TFF3

TFF3
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1E9T, 1PE3
Identifikatori
Aliasi	TFF3
Vanjski ID-jevi	OMIM: 600633 MGI: 104638 HomoloGene: 2427 GeneCards: TFF3
Lokacija gena (čovjek)
Hrom.	Hromosom 21 (čovjek)
Kraj	42,315,409 bp
Lokacija gena (miš)
Hrom.	Hromosom 17 (miš)
Kraj	31,348,620 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • molekularna funkcija;
Ćelijska komponenta	• citoplazma; • Vanćelijsko; • extracellular region; • secretory granule;
Biološki proces	• Zarastanje rana; • regulation of glucose metabolic process; • maintenance of gastrointestinal epithelium;
	Izvori:Amigo / QuickGO
Ortolozi
	7033
	21786
	ENSG00000160180
	ENSMUSG00000024029
	Q07654
	Q62395
	NM_003226
	NM_011575
	NP_003217
	NP_035705
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Trefoilski faktor 3 jest protein koji je kod ljudi kodiran genom TFF3 sa hromosoma 21.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 80 aminokiselina, a molekulska težina 8.641 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10		20		30		40		50
MAARALCMLG		LVLALLSSSS		AEEYVGLSAN		QCAVPAKDRV		DCGYPHVTPK
ECNNRGCCFD		SRIPGVPWCF		KPLQEAECTF

Funkcija

Članovi trefoilske porodice odlikuju se po tome što imaju najmanje jednu kopiju motiv trefoila, domen od 40 aminokiselina koji sadrži tri konzervirane disulfidne veze. Oni su stabilni sekretorni proteini koji se eksprimiraju u gastrointestinalnoj sluznici. Njihove funkcije su raznolike, uključujući zaštitu sluznica, zgušnjavanje sluzi i povećanje brzine zacjeljivanja epitela. Ovaj gen je marker cilindrićnog epitela i eksprimiran je u različitim tkivima uključujući peharaste ćelije crijeva, uključujućij debelo crijevo. Ovaj gen i dva druga srodna gena člana porodice trefoila nalaze se u klastru na hromosomu 21.^[7]

Vezivanje glikana

Svi ljudski faktori trefoila su lektini koji specifično djeluju sa disaharidom GlcNAc-α-1,4-Gal.^[8] Ovaj disaharid je neobičan glikotop za koji se zna da postoji samo na velikim, jako glikozilovanim, mucinima u sluznicama. Unakrsnim povezivanjem mucina putem dvovalentnog vezivanja ovog glikotopa, trefoilski faktori su tada u stanju da reverzibilno moduliraju debljinu i viskoznost sluzi.^[8]

U majčinom mlijeku

Faktori trefoila (TFF) su sekretorni proizvodi ćelija koji proizvode mucin. Oni imaju ključnu ulogu u održavanju površinskog integriteta usne sluznice i poboljšavaju zacjeljivanje gastrointestinalne sluznice, procesom koji se naziva restitucija. TFF sastoji se od želudačnih peptida (TFF1), spazmolitskog peptida (TFF2) i intestinalnog trefoilskog faktora (TFF3, ovaj protein). Imaju važnu i neophodnu ulogu u restituciji epitela u gastrointestinalnom traktu. Značajne količine TFF-a prisutne su u majčinom mlijeku. Predstavljeni su dokazi da TFF3 izolovan iz mlijeka snažno korelira sa smanjenom regulacijom IL-6 i IL-8 u ljudskim intestinalnim epitelnim ćelijama. S druge strane, TFF3 je aktivirao epitelne ćelije u kulturi da proizvedu beta defenzine 2 (hBD2) i beta defenzine 4 (hBD4). Ovi nalazi sugeriraju da TFF može aktivirati crijevne epitelne ćelije i da može aktivno sudjelovati u imunskom sistemu dojenih beba, indukcijom proizvodnje peptida povezanih s urođenom odbranom, kao što su defenzini.^[9]

Aktivacija PAR-2 receptora

Dva glavna mehanizma opisana su za aktivaciju PAR-2: (A) specifičnim cijepanjem zademaskiranje peptidne sekvencu koja aktivira receptore u vanćelijskom N-terminalnom domenu svakog PAR-a, što dovodi do ćelijske signalizacije putem interakcije izloženih vezanih liganda sa tijelom samog receptora i (B) sintetskim peptidima, kao što je SLIGKV, koji se vezuju za receptor, oponašajući djelovanje agonističkih proteaza.^[10]Tokom dojenja, TFF3 izlučen u ljudskom mlijeku može aktivirati crijevne epitelne ćelije preko PAR-2 receptora, što zauzvrat inducira ekspresiju hBD2 i hBD4 i regulaciju citokina.^[10]

Klinički značaj

Koristeći TFF3 kao marker cilindričnog epitela, razvijen je proces koji koristi uređaj za uzimanje uzoraka iz jednjaka (Citospong) u kombinaciji s imunocitohemijskom obradom za trefoiski faktor 3, kako bi se poboljšala tačnost i prihvatljivost detekcije/skrininga Barrettovog jednjaka.^[11] Međutim, klinička korist takvog testa može biti ograničena čestim bojenjem TFF3 u kardiju želuca i kasnijim rizikom od lažno pozitivnih rezultata.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160180 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024029 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K, Podolsky DK (May 1995). "Characterization of human and rat intestinal trefoil factor produced in yeast". Biochemistry. 34 (14): 4757–64. doi:10.1021/bi00014a033. PMID 7718582.
^ 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.
^ ^a ^b ^c "Entrez Gene: TFF3 trefoil factor 3 (intestinal)".
^ ^a ^b 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.
^ Barrera GJ, Sanchez G, Gonzalez JE (November 2012). "Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29". Bosn J Basic Med Sci. 12 (4): 256–64. doi:10.17305/bjbms.2012.2448. PMC 4362502. PMID 23198942.
^ ^a ^b Barrera GJ, Tortolero GS (2016). "Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins". Bratislavské LekáRske Listy. 117 (6): 332–9. doi:10.4149/bll_2016_066. PMID 27546365.
^ Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC (2010). "Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study". BMJ. 341: c4372. doi:10.1136/bmj.c4372. PMC 2938899. PMID 20833740.
^ Peitz U, Kouznetsova I, Wex T, Gebert I, Vieth M, Roessner A, Hoffmann W, Malfertheiner P (2004). "TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD)". Peptides. 25 (5): 771–7. doi:10.1016/j.peptides.2004.01.018. PMID 15177871. S2CID 23122603.

Dopunska literatura

Barrera GJ, Sanchez G, Gonzalez JE (2012). "Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29". Bosn J Basic Med Sci. 12 (4): 256–64. doi:10.17305/bjbms.2012.2448. PMC 4362502. PMID 23198942.
Hoffmann W, Jagla W, Wiede A (2001). "Molecular medicine of TFF-peptides: from gut to brain". Histol. Histopathol. 16 (1): 319–34. PMID 11193208.
Hoffmann W, Jagla W (2002). "Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain". Int. Rev. Cytol. International Review of Cytology. 213: 147–81. doi:10.1016/S0074-7696(02)13014-2. ISBN 978-0-12-364617-0. PMID 11837892.
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. 506 (Pt A): 313–6. doi:10.1007/978-1-4615-0717-8_44. PMID 12613926.
Seib T, Dooley S, Welter C (1995). "Characterization of the genomic structure and the promoter region of the human intestinal trefoil factor". Biochem. Biophys. Res. Commun. 214 (1): 195–9. doi:10.1006/bbrc.1995.2274. PMID 7669039.
Podolsky DK, Gerken G, Eyking A, Cario E (2009). "Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency". Gastroenterology. 137 (1): 209–20. doi:10.1053/j.gastro.2009.03.007. PMC 2812790. PMID 19303021.
Hauser F, Poulsom R, Chinery R, et al. (1993). "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". Proc. Natl. Acad. Sci. U.S.A. 90 (15): 6961–5. Bibcode:1993PNAS...90.6961H. doi:10.1073/pnas.90.15.6961. PMC 47055. PMID 8346203.
Podolsky DK, Lynch-Devaney K, Stow JL, et al. (1993). "Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion". J. Biol. Chem. 268 (9): 6694–702. doi:10.1016/S0021-9258(18)53305-6. PMID 8454642.
Schmitt H, Wundrack I, Beck S, et al. (1996). "A third P-domain peptide gene (TFF3), human intestinal trefoil factor, maps to 21q22.3". Cytogenet. Cell Genet. 72 (4): 299–302. doi:10.1159/000134208. PMID 8641134.
Chinery R, Williamson J, Poulsom R (1997). "The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family". Genomics. 32 (2): 281–4. doi:10.1006/geno.1996.0117. PMID 8833157.
Probst JC, Zetzsche T, Weber M, et al. (1997). "Human intestinal trefoil factor is expressed in human hypothalamus and pituitary: evidence for a novel neuropeptide". FASEB J. 10 (13): 1518–23. doi:10.1096/fasebj.10.13.8940297. PMID 8940297. S2CID 34974159.
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.
Tan XD, Liu QP, Hsueh W, et al. (1999). "Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin". Biochem. J. 338 (3): 745–51. doi:10.1042/0264-6021:3380745. PMC 1220112. PMID 10051448.
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.
Wiede A, Hinz M, Canzler E, et al. (2001). "Synthesis and localization of the mucin-associated TFF-peptides in the human uterus". Cell Tissue Res. 303 (1): 109–15. doi:10.1007/s004410000297. PMID 11235998. S2CID 35516062.
Yamachika T, Werther JL, Bodian C, et al. (2002). "Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma". Clin. Cancer Res. 8 (5): 1092–9. PMID 12006524.
Kimura Y, Leung PS, Kenny TP, et al. (2002). "Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis". Hepatology. 36 (5): 1227–35. doi:10.1053/jhep.2002.36157. PMID 12395334. S2CID 23931292.

Vanjski linkovi

Q07654

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160180 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024029 - Ensembl, maj 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.

[pmid7718582-5] Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K, Podolsky DK (May 1995). "Characterization of human and rat intestinal trefoil factor produced in yeast". Biochemistry. 34 (14): 4757–64. doi:10.1021/bi00014a033. PMID 7718582.

[pmid9043862-6] 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.

[entrez-7] "Entrez Gene: TFF3 trefoil factor 3 (intestinal)".

[Järvå_2020-8] 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.

[pmid23198942-9] Barrera GJ, Sanchez G, Gonzalez JE (November 2012). "Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29". Bosn J Basic Med Sci. 12 (4): 256–64. doi:10.17305/bjbms.2012.2448. PMC 4362502. PMID 23198942.

[Barrera_2016-10] Barrera GJ, Tortolero GS (2016). "Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins". Bratislavské LekáRske Listy. 117 (6): 332–9. doi:10.4149/bll_2016_066. PMID 27546365.

[pmid20833740-11] Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC (2010). "Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study". BMJ. 341: c4372. doi:10.1136/bmj.c4372. PMC 2938899. PMID 20833740.

[pmid15177871-12] Peitz U, Kouznetsova I, Wex T, Gebert I, Vieth M, Roessner A, Hoffmann W, Malfertheiner P (2004). "TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD)". Peptides. 25 (5): 771–7. doi:10.1016/j.peptides.2004.01.018. PMID 15177871. S2CID 23122603.

[1]