COX10

COX10
Identifiers
Aliases	COX10, heme A:farnesyltransferase cytochrome c oxidase assembly factor, cytochrome c oxidase assembly factor heme A:farnesyltransferase MC4DN3
External IDs	OMIM: 602125 MGI: 1917633 HomoloGene: 80170 GeneCards: COX10
Gene location (Human) Chr. Chromosome 17 (human) Band 17p12 Start 14,069,490 bp End 14,231,736 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B3 Start 63,853,453 bp End 63,970,294 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibialis anterior muscle thoracic diaphragm deltoid muscle gastrocnemius muscle triceps brachii muscle vastus lateralis muscle secondary oocyte biceps brachii sperm right ventricle Top expressed in interventricular septum secondary oocyte myocardium of ventricle skeletal muscle tissue extraocular muscle digastric muscle upper arm temporal muscle triceps brachii muscle morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity farnesyltranstransferase activity cytochrome-c oxidase activity protoheme IX farnesyltransferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups Cellular component integral component of membrane membrane mitochondrial membranes cytochrome complex mitochondrial inner membrane nucleolus mitochondrion cytosol Biological process cytochrome complex assembly mitochondrial fission mitochondrion organization heme biosynthetic process aerobic respiration mitochondrial electron transport, cytochrome c to oxygen respiratory chain complex IV assembly cellular respiration heme O biosynthetic process heme A biosynthetic process proton transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 11: 63.85 – 63.97 Mb PubMed search
Wikidata
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Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene. 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.

Structure

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

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.

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.

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.

Interactions

This protein interacts with FAM136A.

External links

• Human COX10 genome location and COX10 gene details page in the UCSC Genome Browser.

Further reading

• Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, et al. (December 2013). "COX10 mutations resulting in complex multisystem mitochondrial disease that remains stable into adulthood". JAMA Neurology. 70 (12): 1556–61. doi:10.1001/jamaneurol.2013.3242. PMID 24100867.
• Glerum DM, Tzagoloff A (August 1994). "Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8452–6. Bibcode:1994PNAS...91.8452G. doi:10.1073/pnas.91.18.8452. PMC 44624. PMID 8078902.
• Reiter LT, Murakami T, Koeuth T, Gibbs RA, Lupski JR (September 1997). "The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs". Human Molecular Genetics. 6 (9): 1595–603. doi:10.1093/hmg/6.9.1595. PMID 9285799.
• Kennerson ML, Nassif NT, Dawkins JL, DeKroon RM, Yang JG, Nicholson GA (November 1997). "The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene". Genomics. 46 (1): 61–9. doi:10.1006/geno.1997.5012. PMID 9403059.
• Kennerson ML, Nassif NT, Nicholson GA (October 1998). "Genomic structure and physical mapping of C17orf1: a gene associated with the proximal element of the CMT1A-REP binary repeat". Genomics. 53 (1): 110–2. doi:10.1006/geno.1998.5453. PMID 9787083.
• 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.
• Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Murri L, Rapoport SI, Solaini G (2002). "Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease". Neurobiology of Aging. 23 (3): 371–6. doi:10.1016/S0197-4580(01)00314-1. PMID 11959398. S2CID 5621542.
• 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.
• 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.
• Coenen MJ, van den Heuvel LP, Ugalde C, Ten Brinke M, Nijtmans LG, Trijbels FJ, Beblo S, Maier EM, Muntau AC, Smeitink JA (October 2004). "Cytochrome c oxidase biogenesis in a patient with a mutation in COX10 gene". Annals of Neurology. 56 (4): 560–4. doi:10.1002/ana.20229. PMID 15455402. S2CID 2348661.
• Veluthakal R, Kaur H, Goalstone M, Kowluru A (January 2007). "Dominant-negative alpha-subunit of farnesyl- and geranyltransferase inhibits glucose-stimulated, but not KCl-stimulated, insulin secretion in INS 832/13 cells". Diabetes. 56 (1): 204–10. doi:10.2337/db06-0668. PMID 17192483. S2CID 25460768.

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