COA5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred mitochondrial localization. COA5/PET191 is a well-established mitochondrial intermembrane-space protein; a broad mitochondrion term is correct, and is corroborated by direct and high-throughput evidence below and by the UniProt-curated subcellular location. Reason: Consistent with the curated subcellular location and with the protein's role in complex IV assembly. More specific compartment terms (IMS, inner membrane) are also present in the annotation set. Supporting Evidence: file:human/COA5/COA5-uniprot.txt Mitochondrion intermembrane space
GO:0033617 mitochondrial respiratory chain complex IV assembly	IBA GO_REF:0000033	ACCEPT	Summary: This is the core, experimentally supported function of COA5. It is an assembly factor for cytochrome c oxidase (complex IV) required at an early step of assembly, participating in the copper/heme metallochaperone modules that mature the MT-CO1/MT-CO2 metal centers. Reason: The IBA inference matches the strong experimental evidence in human cells and the UniProt-curated function. This represents the central biological role of the gene. Supporting Evidence: file:human/COA5/COA5-uniprot.txt Assembly factor for cytochrome c oxidase PMID:35750769 another IMS-resident twin CX9C protein, PET191 (alias COA5), whose overexpression enhanced CcO levels and activity in COX11-KO cells from 15% to 40% of WT, and up to 50% when co-overexpressed with COX17
GO:0005758 mitochondrial intermembrane space	IEA GO_REF:0000044	ACCEPT	Summary: Intermembrane space is the UniProt-curated primary subcellular location of COA5 and the most specific compartment term supported by the literature. As a twin CX9C / CHCH protein it is imported into and oxidatively folded in the IMS. Reason: Matches the curated subcellular location and the twin CX9C IMS-resident description in the primary literature; this is the most informative localization term available. Supporting Evidence: file:human/COA5/COA5-uniprot.txt Mitochondrion intermembrane space PMID:35750769 another IMS-resident twin CX9C protein, PET191 (alias COA5)
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a large-scale binary interactome (Y2H) screen. The recorded partner (KRT31, a keratin) is a non-mitochondrial, non-physiological partner and this term conveys no specific molecular function for a mitochondrial intermembrane-space assembly factor. Reason: Uninformative "protein binding" derived from a high-throughput binary interactome map with an implausible (keratin) partner. Retained per policy (experimental IPI not removed) but flagged as over-annotation; it does not represent a core molecular function. Supporting Evidence: PMID:25416956 we more than doubled the number of high-quality binary PPIs
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the HuRI reference binary interactome map. The recorded partners (CYSRT1, TCF4 isoform, KRTAP1-3) are non-mitochondrial keratin-associated / transcription-factor proteins and are not plausible physiological partners for an IMS complex IV assembly factor. Reason: Uninformative "protein binding" from a systematic binary interactome screen with implausible partners. Retained per policy but flagged as over-annotation; not a core molecular function. Supporting Evidence: PMID:32296183 reference map of the human binary protein interactome
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) localizes COA5 to the mitochondrion, consistent with its curated IMS location and its function as a complex IV assembly factor. Reason: Direct experimental localization consistent with all other evidence; the broad mitochondrion term is correct. Supporting Evidence: file:human/COA5/COA5-uniprot.txt Mitochondrion intermembrane space
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: COA5 was detected in the high-confidence quantitative human mitochondrial proteome, supporting its mitochondrial localization. Reason: High-throughput but high-confidence mitochondrial proteome evidence consistent with the curated location and other localization annotations. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9865449	ACCEPT	Summary: Reactome places COA5 in the metallochaperone complex that inserts copper into MT-CO1 at the inner mitochondrial membrane. This reflects where the complex IV metal-center maturation reactions occur; COA5 is an IMS protein acting at the IMS-facing side of the inner membrane. Reason: Traceable Reactome assertion consistent with COA5's role in the inner-membrane-associated complex IV metallochaperone machinery. The most specific curated location remains the intermembrane space (above). Supporting Evidence: Reactome:R-HSA-9865449 A metallochaperone complex consisting of nine subunits (COA3, COA5, COX10, dimeric COX11, COX15, COX16, COX19, SCO1, SCO2) carries a copper cation
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9865579	ACCEPT	Summary: Reactome associates COA5-containing metallochaperone machinery with the inner-membrane step in which MT-CO1 and MT-CO2 pre-assembly complexes associate and heme moieties are installed during complex IV assembly. Reason: Traceable Reactome assertion consistent with COA5's role at the inner membrane during complex IV biogenesis. Supporting Evidence: Reactome:R-HSA-9865579 The assembly of catalytic metal redox centers (heme and copper) at MT-CO1 and MT-CO2 subunits of Complex IV must be coordinated
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9865630	ACCEPT	Summary: Reactome associates COA5 with the inner-membrane metallochaperone reaction that inserts copper into MT-CO2 (CuA center) during complex IV assembly. Reason: Traceable Reactome assertion consistent with COA5's role in inner-membrane-associated copper delivery for complex IV. Supporting Evidence: file:human/COA5/COA5-uniprot.txt Assembly factor for cytochrome c oxidase