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