Jump to content

NDUFS2

From Wikipedia, the free encyclopedia
NDUFS2
Identifiers
AliasesNDUFS2, CI-49, NADH:ubiquinone oxidoreductase core subunit S2, MC1DN6
External IDsOMIM: 602985; MGI: 2385112; HomoloGene: 56659; GeneCards: NDUFS2; OMA:NDUFS2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4720

226646

Ensembl

ENSG00000158864

ENSMUSG00000013593

UniProt

O75306

Q91WD5

RefSeq (mRNA)

NM_001166159
NM_004550

NM_153064

RefSeq (protein)

NP_694704

Location (UCSC)Chr 1: 161.2 – 161.21 MbChr 1: 171.06 – 171.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure

[edit]

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]

Function

[edit]

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]

Clinical significance

[edit]

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]

Interactions

[edit]

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]

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000158864 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000013593 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fearnley IM, Finel M, Skehel JM, Walker JE (September 1991). "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. doi:10.1042/bj2780821. PMC 1151420. PMID 1832859.
  6. ^ Procaccio V, de Sury R, Martinez P, Depetris D, Rabilloud T, Soularue P, Lunardi J, Issartel J (June 1998). "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. doi:10.1007/s003359900803. PMID 9585441. S2CID 40194269.
  7. ^ a b c d "Entrez Gene: NDUFS2 NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase)".Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-27.
  9. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–1053. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. ^ a b "NDUFS2 - NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial precursor - Homo sapiens (Human) - NDUFS2 gene & protein". www.uniprot.org. Retrieved 2018-08-27. This article incorporates text available under the CC BY 4.0 license.
  11. ^ a b "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  12. ^ Rhein VF, Carroll J, Ding S, Fearnley IM, Walker JE (November 2013). "NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I". The Journal of Biological Chemistry. 288 (46): 33016–33026. doi:10.1074/jbc.M113.518803. PMC 3829151. PMID 24089531.
  13. ^ Zurita Rendón O, Silva Neiva L, Sasarman F, Shoubridge EA (October 2014). "The arginine methyltransferase NDUFAF7 is essential for complex I assembly and early vertebrate embryogenesis". Human Molecular Genetics. 23 (19): 5159–5170. doi:10.1093/hmg/ddu239. PMC 4159157. PMID 24838397.
  14. ^ Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR (September 2004). "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation. 114 (6): 837–845. doi:10.1172/JCI20683. PMC 516258. PMID 15372108.
  15. ^ McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR (January 2004). "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. doi:10.1002/ana.10787. PMID 14705112. S2CID 21076359.
  16. ^ Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H (April 2012). "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing" (PDF). Journal of Medical Genetics. 49 (4): 277–283. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. S2CID 3177674.
  17. ^ Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC, van den Heuvel LP (2000). "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation. 15 (2): 123–134. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. S2CID 35579133.
  18. ^ Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA (2001). "Respiratory chain complex I deficiency". American Journal of Medical Genetics. 106 (1): 37–45. doi:10.1002/ajmg.1397. PMID 11579423.
  19. ^ Robinson BH (May 1998). "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. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
  20. ^ "121 binary interactions found for search term NDUFS2". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-27.

Further reading

[edit]

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


Retrieved from "https://en.wikipedia.org/w/index.php?title=NDUFS2&oldid=1193875959"