Peptide family · 8 members
Human defensins: α-defensins (HNP1–3, HD5, HD6) and β-defensins
Defensins are small cationic peptides with six conserved cysteines, whose three disulfide bonds hold a largely β-sheet structure [1]. They contribute to the killing done by neutrophils, to mucosal defence in the small intestine and to epithelial defence in the skin and elsewhere [2].
Humans make α-defensins, four in neutrophils (HNP1 to HNP4) and two in the Paneth cells of the small intestine (HD5 and HD6), and β-defensins in epithelia [1]. HNP-2 and HNP-3 differ from HNP-1 by one N-terminal residue each, so their notes live here and their former pages redirect to this one.
On this page: HNP-1 · HNP-2 · HNP-3 · HD5 · HD6 · hBD-1 · hBD-2 · hBD-3
HNP-1
One of the three defensins first extracted from neutrophil azurophil granules in 1985, each under 3,500 daltons; the mixture killed Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro, acted against Cryptococcus neoformans and inactivated herpes simplex virus type 1 [3].
HNP-2
Merged into this page, October 2026
HNP-1 without its N-terminal alanine: 29 residues, CYCRIPACIAGERRYGTCIYQGRLWAFCC, with HNP-1's three disulfide bonds; by residue arithmetic C147H217N43O37S6, 3370.98 g/mol. In the 1985 study purified HNP-2 was as microbicidal as the HNP 1–3 mixture [3]. It comes from the same DEFA1/DEFA3 genes as HNP-1, whose copy number varies widely between people [4, 5].
HNP-3
Merged into this page, October 2026
HNP-1 with aspartate in place of its N-terminal alanine: 30 residues, DCYCRIPACIAGERRYGTCIYQGRLWAFCC; by residue arithmetic C151H222N44O40S6, 3486.07 g/mol. In 1985 it was less active than HNP-1 and HNP-2 against most, but not all, of the microbes tested [3]. It is encoded by DEFA3, which some people lack entirely: 11 of 111 UK controls in one study and 7 of 27 subjects in another [5, 4]. The DEFA1 and DEFA3 genes sit in variable tandem arrays, with 4 to 11 or 5 to 14 copies per diploid genome in the two studies, which is why the locus symbol became DEFA1A3; neutrophil HNP-1 and HNP-3 levels tracked the combined copy number [5, 4].
HD5
One of the two α-defensins of Paneth cells in the small intestine [1].
HD6
The other Paneth cell α-defensin, whose properties set it apart from HD5 and the four neutrophil α-defensins [1].
hBD-1
A human β-defensin; the β-defensins provide epithelial defence in the skin and elsewhere [2].
hBD-2
A human β-defensin; the genes DEFB4 and DEFB103A varied in tandem from 2 to 8 copies per diploid genome in one study, independently of DEFA1/DEFA3 [4].
hBD-3
A human β-defensin; see its entry for its activity and the studies behind it.
Related
- LL-37: the other major class of human antimicrobial peptide, a cathelicidin
Sources
- Lehrer RI, et al. "α-Defensins in human innate immunity." Immunol Rev, 2012;245(1):84-112. PMID: 22168415.
- Ganz T. "Defensins: antimicrobial peptides of innate immunity." Nat Rev Immunol, 2003;3(9):710-20. PMID: 12949495.
- Ganz T, et al. "Defensins. Natural peptide antibiotics of human neutrophils." J Clin Invest, 1985;76(4):1427-35. PMID: 2997278.
- Linzmeier RM, et al. "Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23." Genomics, 2005;86(4):423-30. PMID: 16039093.
- Aldred PM, et al. "Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3." Hum Mol Genet, 2005;14(14):2045-52. PMID: 15944200.