Discovery of new human beta-defensins using a genomics-based approach

Gene. 2001 Jan 24;263(1-2):211-8. doi: 10.1016/s0378-1119(00)00569-2.


Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells. In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human beta-defensin-2 (HBD-2) was analyzed for the presence of defensin genes. This sequence survey identified a novel beta-defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction. A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta. Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene. One splice variant of this gene (HE2beta1) encodes a beta-defensin consensus cysteine motif, suggesting it represents a defensin gene product. HE2beta1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of these novel beta-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antigens, Surface / genetics
  • Base Sequence
  • Carrier Proteins*
  • Contig Mapping
  • DNA / chemistry
  • DNA / genetics
  • Exons
  • Female
  • Fetus / metabolism
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Genes / genetics
  • Genomic Library
  • Genomics*
  • Glycopeptides / genetics
  • Glycoproteins
  • Humans
  • Introns
  • Male
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Vesicular Transport Proteins
  • beta-Defensins / genetics*


  • Antigens, Surface
  • Carrier Proteins
  • DEFB103A protein, human
  • DEFB4A protein, human
  • Glycopeptides
  • Glycoproteins
  • NPC2 protein, human
  • RNA, Messenger
  • Recombinant Proteins
  • SPAG11A protein, human
  • Vesicular Transport Proteins
  • beta-Defensins
  • DNA

Associated data

  • GENBANK/AF189745
  • GENBANK/AF202031
  • GENBANK/AF252830
  • GENBANK/AF252831
  • GENBANK/AF285443