| 释义 |
- Structure
- Function
- Clinical Significance
- Interactions
- References
- External links
- Further reading
{{Infobox_gene}}Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene.[1][2] 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.[2] Structure The COX10 gene is located on the p arm of chromosome 17 in position 12 and spans 139,277 base pairs.[2] The gene produces a 48.9 kDa protein composed of 443 amino acids.[3][4] This gene has an unusually long 3' untranslated region measuring 1426 base pairs, compared to a 1329 base pair open reading frame.[5] The COX10 gene has 7 exons totaling 135 kilobases in length.[6] This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane.[2] There are hydrophilic loops between transmembrane domains II/III and VI/VII.[7] This protein is considered a constituent of the mitochondrial inner membrane.[8] 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.[6][7] 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.[7][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.[2] Interactions This protein interacts with FAM136A.[10] References 1. ^{{cite journal | vauthors = Murakami T, Reiter LT, Lupski JR | title = Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene | journal = Genomics | volume = 42 | issue = 1 | pages = 161–4 | date = May 1997 | pmid = 9177788 | pmc = | doi = 10.1006/geno.1997.4711 }}
2. ^1 2 3 4 {{cite web | title = Entrez Gene: COX10 COX10 homolog, cytochrome c oxidase assembly protein, heme A: farnesyltransferase (yeast)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1352| access-date = }}{{PD-notice}}
3. ^{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
4. ^{{cite web | url = https://amino.heartproteome.org/web/protein/Q12887 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = COX10 - Protoheme IX farnesyltransferase, mitochondrial }}
5. ^{{cite journal | vauthors = Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rötig A | title = A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency | journal = Human Molecular Genetics | volume = 9 | issue = 8 | pages = 1245–9 | date = May 2000 | pmid = 10767350 | doi = 10.1093/hmg/9.8.1245 }}
6. ^1 {{OMIM|602125|Cytochrome c Oxidase Assembly Factor COX10}}
7. ^1 2 {{cite journal | vauthors = Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA | title = 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 | journal = Human Molecular Genetics | volume = 12 | issue = 20 | pages = 2693–702 | date = October 2003 | pmid = 12928484 | doi = 10.1093/hmg/ddg284 }}
8. ^{{cite journal | vauthors = Williams SL, Valnot I, Rustin P, Taanman JW | title = Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 9 | pages = 7462–9 | date = February 2004 | pmid = 14607829 | doi = 10.1074/jbc.M309232200 }}
9. ^{{cite journal | vauthors = Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rötig A | title = A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency | journal = Human Molecular Genetics | volume = 9 | issue = 8 | pages = 1245–9 | date = May 2000 | pmid = 10767350 | doi = 10.1093/hmg/9.8.1245 }}
10. ^{{Cite web|url=https://thebiogrid.org/107745|title=COX10 Result Summary {{!}} BioGRID|last= Tyers |first=Mike | name-list-format = vanc |website=thebiogrid.org n|access-date=2018-08-07}}
External links Further reading {{refbegin | 2}}- {{cite journal | vauthors = Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, Hargreaves I, Land JM, Nanji T, Polke JM, Woodward CE, Sweeney MG, Solanki S, Foley AR, Hurles ME, Stalker J, Blake J, Holton JL, Phadke R, Muntoni F, Reilly MM, Hanna MG | display-authors = 6 | title = COX10 mutations resulting in complex multisystem mitochondrial disease that remains stable into adulthood | journal = JAMA Neurology | volume = 70 | issue = 12 | pages = 1556–61 | date = December 2013 | pmid = 24100867 | doi = 10.1001/jamaneurol.2013.3242 }}
- {{cite journal | vauthors = Glerum DM, Tzagoloff A | title = Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 18 | pages = 8452–6 | date = August 1994 | pmid = 8078902 | pmc = 44624 | doi = 10.1073/pnas.91.18.8452 }}
- {{cite journal | vauthors = Reiter LT, Murakami T, Koeuth T, Gibbs RA, Lupski JR | title = The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs | journal = Human Molecular Genetics | volume = 6 | issue = 9 | pages = 1595–603 | date = September 1997 | pmid = 9285799 | doi = 10.1093/hmg/6.9.1595 }}
- {{cite journal | vauthors = Kennerson ML, Nassif NT, Dawkins JL, DeKroon RM, Yang JG, Nicholson GA | title = The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene | journal = Genomics | volume = 46 | issue = 1 | pages = 61–9 | date = November 1997 | pmid = 9403059 | doi = 10.1006/geno.1997.5012 }}
- {{cite journal | vauthors = Kennerson ML, Nassif NT, Nicholson GA | title = Genomic structure and physical mapping of C17orf1: a gene associated with the proximal element of the CMT1A-REP binary repeat | journal = Genomics | volume = 53 | issue = 1 | pages = 110–2 | date = October 1998 | pmid = 9787083 | doi = 10.1006/geno.1998.5453 }}
- {{cite journal | vauthors = Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rötig A | title = A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency | journal = Human Molecular Genetics | volume = 9 | issue = 8 | pages = 1245–9 | date = May 2000 | pmid = 10767350 | doi = 10.1093/hmg/9.8.1245 }}
- {{cite journal | vauthors = Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Murri L, Rapoport SI, Solaini G | title = Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease | journal = Neurobiology of Aging | volume = 23 | issue = 3 | pages = 371–6 | year = 2002 | pmid = 11959398 | doi = 10.1016/S0197-4580(01)00314-1 }}
- {{cite journal | vauthors = Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA | title = 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 | journal = Human Molecular Genetics | volume = 12 | issue = 20 | pages = 2693–702 | date = October 2003 | pmid = 12928484 | doi = 10.1093/hmg/ddg284 }}
- {{cite journal | vauthors = Williams SL, Valnot I, Rustin P, Taanman JW | title = Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 9 | pages = 7462–9 | date = February 2004 | pmid = 14607829 | doi = 10.1074/jbc.M309232200 }}
- {{cite journal | vauthors = Coenen MJ, van den Heuvel LP, Ugalde C, Ten Brinke M, Nijtmans LG, Trijbels FJ, Beblo S, Maier EM, Muntau AC, Smeitink JA | title = Cytochrome c oxidase biogenesis in a patient with a mutation in COX10 gene | journal = Annals of Neurology | volume = 56 | issue = 4 | pages = 560–4 | date = October 2004 | pmid = 15455402 | doi = 10.1002/ana.20229 }}
- {{cite journal | vauthors = Veluthakal R, Kaur H, Goalstone M, Kowluru A | title = Dominant-negative alpha-subunit of farnesyl- and geranyltransferase inhibits glucose-stimulated, but not KCl-stimulated, insulin secretion in INS 832/13 cells | journal = Diabetes | volume = 56 | issue = 1 | pages = 204–10 | date = January 2007 | pmid = 17192483 | doi = 10.2337/db06-0668 }}
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