{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''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.<ref name="pmid9030614">{{cite journal | vauthors = Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM | title = Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes | journal = J Neurosci | volume = 17 | issue = 5 | pages = 1539–47 | date = Mar 1997 | pmid = 9030614 | pmc = 6573369| doi = 10.1523/JNEUROSCI.17-05-01539.1997}}</ref><ref name="pmid15944200">{{cite journal | vauthors = Aldred PM, Hollox EJ, Armour JA | title = Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3 | journal = Hum Mol Genet | volume = 14 | issue = 14 | pages = 2045–52 | date = Jul 2005 | pmid = 15944200 | doi = 10.1093/hmg/ddi209 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DEFA1 defensin, alpha 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1667}}</ref> Human alpha defensin 1 belongs to the alpha defensin family of antimicrobial peptides.
== 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.<ref name="entrez"/>
== 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.<ref>{{cite journal | vauthors = Valore EV, Ganz T | title = Posttranslational processing of defensins in immature human myeloid cells. | journal = Blood | volume = 79 | issue = 6 | pages = 1538–44 | date = Mar 15, 1992 | doi = 10.1182/blood.V79.6.1538.1538 | pmid = 1339298 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Arnljots K, Sørensen O, Lollike K, Borregaard N | title = Timing, targeting and sorting of azurophil granule proteins in human myeloid cells. | journal = Leukemia | volume = 12 | issue = 11 | pages = 1789–95 | date = Nov 1998 | pmid = 9823955 | doi = 10.1038/sj.leu.2401202 | doi-access = free }}</ref> Cationic 29-30 amino acids HNPs associate with the negatively charged proteoglycan serglycin and translocate to azurophil granules.<ref>{{cite journal | vauthors = Glenthøj A, Cowland JB, Heegaard NH, Larsen MT, Borregaard N | title = Serglycin participates in retention of α-defensin in granules during myelopoiesis. | journal = Blood | volume = 118 | issue = 16 | pages = 4440–8 | date = Oct 20, 2011 | pmid = 21849484 | doi = 10.1182/blood-2011-06-362947 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Faurschou M, Kamp S, Cowland JB, Udby L, Johnsen AH, Calafat J, Winther H, Borregaard N | title = Prodefensins are matrix proteins of specific granules in human neutrophils. | journal = Journal of Leukocyte Biology | volume = 78 | issue = 3 | pages = 785–93 | date = Sep 2005 | pmid = 15944211 | doi = 10.1189/jlb.1104688 | s2cid = 14241958 }}</ref>
== References == {{reflist}}
== Further reading == {{refbegin | 2}} *{{cite journal | vauthors=Lehrer RI, Lichtenstein AK, Ganz T |title=Defensins: antimicrobial and cytotoxic peptides of mammalian cells. |journal=Annu. Rev. Immunol. |volume=11 |pages= 105–28 |year= 1993 |pmid= 8476558 |doi= 10.1146/annurev.iy.11.040193.000541 }} *{{cite journal | vauthors=Corda D, Di Girolamo M |title=Mono-ADP-ribosylation: a tool for modulating immune response and cell signaling. |journal=Sci. STKE |volume=2002 |issue= 163 |pages= PE53 |year= 2003 |pmid= 12488509 |doi= 10.1126/stke.2002.163.pe53 |s2cid=26277687 }} *{{cite journal | vauthors=Valore EV, Ganz T |title=Posttranslational processing of defensins in immature human myeloid cells. |journal=Blood |volume=79 |issue= 6 |pages= 1538–44 |year= 1992 |pmid= 1339298 |doi= 10.1182/blood.V79.6.1538.1538|doi-access=free }} *{{cite journal | vauthors=Zhang XL, Selsted ME, Pardi A |title=NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1. |journal=Biochemistry |volume=31 |issue= 46 |pages= 11348–56 |year= 1992 |pmid= 1445872 |doi=10.1021/bi00161a012 }} *{{cite journal | vauthors=Pardi A, Zhang XL, Selsted ME |title=NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1. |journal=Biochemistry |volume=31 |issue= 46 |pages= 11357–64 |year= 1992 |pmid= 1445873 |doi=10.1021/bi00161a013 |display-authors=etal}} *{{cite journal | vauthors=Hill CP, Yee J, Selsted ME, Eisenberg D |title=Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. |journal=Science |volume=251 |issue= 5000 |pages= 1481–5 |year= 1991 |pmid= 2006422 |doi=10.1126/science.2006422 |bibcode=1991Sci...251.1481H }} *{{cite journal | vauthors=Bateman A, Singh A, Shustik C |title=The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells. |journal=J. Biol. Chem. |volume=266 |issue= 12 |pages= 7524–30 |year= 1991 |doi=10.1016/S0021-9258(20)89478-2 |pmid= 2019582 |display-authors=etal|doi-access=free }} *{{cite journal | vauthors=Wagner MJ, Ge Y, Siciliano M, Wells DE |title=A hybrid cell mapping panel for regional localization of probes to human chromosome 8. |journal=Genomics |volume=10 |issue= 1 |pages= 114–25 |year= 1991 |pmid= 2045096 |doi=10.1016/0888-7543(91)90491-V }} *{{cite journal |author2-link= Mitchell Kronenberg | vauthors=Sparkes RS, Kronenberg M, Heinzmann C |title=Assignment of defensin gene(s) to human chromosome 8p23. |journal=Genomics |volume=5 |issue= 2 |pages= 240–4 |year= 1989 |pmid= 2793180 |doi=10.1016/0888-7543(89)90052-9 |display-authors=etal}} *{{cite journal | vauthors=Selsted ME, Harwig SS |title=Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide. |journal=J. Biol. Chem. |volume=264 |issue= 7 |pages= 4003–7 |year= 1989 |doi=10.1016/S0021-9258(19)84952-9 |pmid= 2917986 |doi-access=free }} *{{cite journal | vauthors=Wiedemann LM, Francis GE, Lamb RF |title=Differentiation stage-specific expression of a gene during granulopoiesis. |journal=Leukemia |volume=3 |issue= 3 |pages= 227–34 |year= 1989 |pmid= 2918759 |display-authors=etal}} *{{cite journal | vauthors=Ganz T, Selsted ME, Szklarek D |title=Defensins. Natural peptide antibiotics of human neutrophils. |journal=J. Clin. Invest. |volume=76 |issue= 4 |pages= 1427–35 |year= 1985 |pmid= 2997278 |doi=10.1172/JCI112120 | pmc=424093 |display-authors=etal}} *{{cite journal | vauthors=Daher KA, Lehrer RI, Ganz T, Kronenberg M |title=Isolation and characterization of human defensin cDNA clones. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 19 |pages= 7327–31 |year= 1988 |pmid= 3174637 |doi=10.1073/pnas.85.19.7327 | pmc=282179 |bibcode=1988PNAS...85.7327D |doi-access=free }} *{{cite journal | vauthors=Mars WM, van Tuinen P, Drabkin HA |title=A myeloid-related sequence that localizes to human chromosome 8q21.1-22. |journal=Blood |volume=71 |issue= 6 |pages= 1713–9 |year= 1988 |pmid= 3370315 |doi= 10.1182/blood.V71.6.1713.1713|display-authors=etal|doi-access=free }} *{{cite journal | vauthors=Selsted ME, Harwig SS, Ganz T |title=Primary structures of three human neutrophil defensins. |journal=J. Clin. Invest. |volume=76 |issue= 4 |pages= 1436–9 |year= 1985 |pmid= 4056036 |doi=10.1172/JCI112121 | pmc=424095 |display-authors=etal}} *{{cite journal | vauthors=Panyutich AV, Hiemstra PS, van Wetering S, Ganz T |title=Human neutrophil defensin and serpins form complexes and inactivate each other. |journal=Am. J. Respir. Cell Mol. Biol. |volume=12 |issue= 3 |pages= 351–7 |year= 1995 |pmid= 7873202 |doi= 10.1165/ajrcmb.12.3.7873202}} *{{cite journal | vauthors=Date Y, Nakazato M, Shiomi K |title=Localization of human neutrophil peptide (HNP) and its messenger RNA in neutrophil series. |journal=Ann. Hematol. |volume=69 |issue= 2 |pages= 73–7 |year= 1994 |pmid= 8080882 |doi=10.1007/BF01698485 |s2cid=6651647 |display-authors=etal}} *{{cite journal | vauthors=Linzmeier R, Michaelson D, Liu L, Ganz T |title=The structure of neutrophil defensin genes. |journal=FEBS Lett. |volume=326 |issue= 1–3 |pages= 299–300 |year= 1993 |pmid= 8325384 |doi=10.1016/0014-5793(93)81813-F |bibcode=1993FEBSL.326..299L |s2cid=11526759 }} *{{cite journal | vauthors=Linzmeier R, Michaelson D, Liu L, Ganz T |title=The structure of neutrophil defensin genes |journal=FEBS Lett. |volume=321 |issue= 2–3 |pages= 267–73 |year= 1993 |pmid= 8477861 |doi=10.1016/0014-5793(93)80122-B |bibcode=1993FEBSL.321..267L |s2cid=330693 |doi-access=free }} {{refend}}
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Category:Defensins
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