Biology:NDUFV2

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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. ↑ "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. Nov 1998. doi:10.1159/000015082. PMID 9763677. 
  2. ↑ "Molecular cloning and characterization of the active human mitochondrial NADH:ubiquinone oxidoreductase 24-kDa gene (NDUFV2) and its pseudogene". Genomics 26 (3): 461–6. April 1995. 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". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4729.  This article incorporates text from this source, which is in the public domain.
  4. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/P19404. 
  5. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  6. ↑ 6.0 6.1 6.2 "NDUFV2 - NADH dehydrogenase [ubiquinone flavoprotein 2, mitochondrial precursor - Homo sapiens (Human) - NDUFV2 gene & protein"] (in en). https://www.uniprot.org/uniprot/P19404.  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. PMID 27899622. 
  8. ↑ "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification". The Journal of Biological Chemistry 278 (16): 13619–22. April 2003. doi:10.1074/jbc.C300064200. PMID 12611891. 
  9. ↑ "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. September 2004. doi:10.1172/JCI20683. PMID 15372108. 
  10. ↑ "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. January 2004. doi:10.1002/ana.10787. PMID 14705112. 
  11. ↑ "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–83. April 2012. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf. 
  12. ↑ "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–34. 2000. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. 
  13. ↑ "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. 2001. doi:10.1002/ajmg.1397. PMID 11579423. 
  14. ↑ "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): 271–86. May 1998. 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. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFV2. 

Further reading

  • "Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of import precursors of the bovine and human 24-kDa subunit". Biochemistry 28 (8): 3257–64. April 1989. doi:10.1021/bi00434a021. PMID 2500970. 
  • "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. November 1995. doi:10.1006/bbrc.1995.2688. PMID 7488192. 
  • "Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease". Genomics 49 (1): 52–8. April 1998. doi:10.1006/geno.1997.5192. PMID 9570948. 
  • "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. December 1998. doi:10.1006/bbrc.1998.9786. PMID 9878551. 
  • "Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy". Human Mutation 21 (6): 582–6. June 2003. doi:10.1002/humu.10225. PMID 12754703. 
  • "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. July 2003. doi:10.1002/ajmg.b.20041. PMID 12815743. 
  • "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. October 2004. doi:10.1016/j.biopsych.2004.07.004. PMID 15450783. 
  • "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. September 2005. doi:10.1016/j.cell.2005.08.029. PMID 16169070. 
  • "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. April 2006. doi:10.1002/ajmg.b.30285. PMID 16508936. 

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



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:NDUFV2&oldid=3645841"