COQ8A
Domain
Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains, a number of features are positioned to inhibit the kinase activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop that replaces the canonical glycine-rich (G-rich) nucleotide-binding loop and limits ATP binding by establishing an unusual selectivity for ADP and (2) an N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket (PubMed:25498144). Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture (PubMed:27499294).
Function
Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:21296186, PubMed:25498144, PubMed:25540914, PubMed:27499294). Its substrate specificity is unclear: does not show any protein kinase activity (PubMed:25498144, PubMed:27499294). Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (PubMed:25498144, PubMed:27499294). Shows an unusual selectivity for binding ADP over ATP (PubMed:25498144).
Involvement in disease
Coenzyme Q10 deficiency, primary, 4
COQ10D4
An autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Patient manifest gait ataxia and cerebellar atrophy with slow progression. Additional features include brisk tendon reflexes and Hoffmann sign, variable psychomotor retardation and variable seizures.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Cofactor biosynthesis; ubiquinone biosynthesis.
Sequence Similarities
Belongs to the protein kinase superfamily. ADCK protein kinase family.
Tissue Specificity
Widely expressed, with highest levels in adrenal gland, heart, pancreas, nasal mucosa, stomach, uterus and skeletal muscle.
Cellular localization
- Mitochondrion
- Membrane
- Single-pass membrane protein
Alternative names
ADCK3, CABC1, PP265, COQ8A, Chaperone activity of bc1 complex-like, Coenzyme Q protein 8A, aarF domain-containing protein kinase 3, Chaperone-ABC1-like