COQ7

Last updated
COQ7
Identifiers
Aliases COQ7 , CAT5, CLK-1, CLK1, COQ10D8, coenzyme Q7, hydroxylase
External IDs OMIM: 601683 MGI: 107207 HomoloGene: 6953 GeneCards: COQ7
Orthologs
SpeciesHumanMouse
Entrez

10229

12850

Ensembl

ENSG00000167186

ENSMUSG00000030652

UniProt

Q99807

P97478

RefSeq (mRNA)

NM_001190983
NM_016138

NM_009940
NM_001304758

RefSeq (protein)

NP_001291687
NP_034070

Location (UCSC) Chr 16: 19.07 – 19.08 Mb Chr 7: 118.11 – 118.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mitochondrial 5-demethoxyubiquinone hydroxylase (DMQ hydroxylase), also known as coenzyme Q7, hydroxylase, is an enzyme that in humans is encoded by the COQ7 gene. The clk-1 (clock-1) gene encodes this protein that is necessary for ubiquinone biosynthesis in the worm Caenorhabditis elegans and other eukaryotes. The mouse version of the gene is called mclk-1 and the human, fruit fly and yeast homolog COQ7 (coenzyme Q biosynthesis protein 7). [5] [6]

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

Structure

The protein has two repeats of approximately 90 amino acids, that contain two conserved motifs predicted to be important for coordination of iron. The structure and function of the gene are highly conserved among different species. [7]

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). [8]

Mitochondrial function

Ubiquinone is a small redox active lipid that is found in most cellular membranes where it acts as a cofactor in numerous cellular redox processes, including mitochondrial electron transport. As a cofactor, 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.

It has been shown that mutations in the gene are associated with increased lifespan. [5] [7] 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. [9]

Nuclear function

CLK-1 and COQ7 predominantly localise to mitochondria to participate in the ubiquinone biosynthetic pathway which is found there. However, a small pool of CLK-1 and COQ7 translocates to the nucleus in response to the production of ROS by normally functioning mitochondria in both worms and human cells, respectively. [10] Translocation of CLK-1 and COQ7 represents a mitochondrial to nuclear retrograde signalling pathway that acts to suppress mitochondrial stress responses. The mitochondrial and nuclear pools of CLK-1 are thought to contribute independently to worm lifespan regulation. The nuclear form of CLK-1 and COQ7 is thought to regulate gene expression through an unidentified mechanism.

Related Research Articles

<span class="mw-page-title-main">Dihydroorotate dehydrogenase</span> Class of enzymes

Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the DHODH gene on chromosome 16. The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane (IMM). Inhibitors of this enzyme are used to treat autoimmune diseases such as rheumatoid arthritis.

<span class="mw-page-title-main">NDUFA5</span>

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 is an enzyme that in humans is encoded by the NDUFA5 gene. The NDUFA5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">PDSS1</span> Protein-coding gene in the species Homo sapiens

Decaprenyl-diphosphate synthase subunit 1 is an enzyme that in humans is encoded by the PDSS1 gene.

<span class="mw-page-title-main">COQ2</span> Protein-coding gene in the species Homo sapiens

Para-hydroxybenzoate—polyprenyltransferase, mitochondrial is an enzyme that in humans is encoded by the COQ2 gene.

<span class="mw-page-title-main">NDUFA6</span>

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 is an enzyme that in humans is encoded by the NDUFA6 gene. The NDUFA6 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFB9</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFB9 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">Mitochondrial ribosomal protein L11</span>

39S ribosomal protein L11, mitochondrial is a protein that in humans is encoded by the MRPL11 gene.

<span class="mw-page-title-main">NDUFA8</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 is an enzyme that in humans is encoded by the NDUFA8 gene. The NDUFA8 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFS5</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 is an enzyme that in humans is encoded by the NDUFS5 gene.

<span class="mw-page-title-main">MRPS16</span> Protein-coding gene in the species Homo sapiens

28S ribosomal protein S16, mitochondrial is a protein that in humans is encoded by the MRPS16 gene.

<span class="mw-page-title-main">NDUFB1</span>

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 is an enzyme that in humans is encoded by the NDUFB1 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 1, 7kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">NDUFB2</span>

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial is an enzyme that in humans is encoded by the NDUFB2 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2, 8kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">COQ4</span> Protein-coding gene in the species Homo sapiens

Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial is a protein that in humans is encoded by the COQ4 gene.

<span class="mw-page-title-main">SLC25A39</span>

Solute carrier family 25 member 39 is a protein that in humans is encoded by the SLC25A39 gene. The protein has been shown to be necessary for the import of the major antioxidant glutathione into the mitochondria.

<span class="mw-page-title-main">MRPS33</span> Protein-coding gene in huans

28S ribosomal protein S33, mitochondrial is a protein that in humans is encoded by the MRPS33 gene.

<span class="mw-page-title-main">ADCK3</span> Protein-coding gene in the species Homo sapiens

aarF domain containing kinase 3 is a protein that in humans is encoded by the ADCK3 gene.

Zoltan Vajo is a Hungarian/American scientist, best known for his contributions to the Human Genome Project, including cloning the COQ7 gene, characterizing the human CLK-1 timing protein cDNA and its potential effect on aging, and research on the molecular and genetic background of skeletal dysplasias and fibroblast growth factor receptor 3 disorders, including Achondroplasia, SADDAN, Thanatophoric dysplasia, Muenke coronal craniosynostosis and Crouzon syndrome as well as more recently on genetically engineered insulin analog molecules, including their structure, metabolic effects and cellular processing and the role of recombinant DNA technology in the treatment of diabetes.

<span class="mw-page-title-main">COQ9</span> Protein-coding gene in the species Homo sapiens

Ubiquinone biosynthesis protein COQ9, mitochondrial, also known as coenzyme Q9 homolog (COQ9), is a protein that in humans is encoded by the COQ9 gene.

<span class="mw-page-title-main">PDSS2</span>

Decaprenyl-diphosphate synthase subunit 2 (PDSS2) is a protein that in humans is encoded by the PDSS2 gene.

Catherine Clarke is an American biochemist who is a Professor of Chemistry at the University of California, Los Angeles. She was the first woman to serve as Head of the Department of Chemistry and Biochemistry. Her research considers the functional roles of Coenzyme Q.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167186 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030652 - 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. 1 2 Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S (February 1997). "Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1". Science. 275 (5302): 980–3. doi:10.1126/science.275.5302.980. PMID   9020081. S2CID   32191959.
  6. ↑ "Entrez Gene: COQ7 coenzyme Q7 homolog, ubiquinone (yeast)".
  7. 1 2 Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (October 2005). "Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice". Genes Dev. 19 (20): 2424–34. doi:10.1101/gad.1352905. PMC   1257397 . PMID   16195414.
  8. ↑ Asaumi S, Kuroyanagi H, Seki N, Shirasawa T (June 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.
  9. ↑ Felkai S, Ewbank JJ, Lemieux J, Labbé JC, Brown GG, Hekimi S (April 1999). "CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans". EMBO J. 18 (7): 1783–92. doi:10.1093/emboj/18.7.1783. PMC   1171264 . PMID   10202142.
  10. ↑ Monaghan RM, Barnes RG, Fisher K, Andreou T, Rooney N, Poulin GB, Whitmarsh AJ (June 2015). "A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity". Nature Cell Biology. 17 (6): 782–92. doi:10.1038/ncb3170. PMC   4539581 . PMID   25961505.

Further reading


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