NDUFS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | NDUFS2, CI-49, NADH:ubiquinone oxidoreductase core subunit S2, MC1DN6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 602985; MGI: 2385112; HomoloGene: 56659; GeneCards: NDUFS2; OMA: NDUFS2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. [5] [6] The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase ( complex I). Mutations in this gene are associated with mitochondrial complex I deficiency. [7]
NDUFS2 is located on the q arm of chromosome 1 in position 23.3 and has 15 exons. [7] The NDUFS2 gene produces a 52.5 kDa protein composed of 463 amino acids. [8] [9] NDUFS2, the protein encoded by this gene, is a member of the complex I 49 kDa subunit family. It is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane. It contains a cofactor binding site for a [ 4Fe-4S] cluster, a transit peptide, 5 turns, 11 beta strands, and 18 alpha helixes. [10] [11] Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [7]
Mitochondrial complex I is the first multimeric complex of the respiratory chain that catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mammalian mitochondrial complex I is an assembly of at least 43 different subunits. Seven of the subunits are encoded by the mitochondrial genome; the remainder are the products of nuclear genes. The iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits, including NDUFS2. [7] Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to the stabilization of the early intermediate complex. [12] [13] [10] [11]
Mutations in the NDUFS2 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. [14] [15] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible. [16] However, the majority of cases are caused by mutations in nuclear-encoded genes. [17] [18] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. [19]
NDUFS2 has been shown to have 121 binary protein-protein interactions including 112 co-complex interactions. NDUFS2 appears to interact with NDUFS3, MKLN1, EGR2, HMOX2, CENPU, and TNFRSF14. [20]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
NDUFS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | NDUFS2, CI-49, NADH:ubiquinone oxidoreductase core subunit S2, MC1DN6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 602985; MGI: 2385112; HomoloGene: 56659; GeneCards: NDUFS2; OMA: NDUFS2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. [5] [6] The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase ( complex I). Mutations in this gene are associated with mitochondrial complex I deficiency. [7]
NDUFS2 is located on the q arm of chromosome 1 in position 23.3 and has 15 exons. [7] The NDUFS2 gene produces a 52.5 kDa protein composed of 463 amino acids. [8] [9] NDUFS2, the protein encoded by this gene, is a member of the complex I 49 kDa subunit family. It is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane. It contains a cofactor binding site for a [ 4Fe-4S] cluster, a transit peptide, 5 turns, 11 beta strands, and 18 alpha helixes. [10] [11] Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [7]
Mitochondrial complex I is the first multimeric complex of the respiratory chain that catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mammalian mitochondrial complex I is an assembly of at least 43 different subunits. Seven of the subunits are encoded by the mitochondrial genome; the remainder are the products of nuclear genes. The iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits, including NDUFS2. [7] Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to the stabilization of the early intermediate complex. [12] [13] [10] [11]
Mutations in the NDUFS2 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. [14] [15] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible. [16] However, the majority of cases are caused by mutations in nuclear-encoded genes. [17] [18] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. [19]
NDUFS2 has been shown to have 121 binary protein-protein interactions including 112 co-complex interactions. NDUFS2 appears to interact with NDUFS3, MKLN1, EGR2, HMOX2, CENPU, and TNFRSF14. [20]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.