COQ7

The clk-1 (Clock abnormal protein 1) gene encodes an enzyme (demethoxyubiquinone mono-oxygenase) that is necessary for ubiquinone biosynthesis in the worm C. elegans and other eukaryotes. The mouse version of the gene is called mclk1 and the human, fruit fly and yeast homolog COQ7 (Coenzyme Q biosynthesis protein 7 homolog).

Clk-1 is not to be confused with the unrelated CLK1 human gene which plays a role in RNA splicing.

Structure

In 1999, Zoltan Vajo et al. cloned COQ7 from human heart. They found that the human COQ7 protein contains 179 amino acids, is mostly helical, and contains an alpha-helical membrane insertion. It has a potential N-glycosylation site, a phosphorylation site for protein kinase C and another for casein kinase II, and 3 N-myristoylation sites. Northern blot analysis detected 3 transcripts; a 1-kb transcript was predominant in heart, and a 3-kb transcript was predominant in skeletal muscle, kidney, and pancreas.

The protein has two repeats of about 90 amino acids, that contain two conserved motifs. One of these DXEXXH may be part of an enzyme active site. The structure and function of the gene are highly conserved among different species.

The C. elegans protein contains 187 amino acid residues (20 kilodaltons), the human homolog 217 amino acid residues (24 kilodaltons, gene consisting of six exons spanning 11 kb and located on chromosome 16).

Function

Ubiquinone is a small redox active lipid that is found in all membranes and that is a co-factor in numerous cellular redox processes, including mitochondrial electron transport. As a co-factor, ubiquinone is often involved in processes that produce reactive oxygen species (ROS). In addition, ubiquinone is one of the main endogenous antioxidants of the cell. The CLK-1 enzyme is responsible for the hydroxylation of 5-demethoxyubiquinone to 5-hydroxyubiquinone.

When ubiquinone biosynthesis is interrupted by the absence of the enzyme, cells accumulate an intermediate of ubiquinone biosynthesis, demethoxyubiquinone (DMQ).

It has been shown that mutations in the gene are associated with increased life span. Defects of the gene slow down a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Jonassen T, Proft M, Randez-Gil F; et al. (1998). "Yeast Clk-1 homologue (Coq7/Cat5) is a mitochondrial protein in coenzyme Q synthesis". J. Biol. Chem. 273 (6): 3351–7. doi:10.1074/jbc.273.6.3351. PMID 9452453. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• Asaumi S, Kuroyanagi H, Seki N, Shirasawa T (1999). "Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human". Genomics. 58 (3): 293–301. doi:10.1006/geno.1999.5838. PMID 10373327.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Vajo Z, King LM, Jonassen T; et al. (2000). "Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging". Mamm. Genome. 10 (10): 1000–4. doi:10.1007/s003359901147. PMID 10501970. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Wiemann S, Weil B, Wellenreuther R; et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Simpson JC, Wellenreuther R, Poustka A; et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Stenmark P, Grünler J, Mattsson J; et al. (2001). "A new member of the family of di-iron carboxylate proteins. Coq7 (clk-1), a membrane-bound hydroxylase involved in ubiquinone biosynthesis". J. Biol. Chem. 276 (36): 33297–300. doi:10.1074/jbc.C100346200. PMID 11435415. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• Takahashi M, Asaumi S, Honda S; et al. (2001). "Mouse coq7/clk-1 orthologue rescued slowed rhythmic behavior and extended life span of clk-1 longevity mutant in Caenorhabditis elegans". Biochem. Biophys. Res. Commun. 286 (3): 534–40. doi:10.1006/bbrc.2001.5439. PMID 11511092. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Rea S (2002). "CLK-1/Coq7p is a DMQ mono-oxygenase and a new member of the di-iron carboxylate protein family". FEBS Lett. 509 (3): 389–94. doi:10.1016/S0014-5793(01)03099-X. PMID 11749961.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Wiemann S, Arlt D, Huber W; et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Mehrle A, Rosenfelder H, Schupp I; et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)