The COXFA4 gene is located on the p arm of chromosome 7 at position 21.3 with a total length of 8,234 base pairs. The COXFA4 gene produces a 9.4 kDa protein composed of 81 amino acids.
COXFA4 (then called NDUFA4) was previously believed to be 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 COXFA4 deletion, calling into question its role in this complex. It has been demonstrated that COXFA4 plays a role in Complex IV function and biogenesis, however, with some authors suggesting that the COXFA4 gene be renamed and the structure of both Complex I and Complex IV be re-evaluated.
Clinical significance
Mutations in the COXFA4 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 COXFA4 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.
Interactions
COXFA4 has many protein-protein interactions, including ubiquitin proteins such as ubiquitin C and UBL4A, as well as CUL3 and PARK7.
↑Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry: life at the molecular level (4thed.). Hoboken, NJ: Wiley. pp.581–620. ISBN9780470547847.{{cite book}}: CS1 maint: multiple names: authors list (link)
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