Trefoil factor 2

Trefoil factor 2 is a protein that in humans is encoded by the TFF2 gene.[5][6][7]

TFF2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DYZ, 2DZ0, 2DZ1
Identifiers
Aliases	TFF2, SML1, SP, trefoil factor 2
External IDs	OMIM: 182590 MGI: 1306805 HomoloGene: 3956 GeneCards: TFF2
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.3 Start 42,346,357 bp[1] End 42,350,997 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 A3.3|17 15.8 cM Start 31,141,049 bp[2] End 31,144,282 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • CXCR4 chemokine receptor binding Cellular component • extracellular region • extracellular Biological process • wound healing • maintenance of gastrointestinal epithelium • negative regulation of gastric acid secretion • chemokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7032	21785
Ensembl	ENSG00000160181	ENSMUSG00000024028
UniProt	Q03403	Q03404 Q9QX97
RefSeq (mRNA)	NM_005423	NM_009363
RefSeq (protein)	NP_005414	NP_033389
Location (UCSC)	Chr 21: 42.35 – 42.35 Mb	Chr 17: 31.14 – 31.14 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. The encoded protein inhibits gastric acid secretion. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.[7]

Glycan binding

All 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 reversible modulate the thickness and viscosity of the mucus.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000160181 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024028 - 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. Tomasetto C, Rockel N, Mattei MG, Fujita R, Rio MC (Sep 1992). "The gene encoding the human spasmolytic protein (SML1/hSP) is in 21q 22.3, physically linked to the homologous breast cancer marker gene BCEI/pS2". Genomics. 13 (4): 1328–30. doi:10.1016/0888-7543(92)90059-2. PMID 1505966.
6. Gott 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.
7. "Entrez Gene: TFF2 trefoil factor 2 (spasmolytic protein 1)".
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.

Further reading

• Advenier C, Lagente V, Boichot E (1997). "The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough". Eur. Respir. J. 10 (8): 1892–906. doi:10.1183/09031936.97.10081892. PMID 9272936.
• Langer G, Jagla W, Behrens-Baumann W, et al. (2003). "Ocular TFF-peptides: new mucus-associated secretory products of conjunctival goblet cells". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 506 (Pt A): 313–6. doi:10.1007/978-1-4615-0717-8_44. ISBN 978-1-4613-5208-2. PMID 12613926.
• Tomasetto C, Rio MC, Gautier C, et al. (1990). "hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma". EMBO J. 9 (2): 407–14. doi:10.1002/j.1460-2075.1990.tb08125.x. PMC 551681. PMID 2303034.
• Bhogal N, Donnelly D, Findlay JB (1994). "The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor". J. Biol. Chem. 269 (44): 27269–74. PMID 7961636.
• Hanby AM, Poulsom R, Singh S, et al. (1993). "Spasmolytic polypeptide is a major antral peptide: distribution of the trefoil peptides human spasmolytic polypeptide and pS2 in the stomach". Gastroenterology. 105 (4): 1110–6. doi:10.1016/0016-5085(93)90956-d. PMID 8405856.
• Itoh H, Tomita M, Uchino H, et al. (1996). "cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis". Biochem. J. 318 (3): 939–44. doi:10.1042/bj3180939. PMC 1217708. PMID 8836141.
• May FE, Westley BR (1997). "Close physical linkage of the genes encoding the pNR-2/pS2 protein and human spasmolytic protein (hSP)". Hum. Genet. 99 (3): 303–7. doi:10.1007/s004390050362. PMID 9050913. S2CID 22603186.
• Seib T, Blin N, Hilgert K, et al. (1997). "The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3". Genomics. 40 (1): 200–2. doi:10.1006/geno.1996.4511. PMID 9070946.
• Kayademir T, Silva Edos S, Pusch C, et al. (1998). "A novel 25 bp tandem repeat within the human trefoil peptide gene TFF2 in 21q22.3: polymorphism and mammalian evolution". Eur. J. Hum. Genet. 6 (2): 121–8. doi:10.1038/sj.ejhg.5200166. PMID 9781055.
• Brunelleschi S, Bordin G, Colangelo D, Viano I (1999). "Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis". Neuropeptides. 32 (3): 215–23. doi:10.1016/S0143-4179(98)90040-3. PMID 10189055. S2CID 40222022.
• May FE, Semple JI, Newton JL, Westley BR (2000). "The human two domain trefoil protein, TFF2, is glycosylated in vivo in the stomach". Gut. 46 (4): 454–9. doi:10.1136/gut.46.4.454. PMC 1727891. PMID 10716671.
• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
• Berry A, Scott HS, Kudoh J, et al. (2001). "Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region". Genomics. 68 (1): 22–9. doi:10.1006/geno.2000.6253. PMID 10950923.
• Bulitta CJ, Fleming JV, Raychowdhury R, et al. (2002). "Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element". Biochem. Biophys. Res. Commun. 293 (1): 366–74. doi:10.1016/S0006-291X(02)00199-7. PMID 12054609.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Hu GY, Yu BP, Dong WG, et al. (2003). "Expression of TFF2 and Helicobacter pylori infection in carcinogenesis of gastric mucosa". World J. Gastroenterol. 9 (5): 910–4. doi:10.3748/wjg.v9.i5.910. PMC 4611396. PMID 12717829.