| Aspect | Key points | Best supporting sources |
|---|---|---|
| identity | COX6A1 in this evidence base corresponds to the human cytochrome c oxidase subunit 6A1, a nuclear-encoded accessory subunit of mitochondrial complex IV (cytochrome c oxidase). Structural work on human complex IV identifies COX6A1 as the human isoform replacing bovine COX6A2 in the resolved 14-subunit enzyme. | (pqac-00000003, pqac-00000012) |
| subcellular localization | COX6A1 is a mitochondrial complex IV subunit embedded in the inner mitochondrial membrane context of cytochrome c oxidase/respirasome assemblies. Structural data place COX6A1 within human CIV purified from mitochondrial supercomplexes, supporting mitochondrial localization at the respiratory chain. | (pqac-00000001, pqac-00000012) |
| complex/pathway role | COX6A1 functions within complex IV of the oxidative phosphorylation system, the terminal respiratory-chain complex that transfers electrons to oxygen and helps generate the proton gradient for ATP synthesis. Reviews further place COX6A among late-incorporating nuclear subunits that modulate assembled CIV and may contribute to holoenzyme/supercomplex stability. | (pqac-00000003, pqac-00000002) |
| molecular function | COX6A1 is not the catalytic center itself; rather, it is an accessory/modulatory subunit of CIV. Evidence summarized in reviews indicates COX6A isoforms can influence proton pumping efficiency and allosteric regulation of cytochrome c oxidase, while COX6A also contacts the opposite protomer in dimeric models and is proposed to stabilize quaternary structure. | (pqac-00000000, pqac-00000002) |
| isoforms/tissue specificity | The COX6A family has two mammalian isoforms: COX6A1 (liver-type/COX6A-L) and COX6A2 (heart-type/COX6A-H). COX6A1 is described as ubiquitously expressed, whereas COX6A2 is largely restricted to heart and skeletal muscle, with developmental isoform switching reported in muscle. | (pqac-00000000, pqac-00000012) |
| regulation | Experimental data show COX6A1 can be selectively downregulated by PLK1-dependent autophagy during gefitinib hepatotoxicity, with lysosomal inhibition rescuing COX6A1 levels. In inflammatory microglia and AD-model microglia, COX6A1 transcript levels rise with broader mitochondrial biogenesis/respiratory remodeling and are reduced by SDH inhibition with dimethyl malonate. | (pqac-00000004, pqac-00000005, pqac-00000007, pqac-00000011) |
| disease links | Disease-focused resources associate COX6A1 with peripheral neuropathy, Charcot-Marie-Tooth disease recessive intermediate D, distal hereditary motor neuropathy type 5, and mitochondrial disease. Functional experimental evidence also links COX6A1 loss to impaired complex IV activity and apoptosis in drug-induced liver injury models. | (pqac-00000009, pqac-00000006, pqac-00000007) |
| applications/biomarker evidence | COX6A1 has emerging translational relevance as a mechanistic marker in gefitinib hepatotoxicity, where preserving COX6A1 mitigates liver injury in vivo. In AML machine-learning models, low-variance COX6A1 expression paired with CD300E formed a relative-expression feature predictive of sensitivity to several drugs including selumetinib, trametinib, axitinib, dasatinib, tanespimycin, and JNJ-28312141. | (pqac-00000005, pqac-00000014) |


*Table: This table summarizes the core functional annotation of human COX6A1 using only the cited evidence contexts. It highlights its identity, mitochondrial complex IV role, isoform biology, regulatory mechanisms, disease links, and emerging biomarker applications.*