ADP-Ribosylation of HNP-1 HNP1-3 bind gp120 HNP1-3 bind CD4 Alpha-defensins form biologically active dimers pro-HD5 is cleaved by trypsin Alpha-defensin dimers multimerize to form a pore complex Alpha-defensin dimers adsorb onto microbial membrane anionic phospholipids HNP1-4 are released into phagocytic vacuoles HNP1-4 are stored in primary neutrophil granules pro-defensin alpha 5 is secreted pro-defensin alpha 5 is stored in Paneth cell granules Pro-HNP1-4 are cleaved to biologically active defensin PathwayStep6970 PathwayStep6974 PathwayStep6973 PathwayStep6972 PathwayStep6971 PathwayStep6968 PathwayStep6969 PathwayStep6975 PathwayStep6976 PathwayStep6977 PathwayStep6978 PathwayStep6979 Alpha-defensins Authored: Jupe, S, 2011-04-28 Edited: Jupe, S, 2011-07-27 Humans have 7 alpha defensin genes plus 5 pseudogenes (see HGNC at http://www.genenames.org/genefamilies/DEFA). Alpha-defensins have six cysteines linked 1-6, 2-4, 3-5. The canonical sequence of alpha-defensins in humans is x1-2CXCRx2-3Cx3Ex3GxCx3Gx5CCx1-4, where x represents any amino acid residue. <br>Human alpha-defensins 1-4 are often called human neutrophil peptides (HNP1-4) as they were initially identified in neutrophil primary (azurophilic) granules. Alpha-defensins 5 and 6 (HD5, HD6) are products of Paneth cells. HNP-1 and -3 peptides are 30 residues long, differing only in the first amino acid. They are encoded by the genes DEFA1 and DEFA3 respectively. These exhibit copy number polymorphism, with some individuals having 4-14 copies per diploid genome, while 10-37% of individuals have no copies of DEFA3 (Aldred et al. 2005, Linzmier & Ganz 2005, Ballana et al. 2007). HNP-4, encoded by DEFA4, is 33 amino acids long of which 22 differ from the other HNPs (Wilde et al. 1989). It is a minor component of neutrophil granules compared to HNP1-3. In contrast to DEFA1 and DEFA3, the genes for HNP-4, HD-5 and HD-6 are only found as two copies per diploid genome (Linzmeier & Ganz 2005). HNP-2 is 29 amino acids in length and is the proteolytic product of cleavage of the N-terminal amino acid from either HNP-1 and/or HNP-3 (Selsted et al. 1985). Pubmed12949495 Pubmed15944200 Pubmed16039093 Pubmed17214878 Pubmed2500436 Pubmed4056036 Reactome Database ID Release 431462054 Reactome, http://www.reactome.org ReactomeREACT_115574 Reviewed: McDermott, AM, 2011-11-03