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]
^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.
PMID15944211.
S2CID14241958.
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.
PMID8476558.
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.
PMID2045096.
Wiedemann LM, Francis GE, Lamb RF, et al. (1989). "Differentiation stage-specific expression of a gene during granulopoiesis". Leukemia. 3 (3): 227–34.
PMID2918759.
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.
PMID7873202.
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.
PMID8080882.
S2CID6651647.
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]
^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.
PMID15944211.
S2CID14241958.
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.
PMID8476558.
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.
PMID2045096.
Wiedemann LM, Francis GE, Lamb RF, et al. (1989). "Differentiation stage-specific expression of a gene during granulopoiesis". Leukemia. 3 (3): 227–34.
PMID2918759.
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.
PMID7873202.
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.
PMID8080882.
S2CID6651647.