Defensin, alpha 1 also known as human alpha defensin 1, human neutrophil peptide 1 (HNP-1) or neutrophil defensin 1 is a human protein that is encoded by the DEFA1gene.[3][4][5] Human alpha defensin 1 belongs to the alpha defensin family of antimicrobialpeptides.
Defensins are a family of microbicidal and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes are clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 1, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. It differs from the defensins, alpha 2 and alpha 3 by only one amino acid.[5]
HNPs are generated as 94 amino acids preproHNPs, which are co-translationally cleaved to 75 amino acids pro-peptides with a N-terminal prosegment having a negative charge that neutralizes the highly positively charged C terminal peptide. Processing of proHNPs occurs mainly in late promyelocytes, where the 75 amino acids proHNPs are cleaved to a 56 amino acids intermediate form and onward to 29-30 amino acids mature peptides designated HNPs.[6][7] Cationic 29-30 amino acids HNPs associate with the negatively charged proteoglycan serglycin and translocate to azurophil granules.[8] At later stages of granulocytic differentiation in which HNP expression peaks (i.e. myelocytes and metamyelocytes), proHNPs are not cleaved, rendering the peptides overall neutral. This prevents binding to serglycin and most proHNP is accordingly secreted into the bone marrow plasma although some is retained in specific granules.[9]
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Zhang XL, Selsted ME, Pardi A (1992). "NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1". Biochemistry. 31 (46): 11348–56. doi:10.1021/bi00161a012. PMID1445872.
Pardi A, Zhang XL, Selsted ME, et al. (1992). "NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1". Biochemistry. 31 (46): 11357–64. doi:10.1021/bi00161a013. PMID1445873.
Wagner MJ, Ge Y, Siciliano M, Wells DE (1991). "A hybrid cell mapping panel for regional localization of probes to human chromosome 8". Genomics. 10 (1): 114–25. doi:10.1016/0888-7543(91)90491-V. PMID2045096.
Wiedemann LM, Francis GE, Lamb RF, et al. (1989). "Differentiation stage-specific expression of a gene during granulopoiesis". Leukemia. 3 (3): 227–34. PMID2918759.
Panyutich AV, Hiemstra PS, van Wetering S, Ganz T (1995). "Human neutrophil defensin and serpins form complexes and inactivate each other". Am. J. Respir. Cell Mol. Biol. 12 (3): 351–7. doi:10.1165/ajrcmb.12.3.7873202. PMID7873202.
Date Y, Nakazato M, Shiomi K, et al. (1994). "Localization of human neutrophil peptide (HNP) and its messenger RNA in neutrophil series". Ann. Hematol. 69 (2): 73–7. doi:10.1007/BF01698485. PMID8080882. S2CID6651647.
