COX10

Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene.[5][6] Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene, COX10, encodes heme A: farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion.[6]

COX10
Identifiers
AliasesCOX10, heme A:farnesyltransferase cytochrome c oxidase assembly factor, cytochrome c oxidase assembly factor heme A:farnesyltransferase MC4DN3
External IDsOMIM: 602125 MGI: 1917633 HomoloGene: 80170 GeneCards: COX10
Orthologs
SpeciesHumanMouse
Entrez

1352

70383

Ensembl

ENSG00000006695

ENSMUSG00000042148

UniProt

Q12887

Q8CFY5

RefSeq (mRNA)

NM_001303

NM_178379

RefSeq (protein)

NP_001294

NP_848466

Location (UCSC)Chr 17: 14.07 – 14.23 MbChr 11: 63.85 – 63.97 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

The COX10 gene is located on the p arm of chromosome 17 in position 12 and spans 139,277 base pairs.[6] The gene produces a 48.9 kDa protein composed of 443 amino acids.[7][8] This gene has an unusually long 3' untranslated region measuring 1426 base pairs, compared to a 1329 base pair open reading frame.[9] The COX10 gene has 7 exons totaling 135 kilobases in length.[10] This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane.[6] There are hydrophilic loops between transmembrane domains II/III and VI/VII.[11] This protein is considered a constituent of the mitochondrial inner membrane.[12]

Function

The protein encoded by COX10 is an assembly factor essential to COX synthesis, participating in the first step of the mitochondrial heme A biosynthetic pathway. It catalyzes the farnesylation of the vinyl group at position C2 of protoheme (heme B) and converts it to heme O.[10][11]

Clinical Significance

Mutations in the COX10 gene can result in numerous clinical phenotypes, from tubulopathy and leukodystrophy to Leigh syndrome to fatal infantile cardiomyopathy to a French Canadian form of Leigh Syndrome. A wide variety of symptoms encompassing the entire range of COX deficiency symptoms have been reported, including ataxia, hypotonia, ptosis, lactic acidosis, proximal tubulopathy, anemia, myopathy, hypertrophic cardiomyopathy, sensorineural hearing loss, and leukodystrophy.[11][9]

In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion.[6]

Interactions

This protein interacts with FAM136A.[13]

References

  1. GRCh38: Ensembl release 89: ENSG00000006695 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000042148 - 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. Murakami T, Reiter LT, Lupski JR (May 1997). "Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene". Genomics. 42 (1): 161–4. doi:10.1006/geno.1997.4711. PMID 9177788.
  6. "Entrez Gene: COX10 COX10 homolog, cytochrome c oxidase assembly protein, heme A: farnesyltransferase (yeast)".Public Domain This article incorporates text from this source, which is in the public domain.
  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 (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.
  8. "COX10 - Protoheme IX farnesyltransferase, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  9. Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rötig A (May 2000). "A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency". Human Molecular Genetics. 9 (8): 1245–9. doi:10.1093/hmg/9.8.1245. PMID 10767350.
  10. Online Mendelian Inheritance in Man (OMIM): Cytochrome c Oxidase Assembly Factor COX10 - 602125
  11. Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA (October 2003). "Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency". Human Molecular Genetics. 12 (20): 2693–702. doi:10.1093/hmg/ddg284. PMID 12928484.
  12. Williams SL, Valnot I, Rustin P, Taanman JW (February 2004). "Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1". The Journal of Biological Chemistry. 279 (9): 7462–9. doi:10.1074/jbc.M309232200. PMID 14607829.
  13. Tyers M. "COX10 Result Summary | BioGRID". thebiogrid.org n. Retrieved 2018-08-07.

Further reading

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

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