DEFA5
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesDEFA5, DEF5, HD-5, defensin alpha 5, alpha defensin 5
External IDsOMIM: 600472 HomoloGene: 128604 GeneCards: DEFA5
Orthologs
SpeciesHumanMouse
Entrez

1670

n/a

Ensembl

ENSG00000164816
ENSG00000285251

n/a

UniProt

Q01523

n/a

RefSeq (mRNA)

NM_021010

n/a

RefSeq (protein)

NP_066290

n/a

Location (UCSC)Chr 8: 7.06 – 7.06 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Defensin, alpha 5 (DEFA5) also known as human alpha defensin 5 (HD5) is a protein that in humans is encoded by the DEFA5 gene.[3][4] DEFA5 is expressed in the Paneth cells of the ileum.[5]

Defensins are a family of microbicidal and cytotoxic peptides (antimicrobial peptides; AMP) that are involved in host defense, and help to maintain homeostasis of intestinal microbiota. DEFA5 is the main AMP that controls the enteric microbiota composition by selective killing of bacterial pathogens while preserving commensals.[6]

Structure

Defensins are small cationic peptides linked via three intra-molecular disulfide bridges, and contain six intra-molecular cysteine residues which form an unalterable and specific pattern of disulfide bridges which protects them from proteolysis and maintains function in the intestinal lumen.[7][8] Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif.

Gene and tissue distribution

Several of the human alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, α-defensin-5, is highly expressed in the secretory granules of Paneth cells of the ileum.[3]

Function

In addition to antimicrobial activity, inactivation and neutralization of several bacterial toxins, especially an inhibitory potency against Clostridioides difficile toxins were reported.[9][10] α-defensin-5 is able to inhibit all three C. difficile toxins A (TcdA), B (TcdB) and CDT in the concentration-dependent manner, and inhibitory mechanism is different for each of them. TcdA and TcdB are inhibited by co-precipitation with DEFA5, and CDT is inhibited by the inactivation of the CDTb pore.[11] In addition to toxin neutralization, DEFA5 is capable to direcrly kill C. difficile cells by damaging the bacterial wall[12]

References

  1. 1 2 3 ENSG00000285251 GRCh38: Ensembl release 89: ENSG00000164816, ENSG00000285251 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 "Entrez Gene: DEFA5 defensin, alpha 5, Paneth cell-specific".
  4. ↑ Jones DE, Bevins CL (January 1993). "Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel". FEBS Letters. 315 (2): 187–92. doi:10.1016/0014-5793(93)81160-2. PMID 8417977. S2CID 45099115.
  5. ↑ Zhao C, Wang I, Lehrer RI (November 1996). "Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells". FEBS Letters. 396 (2–3): 319–22. doi:10.1016/0014-5793(96)01123-4. PMID 8915011. S2CID 22367037.
  6. ↑ Bevins CL, Salzman NH (May 2011). "Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis". Nature Reviews. Microbiology. 9 (5): 356–68. doi:10.1038/nrmicro2546. PMID 21423246. S2CID 39332656.
  7. ↑ Ganz T, Lehrer RI (August 1994). "Defensins". Current Opinion in Immunology. 6 (4): 584–9. doi:10.1016/0952-7915(94)90145-7. PMID 7946046.
  8. ↑ Selsted ME, Harwig SS (March 1989). "Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide". The Journal of Biological Chemistry. 264 (7): 4003–7. doi:10.1016/S0021-9258(19)84952-9. PMID 2917986.
  9. ↑ Kim C, Slavinskaya Z, Merrill AR, Kaufmann SH (October 2006). "Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family". The Biochemical Journal. 399 (2): 225–9. doi:10.1042/BJ20060425. PMC 1609915. PMID 16817779.
  10. ↑ Giesemann T, Guttenberg G, Aktories K (June 2008). "Human alpha-defensins inhibit Clostridium difficile toxin B". Gastroenterology. 134 (7): 2049–58. doi:10.1053/j.gastro.2008.03.008. PMID 18435932.
  11. ↑ Korbmacher M, Fischer S, Landenberger M, Papatheodorou P, Aktories K, Barth H (2020). "Human α-Defensin-5 Efficiently Neutralizes Clostridioides difficile Toxins TcdA, TcdB, and CDT". Frontiers in Pharmacology. 11: 1204. doi:10.3389/fphar.2020.01204. PMC 7435013. PMID 32903430.
  12. ↑ Furci L, Baldan R, Bianchini V, Trovato A, Ossi C, Cichero P, Cirillo DM (March 2015). Morrison RP (ed.). "New role for human α-defensin 5 in the fight against hypervirulent Clostridium difficile strains". Infection and Immunity. 83 (3): 986–95. doi:10.1128/IAI.02955-14. PMC 4333456. PMID 25547793.

Further reading


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