The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry.
We cloned a novel human beta-defensin gene and determined its full-length cDNA sequence. The entire gene spanned more than 7 kb and included a large 6962-bp intron. The 362-bp cDNA encoded a prepropeptide that corresponded precisely to the recently identified human beta-defensin HBD-1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. By two-color fluorescence in situ hybridization on both metaphase chromosome and released chromatin fiber, HBD-1 gene (DEFB1 in HUGO/GDB nomenclature) mapped to chromosomal region 8p23.1-p23.2 in close proximity (within 100-150 kb) to the gene for the human neutrophil alpha-defensin HNP-1 (DEFA1). Thus, despite a complete lack of DNA sequence similarity and despite differences in their disulfide-pairing pattern, the alpha- and beta-families appear to have evolved from a common premammalian defensin gene.
Liu
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Department of Medicine and Will Rogers Institute for Pulmonary Research, University of California at Los Angeles School of Medicine, 90095, USA.
Zhao
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Heng
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HH
Ganz
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D000465:Algorithms; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000378:metabolism*; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D016208:Databases, Factual; D023082:Defensins; D004220:Disulfides / Q000737:chemistry; D019143:Evolution, Molecular; D005796:Genes / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D017433:Protein Structure, Secondary; D016415:Sequence Alignment / Q000379:methods; D017386:Sequence Homology, Amino Acid; D023084:alpha-Defensins; D023083:beta-Defensins
D000890:Anti-Infective Agents; D001798:Blood Proteins; C406407:DEFB1 protein, human; D018076:DNA, Complementary; D023082:Defensins; D004220:Disulfides; D010455:Peptides; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1