人全羧化酶合成酶cDNA中突变的分离与鉴定

Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA.

作者信息

Suzuki Y, Aoki Y, Ishida Y, Chiba Y, Iwamatsu A, Kishino T, Niikawa N, Matsubara Y, Narisawa K

机构信息

Department of Biomedical Genetics, Tohoku University School of Medicine, Sendai, Japan.

出版信息

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

DOI:10.1038/ng1094-122

PMID:7842009

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.

摘要

全羧化酶合成酶（HCS）在真核细胞生物素利用中起关键作用，其缺乏会导致人类生物素反应性多种羧化酶缺乏症。我们克隆了人类HCS cDNA，并表明针对重组蛋白的抗血清可免疫沉淀人类HCS。在患有HCS缺乏症的兄弟姐妹的细胞中发现了一个导致提前终止的单碱基缺失和一个错义突变（亮氨酸突变为脯氨酸）。人类HCS与BirA具有同源性，BirA在大肠杆菌中既是生物素-[乙酰辅酶A羧化酶]连接酶又是生物素阻遏物，这表明这两种蛋白质之间存在功能关系。人类HCS基因定位于21号染色体q22.1区域。