ArticleAmerican journal of human genetics1995
A single amino acid substitution within the mature sequence of ornithine aminotransferase obstructs mitochondrial entry of the precursor.
Article in American journal of human genetics, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Article
- Role of lung ornithine aminotransferase in idiopathic pulmonary fibrosis: regulation of mitochondrial ROS generation and TGF-β1 activity.Experimental & molecular medicine · 2024Article
- Molecular and Cellular Studies Reveal Folding Defects of Human Ornithine Aminotransferase Variants Associated With Gyrate Atrophy of the Choroid and Retina.Frontiers in molecular biosciences · 2021Article
- Disease-Associated Genetic Variation in Human Mitochondrial Protein Import.American journal of human genetics · 2019Review
- Adaptive effect of sericin on hepatic mitochondrial conformation through its regulation of apoptosis, autophagy and energy maintenance: a proteomics approach.Scientific reports · 2018Article
- OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina.Documenta ophthalmologica. Advances in ophthalmology · 2014Article
- A sensitive assay for ornithine amino transferase in rat brain mitochondria by ninhydrin method.Indian journal of clinical biochemistry : IJCB · 2009Article
- Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up.Journal of inherited metabolic disease · 2004Article
- Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: a hypothesis on the molecular mechanism of the OTC deficiency.Journal of inherited metabolic disease · 1997Article
- Mitochondrial encephalomyopathies: what next?Journal of inherited metabolic disease · 1996Review
- Mitochondrial protein transport--a system in search of mutations.American journal of human genetics · 1995Article
- A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy.Journal of ophthalmic & vision researchArticle
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe here evidence of congenital enzyme mistargeting induced not by abnormalities in the signal sequence. We examined the molecular mechanism of hereditary ornithine aminotransferase (OAT) deficiency causing gyrate atrophy of the choroid and retina (GACR). Nucleotide sequencing of OAT cDNA generated from a GACR patient's mRNA revealed a single base change from C to G at position 268, resulting in an amino acid substitution of neutral Gln(CAA) with negatively charged Glu(GAA) at position 90 (Q90E). Immunohistochemical and transient expression analyses suggested expression of a defective labile OAT in the patient's tissues. However, high-level expression and immunocytochemical analyses elucidated that Q90E OAT (the patient's OAT) was localized within the limits of cytoplasmic free ribosomes in precursor form without any mitochondrial entry, indicating that the patient's precursor OAT was synthesized and rapidly degraded because of accumulation in the cytosol. It is interesting that, although the mutation site (Q90E) in this GACR patient's OAT was within the coding sequence of the mature protein, the precursor exhibited loss of mitochondrial targeting function. These findings suggest that not only the signal sequence but a critical part of the mature sequence plays an essential role in mitochondrial entry of the OAT precursor protein.
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Identifiers
7668253PMC1801533W273162175What OpenQuestion holds
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