NDUFA4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNDUFA4, CI-9k, CI-MLRQ, MLRQ, mitochondrial complex associated, COXFA4, NDUFA4 mitochondrial complex associated, MC4DN21, MRCAF1, MISTR1
External IDsOMIM: 603833 MGI: 107686 HomoloGene: 37629 GeneCards: NDUFA4
Orthologs
SpeciesHumanMouse
Entrez

4697

17992

Ensembl

ENSG00000189043

ENSMUSG00000029632

UniProt

O00483

Q62425

RefSeq (mRNA)

NM_002489

NM_010886

RefSeq (protein)

NP_002480

NP_035016

Location (UCSC)Chr 7: 10.93 – 10.94 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

NDUFA4, mitochondrial complex associated is a protein that in humans is encoded by the NDUFA4 gene.[4] 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.[5] However, recent research has described NDUFA4 as a subunit of cytochrome c oxidase.[6] Mutations in the NDUFA4 gene are associated with Leigh's syndrome.[4]

Structure

The NDUFA4 gene is located on the p arm of chromosome 7 at position 21.3 with a total length of 8,234 base pairs.[4] The NDUFA4 gene produces a 9.4 kDa protein composed of 81 amino acids.[7][8]

NDUFA4 has traditionally been defined as a subunit of the enzyme NADH dehydrogenase (ubiquinone) (Complex I), the largest of the respiratory complexes.

More recent research has demonstrated that no perturbation of Complex I occurs upon NDUFA4 deletion, calling into question its role in this complex. It has been demonstrated that NDUFA4 plays a role in Complex IV function and biogenesis, however, with some authors suggesting that the NDUFA4 gene be renamed and the structure of both Complex I and Complex IV be re-evaluated.[6]

Clinical significance

Mutations in the NDUFA4 gene can result in Leigh's syndrome, a severe neurological disorder that typically arises in the first year of life. Disruption of Complex IV, also called cytochrome c oxidase or COX, is the most common cause of Leigh syndrome. Given that NDUFA4 has only recently been identified as a subunit of Complex IV rather than Complex I, patients with previously unexplained COX deficiencies could be genetically tested for NDUFA4 mutations.[4][9][10]

Interactions

NDUFA4 has many protein-protein interactions, including ubiquitin proteins such as ubiquitin C and UBL4A, as well as CUL3 and PARK7.[4]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000189043 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. 1 2 3 4 5 "Entrez Gene: NDUFA4, mitochondrial complex associated". Retrieved 2015-03-24.
  5. ↑ Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.{{cite book}}: CS1 maint: multiple names: authors list (link)
  6. 1 2 Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO, Enríquez JA (Sep 2012). "NDUFA4 is a subunit of complex IV of the mammalian electron transport chain". Cell Metabolism. 16 (3): 378–386. doi:10.1016/j.cmet.2012.07.015. PMID 22902835.
  7. ↑ 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 (Oct 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.
  8. ↑ "NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  9. ↑ "Leigh syndrome". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 30 March 2015.
  10. ↑ Pitceathly RD, Rahman S, Wedatilake Y, Polke JM, Cirak S, Foley AR, Sailer A, Hurles ME, Stalker J, Hargreaves I, Woodward CE, Sweeney MG, Muntoni F, Houlden H, Taanman JW, Hanna MG (Jun 2013). "NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease". Cell Reports. 3 (6): 1795–805. doi:10.1016/j.celrep.2013.05.005. PMC 3701321. PMID 23746447.

Further reading

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