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词条 NDUFS1
释义

  1. Structure

  2. Function

  3. Clinical significance

  4. Interactions

  5. See also

  6. References

  7. Further reading

{{Infobox_gene}}NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene.[1] The encoded protein, NDUFS1, is the largest subunit of complex I, located on the inner mitochondrial membrane, and is important for mitochondrial oxidative phosphorylation. Mutations in this gene are associated with complex I deficiency.[2]

Structure

NDUFS1 is located on the q arm of chromosome 2 in position 33.3 and has 20 exons.[3] The NDUFS1 gene produces a 79.5 kDa protein composed of 727 amino acids.[4][5] NDUFS1, the protein encoded by this gene, is a member of the complex I 75 kDa subunit family. It contains a transit peptide, 10 turns, 19 beta strands, 27 alpha helixes, and cofactor binding sites for [2Fe-2S] and [4Fe-4S] clusters. The cluster domains consist of a 79 amino acid 2Fe-2S ferredoxin-type from positions 30-108, a 40 amino acid 4Fe-4S His(Cys)3-ligated-type from positions 108-147, and a 57 amino acid 4Fe-4S Mo/W bis-MGD-type from positions 245-301.[6][7] Several transcript variants encoding different isoforms have been found for this gene.[2]

Function

The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized.[2]

Clinical significance

Mutations in the NDUFS1 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.[8][9] 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.[10] However, the majority of cases are caused by mutations in nuclear-encoded genes.[11][12] 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.[13]

Interactions

NDUFS1 has been shown to have 124 binary protein-protein interactions including 110 co-complex interactions. NDUFS1 appears to interact with SOAT1, NDUFA9, HLA-B, ECE2, C1QTNF9, GPAA1, STOM, GDI1, ACAP2, EHBP1, MBOAT7, PIGS.[14]

See also

  • NDUFS2

References

1. ^{{cite journal | vauthors = Chow W, Ragan I, Robinson BH | title = Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase | journal = European Journal of Biochemistry | volume = 201 | issue = 3 | pages = 547–50 | date = November 1991 | pmid = 1935949 | pmc = | doi = 10.1111/j.1432-1033.1991.tb16313.x }}
2. ^1 2 {{cite web | title = Entrez Gene: NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4719| access-date = }}{{PD-notice}}
3. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/65260|title=Entrez Gene: Cytochrome c oxidase assembly factor 7 (putative)|access-date=2018-08-08}}{{PD-notice}}
4. ^{{Cite web|url=https://amino.heartproteome.org/web/protein/P28331|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-08-27}}
5. ^{{cite journal | vauthors = 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 | display-authors = 6 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
6. ^{{Cite web|url=https://www.uniprot.org/uniprot/P28331|title=NDUFS1 - NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial precursor - Homo sapiens (Human) - NDUFS1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-27}}{{CC-notice|cc=by4}}
7. ^{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}
8. ^{{cite journal | vauthors = Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR | title = NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency | journal = The Journal of Clinical Investigation | volume = 114 | issue = 6 | pages = 837–45 | date = September 2004 | pmid = 15372108 | pmc = 516258 | doi = 10.1172/JCI20683 }}
9. ^{{cite journal | vauthors = McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR | title = De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency | journal = Annals of Neurology | volume = 55 | issue = 1 | pages = 58–64 | date = January 2004 | pmid = 14705112 | doi = 10.1002/ana.10787 }}
10. ^{{cite journal | vauthors = 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 | title = Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing | journal = Journal of Medical Genetics | volume = 49 | issue = 4 | pages = 277–83 | date = April 2012 | pmid = 22499348 | doi = 10.1136/jmedgenet-2012-100846 }}
11. ^{{cite journal | vauthors = Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC, van den Heuvel LP | title = Isolated complex I deficiency in children: clinical, biochemical and genetic aspects | journal = Human Mutation | volume = 15 | issue = 2 | pages = 123–34 | date = 2000 | pmid = 10649489 | doi = 10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P }}
12. ^{{cite journal | vauthors = Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA | title = Respiratory chain complex I deficiency | journal = American Journal of Medical Genetics | volume = 106 | issue = 1 | pages = 37–45 | date = 2001 | pmid = 11579423 | doi = 10.1002/ajmg.1397 }}
13. ^{{cite journal | vauthors = Robinson BH | title = Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect | journal = Biochimica et Biophysica Acta | volume = 1364 | issue = 2 | pages = 271–86 | date = May 1998 | pmid = 9593934 | doi = 10.1016/s0005-2728(98)00033-4 }}
14. ^{{cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFS1 | title = 124 binary interactions found for search term NDUFS1 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-25 }}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Baertling F, Schaper J, Mayatepek E, Distelmaier F | title = Teaching NeuroImages: rapidly progressive leukoencephalopathy in mitochondrial complex I deficiency | journal = Neurology | volume = 81 | issue = 2 | pages = e10-1 | date = July 2013 | pmid = 23836946 | doi = 10.1212/WNL.0b013e31829a339b }}
  • {{cite journal | vauthors = Duncan AM, Chow W, Robinson BH | title = Localization of the human 75-kDal Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33----q34 | journal = Cytogenetics and Cell Genetics | volume = 60 | issue = 3-4 | pages = 212–3 | year = 1992 | pmid = 1505218 | doi = 10.1159/000133340 }}
  • {{cite journal | vauthors = Sumegi B, Srere PA | title = Complex I binds several mitochondrial NAD-coupled dehydrogenases | journal = The Journal of Biological Chemistry | volume = 259 | issue = 24 | pages = 15040–5 | date = December 1984 | pmid = 6439716 | doi = }}
  • {{cite journal | vauthors = Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA | title = cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed | journal = Biochemical and Biophysical Research Communications | volume = 253 | issue = 2 | pages = 415–22 | date = December 1998 | pmid = 9878551 | doi = 10.1006/bbrc.1998.9786 }}
  • {{cite journal | vauthors = Bénit P, Chretien D, Kadhom N, de Lonlay-Debeney P, Cormier-Daire V, Cabral A, Peudenier S, Rustin P, Munnich A, Rötig A | title = Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency | journal = American Journal of Human Genetics | volume = 68 | issue = 6 | pages = 1344–52 | date = June 2001 | pmid = 11349233 | pmc = 1226121 | doi = 10.1086/320603 }}
  • {{cite journal | vauthors = Ricci JE, Muñoz-Pinedo C, Fitzgerald P, Bailly-Maitre B, Perkins GA, Yadava N, Scheffler IE, Ellisman MH, Green DR | title = Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain | journal = Cell | volume = 117 | issue = 6 | pages = 773–86 | date = June 2004 | pmid = 15186778 | doi = 10.1016/j.cell.2004.05.008 }}
  • {{cite journal | vauthors = Martín MA, Blázquez A, Gutierrez-Solana LG, Fernández-Moreira D, Briones P, Andreu AL, Garesse R, Campos Y, Arenas J | title = Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene | journal = Archives of Neurology | volume = 62 | issue = 4 | pages = 659–61 | date = April 2005 | pmid = 15824269 | doi = 10.1001/archneur.62.4.659 }}
  • {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
  • {{cite journal | vauthors = Iuso A, Scacco S, Piccoli C, Bellomo F, Petruzzella V, Trentadue R, Minuto M, Ripoli M, Capitanio N, Zeviani M, Papa S | title = Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I | journal = The Journal of Biological Chemistry | volume = 281 | issue = 15 | pages = 10374–80 | date = April 2006 | pmid = 16478720 | doi = 10.1074/jbc.M513387200 }}
  • {{cite journal | vauthors = Piccoli C, Scacco S, Bellomo F, Signorile A, Iuso A, Boffoli D, Scrima R, Capitanio N, Papa S | title = cAMP controls oxygen metabolism in mammalian cells | journal = FEBS Letters | volume = 580 | issue = 18 | pages = 4539–43 | date = August 2006 | pmid = 16870178 | doi = 10.1016/j.febslet.2006.06.085 }}
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2 : Human proteins|EC 1.6.5
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