DEFA1
Description
The DEFA1 (defensin alpha 1) is a protein-coding gene located on chromosome 8.
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 DEFA1 gene. Human alpha defensin 1 belongs to the alpha defensin family of antimicrobial peptides. 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. 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.
Defensin, alpha 1 (DEFA1) is a crucial component of the innate immune system, exhibiting broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. It exerts its effects through various mechanisms, including: inhibiting bacterial cell wall synthesis by interacting with lipid II, a key precursor molecule; blocking adenovirus infection by hindering viral disassembly and preventing the release of capsid protein pVI, essential for cell entry; and promoting an inflammasome response and IL-1beta production through TLR4 redirection of adenovirus particles. DEFA1 further stimulates the production of proinflammatory cytokines, including type I interferon (IFN), in plasmacytoid dendritic cells (pDCs) by inducing NFKBIA degradation and IRF1 nuclear translocation, both necessary for pDC activation.
DEFA1 is also known as DEF1, DEFA2, HNP-1, HP-1, HP1, MRS.
