NDUFV2

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial (NDUFV2)''' is an enzyme that in humans is encoded by the ''NDUFV2'' gene.<ref name="pmid9763677">{{cite journal | vauthors = Emahazion T, Beskow A, Gyllensten U, Brookes AJ | title = Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain | journal = Cytogenetics and Cell Genetics | volume = 82 | issue = 1–2 | pages = 115–9 | date = Nov 1998 | pmid = 9763677 | doi = 10.1159/000015082 | s2cid = 46818955 }}</ref><ref name="pmid7607668">{{cite journal | vauthors = de Coo R, Buddiger P, Smeets H, Geurts van Kessel A, Morgan-Hughes J, Weghuis DO, Overhauser J, van Oost B | title = Molecular cloning and characterization of the active human mitochondrial NADH:ubiquinone oxidoreductase 24-kDa gene (NDUFV2) and its pseudogene | journal = Genomics | volume = 26 | issue = 3 | pages = 461–6 | date = April 1995 | pmid = 7607668 | doi = 10.1016/0888-7543(95)80163-G | s2cid = 6919815 }}</ref> The encoded protein, NDUFV2, is a subunit of complex I of the mitochondrial respiratory chain, which is located on the inner mitochondrial membrane and involved in oxidative phosphorylation. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy.<ref name="entrez">{{cite web | title = Entrez Gene: NDUFV2 NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4729}}{{PD-notice}}</ref>

== Structure == ''NDUFV2'' is located on the p arm of chromosome 18 in position 11.22 and has 9 exons.<ref name="entrez" /> The ''NDUFV2'' gene produces a 27.4 kDa protein composed of 249 amino acids.<ref>{{Cite web|url=https://amino.heartproteome.org/web/protein/P19404|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-08-27}}{{Dead link|date=July 2025 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref>{{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 }}</ref> NDUFV2, the protein encoded by this gene, is a member of the complex I 24 kDa subunit family. It contains a cofactor binding site for a 2Fe-2S cluster and a transit peptide domain. The protein consists of 2 turns, 3 beta strands, and 7 alpha helixes.<ref name=":1">{{Cite web|url=https://www.uniprot.org/uniprot/P19404|title=NDUFV2 - NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial precursor - Homo sapiens (Human) - NDUFV2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-27}}{{CC-notice|cc=by4}}</ref><ref name=":0">{{cite journal | 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 }}</ref> A non-transcribed pseudogene of this locus is found on chromosome 19.<ref name="entrez" />

== Function == The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes the 24 kDa subunit of complex I, and is involved in electron transfer.<ref name="entrez" /> NDUFV2 is an oxidoreductase and a component of the flavoprotein-sulfur (FP) fragment of the enzyme.<ref>{{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 | doi-access = free }}</ref> It is thought to be required for assembly and catalysis.<ref name=":1" /><ref name=":0" />

=== Catalytic activity === NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).

NADH + acceptor = NAD+ + reduced acceptor.<ref name=":1" /><ref name=":0" />

== Clinical significance ==

Mutations in the ''NDUFV2'' 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.<ref>{{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 }}</ref><ref>{{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 | s2cid = 21076359 }}</ref> 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.<ref>{{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 | s2cid = 3177674 | url = https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf }}</ref> However, the majority of cases are caused by mutations in nuclear-encoded genes.<ref>{{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 | s2cid = 35579133 | doi-access = free }}</ref><ref>{{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 }}</ref> 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.<ref>{{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 (BBA) - Bioenergetics | volume = 1364 | issue = 2 | pages = 271–86 | date = May 1998 | pmid = 9593934 | doi = 10.1016/s0005-2728(98)00033-4 | doi-access = free }}</ref>

== Interactions == NDUFV2 has been shown to have 102 binary protein-protein interactions including 80 co-complex interactions. NDUFV2 appears to interact with HSCB, CCNC, GOLM1, FAM114A2, CRMP1, KAT5, SP110.<ref>{{cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFV2 | title = 102 binary interactions found for search term NDUFV2 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-27 }}</ref>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Pilkington SJ, Walker JE | title = Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of import precursors of the bovine and human 24-kDa subunit | journal = Biochemistry | volume = 28 | issue = 8 | pages = 3257–64 | date = April 1989 | pmid = 2500970 | doi = 10.1021/bi00434a021 }} * {{cite journal | vauthors = Hattori N, Suzuki H, Wang Y, Minoshima S, Shimizu N, Yoshino H, Kurashima R, Tanaka M, Ozawa T, Mizuno Y | title = Structural organization and chromosomal localization of the human nuclear gene (NDUFV2) for the 24-kDa iron-sulfur subunit of complex I in mitochondrial respiratory chain | journal = Biochemical and Biophysical Research Communications | volume = 216 | issue = 3 | pages = 771–7 | date = November 1995 | pmid = 7488192 | doi = 10.1006/bbrc.1995.2688 }} * {{cite journal | vauthors = Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y | title = Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease | journal = Genomics | volume = 49 | issue = 1 | pages = 52–8 | date = April 1998 | pmid = 9570948 | doi = 10.1006/geno.1997.5192 }} * {{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, Beugnot R, Chretien D, Giurgea I, De Lonlay-Debeney P, Issartel JP, Corral-Debrinski M, Kerscher S, Rustin P, Rötig A, Munnich A | title = Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy | journal = Human Mutation | volume = 21 | issue = 6 | pages = 582–6 | date = June 2003 | pmid = 12754703 | doi = 10.1002/humu.10225 | s2cid = 19514743 | doi-access = free }} * {{cite journal | vauthors = Washizuka S, Kakiuchi C, Mori K, Kunugi H, Tajima O, Akiyama T, Nanko S, Kato T | title = Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 120B | issue = 1 | pages = 72–8 | date = July 2003 | pmid = 12815743 | doi = 10.1002/ajmg.b.20041 | s2cid = 10851458 }} * {{cite journal | vauthors = Washizuka S, Iwamoto K, Kazuno AA, Kakiuchi C, Mori K, Kametani M, Yamada K, Kunugi H, Tajima O, Akiyama T, Nanko S, Yoshikawa T, Kato T | title = Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder in Japanese and the National Institute of Mental Health pedigrees | journal = Biological Psychiatry | volume = 56 | issue = 7 | pages = 483–9 | date = October 2004 | pmid = 15450783 | doi = 10.1016/j.biopsych.2004.07.004 | s2cid = 35140676 }} * {{cite journal | vauthors = Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE | title = A human protein-protein interaction network: a resource for annotating the proteome | journal = Cell | volume = 122 | issue = 6 | pages = 957–68 | date = September 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 | hdl = 11858/00-001M-0000-0010-8592-0 | s2cid = 8235923 | hdl-access = free }} * {{cite journal | vauthors = Washizuka S, Kametani M, Sasaki T, Tochigi M, Umekage T, Kohda K, Kato T | title = Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 141B | issue = 3 | pages = 301–4 | date = April 2006 | pmid = 16508936 | doi = 10.1002/ajmg.b.30285 | s2cid = 34154064 | doi-access = free }} {{refend}}

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{{DEFAULTSORT:Ndufv2}} Category:Biology of bipolar disorder Category:Human proteins