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Gene Review

DEFA4  -  defensin, alpha 4, corticostatin

Homo sapiens

Synonyms: DEF4, Defensin, alpha 4, HNP-4, HP-4, HP4, ...
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Disease relevance of DEFA4

  • Compared to a mixture of the other human defensins, HNP-4 was found to be approximately 100 times more potent against E. coli and four times more potent against both S. faecalis and C. albicans [1].
  • HD5 was as effective as HNP2 against S. aureus and as effective as HNP4 against the gram-negative bacteria in our panel [2].
  • Human neutrophil alpha-defensin 4 (HNP4) is more effective than HNP1-3 in protecting human peripheral blood mononuclear cells from infection by both X4 and R5 HIV-1 strains [3].
  • HNP-4 and eotaxin-2 expressions were positively correlated ( P <0.05) in the acute tonsillitis group [4].

High impact information on DEFA4

  • Synchronized assays revealed that HNP-4, HD6, and hBD3 acted primarily by preventing binding and entry, whereas HNP1-3 and HD5 also inhibited postentry events [5].
  • In contrast, HNP-4 and HD6 bound heparan sulfate, but not gB [5].
  • We have named this peptide human neutrophil peptide 4 (HNP-4) based on its structural similarity to a group of antimicrobial polypeptides known as defensins (HNP 1-3) [1].
  • The amino acid sequence determined from isolated HNP-4 and from tryptic fragments of reduced and alkylated peptide is: NH2-Val-Cys-Ser-Cys-Arg-Leu-Val-Phe-Cys-Arg-Arg-Thr-Glu- Leu-Arg-Val-Gly-Asn-Cys-Leu-Ile-Gly-Gly-Val-Ser-Phe-Thr-Tyr-Cys-Cys-Thr- Arg-Val - COOH [1].
  • HNP-4 and the defensins have identical cysteine backbones and, like the defensins, HNP-4 is rich in arginine (15.2 mol %) [1].

Biological context of DEFA4

  • The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8 [6].
  • Complementary DNA clones encoding the HP-4 precursor have been isolated from a human bone marrow cDNA library by screening with oligonucleotide probes [6].
  • HP-1 and HP-1-56, but not HP-4, inhibited DNA synthesis at 1-50 nM without causing cell death [7].

Anatomical context of DEFA4

  • By analysis of DNA from a pannel of hamster/human hybrid cell lines, the HP-4 gene was found to be on chromosome 8, as is the gene for human peptide HP-1 [6].
  • The peptide HP-4 is homologous to a previously described human granulocyte peptide HP-1 that has no anti-ACTH activity [8].
  • In contrast HP-4 had no effect on HL60 cells at nanomolar concentrations but was strongly cytotoxic at micromolar concentrations [7].
  • We report the effects of three of these peptides HP-1, HP-1-56 and HP-4 on the incorporation of [3H]thymidine into the DNA of the leukemic cell line HL60 [7].

Other interactions of DEFA4

  • Human PMNs contain four defensins termed HNP-1 to HNP-4 [9].
  • Human neutrophils contain large amounts of three alpha-defensins (HNP-1-HNP-3), and smaller amounts of a fourth, HNP-4 [10].
  • Human neutrophils contain two structurally distinct types of antimicrobial peptides, beta-sheet defensins (HNP-1 to HNP-4) and the alpha-helical peptide LL-37 [11].

Analytical, diagnostic and therapeutic context of DEFA4

  • Further, HNP-4 is significantly more hydrophobic than the defensins, as determined by its retention time on reverse-phase high performance liquid chromatography [1].
  • Using size exclusion and reverse-phase high performance liquid chromatography, HNP-4 was purified to homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino-terminal sequence analysis [1].
  • Using Western blot analysis, we showed for the first time that HNP-4, a novel human defensin, was also deficient in the patient's neutrophils [12].


  1. Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family. Wilde, C.G., Griffith, J.E., Marra, M.N., Snable, J.L., Scott, R.W. J. Biol. Chem. (1989) [Pubmed]
  2. Antibacterial activity and specificity of the six human {alpha}-defensins. Ericksen, B., Wu, Z., Lu, W., Lehrer, R.I. Antimicrob. Agents Chemother. (2005) [Pubmed]
  3. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. Wu, Z., Cocchi, F., Gentles, D., Ericksen, B., Lubkowski, J., Devico, A., Lehrer, R.I., Lu, W. FEBS Lett. (2005) [Pubmed]
  4. Defensin and chemokine expression patterns in the palatine tonsil: a model of their local interaction. Meyer, J.E., Beier, U.H., Görögh, T., Schreiber, S., Beck, C., Maune, S. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2006) [Pubmed]
  5. Human {alpha}- and beta-Defensins Block Multiple Steps in Herpes Simplex Virus Infection. Hazrati, E., Galen, B., Lu, W., Wang, W., Ouyang, Y., Keller, M.J., Lehrer, R.I., Herold, B.C. J. Immunol. (2006) [Pubmed]
  6. The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8. Palfree, R.G., Sadro, L.C., Solomon, S. Mol. Endocrinol. (1993) [Pubmed]
  7. The effect of HP-1 and related neutrophil granule peptides on DNA synthesis in HL60 cells. Bateman, A., Singh, A., Congote, L.F., Solomon, S. Regul. Pept. (1991) [Pubmed]
  8. Structure of a novel human granulocyte peptide with anti-ACTH activity. Singh, A., Bateman, A., Zhu, Q.Z., Shimasaki, S., Esch, F., Solomon, S. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  9. Evaluation of susceptibility of gram-positive and -negative bacteria to human defensins by using radial diffusion assay. Takemura, H., Kaku, M., Kohno, S., Hirakata, Y., Tanaka, H., Yoshida, R., Tomono, K., Koga, H., Wada, A., Hirayama, T., Kamihira, S. Antimicrob. Agents Chemother. (1996) [Pubmed]
  10. Multispecific myeloid defensins. Lehrer, R.I. Curr. Opin. Hematol. (2007) [Pubmed]
  11. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Turner, J., Cho, Y., Dinh, N.N., Waring, A.J., Lehrer, R.I. Antimicrob. Agents Chemother. (1998) [Pubmed]
  12. A marked decrease in defensin mRNA in the only case of congenital neutrophil-specific granule deficiency reported in Japan. Tamura, A., Agematsu, K., Mori, T., Kawai, H., Kuratsuji, T., Shimane, M., Tani, K., Asano, S., Komiyama, A. Int. J. Hematol. (1994) [Pubmed]
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