Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA.
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.
Department of Biomedical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Y
Y
Suzuki
Y
Y
Aoki
Y
Y
Ishida
Y
Y
Chiba
A
A
Iwamatsu
T
T
Kishino
N
N
Niikawa
Y
Y
Matsubara
K
K
Narisawa
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D001710:Biotin / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases; D002417:Cattle; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005260:Female; D005796:Genes; D006801:Humans; D008025:Ligases / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012097:Repressor Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D001426:Bacterial Proteins; D018076:DNA, Complementary; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D001710:Biotin; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases; C058125:birA protein, E coli