NDUFV1

Last updated
NDUFV1
Identifiers
Aliases NDUFV1 , CI-51K, CI51KD, UQOR1, NADH:ubiquinone oxidoreductase core subunit V1, MC1DN4
External IDs OMIM: 161015 MGI: 107851 HomoloGene: 5151 GeneCards: NDUFV1
Orthologs
SpeciesHumanMouse
Entrez

4723

17995

Ensembl

ENSG00000167792

ENSMUSG00000037916

UniProt

P49821

Q91YT0

RefSeq (mRNA)

NM_007103
NM_001166102

NM_133666

RefSeq (protein)

NP_001159574
NP_009034

NP_598427

Location (UCSC) Chr 11: 67.61 – 67.61 Mb Chr 19: 4.06 – 4.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial (NDUFV1) is an enzyme that in humans is encoded by the NDUFV1 gene. [5] The NDUFV1 gene encodes the 51-kD subunit of complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain. Defects in complex I are a common cause of mitochondrial dysfunction. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. [6]

Contents

Structure

NDUFV1 is located on the q arm of chromosome 11 in position 13.2 and has 10 exons. [6] The NDUFV1 gene produces a 50.8 kDa protein composed of 464 amino acids. [7] [8] 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. [6] It also contains a transit peptide domain and is composed of 6 turns, 14 beta strands, and 19 alpha helixes. [9] [10]

Function

Complex I is composed of 45 different subunits. NDUFV1 is a component of the flavoprotein-sulfur (FP) fragment of the enzyme. [11] 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. [9] [10]

Catalytic Activity

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

NADH + acceptor = NAD+ + reduced acceptor. [9] [10]

Clinical significance

Mutations 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. [12] [13] 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. [14] However, the majority of cases are caused by mutations in nuclear-encoded genes. [15] [16] 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. [17] Clinical manifestations can include lactic acidosis, cerebral degeneration, ophthalmoplegia, ataxia, spasticity, and dystonia resulting from mutations in NDUFV1. [18] [19]

Interactions

NDUFV1 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. [20]

Related Research Articles

<span class="mw-page-title-main">NDUFS4</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial (NDUFS4) also known as NADH-ubiquinone oxidoreductase 18 kDa subunit is an enzyme that in humans is encoded by the NDUFS4 gene. This gene encodes a nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome.

<span class="mw-page-title-main">NDUFS3</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial is an enzyme that in humans is encoded by the NDUFS3 gene on chromosome 11. This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase. Mutations in this gene are associated with Leigh syndrome resulting from mitochondrial complex I deficiency.

<span class="mw-page-title-main">NDUFS8</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial also known as NADH-ubiquinone oxidoreductase 23 kDa subunit, Complex I-23kD (CI-23kD), or TYKY subunit is an enzyme that in humans is encoded by the NDUFS8 gene. The NDUFS8 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with Leigh syndrome.

<span class="mw-page-title-main">NDUFS2</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Mutations in this gene are associated with mitochondrial complex I deficiency.

<span class="mw-page-title-main">NADH dehydrogenase (ubiquinone), alpha 1</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 is a protein that in humans is encoded by the NDUFA1 gene. The NDUFA1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in the NDUFA1 gene are associated with mitochondrial Complex I deficiency.

<span class="mw-page-title-main">NDUFS1</span> Protein-coding gene in the species Homo sapiens

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene. 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.

<span class="mw-page-title-main">NDUFV2</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">NDUFS7</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial, also knowns as NADH-ubiquinone oxidoreductase 20 kDa subunit, Complex I-20kD (CI-20kD), or PSST subunit is an enzyme that in humans is encoded by the NDUFS7 gene. The NDUFS7 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFB6</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6, also known as complex I-B17, is a protein that in humans is encoded by the NDUFB6 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6, is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFA2</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 is a protein that in humans is encoded by the NDUFA2 gene. The NDUFA2 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in the NDUFA2 gene are associated with Leigh's syndrome.

<span class="mw-page-title-main">NDUFA9</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFA9 gene. The NDUFA9 protein is a subunit of NADH:ubiquinone oxidoreductase, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. In the case of NDUFA9, a mutation to the MT-ND3 gene might interrupt their interaction and formation of subcomplexes, compromising Complex I function and leading to disease.

<span class="mw-page-title-main">NDUFS6</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial is an enzyme that in humans is encoded by the NDUFS6 gene.

<span class="mw-page-title-main">NDUFA8</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 is an enzyme that in humans is encoded by the NDUFA8 gene. The NDUFA8 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFS5</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 is an enzyme that in humans is encoded by the NDUFS5 gene.

<span class="mw-page-title-main">NDUFA10</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFA10 gene. The NDUFA10 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Furthermore, reduced NDUFA10 expression levels due to FOXM1-directed hypermethylation are associated with human squamous cell carcinoma and may be related to other forms of cancer.

<span class="mw-page-title-main">NDUFB2</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial is an enzyme that in humans is encoded by the NDUFB2 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2, 8kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFB7</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7, also known as complex I-B18, is an enzyme that in humans is encoded by the NDUFB7 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 7 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

In molecular biology, the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 7 family of proteins form a part of NADH dehydrogenase. In mammals, it is encoded by the NDUFA7 gene.

<span class="mw-page-title-main">NDUFA4</span> Protein-coding gene in the species Homo sapiens

NDUFA4, mitochondrial complex associated is a protein that in humans is encoded by the NDUFA4 gene. The NDUFA4 protein was first described to be a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. However, recent research has described NDUFA4 as a subunit of cytochrome c oxidase. Mutations in the NDUFA4 gene are associated with Leigh's syndrome.

<span class="mw-page-title-main">NDUFA11</span> Protein and coding gene in humans

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 is an enzyme that in humans is encoded by the NDUFA11 gene. The NDUFA11 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Mutations in this gene are associated with severe mitochondrial complex I deficiency.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167792 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037916 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Spencer SR, Taylor JB, Cowell IG, Xia CL, Pemble SE, Ketterer B (December 1992). "The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase P1-1 gene on chromosome 11q13". Genomics. 14 (4): 1116–8. doi:10.1016/S0888-7543(05)80144-2. PMID   1478657.
  6. 1 2 3 "Entrez Gene: NDUFV1 NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa".PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-27.
  8. ↑ 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.
  9. 1 2 3 "NDUFV1 - NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial precursor - Homo sapiens (Human) - NDUFV1 gene & protein". www.uniprot.org. Retrieved 2018-08-27. Creative Commons by small.svg  This article incorporates text available under the CC BY 4.0 license.
  10. 1 2 3 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC   5210571 . PMID   27899622.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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. S2CID   21076359.
  14. ↑ 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" (PDF). Journal of Medical Genetics. 49 (4): 277–83. doi:10.1136/jmedgenet-2012-100846. PMID   22499348. S2CID   3177674.
  15. ↑ 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. S2CID   35579133.
  16. ↑ 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.
  17. ↑ 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 (BBA) - Bioenergetics. 1364 (2): 271–86. doi: 10.1016/s0005-2728(98)00033-4 . PMID   9593934.
  18. ↑ Zafeiriou DI, Rodenburg RJ, Scheffer H, van den Heuvel LP, Pouwels PJ, Ververi A, Athanasiadou-Piperopoulou F, van der Knaap MS (June 2008). "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". Neuropediatrics. 39 (3): 172–5. doi:10.1055/s-0028-1093336. PMID   18991197. S2CID   260240393.
  19. ↑ Laugel V, This-Bernd V, Cormier-Daire V, Speeg-Schatz C, de Saint-Martin A, Fischbach M (January 2007). "Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations". Pediatric Neurology. 36 (1): 54–7. doi:10.1016/j.pediatrneurol.2006.08.007. PMID   17162199.
  20. ↑ "103 binary interactions found for search term NDUFV1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-27.

Further reading

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