Defensin alpha 5 (DEFA5)

Defensin alpha 5 (DEFA5), commonly known as HD5, is a cysteine-rich, small antimicrobial peptide predominantly expressed by Paneth cells in the small intestine, especially the ileum[1][2][4][5][7][8]. It is synthesized as an inactive precursor (proHD5) and is cleaved by proteases such as trypsin to generate the active peptide, which is then secreted into the intestinal lumen[1][2]. DEFA5 exhibits potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria, as well as some viruses, through mechanisms including membrane disruption and aggregation of pathogens[1][2][4][5]. It plays a key role in shaping and defending the gut microbiome, maintaining epithelial barrier integrity, and modulating immune responses (e.g., inducing IL-8 secretion)[1][2][3][5]. Dysregulation or deficiency of DEFA5 has been associated with inflammatory bowel diseases such as Crohn’s disease, increased susceptibility to infection, and altered responses to intestinal radiation injury[5][6]. There are currently no known drugs that target DEFA5 directly; it is itself a peptide effector of innate immunity rather than a traditional drug target[1][2][4][5].

Other names

Defensin alpha 5HD5DEF5HD-5Defensin-5defensin, alpha 5Paneth cell-specific defensinpreprodefensin alpha 5HD5(20-94)HD5(23-94)HD5(29-94)HD5(56-94)HD5(63-94)

Direct disruption of microbial membranes; Induction of bacterial morphological changes; Binding and neutralization of bacterial/viral factors; Aggregation of virions; Modulation of immune signaling (e.g. chemokine induction like IL-8)