP_003216

NP_033388

Location (UCSC)Chr 21: 42.36 – 42.37 MbChr 17: 31.38 – 31.38 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer, and affect healing of the epithelium. This gene, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.[6]

Glycan binding

All three human trefoil factors are lectins that interact specifically with the disaccharide GlcNAc-α-1,4-Gal.[8] This disaccharide is an unusual glycotope that is only known to exist on the large, heavily glycosylated, mucins in the mucosa. By cross-linking mucins through the bivalent binding of this glycotope, the trefoil factors are then able to reversibly modulate the thickness and viscosity of the mucus.[8]

In gastric carcinoma

TFF1 expression is frequently lost in gastric carcinoma, probably through mechanism of DNA methylation, and it is therefore considered as a tumor suppressor gene.[9]

References

  1. GRCh38: Ensembl release 89: ENSG00000160182 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000024032 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Gött P, Beck S, Machado JC, Carneiro F, Schmitt H, Blin N (May 1997). "Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression". Eur J Hum Genet. 4 (6): 308–15. doi:10.1159/000472224. PMID 9043862. S2CID 25235589.
  6. "Entrez Gene: TFF1 trefoil factor 1".
  7. Chatagnon A, Ballestar E, Esteller M, Dante R (2010). "A Role for Methyl-CpG Binding Domain Protein 2 in the Modulation of the Estrogen Response of pS2/TFF1 Gene". PLOS ONE. 5 (3): e9665. Bibcode:2010PLoSO...5.9665C. doi:10.1371/journal.pone.0009665. PMC 2837351. PMID 20300195.
  8. Järvå MA, Lingford JP, John A, Soler NM, Scott NE, Goddard-Borger ED (May 2020). "Trefoil factors share a lectin activity that defines their role in mucus". Nature Communications. 11 (1): 2265. Bibcode:2020NatCo..11.2265J. doi:10.1038/s41467-020-16223-7. PMC 7221086. PMID 32404934.
  9. Feng G, Zhang Y, Yuan H, Bai R, Zheng J, Zhang J, Song M (Jan 2014). "DNA methylation of trefoil factor 1 (TFF1) is associated with the tumorigenesis of gastric carcinoma". Mol Med Rep. 9 (1): 109–117. doi:10.3892/mmr.2013.1772. PMID 24190027.

Further reading


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