Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA

Nat Genet. 1994 Oct;8(2):122-8. doi: 10.1038/ng1094-122.

Abstract

Holocarboxylase synthetase (HCS) plays an essential role in biotin utilization in eukaryotic cells and its deficiency causes biotin-responsive multiple carboxylase deficiency in humans. We have cloned the human HCS cDNA and show that antiserum against the recombinant protein immunoprecipitates human HCS. A one base deletion resulting in a premature termination and a missense mutation (Leu to Pro) were found in cells from siblings with HCS deficiency. Human HCS shows homology to BirA, which acts as both a biotin-[acetyl-CoA-carboxylase] ligase and a biotin repressor in E. coli, suggesting a functional relationship between the two proteins. The human HCS gene maps to chromosome 21q22.1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • Base Sequence
  • Biotin / metabolism
  • Carbon-Nitrogen Ligases*
  • Cattle
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21
  • Cloning, Molecular
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Female
  • Genes
  • Humans
  • Ligases / deficiency
  • Ligases / genetics*
  • Ligases / immunology
  • Molecular Sequence Data
  • Point Mutation
  • Recombinant Fusion Proteins / immunology
  • Repressor Proteins*
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Transcription Factors*

Substances

  • Bacterial Proteins
  • DNA, Complementary
  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • Biotin
  • Ligases
  • Carbon-Nitrogen Ligases
  • holocarboxylase synthetases
  • birA protein, E coli

Associated data

  • GENBANK/D23672