DEFA5

Function

Host-defense peptide that maintains sterility in the urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305, PubMed:19589339, PubMed:22359618, PubMed:22573326, PubMed:25354318, PubMed:25782105, PubMed:30808760). Has antimicrobial activity against a wide range of bacteria, including Gram-negative E.coli, P.aeruginosa and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B.cereus, E.faecium and L.monocytogenes (PubMed:12021776, PubMed:15616305, PubMed:19589339, PubMed:22359618, PubMed:22573326, PubMed:25354318, PubMed:30808760). Confers resistance to intestinal infection by S.typhimurium (PubMed:12660734). Exhibits antimicrobial activity against enteric commensal bacteria such as B.adolescentis, L.acidophilus, B.breve, L.fermentum, B.longum and S.thermophilus (PubMed:25354318). Binds to bacterial membranes and causes membrane disintegration (PubMed:25782105). Induces the secretion of the chemokine IL-8 by intestinal epithelial cells (PubMed:19589339). Binds to B.antracis lef/lethal factor, a major virulence factor from B.anthracis, and neutralizes its enzymatic activity (PubMed:22573326).

(Microbial infection) Acts as a target for S.flexneri infection by binding to the bacterium, possibly via bacterial surface proteins, and thereby augmenting infectivity via enhanced bacterial adhesion and invasion of epithelial cells and tissues.

Post-translational modifications

Glycosylated.

Proteolytically cleaved at Arg-62 by trypsin (PubMed:12021776). Both the propeptide form proHD5/HD5(20-94) and HD5(56-94) are cleaved into the lumenal peptide form HD5(63-94) by trypsin (PubMed:12021776). Unprocessed proHD5 exerts antimicrobial activities, but peptide potency is enhanced by peptide processing (PubMed:12021776). Proteolytically cleaved in duodenal fluid; derived fragments are antimicrobially active against commensal bacteria (in vitro) (PubMed:30808760).

(Microbial infection) The disulfide bridges and homodimerization are a prerequisite for the enhancement of S.flexneri adhesion and invasion.

Sequence Similarities

Belongs to the alpha-defensin family.

Tissue Specificity

Expressed in the gastrointestinal, reproductive, and urinary tracts (at protein level) (PubMed:12021776, PubMed:1429669, PubMed:22359618, PubMed:9588893). Expressed in Paneth cells of the small intestine (at protein level) (PubMed:12021776, PubMed:1429669). Expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney (at protein level) (PubMed:22359618). Expressed in stratified squamous epithelial cells of the female genital tract epithelia, such as in vagina, ectocervix, endocervix, endometrium, and fallopian tube (at protein level) (PubMed:9588893). Endometrial expression correlates with stages of the menstrual cycle: Expression is low during the early proliferative phase, increased during the mid- to late proliferative phase, peaks during the early secretory phase of the cycle, and decreases during the mid- to late secretory phase (PubMed:9588893).

Cellular localization

• Secreted
• Cytoplasmic vesicle
• Secretory vesicle
• Stored as propeptide HD5(20-94) in secretory granules of small intestinal Paneth cells and found in the ileum lumen as processed mature peptides, predominantly in the HD5(63-94) form (PubMed:12021776). Peptides HD5(20-94), HD5(23-94) and HD5(29-94) are found within tissues, HD5(20-94) being the predominant intracellular form. Peptides HD5(56-94) and HD5(63-94) are found in the extracellular milieu, HD5(63-94) being the most abundant form (PubMed:12021776). Secreted into the female genital tract lumen (PubMed:9588893).

Alternative names

DEF5, DEFA5, Defensin alpha 5, Defensin-5, HD5(20-94)

Database links

swissprot:Q01523 omim:600472 entrezGene:1670 swissprot:A0JDY6