TACO1 (Translational Activator of Cytochrome c Oxidase 1; also CCDC44) is a nuclear-encoded, mitochondrial-matrix RNA-binding translational activator of the conserved YebC/TACO1 family. It associates with the mitochondrial ribosome and the MT-CO1 (COX1) mitochondrial mRNA and promotes translation of MT-CO1, the catalytic core subunit of cytochrome c oxidase (respiratory chain complex IV). Mechanistically it acts as the mitochondrial functional counterpart of bacterial elongation factor EF-P / eukaryotic-archaeal eIF5A, binding the mitoribosome large subunit and alleviating ribosome stalling at polyproline stretches, thereby enabling rapid synthesis of the polyproline-rich COX1 and COX3 subunits and, in turn, complex IV assembly. Loss of TACO1 function reduces COX1 synthesis and complex IV levels/activity. Biallelic TACO1 variants cause mitochondrial complex IV deficiency with a late-onset (juvenile) Leigh syndrome-like neurodegeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0070131 positive regulation of mitochondrial translation | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of the core biological process for TACO1: positive regulation of mitochondrial translation. This is the experimentally established role of TACO1 and is corroborated by direct assay (IDA, PMID:39036954). Reason: Consistent with the direct experimental annotation and with the demonstrated requirement of TACO1 for mitochondrial protein synthesis of COX1/COX3. This is a core function of the gene. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) localization to the mitochondrion, where TACO1 is active. Correct but non-specific; TACO1 functions in the mitochondrial matrix at the mitoribosome (captured more precisely in core_functions as GO:0005759 mitochondrial matrix). Reason: Mitochondrial localization is well established by UniProt and multiple experimental sources; the IBA is-active-in annotation is accurate at this level of granularity. Supporting Evidence: file:human/TACO1/TACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (ARBA/UniProt SubCell) localization to the mitochondrion. Consistent with the curated UniProt subcellular location and experimental data. Reason: Correct organelle-level localization; broader than the mitochondrial matrix but not wrong. Supporting Evidence: file:human/TACO1/TACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0070129 regulation of mitochondrial translation | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) annotation to regulation of mitochondrial translation, the parent of the experimentally supported positive regulation of mitochondrial translation (GO:0070131). Reason: Correct but broader than the specific direction of regulation shown experimentally (positive regulation). Retained as a redundant broader term; the more specific GO:0070131 is the core BP. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. |
| GO:0097177 mitochondrial ribosome binding | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) annotation of the core molecular function, mitochondrial ribosome binding. This is directly supported by experiment (IDA, PMID:39036954). Reason: Accurately captures the experimentally demonstrated interaction of TACO1 with the mitoribosome; duplicate of the IDA annotation and consistent with it. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: IntAct-derived protein binding annotation from a proteome-scale yeast-two-hybrid interactome screen (interactor SAT1, UniProtKB:P21673). "protein binding" is uninformative and this high-throughput interactor is not a mitochondrial-matrix / mitoribosome partner. Reason: Bare GO:0005515 conveys no functional specificity, and the reported interactor (spermidine/spermine N1-acetyltransferase SAT1) is a cytosolic protein, not a plausible physiological partner of a mitochondrial-matrix translational activator. Per curation policy the experimental IPI is retained (not removed) but flagged as an over-annotation from a high-throughput binary interactome map. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: IntAct-derived protein binding annotations from the HuRI human binary interactome reference map (interactors include CIB4, GOLGA6L9, keratins KRT31/KRT34/KRT40, DR1, GTF3C3, LNX1, MDFI, MTUS2, PPP1R16B, RINT1, SAT1, TRIM23, CALCOCO2). "protein binding" is uninformative and none of these are mitochondrial-matrix / mitoribosome partners. Reason: Bare GO:0005515 is uninformative, and the interactors from this high-throughput binary (Y2H) interactome map are extramitochondrial proteins that do not reflect the physiological mitoribosome/MT-CO1-mRNA interaction of TACO1. Retained per policy but marked as over-annotated. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IntAct-derived protein binding annotations from a neurodegenerative-disease interactome-mapping study (interactors CALCOCO2/NDP52 UniProtKB:Q13137 and GTF3C3 UniProtKB:Q9Y5Q9). "protein binding" is uninformative and these are not mitochondrial-matrix / mitoribosome partners. Reason: Bare GO:0005515 conveys no functional information, and the interactors from this high-throughput interactome screen are non-mitochondrial proteins not representing TACO1's physiological function. Retained per policy but flagged as over-annotated. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) localization of TACO1 to the mitochondrion. Consistent with all other evidence for mitochondrial localization. Reason: Experimental (IDA) support for mitochondrial localization; accurate at the organelle level. Matrix sub-localization is captured in core_functions. Supporting Evidence: file:human/TACO1/TACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0070131 positive regulation of mitochondrial translation | IDA PMID:39036954 The human mitochondrial translation factor TACO1 alleviates ... | ACCEPT | Summary: Direct experimental demonstration that TACO1 positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling, required for rapid synthesis of COX1/COX3 and hence complex IV assembly. Core biological process. Reason: Well supported by metabolic labeling, puromycin-release and mitoribosome profiling in a TACO1 knockout (severe reduction in COX1 synthesis and reduced fully assembled complex IV). This is a core function of TACO1. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. PMID:39036954 Metabolic labeling of mitochondrial translation products with 35S-methionine revealed a severe reduction in COX1 synthesis |
| GO:0097177 mitochondrial ribosome binding | IDA PMID:39036954 The human mitochondrial translation factor TACO1 alleviates ... | ACCEPT | Summary: Direct experimental demonstration that TACO1 binds the mitoribosome (it cosediments with and functions on the mitoribosome large subunit, cooperating with the bL27m N-terminal extension). This is the core, experimentally supported molecular function of TACO1. Reason: Directly assayed mitoribosome association; the most informative molecular function term available and the current experimental MF for TACO1. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput proteomic identification of TACO1 in the human mitochondrial proteome. Corroborates mitochondrial localization. Reason: Consistent with all other localization evidence; accurate at the organelle level. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. |
| GO:0005759 mitochondrial matrix | IDA PMID:39036954 The human mitochondrial translation factor TACO1 alleviates ... | NEW | Summary: Proposed refined localization. TACO1 acts on the mitoribosome in the mitochondrial matrix, so the more specific matrix location (GO:0005759) is warranted alongside the existing organelle-level GO:0005739 annotations. Reason: TACO1 is a soluble matrix-side translational activator that binds the mitoribosome; GO:0005759 mitochondrial matrix is the appropriate anatomical location, refining the broader mitochondrion annotations already present. Supporting Evidence: PMID:39036954 TACO1 binds to the mitoribosome and positively regulates mitochondrial protein synthesis by alleviating polyproline-induced mitoribosome stalling. |
| GO:0032543 mitochondrial translation | IDA PMID:39036954 The human mitochondrial translation factor TACO1 alleviates ... | NEW | Summary: Proposed annotation to the general process of mitochondrial translation, in which TACO1 acts as a translation-elongation factor (EF-P/eIF5A counterpart) required for rapid synthesis of polyproline-rich COX1/COX3. Reason: TACO1 directly participates in mitochondrial protein synthesis at the mitoribosome (not only its regulation), complementing the positive regulation of mitochondrial translation annotation. Supporting Evidence: PMID:39036954 The absence of TACO1 leads to decreased COX1 and COX3 synthesis |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:39036954 The human mitochondrial translation factor TACO1 alleviates ... | NEW | Summary: Proposed annotation to complex IV (cytochrome c oxidase) assembly. By driving synthesis of the MT-CO1 catalytic core subunit, TACO1 is required for assembly of respiratory chain complex IV; loss of TACO1 reduces fully assembled complex IV and supercomplexes. Reason: TACO1 knockout reduces levels of fully assembled complex IV, establishing a requirement for TACO1 in complex IV assembly downstream of its role in MT-CO1 translation. Consistent with the MC4DN8 (complex IV deficiency) disease phenotype and Reactome R-HSA-9864848 Complex IV assembly. Supporting Evidence: PMID:39036954 reduced levels of fully assembled monomeric and dimeric forms of respiratory chain CIV file:human/TACO1/TACO1-uniprot.txt cytochrome c oxidase deficiency and late-onset Leigh syndrome |
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