NDUFS2
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
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.3 Start 161,197,104 bp[1] End 161,214,395 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 H3 Start 171,062,422 bp[2] End 171,078,957 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart gastrocnemius muscle left ventricle mucosa of transverse colon right adrenal gland right adrenal cortex right ventricle right auricle myocardium of left ventricle muscle of thigh Top expressed in cardiac muscle tissue of left ventricle extensor digitorum longus muscle interventricular septum extraocular muscle plantaris muscle thoracic diaphragm soleus muscle digastric muscle tibialis anterior muscle temporal muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity, acting on NAD(P)H 4 iron, 4 sulfur cluster binding quinone binding NADH dehydrogenase (ubiquinone) activity iron-sulfur cluster binding NAD binding metal ion binding protein binding electron transfer activity oxidoreductase activity ubiquitin protein ligase binding NADH dehydrogenase activity Cellular component membrane mitochondrial respiratory chain complex I nucleoplasm mitochondrial matrix mitochondrion mitochondrial inner membrane respirasome Biological process response to oxidative stress mitochondrial respiratory chain complex I assembly mitochondrial electron transport, NADH to ubiquinone mitochondrial ATP synthesis coupled electron transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4720 226646 Ensembl ENSG00000158864 ENSMUSG00000013593 UniProt O75306 Q91WD5 RefSeq (mRNA) NM_001166159 NM_004550 NM_153064 RefSeq (protein) NP_001159631 NP_004541 NP_001364227 NP_001364228 NP_001364229 NP_001364230 NP_001364231 NP_694704 Location (UCSC) Chr 1: 161.2 – 161.21 Mb Chr 1: 171.06 – 171.08 Mb PubMed search [3] [4]
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]

• NDUFS1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.