COXFA4 is the accepted human symbol for the protein historically called NDUFA4 (HGNC:7687; UniProt O00483). The 81-aa protein is a single-pass mitochondrial inner-membrane subunit of cytochrome c oxidase. Its central role is a structural contribution to complex IV and its terminal respiratory activity, rather than autonomous oxidase catalysis. The historical complex-I classification is superseded by affirmative later experiments; earlier cloning or copurification observations are not thereby erased.
The original Balsa study is available in an author-deposited UAM thesis, PDF pages 93–101 (article pages 1–9; thesis pages 85–93). The independent core consultation read its main Methods, Results and Discussion and inspected selected original figure pages. Endogenous human HeLa immunocapture, two shRNAs and interference-resistant myc-NDUFA4 rescue distinguish complex-IV effects from complex I. The human experiments and separate mouse mutant-complex comparisons are not interchangeable. PMID:22902835(https://pubmed.ncbi.nlm.nih.gov/22902835/)
Human patient muscle and fibroblast findings independently establish complex-IV dysfunction. Native gels retain detectable holoenzyme without abnormal subassemblies when COXFA4 is deficient. Thus structural/function participation is supported, whereas an obligatory assembly-factor role is not established. Detergent sensitivity depends on buffer and preparation: the patient study explicitly reports different dissociation thresholds from the earlier HeLa work. PMID:23746447(https://pmc.ncbi.nlm.nih.gov/articles/PMC3701321/)
The human complex-IV cryo-EM structure resolves COXFA4 within a 14-subunit enzyme derived from a respirasome. The selected normal cache is partial even though it has a full-text flag; the bounded core consultation used the actual original Results/Methods. Human structural observations are kept distinct from separate porcine detergent experiments. A particular dimer-interface geometry is not a universal claim excluding all physiological oligomers. PMID:30030519(https://doi.org/10.1038/s41422-018-0071-1)
The one core therefore uses contribution to cytochrome-c oxidase activity, in complex IV at the inner membrane, with the existing terminal cytochrome-c-to-oxygen and proton-transport processes. Both belong to the primary respiratory role, with proton participation limited to the structural contribution to the coupled enzyme. The inherited oxidase proposal remains an inherited NEW record; no additional process is introduced. The proton-transport annotation is retained at structural participation in proton-coupled complex IV. Its present electronic GO:0008137 premise is separately wrong: the literal current record does not infer from GO:0004129, and the source review explicitly records that failure. No isolated COXFA4 proton-channel assay or pumping stoichiometry is asserted.
The three historical generic-binding judgments are reassessed from positive evidence, not from the informativeness of their original labels or expected cellular compartments.
The Radil paper requires a different conclusion. Its actual main text describes broad human interaction screens despite a KIF14-focused title. The bounded independent consultation read 17 primary entries and Fig. 1, but target-bearing S1/S2 tables could not be recovered; the available supplementary ZIP contained only main-figure images. The historical categorical claim that the paper contains no relevant target evidence is therefore unverified. The existing complex-binding annotation is UNDECIDED, with no wrong-gene assertion. PMID:23209302(https://pmc.ncbi.nlm.nih.gov/articles/PMC3518219/)
Actual MitoCoP workbook target rows A792/B702 identify O00483/NDUFA4 with mitochondrial evidence and 73.125% sequence coverage. Presence and curated functional columns are not treated as separate catalytic experiments. HPA localization is consistent but its XML warns of an antibody recognizing multiple gene products. The OCTN1-focused PMID:16729965 remains target-specific full-text unverified; broad mitochondrial localization is retained with curator deference because it is independently established. PMID:34800366(https://pubmed.ncbi.nlm.nih.gov/34800366/)
PTHR14256 places human target PTN002494450 below both source nodes PTN001023184 and PTN002682197. The actual aligned sequence reconstructs the official 81-aa protein. Current donor records include direct mitochondrial and complex-IV grounding, as well as a presently inferred-only fly mitochondrial record. These differences are recorded individually; donor count is not a proxy for PAINT quality, and the target’s own direct evidence is not circularity. The extra rat donor in the saved local IBD list is distinguished from the current GOA WITH set.
All three cited Reactome events have actual target paths to O00483 through COXFA4:cardiolipin and/or complex IV at the mitochondrial inner membrane. The five paths support location; incorporation into a complex is not itself a new assembly-factor activity, and membership in CO-bound complex IV does not demonstrate individual COXFA4 carbon-monoxide binding.
The 28-row union retains all 24 historical assertions, including the inherited oxidase proposal. Twenty historical source objects match current annotations on their available source fields; three absent historical records are explicitly retired, and four complete genuinely new current-source objects are appended. Historical missing WITH/FROM and qualifier fields remain missing. Complete current objects are recorded separately in the evidence index, so source-compatible matching is not mislabeled as complete-field equality.
The new human deletion report supports reduced complex-IV activity in patient fibroblasts while complex I lies within the measured normal range. Its clinical scope is kept separate from a molecular activity assay. PMID:38674434(https://pmc.ncbi.nlm.nih.gov/articles/PMC11050323/)
Human-cell C15ORF48/miR-147 experiments provide direct evidence for COXFA4 abundance regulation, respiratory effects and context-dependent innate-response phenotypes. Selected actual Results/Discussion were read; detailed supplementary Methods were not inspected. The precise COXFA4-performed step connecting these effects remains unresolved, so no new immune-process annotation is manufactured from perturbation alone. PMID:38917002(https://pmc.ncbi.nlm.nih.gov/articles/PMC11228508/)
The historical Falcon report remains a preserved research lead at its original NDUFA4 identity. Clinical and regulated-abundance claims are assessed against the original papers above. Its separate in-situ cryo-EM claim remains unverified in this bounded review. The evidence index records source URLs, hashes, exact assay/table locators and the distinction between direct owner reading and independent consultations.
Six previously absent supporting_entities lists now preserve the current GOA WITH/FROM values directly in the review: the complex-IV IBA sources, the proton-transport premise, the inner-membrane vocabulary identifier and the DPF1, RAB5IF and PARK7 interaction partners. The earlier reconciliation and its historical source snapshots document the pre-backfill state. The three retired records keep their original source fields. Ordinary qualifiers remain unchanged, following the annotation-reviewer instructions; they do not enter the biological judgments.
The retired respiratory-electron-transport-chain annotation is now MODIFY to GO:0006123, using the same specificity criterion as cellular respiration. This identifies an already represented complex-IV step and adds no new assertion. The supported core and all physical-interaction decisions are unchanged.
Two primary-reference findings now anchor the description's existing clinical and abundance-regulation statements: PMID:38674434 and PMID:38917002. The latter is an upstream regulation result, not evidence that COXFA4 itself executes an immune-signaling step. Source-exact snippets were checked in the immutable caches; the original evidence-index locators and reading limits still apply.
The old UniProt reference identity and inherited quotations remain traceable to the preserved historical NDUFA4 source file. The current official COXFA4 record and original studies independently support the review. Paper-title anchors inherited from the historical review are not reinterpreted as target-level experimental evidence; target tables and access limitations are documented above and in the evidence index.
The current OXPHOS gene list, row and status links now use COXFA4, with the historical NDUFA4 name retained where useful for readers. The unrelated project-wide source audit remains separate from this four-line symbol correction.