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{{Underlinked|date=July 2016}}
{{Infobox_gene}}
{{Infobox_gene}}
'''NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial''' 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 | pmc =  | doi = 10.1159/000015082 }}</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 = Apr 1995 | pmid = 7607668 | pmc =  | doi = 10.1016/0888-7543(95)80163-G }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: NDUFV2 NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4729| accessdate = }}</ref>
'''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 | pmc =  | doi = 10.1159/000015082 }}</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 | pmc =  | doi = 10.1016/0888-7543(95)80163-G }}</ref> The encoded [[protein]], NDUFV2, is a subunit of complex I of the [[Electron transport chain|mitochondrial respiratory chain]], which is located on the [[inner mitochondrial membrane]] and involved in [[oxidative phosphorylation]]. [[Mutation|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/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4729| access-date = }}{{PD-notice}}</ref>
 
== Structure ==
''NDUFV2'' is located on the [[Locus (genetics)|p arm]] of [[chromosome 18]] in position 11.22 and has 9 [[Exon|exons]].<ref name="entrez" /> The ''NDUFV2'' gene produces a 27.4 kDa protein composed of 249 [[Amino acid|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}}</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 (biochemistry)|cofactor]] binding site for a [[2Fe-2S cluster]] and a [[transit peptide]] domain. The protein consists of 2 turns, 3 [[Beta sheet|beta strands]], and 7 [[Alpha helix|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 | 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 }}</ref> A non-transcribed [[pseudogene]] of this locus is found on [[chromosome 19]].<ref name="entrez" />
 
== Function ==
The [[Respiratory complex I|NADH-ubiquinone oxidoreductase]] complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from [[Nicotinamide adenine dinucleotide|NADH]] to [[Coenzyme Q10|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 }}</ref> It is thought to be required for assembly and catalysis.<ref name=":1" /><ref name=":0" />
 
=== Catalytic activity ===
NADH + [[Coenzyme Q10|ubiquinone]] + 5 H+(In) = NAD+ + [[ubiquinol]] + 4 H+(Out).
 
NADH + acceptor = NAD+ + reduced acceptor.<ref name=":1" /><ref name=":0" />


== Clinical significance ==
== 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 = Sep 2004 | pmid = 15372108 | doi = 10.1172/JCI20683 | pmc=516258}}</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 = Jan 2004 | pmid = 14705112 | doi = 10.1002/ana.10787 }}</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 = Apr 2012 | pmid = 22499348 | doi = 10.1136/jmedgenet-2012-100846 }}</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 }}</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 | volume = 1364 | issue = 2 | pages = 271–86 | date = May 1998 | pmid = 9593934 | doi=10.1016/s0005-2728(98)00033-4}}</ref>
[[Mutation|Mutations]] in the ''NDUFV2'' gene are associated with [[Mitochondrial complex I|Mitochondrial Complex I]] Deficiency, which is [[Dominance (genetics)|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 }}</ref> Mitochondrial complex I deficiency shows extreme [[genetic heterogeneity]] and can be caused by mutation in [[Nuclear gene|nuclear-encoded genes]] or in [[Mitochondrial DNA|mitochondrial-encoded genes]]. There are no obvious [[Genotype–phenotype distinction|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 }}</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 }}</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 [[Neurodegeneration|neurodegenerative disorders]]. [[Phenotype|Phenotypes]] include [[macrocephaly]] with progressive [[leukodystrophy]], nonspecific [[encephalopathy]], [[hypertrophic cardiomyopathy]], [[myopathy]], [[liver disease]], [[Leigh disease|Leigh syndrome]], [[Leber's hereditary optic neuropathy|Leber hereditary optic neuropathy]], and some forms of [[Parkinson's disease|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 | volume = 1364 | issue = 2 | pages = 271–86 | date = May 1998 | pmid = 9593934 | doi = 10.1016/s0005-2728(98)00033-4 }}</ref>
 
== Interactions ==
NDUFV2 has been shown to have 102 binary [[Protein–protein interaction|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 ==
== References ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{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 = Apr 1989 | pmid = 2500970 | doi = 10.1021/bi00434a021 }}
* {{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 = Nov 1995 | pmid = 7488192 | doi = 10.1006/bbrc.1995.2688 }}
* {{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 = Apr 1998 | pmid = 9570948 | doi = 10.1006/geno.1997.5192 }}
* {{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 = Dec 1998 | pmid = 9878551 | doi = 10.1006/bbrc.1998.9786 }}
* {{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 = Jun 2003 | pmid = 12754703 | doi = 10.1002/humu.10225 }}
* {{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 }}
* {{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 | volume = 120B | issue = 1 | pages = 72–8 | date = Jul 2003 | pmid = 12815743 | doi = 10.1002/ajmg.b.20041 }}
* {{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 }}
* {{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 = Oct 2004 | pmid = 15450783 | doi = 10.1016/j.biopsych.2004.07.004 }}
* {{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 }}
* {{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 = Sep 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 }}
* {{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 }}
* {{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 | volume = 141B | issue = 3 | pages = 301–4 | date = Apr 2006 | pmid = 16508936 | doi = 10.1002/ajmg.b.30285 }}
* {{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 }}
{{refend}}
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{{Portal bar|Mitochondria|Gene Wiki|border=no}}


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[[Category:Biology of bipolar disorder]]
[[Category:Biology of bipolar disorder]]
[[Category:Human proteins]]
[[Category:Human proteins]]
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Latest revision as of 09:03, 9 January 2019

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NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial (NDUFV2) is an enzyme that in humans is encoded by the NDUFV2 gene.[1][2] 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.[3]

Structure

NDUFV2 is located on the p arm of chromosome 18 in position 11.22 and has 9 exons.[3] The NDUFV2 gene produces a 27.4 kDa protein composed of 249 amino acids.[4][5] 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.[6][7] A non-transcribed pseudogene of this locus is found on chromosome 19.[3]

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.[3] NDUFV2 is an oxidoreductase and a component of the flavoprotein-sulfur (FP) fragment of the enzyme.[8] It is thought to be required for assembly and catalysis.[6][7]

Catalytic activity

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

NADH + acceptor = NAD+ + reduced acceptor.[6][7]

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.[9][10] 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.[11] However, the majority of cases are caused by mutations in nuclear-encoded genes.[12][13] 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.[14]

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.[15]


References

  1. ↑ Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenetics and Cell Genetics. 82 (1–2): 115–9. doi:10.1159/000015082. PMID 9763677.
  2. ↑ de Coo R, Buddiger P, Smeets H, Geurts van Kessel A, Morgan-Hughes J, Weghuis DO, Overhauser J, van Oost B (April 1995). "Molecular cloning and characterization of the active human mitochondrial NADH:ubiquinone oxidoreductase 24-kDa gene (NDUFV2) and its pseudogene". Genomics. 26 (3): 461–6. doi:10.1016/0888-7543(95)80163-G. PMID 7607668.
  3. ↑ 3.0 3.1 3.2 3.3 "Entrez Gene: NDUFV2 NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa". This article incorporates text from this source, which is in the public domain.
  4. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-27.
  5. ↑ 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): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  6. ↑ 6.0 6.1 6.2 "NDUFV2 - NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial precursor - Homo sapiens (Human) - NDUFV2 gene & protein". www.uniprot.org. Retrieved 2018-08-27.File:CC-BY-icon-80x15.png This article incorporates text available under the CC BY 4.0 license.
  7. ↑ 7.0 7.1 7.2 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  8. ↑ Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA (April 2003). "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification". The Journal of Biological Chemistry. 278 (16): 13619–22. doi:10.1074/jbc.C300064200. PMID 12611891.
  9. ↑ 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): 837–45. doi:10.1172/JCI20683. PMC 516258. PMID 15372108.
  10. ↑ 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.
  11. ↑ 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". Journal of Medical Genetics. 49 (4): 277–83. doi:10.1136/jmedgenet-2012-100846. PMID 22499348.
  12. ↑ 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): 123–34. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489.
  13. ↑ 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.
  14. ↑ 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. 1364 (2): 271–86. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
  15. ↑ "102 binary interactions found for search term NDUFV2". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-27.

Further reading

  • Pilkington SJ, Walker JE (April 1989). "Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of import precursors of the bovine and human 24-kDa subunit". Biochemistry. 28 (8): 3257–64. doi:10.1021/bi00434a021. PMID 2500970.
  • Hattori N, Suzuki H, Wang Y, Minoshima S, Shimizu N, Yoshino H, Kurashima R, Tanaka M, Ozawa T, Mizuno Y (November 1995). "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". Biochemical and Biophysical Research Communications. 216 (3): 771–7. doi:10.1006/bbrc.1995.2688. PMID 7488192.
  • Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y (April 1998). "Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease". Genomics. 49 (1): 52–8. doi:10.1006/geno.1997.5192. PMID 9570948.
  • Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (December 1998). "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications. 253 (2): 415–22. doi:10.1006/bbrc.1998.9786. PMID 9878551.
  • 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 (June 2003). "Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy". Human Mutation. 21 (6): 582–6. doi:10.1002/humu.10225. PMID 12754703.
  • Washizuka S, Kakiuchi C, Mori K, Kunugi H, Tajima O, Akiyama T, Nanko S, Kato T (July 2003). "Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 120B (1): 72–8. doi:10.1002/ajmg.b.20041. PMID 12815743.
  • 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 (October 2004). "Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder in Japanese and the National Institute of Mental Health pedigrees". Biological Psychiatry. 56 (7): 483–9. doi:10.1016/j.biopsych.2004.07.004. PMID 15450783.
  • 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 (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
  • Washizuka S, Kametani M, Sasaki T, Tochigi M, Umekage T, Kohda K, Kato T (April 2006). "Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 141B (3): 301–4. doi:10.1002/ajmg.b.30285. PMID 16508936.

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