词条 | NDUFV1 |
释义 |
StructureNDUFV1 is located on the q arm of chromosome 11 in position 13.2 and has 10 exons.[2] The NDUFV1 gene produces a 50.8 kDa protein composed of 464 amino acids.[3][4] NDUFV1, the protein encoded by this gene, is a member of the complex I 51 kDa subunit family. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-binding sites.[2] It also contains a transit peptide domain and is composed of 6 turns, 14 beta strands, and 19 alpha helixes.[5][6]FunctionComplex I is composed of 45 different subunits. NDUFV1 is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.[7] NDUFV1 is an oxidoreductase and core subunit of complex I that is thought to be required for assembly and catalysis. It is a peripheral membrane protein located on the matrix side of the mitochondrion inner membrane.[5][6]Catalytic ActivityNADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out). NADH + acceptor = NAD+ + reduced acceptor.[5][6] Clinical significanceMutations in the NDUFV1 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] Clinical manifestations can include lactic acidosis, cerebral degeneration, ophthalmoplegia, ataxia, spasticity, and dystonia resulting from mutations in NDUFV1.[14][15] InteractionsNDUFV1 has been shown to have 103 binary protein-protein interactions including 97 co-complex interactions. NDUFV1 appears to interact with EWSR1, CREB1, NCOR1, and VDAC1.[16] References1. ^{{cite journal | vauthors = Spencer SR, Taylor JB, Cowell IG, Xia CL, Pemble SE, Ketterer B | title = The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase P1-1 gene on chromosome 11q13 | journal = Genomics | volume = 14 | issue = 4 | pages = 1116–8 | date = December 1992 | pmid = 1478657 | pmc = | doi = 10.1016/S0888-7543(05)80144-2 }} 2. ^1 2 {{cite web | title = Entrez Gene: NDUFV1 NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4723| access-date = }}{{PD-notice}} 3. ^{{Cite web|url=https://amino.heartproteome.org/web/protein/P49821|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-08-27}} 4. ^{{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 | 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 }} 5. ^1 2 {{Cite web|url=https://www.uniprot.org/uniprot/P49821|title=NDUFV1 - NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial precursor - Homo sapiens (Human) - NDUFV1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-27}}{{CC-notice|cc=by4}} 6. ^1 2 {{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 }} 7. ^{{cite journal | vauthors = Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA | title = The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification | journal = The Journal of Biological Chemistry | volume = 278 | issue = 16 | pages = 13619–22 | date = April 2003 | pmid = 12611891 | doi = 10.1074/jbc.C300064200 }} 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 journal | vauthors = Zafeiriou DI, Rodenburg RJ, Scheffer H, van den Heuvel LP, Pouwels PJ, Ververi A, Athanasiadou-Piperopoulou F, van der Knaap MS | title = MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course | journal = Neuropediatrics | volume = 39 | issue = 3 | pages = 172–5 | date = June 2008 | pmid = 18991197 | doi = 10.1055/s-0028-1093336 }} 15. ^{{cite journal | vauthors = Laugel V, This-Bernd V, Cormier-Daire V, Speeg-Schatz C, de Saint-Martin A, Fischbach M | title = Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations | journal = Pediatric Neurology | volume = 36 | issue = 1 | pages = 54–7 | date = January 2007 | pmid = 17162199 | doi = 10.1016/j.pediatrneurol.2006.08.007 }} 16. ^{{cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFV1 | title = 103 binary interactions found for search term NDUFV1 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-27 }} Further reading{{refbegin | 2}}
2 : Human proteins|EC 1.6.5 |
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