| Annotation aspect | Finding for human COX5B (UniProt P10606) | Evidence type | Source / date / URL | Citation |
|---|---|---|---|---|
| Gene/protein identity | COX5B corresponds to **cytochrome c oxidase subunit 5B, mitochondrial** in **Homo sapiens**; it is a subunit of mitochondrial **cytochrome c oxidase (Complex IV / CIV)**. | Review synthesis of mammalian COX composition | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446 | (pqac-00000002, pqac-00000003) |
| Complex membership | COX5B is a **stoichiometric nuclear-encoded accessory subunit** of mammalian Complex IV that surrounds the mtDNA-encoded catalytic core rather than forming the catalytic center itself. | Review of COX structure | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446 | (pqac-00000002, pqac-00000003) |
| Catalytic role of the holoenzyme | Complex IV is the **terminal enzyme of the respiratory chain**: it accepts electrons from **reduced cytochrome c**, transfers them through **CuA → heme a → heme a3-CuB**, reduces **O2 to H2O**, and contributes to the **proton gradient** used for ATP synthesis. | Mechanistic reviews | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446; Nývltová et al., 2023-01, https://doi.org/10.25376/hra.21892989; Watson & McStay, 2020-09, https://doi.org/10.3390/ijms21197254 | (pqac-00000008, pqac-00000013, pqac-00000014) |
| Catalytic contribution of COX5B itself | COX5B is **not the catalytic redox center**; like other nuclear-encoded accessory CIV subunits, it is understood to **modulate assembly, stability, and regulation** of the holoenzyme. | Review synthesis | Čunátová, 2022, URL not available in extracted record; Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446 | (pqac-00000001, pqac-00000002, pqac-00000009) |
| Submitochondrial/topological placement | COX5B is described as **matrix-facing** and **lacking a transmembrane domain**, consistent with a peripheral accessory role on the matrix side of CIV. | Subunit-specific review statement | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446 | (pqac-00000000) |
| Mitochondrial targeting / precursor status | As a **nuclear-encoded COX subunit**, COX5B is synthesized outside mitochondria and incorporated during coordinated COX biogenesis; the extracted review evidence supports cytosolic synthesis with mitochondrial import/processing for nuclear-encoded COX subunits, though COX5B-specific targeting-sequence details were not provided in the extracted passages. | Inference from COX biogenesis reviews | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446; Watson & McStay, 2020-09, https://doi.org/10.3390/ijms21197254 | (pqac-00000002, pqac-00000014) |
| Assembly role | COX5B appears in defined **assembly intermediates** of human CIV, including the **S3 intermediate**; broader modular assembly models place COX5B in early/intermediate steps of holoenzyme biogenesis. | Assembly pathway reviews | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446; Čunátová, 2022, URL not available in extracted record | (pqac-00000001, pqac-00000002, pqac-00000003) |
| Functional effect of depletion | **Knockdown of COX5B** in a macrophage model decreased **COX activity** and **mitochondrial membrane potential (Δψm)** and increased **ROS**, supporting a nonredundant role in maintaining functional CIV and mitochondrial homeostasis. | Cell-based perturbation study summarized in review | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446 | (pqac-00000000) |
| Supercomplex involvement | COX5B-containing CIV subassemblies can associate with **respiratory supercomplexes**; in CIV-defective human cells, COX5B was detected with **COX1/COX4/COX7A2** in an atypical **I+III2+** species, supporting a role in **supercomplex-associated assembly/stabilization**. | Human cell biochemical / complexome profiling evidence | Lobo-Jarne et al., 2020-06, https://doi.org/10.15252/embj.2019103912 | (pqac-00000004) |
| Current best functional annotation | The most evidence-supported annotation is that human COX5B is a **mitochondrial, matrix-facing, nuclear-encoded accessory subunit of Complex IV** required for efficient **assembly/maintenance** of CIV and linked to proper respiratory activity, membrane polarization, and suppression of excess ROS, rather than directly catalyzing oxygen reduction. | Integrated conclusion from reviews and human cell studies | Čunátová et al., 2020-11, https://doi.org/10.33549/physiolres.934446; Lobo-Jarne et al., 2020-06, https://doi.org/10.15252/embj.2019103912; Nývltová et al., 2023-01, https://doi.org/10.25376/hra.21892989 | (pqac-00000000, pqac-00000004, pqac-00000008, pqac-00000013) |


*Table: This table summarizes authoritative functional annotation for human COX5B (UniProt P10606), emphasizing its verified identity, role as a nuclear-encoded accessory subunit of mitochondrial Complex IV, its topological/assembly features, and the core catalytic function of the Complex IV holoenzyme.*