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.
Function
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]
Biosynthesis
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]
References
^ a b cENSG00000284983 GRCh38: Ensembl release 89: ENSG00000206047, ENSG00000284983 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM (Mar 1997). "Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes". J Neurosci. 17 (5): 1539–47. doi:10.1523/JNEUROSCI.17-05-01539.1997. PMC6573369. PMID 9030614.
^Aldred PM, Hollox EJ, Armour JA (Jul 2005). "Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3". Hum Mol Genet. 14 (14): 2045–52. doi:10.1093/hmg/ddi209. PMID 15944200.
^ a b"Entrez Gene: DEFA1 defensin, alpha 1".
^Valore EV, Ganz T (Mar 15, 1992). "Posttranslational processing of defensins in immature human myeloid cells". Blood. 79 (6): 1538–44. doi:10.1182/blood.V79.6.1538.1538. PMID 1339298.
^Arnljots K, Sørensen O, Lollike K, Borregaard N (Nov 1998). "Timing, targeting and sorting of azurophil granule proteins in human myeloid cells". Leukemia. 12 (11): 1789–95. doi:10.1038/sj.leu.2401202. PMID 9823955.
^Glenthøj A, Cowland JB, Heegaard NH, Larsen MT, Borregaard N (Oct 20, 2011). "Serglycin participates in retention of α-defensin in granules during myelopoiesis". Blood. 118 (16): 4440–8. doi:10.1182/blood-2011-06-362947. PMID 21849484.
^Faurschou M, Kamp S, Cowland JB, Udby L, Johnsen AH, Calafat J, Winther H, Borregaard N (Sep 2005). "Prodefensins are matrix proteins of specific granules in human neutrophils". Journal of Leukocyte Biology. 78 (3): 785–93. doi:10.1189/jlb.1104688. PMID 15944211. S2CID 14241958.
Further reading
Lehrer RI, Lichtenstein AK, Ganz T (1993). "Defensins: antimicrobial and cytotoxic peptides of mammalian cells". Annu. Rev. Immunol. 11: 105–28. doi:10.1146/annurev.iy.11.040193.000541. PMID 8476558.
Corda D, Di Girolamo M (2003). "Mono-ADP-ribosylation: a tool for modulating immune response and cell signaling". Sci. STKE. 2002 (163): PE53. doi:10.1126/stke.2002.163.pe53. PMID 12488509. S2CID 26277687.
Valore EV, Ganz T (1992). "Posttranslational processing of defensins in immature human myeloid cells". Blood. 79 (6): 1538–44. doi:10.1182/blood.V79.6.1538.1538. PMID 1339298.
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. PMID 1445872.
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. PMID 1445873.
Hill CP, Yee J, Selsted ME, Eisenberg D (1991). "Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization". Science. 251 (5000): 1481–5. Bibcode:1991Sci...251.1481H. doi:10.1126/science.2006422. PMID 2006422.
Bateman A, Singh A, Shustik C, et al. (1991). "The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells". J. Biol. Chem. 266 (12): 7524–30. doi:10.1016/S0021-9258(20)89478-2. PMID 2019582.
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. PMID 2045096.
Sparkes RS, Kronenberg M, Heinzmann C, et al. (1989). "Assignment of defensin gene(s) to human chromosome 8p23". Genomics. 5 (2): 240–4. doi:10.1016/0888-7543(89)90052-9. PMID 2793180.
Selsted ME, Harwig SS (1989). "Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide". J. Biol. Chem. 264 (7): 4003–7. doi:10.1016/S0021-9258(19)84952-9. PMID 2917986.
Wiedemann LM, Francis GE, Lamb RF, et al. (1989). "Differentiation stage-specific expression of a gene during granulopoiesis". Leukemia. 3 (3): 227–34. PMID 2918759.
Ganz T, Selsted ME, Szklarek D, et al. (1985). "Defensins. Natural peptide antibiotics of human neutrophils". J. Clin. Invest. 76 (4): 1427–35. doi:10.1172/JCI112120. PMC424093. PMID 2997278.
Daher KA, Lehrer RI, Ganz T, Kronenberg M (1988). "Isolation and characterization of human defensin cDNA clones". Proc. Natl. Acad. Sci. U.S.A. 85 (19): 7327–31. Bibcode:1988PNAS...85.7327D. doi:10.1073/pnas.85.19.7327. PMC282179. PMID 3174637.
Mars WM, van Tuinen P, Drabkin HA, et al. (1988). "A myeloid-related sequence that localizes to human chromosome 8q21.1-22". Blood. 71 (6): 1713–9. doi:10.1182/blood.V71.6.1713.1713. PMID 3370315.
Selsted ME, Harwig SS, Ganz T, et al. (1985). "Primary structures of three human neutrophil defensins". J. Clin. Invest. 76 (4): 1436–9. doi:10.1172/JCI112121. PMC424095. PMID 4056036.
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. PMID 7873202.
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. PMID 8080882. S2CID 6651647.
Linzmeier R, Michaelson D, Liu L, Ganz T (1993). "The structure of neutrophil defensin genes". FEBS Lett. 326 (1–3): 299–300. doi:10.1016/0014-5793(93)81813-F. PMID 8325384. S2CID 11526759.
Linzmeier R, Michaelson D, Liu L, Ganz T (1993). "The structure of neutrophil defensin genes". FEBS Lett. 321 (2–3): 267–73. doi:10.1016/0014-5793(93)80122-B. PMID 8477861. S2CID 330693.
