DEFA4 explained

Defensin, alpha 4 (DEFA4), also known as neutrophil defensin 4 or HNP4, is a human defensin peptide that is encoded by the DEFA4 gene.^{[1] [2]} HNP4 is expressed in the granules of the neutrophil where it defends the host against bacteria^[3] and viruses.^[4]

Function

Defensins are a peptide family of cytotoxic microbicides involved in innate immunity.^[5] Members of the defensin family are distinguished by a conserved six-cysteine motif. Several human alpha defensin genes including HNP4 are clustered on chromosome 8. DEFA4 differs from other defensin genes by an extra 83-base segment that is apparently the result of a recent duplication within the coding region. HNP4 inhibits corticotropin-stimulated corticosterone production.^[1]

Further reading

• Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J . Crystal structures of human alpha-defensins HNP4, HD5, and HD6 . Protein Science . 15 . 12 . 2749–60 . December 2006 . 17088326 . 2242434 . 10.1110/ps.062336606 .
• Mallow EB, Harris A, Salzman N, Russell JP, DeBerardinis RJ, Ruchelli E, Bevins CL . Human enteric defensins. Gene structure and developmental expression . The Journal of Biological Chemistry . 271 . 8 . 4038–45 . February 1996 . 8626737 . 10.1074/jbc.271.8.4038 . free .
• Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M . Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships . Genomics . 31 . 1 . 95–106 . January 1996 . 8808285 . 10.1006/geno.1996.0014 .
• Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF . 6 . Antibiotic proteins of human polymorphonuclear leukocytes . Proceedings of the National Academy of Sciences of the United States of America . 86 . 14 . 5610–4 . July 1989 . 2501794 . 297672 . 10.1073/pnas.86.14.5610 . 1989PNAS...86.5610G . free .
• Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, Hibberd ML, Seielstad M . 6 . New genetic associations detected in a host response study to hepatitis B vaccine . Genes and Immunity . 11 . 3 . 232–8 . April 2010 . 20237496 . 10.1038/gene.2010.1 . free .
• Kim E, Lee JE, Namkung JH, Kim PS, Kim S, Shin ES, Cho EY, Yang JM . 6 . Single nucleotide polymorphisms and the haplotype in the DEFB1 gene are associated with atopic dermatitis in a Korean population . Journal of Dermatological Science . 54 . 1 . 25–30 . April 2009 . 19135873 . 10.1016/j.jdermsci.2008.12.005 .
• Milanese M, Segat L, Arraes LC, Garzino-Demo A, Crovella S . Copy number variation of defensin genes and HIV infection in Brazilian children . Journal of Acquired Immune Deficiency Syndromes . 50 . 3 . 331–3 . March 2009 . 19194307 . 10.1097/QAI.0b013e3181945f39 . 33161105 . free .
• Palfree RG, Sadro LC, Solomon S . The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8 . Molecular Endocrinology . 7 . 2 . 199–205 . February 1993 . 10.1210/mend.7.2.8469233 . 8469233 . 13126788 . free .
• Furci L, Sironi F, Tolazzi M, Vassena L, Lusso P . Alpha-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4 . Blood . 109 . 7 . 2928–35 . April 2007 . 17132727 . 10.1182/blood-2006-05-024489 . free .
• Wilde CG, Griffith JE, Marra MN, Snable JL, Scott RW . Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family . The Journal of Biological Chemistry . 264 . 19 . 11200–3 . July 1989 . 2500436 . 10.1016/S0021-9258(18)60449-1 . free .
• Singh A, Bateman A, Zhu QZ, Shimasaki S, Esch F, Solomon S . Structure of a novel human granulocyte peptide with anti-ACTH activity . Biochemical and Biophysical Research Communications . 155 . 1 . 524–9 . August 1988 . 2843187 . 10.1016/S0006-291X(88)81118-5 .
• Konishi K, Gibson KF, Lindell KO, Richards TJ, Zhang Y, Dhir R, Bisceglia M, Gilbert S, Yousem SA, Song JW, Kim DS, Kaminski N . 6 . Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis . American Journal of Respiratory and Critical Care Medicine . 180 . 2 . 167–75 . July 2009 . 19363140 . 2714820 . 10.1164/rccm.200810-1596OC .
• Emonts M, Vermont CL, Houwing-Duistermaat JJ, Haralambous E, Gaast-de Jongh CE, Hazelzet JA, Faust SN, Betts H, Hermans PW, Levin M, de Groot R . 6 . Polymorphisms in PARP, IL1B, IL4, IL10, C1INH, DEFB1, and DEFA4 in meningococcal disease in three populations . Shock . 34 . 1 . 17–22 . July 2010 . 20016407 . 10.1097/SHK.0b013e3181ce2c7d . 21743951 . free .

Notes and References

1. Web site: Entrez Gene: DEFA4; defensin, alpha 4, corticostatin (Homo sapiens) .
2. Wu Z, Ericksen B, Tucker K, Lubkowski J, Lu W . Synthesis and characterization of human alpha-defensins 4-6 . The Journal of Peptide Research . 64 . 3 . 118–25 . September 2004 . 15317502 . 10.1111/j.1399-3011.2004.00179.x .
3. Ericksen B, Wu Z, Lu W, Lehrer RI . Antibacterial activity and specificity of the six human -defensins . Antimicrobial Agents and Chemotherapy . 49 . 1 . 269–75 . January 2005 . 15616305 . 538877 . 10.1128/AAC.49.1.269-275.2005 .
4. Wu Z, Cocchi F, Gentles D, Ericksen B, Lubkowski J, Devico A, Lehrer RI, Lu W . 6 . Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro . FEBS Letters . 579 . 1 . 162–6 . January 2005 . 15620707 . 10.1016/j.febslet.2004.11.062 . 84062495 . free .
5. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI . Defensins. Natural peptide antibiotics of human neutrophils . The Journal of Clinical Investigation . 76 . 4 . 1427–35 . October 1985 . 2997278 . 424093 . 10.1172/JCI112120 .