COXFA4, formerly named NDUFA4, is an 81-amino-acid single-pass membrane subunit of mitochondrial cytochrome c oxidase (complex IV). Its transmembrane helix and intermembrane-space region contribute to the architecture of the terminal respiratory enzyme, which transfers electrons from cytochrome c to oxygen and couples this reaction to proton translocation. COXFA4 supports efficient complex-IV oxidase function as part of the enzyme, rather than acting as an autonomous oxidase or a complex-I NADH dehydrogenase subunit. Pathogenic loss of COXFA4 causes mitochondrial complex-IV deficiency and neurological disease. COXFA4 abundance can also be regulated by the C15ORF48/miR-147 system, with respiratory and innate-response effects demonstrated in defined human cell models.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045277 respiratory chain complex IV | IBA GO_REF:0000033 | ACCEPT | Summary: COXFA4 is a structural component of respiratory complex IV. Reason: The current PTHR14256 tree places human O00483 at PTN002494450 below the actual IBD source node PTN002682197. Human and mouse complex-IV evidence includes the original biochemical reassignment study, and the human structure directly resolves COXFA4 in complex IV. The target appearing among descendant sources is legitimate experimental grounding, not circularity. The old source object omits WITH/FROM; complete current and local PAINT records are recorded separately. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002682197 SUPPORTS TRANSFER Actual ancestor of the human target in the retrieved PTHR14256 tree; local IBD and current GOA source lists are preserved separately. MGI:MGI:107686 SUPPORTS TRANSFER Mouse Coxfa4/Q62425 has complex-IV IDA PMID22902835; that paper is independently read at its species-specific scope. UniProtKB:O00483 SUPPORTS TRANSFER Current IDA22902835 and IPI30030519 supply direct target grounding. Supporting Evidence: PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). Deletion of NDUFA4 does not perturb CI. Rather, proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis. PMID:30030519 Combining previous structural and biochemical data shown by us and other groups, we propose that the intact complex-IV is a monomer containing 14 subunits. file:human/NDUFA4/NDUFA4-deep-research-falcon.md Belongs to the complex IV COXFA4 subunit family. |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: Structural participation in proton-coupled complex IV supports this process, but the current electronic premise is wrong. Reason: GO:1902600 concerns proton movement across a membrane. COXFA4 supplies part of the human complex-IV structure and supports oxidase function in depletion/rescue and patient experiments. Retain participation at this complex-subunit scope; this is not a claim that isolated COXFA4 is a proton channel or that its individual pumping stoichiometry was measured. The complete current GO_REF:0000108 record is inferred from GO:0008137, not GO:0004129. That complex-I activity premise is contradicted by reassignment and is marked adverse independently of the retained biological conclusion. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: GO:0008137 SOURCE BAD Literal current WITH/FROM premise is NADH dehydrogenase activity; COXFA4 is a complex-IV subunit, so this inference route should be repaired. The historical omitted WITH value is not silently filled. Supporting Evidence: PMID:30030519 It accepts electrons from cytochrome c to reduce the oxygen to water and meanwhile pumps two protons from the matrix side to the intermembrane space (IMS) PMID:22902835 NDUFA4 plays a role in CIV function and biogenesis |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: COXFA4 spans the mitochondrial inner membrane. Reason: The current mapping source is UniProtKB-SubCell:SL-0168. The official human sequence/topology and the human complex-IV structure support this specific location, independently of the electronic mapping. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0168 SUPPORTS TRANSFER Current official location is mitochondrial inner membrane; its literal source identifier is also recorded in supporting_entities. Supporting Evidence: file:human/NDUFA4/NDUFA4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein PMID:30030519 Here we obtained the 3.3 Å resolution structure of complex-IV derived from the human supercomplex I 1 III 2 IV 1 and assigned the NDUFA4 subunit into complex-IV |
| GO:0022904 respiratory electron transport chain | IEA GO_REF:0000043 | MODIFY | Summary: The historical broad respiratory-chain process is refined to the complex-IV step. Reason: COXFA4 contributes structure to complex IV, whose terminal cytochrome-c-to-oxygen step is captured more precisely by GO:0006123. Apply the same specificity criterion used for the broader cellular-respiration annotation. This refinement points to an already represented process; it proposes no additional annotation or independent catalytic activity. The historical source record remains retired because it is absent from current GOA, not because respiratory participation is false. Propagation Review Root cause: UNRESOLVED Sources checked: GO_REF:0000043 SOURCE STALE OR MISSING Historical keyword mapping no longer appears in current GOA; the exact old keyword premise was not recovered. Independent complex-IV evidence establishes the broad process. Proposed replacements: mitochondrial electron transport, cytochrome c to oxygen Supporting Evidence: PMID:22902835 NDUFA4 plays a role in CIV function and biogenesis file:human/NDUFA4/NDUFA4-uniprot.txt Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The NeuroNet screen provides positive DPF1–COXFA4 interaction evidence. Reason: Three literal 42-field IntAct records from PMID:32814053 report array, pool and validated two-hybrid assays with DPF1 isoform 2. The historical 414-aa DPF1 sequence matches the exported checksum; its sufficient binding region 28–414 equals the current 387-aa displayed sequence. Retain this positive assay result without inferring a transcriptional activity for COXFA4. DPF1 has nBAF/chromatin-reader context and a coregulator IBA, but the available class evidence also includes direct DNA binding; a specific DNA-binding transcription-factor or non-DNA-binding coregulator class is not resolved here. The generic interaction is non-core, not invalidated by compartment expectations. Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. |
| GO:0045271 respiratory chain complex I | IEA GO_REF:0000107 | REMOVE | Summary: The retired complex-I classification is contradicted by later direct evidence. Reason: The historical ortholog-transfer object is preserved and marked retired. Its complex-I membership conclusion is superseded by human endogenous immunocapture, depletion and resistant-cDNA rescue in PMID:22902835, patient biochemistry in PMID:23746447 and human complex-IV structure in PMID:30030519. Historical copurification is not denied; stable complex-I assignment is the contradicted inference. No absence claim about the unrecovered historical donor is needed. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: GO_REF:0000107 UNRESOLVED Historical donor identity was omitted and is not reconstructed from a present-day record. GO:0045271 SOURCE BAD Target complex-I assignment is directly superseded by later complex-IV experiments. Supporting Evidence: PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). Deletion of NDUFA4 does not perturb CI. file:human/NDUFA4/NDUFA4-uniprot.txt Was initially believed to be a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). |
| GO:0045277 respiratory chain complex IV | IEA GO_REF:0000120 | ACCEPT | Summary: The retired combined electronic complex-IV assertion is biologically supported. Reason: This historical source is no longer in current GOA, but the complex-IV membership itself is directly established. Preserve the old source object and retirement metadata separately from the biological ACCEPT judgment. No particular historical ARBA branch is inferred from the generic GO_REF:0000120 identity. Propagation Review Root cause: UNRESOLVED Sources checked: GO_REF:0000120 SOURCE STALE OR MISSING Exact historical combined-rule premise is unavailable; current direct structural/biochemical evidence supports the conclusion. Supporting Evidence: PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: HPA supports mitochondrial localization with an antibody-specificity caveat. Reason: The current HPA XML reports mitochondrial localization and supported reliability, while warning that the antibody targets proteins from multiple genes. Retain the curator localization with that limitation and the independent COXFA4 structural and proteomic evidence. No claim of inspecting the original HPA image pixels is made. Supporting Evidence: file:human/NDUFA4/NDUFA4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein |
| GO:0006123 mitochondrial electron transport, cytochrome c to oxygen | NAS PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: COXFA4 contributes structurally to the terminal respiratory electron-transfer step. Reason: The human complex-IV structure places COXFA4 in the enzyme that transfers electrons from cytochrome c to oxygen. Human depletion/rescue and patient complex-IV dysfunction supply complementary functional support. This is participation through the complex structure, not independent electron-transfer catalysis or a generic necessity-only inference. Supporting Evidence: PMID:30030519 CIV is the terminal oxidase of the electron transport chain in mitochondria. PMID:22902835 proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis |
| GO:0031966 mitochondrial membrane | IDA PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | MODIFY | Summary: The same source establishes the more specific inner-membrane location. Reason: The human transmembrane COXFA4 chain is resolved within inner-membrane complex IV in PMID:30030519. Replace mitochondrial membrane with mitochondrial inner membrane while retaining the original source term and evidence fields. Other annotations to that location do not prevent a source-specific refinement. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:30030519 Here we obtained the 3.3 Å resolution structure of complex-IV derived from the human supercomplex I 1 III 2 IV 1 and assigned the NDUFA4 subunit into complex-IV file:human/NDUFA4/NDUFA4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein |
| GO:0045333 cellular respiration | NAS PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | MODIFY | Summary: Terminal complex-IV electron transport specifies the broad respiration statement. Reason: The cited human structure directly assigns COXFA4 to complex IV, the terminal respiratory enzyme. GO:0006123 captures the specific step supported by this source more accurately than cellular respiration. It does not imply an autonomous catalytic site on COXFA4. Proposed replacements: mitochondrial electron transport, cytochrome c to oxygen Supporting Evidence: PMID:30030519 CIV is the terminal oxidase of the electron transport chain in mitochondria. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: The original MitoCoP target tables positively identify COXFA4 in the mitochondrial proteome. Reason: The authenticated supplementary workbook lists O00483/NDUFA4 in sheet A Excel row 792 and sheet B row 702. The target is identified, assigned to MitoCoP and supported by mitochondrial enrichment/localization measurements; the recorded sequence coverage is 73.125%. These target-specific entries substantiate the HTP location. Functional annotation columns in the workbook are not treated as new catalytic experiments. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context |
| GO:0045277 respiratory chain complex IV | IDA PMID:22902835 NDUFA4 is a subunit of complex IV of the mammalian electron ... | ACCEPT | Summary: Original human biochemical experiments establish complex-IV membership. Reason: The authentic 2012 author reprint documents endogenous human HeLa complex-IV immunocapture with complex-I controls, two shRNA perturbations, and resistant myc-NDUFA4 rescue of complex-IV abundance and activity. Mouse mutant-complex comparisons are separate evidence. These results substantiate complex-IV membership; human patient results show that a detectable holoenzyme can remain without normal COXFA4 function, so this is not an obligatory assembly-factor assertion. Supporting Evidence: PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). Deletion of NDUFA4 does not perturb CI. Rather, proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis. |
| GO:0005515 protein binding | IPI PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | KEEP AS NON CORE | Summary: The RAB5IF/C20orf24 association has positive cofractionation and co-IP support. Reason: The original PMID:31536960 Table S2 contains the exact O00483–Q9BUV8 pair in the differentiated-neuronal network (DN PPI Excel row 1786), and Fig. 5A(iii) shows C20orf24/NDUFA4 co-immunoprecipitation with bead controls in the indicated human-cell and mouse-brain contexts. Supplementary IP Methods were inspected. This is positive co-complex association, not proof of a defined binary contact or of an enzyme/adaptor activity of COXFA4. Retain generic binding as non-core. The paper’s historical complex-I naming does not invalidate its physical-association data. Supporting Evidence: PMID:31536960 Association of CI subunit (NDUFA4) or TFAM with the components of the respirasome file:human/NDUFA4/NDUFA4-uniprot.txt Interacts with RAB5IF |
| GO:0044877 protein-containing complex binding | IDA PMID:23209302 KIF14 negatively regulates Rap1a-Radil signaling during brea... | UNDECIDED | Summary: The target-specific support in the Radil proteomic screens remains unresolved. Reason: The actual paper contains broad FLAG-Radil interaction screens in human HEK293T and MDA-MB-231 contexts, so its KIF14-focused title and lack of a main-text COXFA4 name cannot justify the previous REMOVE. Main Methods/Results and Fig. 1 were inspected, but supplementary S1/S2 tables needed to identify the target and complex were not recovered. The accessible EPMC supplement archive contained only main-figure images. Preserve curator deference and uncertainty rather than asserting a wrong-gene assignment. Supporting Evidence: PMID:23209302 KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression |
| GO:0005515 protein binding | IPI PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | MODIFY | Summary: Direct binding to the enzymatic partner PARK7 supports enzyme binding. Reason: The original human study used brain-library two-hybrid discovery, Flag-NDUFA4 co-IP of endogenous DJ-1 in 293T cells, and purified GST–DJ-1 versus GST pull-down of radiolabeled NDUFA4. These positive experiments survive the later reassignment of COXFA4 from complex I to IV. Current reviewed PARK7/Q99497 records include experimentally supported glyoxalase and peptidase activities, supporting the partner class in GO:0019899. This refinement does not assign catalysis to COXFA4, establish a chaperone-client mechanism, or prove that this interaction mediates the reported complex-I activity phenotype. Proposed replacements: enzyme binding Supporting Evidence: PMID:19822128 DJ-1 directly bound to NDUFA4 and ND1, nuclear and mitochondrial DNA-encoding subunits of mitochondrial complex I, respectively PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-163214 | ACCEPT | Summary: The actual Reactome target route places COXFA4 at the inner membrane. Reason: The current R-HSA-163214 graph reaches reference entity O00483 through catalyst complex IV, COXFA4:cardiolipin node 9864472 and COXFA4 node 60617. The target entity explicitly has mitochondrial inner membrane compartment GO:0005743. This supports location; it does not assign carbon-monoxide binding or an independent assembly-factor activity to COXFA4. Supporting Evidence: Reactome:R-HSA-163214 Electron transfer from reduced cytochrome c to molecular oxygen |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9709406 | ACCEPT | Summary: The actual Reactome target route places COXFA4 at the inner membrane. Reason: The current R-HSA-9709406 graph reaches reference entity O00483 through input and CO-bound output complex IV, COXFA4:cardiolipin node 9864472 and COXFA4 node 60617. The target entity explicitly has mitochondrial inner membrane compartment GO:0005743. This supports location; it does not assign carbon-monoxide binding or an independent assembly-factor activity to COXFA4. Supporting Evidence: Reactome:R-HSA-9709406 CO binds to Cytochrome c oxidase |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9865663 | ACCEPT | Summary: The actual Reactome target route places COXFA4 at the inner membrane. Reason: The current R-HSA-9865663 graph reaches reference entity O00483 through COXFA4–cardiolipin input and assembled complex-IV output, COXFA4:cardiolipin node 9864472 and COXFA4 node 60617. The target entity explicitly has mitochondrial inner membrane compartment GO:0005743. This supports location; it does not assign carbon-monoxide binding or an independent assembly-factor activity to COXFA4. Supporting Evidence: Reactome:R-HSA-9865663 MT-CO3, COX6A,B,7A and NDUFA4 bind to holo-MT-CO1,2 complex |
| GO:0005739 mitochondrion | IDA PMID:16729965 Novel localization of OCTN1, an organic cation/carnitine tra... | ACCEPT | Summary: Retain the curator mitochondrial localization with an explicit source-access limit. Reason: The complete accessible PMID:16729965 abstract foregrounds OCTN1, and target-specific full Methods were not recovered. That does not establish misattribution. COXFA4 mitochondrial localization is independently clear from human complex-IV structure, patient biochemistry and exact MitoCoP target rows; retain this experimental location with curator deference while marking the individual reference’s target support unverified. Supporting Evidence: file:human/NDUFA4/NDUFA4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein PMID:16729965 Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria. |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox... | REMOVE | Summary: The historical complex-I functional assignment is superseded. Reason: The preserved cloning-era source records arose under the complex-I classification. Later direct endogenous complex-IV immunocapture, depletion/rescue and human structure affirmatively establish the reassignment and contradict this complex-I-specific function. Original cloning and copurification observations remain historical evidence; their full original Methods were not recovered, and no claim that they lacked COXFA4 is made. Existing complex-IV annotations provide the correct functional context. Supporting Evidence: PMID:22902835 NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). Deletion of NDUFA4 does not perturb CI. PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed [predates the reclassification] |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox... | REMOVE | Summary: The historical complex-I functional assignment is superseded. Reason: The preserved cloning-era source records arose under the complex-I classification. Later direct endogenous complex-IV immunocapture, depletion/rescue and human structure affirmatively establish the reassignment and contradict this complex-I-specific function. Original cloning and copurification observations remain historical evidence; their full original Methods were not recovered, and no claim that they lacked COXFA4 is made. Existing complex-IV annotations provide the correct functional context. Supporting Evidence: PMID:22902835 Deletion of NDUFA4 does not perturb CI. Rather, proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis. file:human/NDUFA4/NDUFA4-uniprot.txt Was initially believed to be a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | TAS PMID:9352085 Cloning of the human cDNA sequence encoding the NADH:ubiquin... | REMOVE | Summary: The historical complex-I functional assignment is superseded. Reason: The preserved cloning-era source records arose under the complex-I classification. Later direct endogenous complex-IV immunocapture, depletion/rescue and human structure affirmatively establish the reassignment and contradict this complex-I-specific function. Original cloning and copurification observations remain historical evidence; their full original Methods were not recovered, and no claim that they lacked COXFA4 is made. Existing complex-IV annotations provide the correct functional context. Supporting Evidence: PMID:9352085 A cDNA clone encoding human NADH:ubiquinone oxidoreductase (complex I of mitochondrial respiratory chain) MLRQ subunit was isolated [predates reclassification] PMID:22902835 The change in the attribution of the NDUFA4 protein requires renaming of the gene and reconsideration of the structure of CIV. |
| GO:0004129 cytochrome-c oxidase activity | IDA PMID:22902835 NDUFA4 is a subunit of complex IV of the mammalian electron ... | NEW | Summary: Preserve the inherited cytochrome-c oxidase contribution proposal. Reason: This NEW assertion already existed in the historical NDUFA4 review and is not manufactured by the symbol migration. Human direct complex-IV membership, depletion and resistant-cDNA rescue support contribution to the complex’s oxidase activity. The one core uses contributes_to_molecular_function explicitly; no autonomous catalytic activity is claimed and the historical source fields are unchanged. The current genuine GOA seed does not contain this proposed row. Supporting Evidence: PMID:22902835 proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis file:human/NDUFA4/NDUFA4-uniprot.txt Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. COXFA4 is required for complex IV maintenance. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetic mitochondrial annotation is supported by target and donor evidence. Reason: PTN001023184 is an actual ancestor of the human target in the PTHR14256 tree, and the aligned target sequence reconstructs the official 81-aa protein. Current human COXFA4, human COXFA4L2 and mouse Coxfa4l2 records contain direct mitochondrial grounding; the inspected fly record is presently inferred-only and does not substitute for a primary experiment. This source-specific distinction does not invalidate the curator’s ancestral placement or treat the target’s own evidence as circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001023184 SUPPORTS TRANSFER Actual target ancestor; target MSA reconstruction matches the official sequence. FB:FBgn0052230 SOURCE WEAK OR INFERRED Current Q8SYJ2 mitochondrial record is IBA only; historical experimental donor scope remains unverified. MGI:MGI:3039567 SUPPORTS TRANSFER Mouse Coxfa4l2/Q4FZG9 currently has mitochondrial IDA records; primary donor papers were not newly reread. UniProtKB:Q9NRX3 SUPPORTS TRANSFER Human paralog has mitochondrial IDA/HTP records; relevant organelle scope only. UniProtKB:O00483 SUPPORTS TRANSFER Direct human target evidence independently grounds the inherited location. |
| GO:0005743 mitochondrial inner membrane | EXP PMID:23746447 NDUFA4 mutations underlie dysfunction of a cytochrome c oxid... | ACCEPT | Summary: Human patient biochemistry supports inner-membrane complex-IV membership. Reason: PMID:23746447 reports reduced cytochrome-c oxidase activity with normal complex-I activity in patient muscle and COXFA4 comigration with complex IV rather than NDUFA9. A detectable complex-IV holoenzyme remains, which limits obligatory-assembly claims. Combined with the membrane-complex context, retain the curator’s specific localization. Supporting Evidence: PMID:23746447 one- and two-dimensional blots confirmed association of NDUFA4 with complex IV |
| GO:0005743 mitochondrial inner membrane | EXP PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: The human structure directly resolves the inner-membrane subunit. Reason: PMID:30030519 resolves human COXFA4 in intact complex IV from a respirasome. The membrane-spanning chain establishes the specific location. Human structural evidence is distinguished from the paper’s separate porcine detergent experiments. |
| GO:0045277 respiratory chain complex IV | IPI PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: The human complex-IV structure establishes subunit association. Reason: COXFA4 is resolved as part of the intact human 14-subunit complex-IV structure. Preserve the source IPI/part_of record and its complex identity; this does not turn an individual structural subunit into an autonomous oxidase. |
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Download this section (compressed HTML)Q: How does the COXFA4 structural contribution alter complex-IV electron-transfer and proton-coupling kinetics independently of changes in enzyme abundance?
Q: What functional consequence follows from the direct PARK7–COXFA4 interaction after distinguishing complex-IV biology from the original complex-I interpretation?
Q: Which molecular step links regulated COXFA4 abundance to innate-response changes in the C15ORF48/miR-147 cell models?
Experiment: Compare matched amounts of purified or membrane-reconstituted complex IV with defined COXFA4 occupancy, measuring oxidase turnover and proton coupling together with structural integrity.
Experiment: Test the consequences of selectively disrupting the PARK7–COXFA4 interface while preserving each protein’s abundance, localization and intrinsic properties.
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