Biology:NDUFS2

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Short description: Protein-coding gene in the species Homo sapiens


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Generic protein structure example

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.[1][2] 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.[3]

Structure

NDUFS2 is located on the q arm of chromosome 1 in position 23.3 and has 15 exons.[3] The NDUFS2 gene produces a 52.5 kDa protein composed of 463 amino acids.[4][5] 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.[6][7] Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[3]

Function

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.[3] Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to the stabilization of the early intermediate complex.[8][9][6][7]

Clinical significance

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.[10][11] 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.[12] However, the majority of cases are caused by mutations in nuclear-encoded genes.[13][14] 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.[15]

Interactions

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.[16]

See also

References

  1. ↑ "NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits". The Biochemical Journal. 278 278 ( Pt 3) (3): 821–829. September 1991. doi:10.1042/bj2780821. PMID 1832859. 
  2. ↑ "Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of the mitochondrial respiratory Complex I and immunodetection of the mature protein in mitochondria". Mammalian Genome 9 (6): 482–484. June 1998. doi:10.1007/s003359900803. PMID 9585441. 
  3. ↑ 3.0 3.1 3.2 3.3 "Entrez Gene: NDUFS2 NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4720.  This article incorporates text from this source, which is in the public domain.
  4. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/O75306. 
  5. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–1053. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  6. ↑ 6.0 6.1 "NDUFS2 - NADH dehydrogenase [ubiquinone iron-sulfur protein 2, mitochondrial precursor - Homo sapiens (Human) - NDUFS2 gene & protein"] (in en). https://www.uniprot.org/uniprot/O75306.  This article incorporates text available under the CC BY 4.0 license.
  7. ↑ 7.0 7.1 "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622. 
  8. ↑ "NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I". The Journal of Biological Chemistry 288 (46): 33016–33026. November 2013. doi:10.1074/jbc.M113.518803. PMID 24089531. 
  9. ↑ "The arginine methyltransferase NDUFAF7 is essential for complex I assembly and early vertebrate embryogenesis". Human Molecular Genetics 23 (19): 5159–5170. October 2014. doi:10.1093/hmg/ddu239. PMID 24838397. 
  10. ↑ "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–845. September 2004. doi:10.1172/JCI20683. PMID 15372108. 
  11. ↑ "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55 (1): 58–64. January 2004. doi:10.1002/ana.10787. PMID 14705112. 
  12. ↑ "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–283. April 2012. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf. 
  13. ↑ "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–134. 2000. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. 
  14. ↑ "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. 2001. doi:10.1002/ajmg.1397. PMID 11579423. 
  15. ↑ "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1364 (2): 271–286. May 1998. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934. 
  16. ↑ "121 binary interactions found for search term NDUFS2". IntAct Molecular Interaction Database. EMBL-EBI. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFS2. 

Further reading

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




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