Host-defense peptide that maintains sterility in the urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305, PubMed:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339, PubMed:22573326, PubMed:25782105). 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:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339, PubMed:22573326). 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. Homodimer (PubMed:17088326, PubMed:22573326, PubMed:25782105, PubMed:29858013). Homotetramer (PubMed:23163963). Interacts with B.antracis lef/lethal factor (PubMed:22573326). 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). Expressed in the gastrointestinal, reproductive, and urinary tracts (at protein level) (PubMed:1429669, PubMed:12021776, PubMed:9588893, PubMed:22359618). Expressed in Paneth cells of the small intestine (at protein level) (PubMed:1429669, PubMed:12021776). 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). Up-regulated in fallopian tubes upon infection (PubMed:9588893). Increased expression in kidneys with pyelonephritis (PubMed:22359618). 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. Belongs to the alpha-defensin family. It was shown by two studies that dimerization of DEFA5 is crucial for antimicrobial activity (PubMed:17088326, PubMed:22573326). Another study, however, states that dimer formation is not indispensable for antimicrobial activity of DEFA5 (PubMed:25782105).