COX18

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (PAN-GO) inference placing COX18 in the mitochondrial inner membrane, where it acts as a membrane insertase. This is the correct anatomical location supported by direct experimental data in human and yeast orthologues. Reason: COX18 is an OXA1/YidC-family multi-pass inner-membrane insertase; localisation to the mitochondrial inner membrane is directly supported experimentally, and the IBA is consistent with the family's conserved localisation. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0032977 membrane insertase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of membrane insertase activity, the defining molecular function of the OXA1/ALB3/YidC insertase family to which COX18 belongs. This is the core molecular function. Reason: Membrane insertase activity is directly demonstrated for human COX18 and its yeast orthologue Cox18p, and is the conserved family function; the IBA is at the correct level of specificity. Supporting Evidence: PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the PMID:16212937 Cox18p catalyses the insertion of Cox2p COOH-tail into the
GO:0032979 protein insertion into mitochondrial inner membrane from matrix	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that COX18 participates in insertion of protein (the MT-CO2 C-tail) into the mitochondrial inner membrane from the matrix side. This matches the experimentally established mechanism (translocation of the MT-CO2 C-terminus across the inner membrane). Reason: The direction (from the matrix) is consistent with COX18's role in exporting/ translocating the MT-CO2 C-tail across the inner membrane, and is directly supported by IDA in PMID:28330871; retained as a core biological process. Supporting Evidence: PMID:28330871 transiently interacts with COX2 to promote translocation across the inner PMID:16212937 Cox18p catalyses the insertion of Cox2p COOH-tail into the
GO:0033617 mitochondrial respiratory chain complex IV assembly	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that COX18 is required for mitochondrial respiratory chain complex IV (cytochrome c oxidase) assembly. This is the core biological process and is directly supported by loss-of-function studies in human cells. Reason: COX18 knockout causes isolated complex IV deficiency and its C-tail translocation activity is required for MT-CO2 maturation and complex IV assembly; IBA is well supported and mitochondria-specific. Supporting Evidence: PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the PMID:40830826 reduced assembly and activity of Complex IV
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation of mitochondrial inner-membrane localisation derived from the UniProt Subcellular Location vocabulary. This matches the experimentally determined localisation. Reason: The UniProt subcellular location mapping is correct and concordant with the IDA/EXP inner-membrane annotations; this is the anatomical location where COX18 functions. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic annotation to the generic parent term "membrane". Correct but far less informative than the specific mitochondrial inner membrane localisation established experimentally. Reason: Not wrong (COX18 is an integral membrane protein), but "membrane" is a broad parent of the specific and experimentally supported GO:0005743 mitochondrial inner membrane; retained as non-core. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0032977 membrane insertase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation of membrane insertase activity based on membership of the YidC/ALB3/OXA1/COX18 family (IPR001708). Concordant with the experimentally supported core molecular function. Reason: The InterPro domain-to-GO mapping correctly assigns the family-defining insertase activity, which is directly demonstrated for COX18. Supporting Evidence: file:human/COX18/COX18-uniprot.txt Belongs to the OXA1/ALB3/YidC family PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the
GO:0051205 protein insertion into membrane	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning electronic annotation to the broad process "protein insertion into membrane". Correct in essence but more general than the specific mitochondrial-inner-membrane insertion process COX18 mediates. Reason: COX18 specifically inserts the MT-CO2 C-tail into the mitochondrial inner membrane from the matrix; the more specific GO:0032979 (protein insertion into mitochondrial inner membrane from matrix) better captures this. Modify to the specific term rather than the generic parent. Proposed replacements: protein insertion into mitochondrial inner membrane from matrix Supporting Evidence: PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0032977 membrane insertase activity	IMP PMID:40830826 Biallelic variants in COX18 cause a mitochondrial disorder p...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence that COX18 has membrane insertase activity, from disease-variant functional studies showing patient variants impair the insertase-dependent translocation of the MT-CO2 C-terminus. Reason: Loss-of-function COX18 variants reduce the ability to translocate the MT-CO2 C-terminus across the inner membrane, directly supporting the insertase molecular function; this is the core MF. Supporting Evidence: PMID:40830826 reduced ability to translocate MTCO2 C-terminus PMID:40830826 essential for the insertase function of proteins from the same family
GO:0033617 mitochondrial respiratory chain complex IV assembly	IMP PMID:40830826 Biallelic variants in COX18 cause a mitochondrial disorder p...	ACCEPT	Summary: Mutant-phenotype evidence that COX18 is required for mitochondrial complex IV assembly; biallelic patient variants cause partial loss of function that reduces complex IV assembly and activity. Reason: Direct disease-variant functional data show reduced complex IV assembly and activity upon COX18 loss of function; this is a core biological process. Supporting Evidence: PMID:40830826 reduced assembly and activity of Complex IV
GO:0033617 mitochondrial respiratory chain complex IV assembly	TAS Reactome:R-HSA-9864848	ACCEPT	Summary: Reactome traceable-author-statement annotation placing COX18 in complex IV assembly. Concordant with the experimental evidence. Reason: The Reactome pathway curation correctly captures COX18's role in complex IV assembly; consistent with IMP/IBA evidence for the same core process. Supporting Evidence: PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput proteomics localisation of COX18 to the mitochondrion. Correct but broad; the specific compartment is the inner membrane. Reason: A correct but less-informative parent of the experimentally established GO:0005743 mitochondrial inner membrane; retained as non-core. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0032977 membrane insertase activity	EXP PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	ACCEPT	Summary: Experimental evidence that human COX18 acts as a membrane insertase within the MT-CO2 maturation module, transiently interacting with COX2 to promote translocation of its C-tail across the inner membrane. Reason: Direct experimental demonstration of the insertase molecular function in a human COX18 knockout / complementation system; this is the core MF. Supporting Evidence: PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0005743 mitochondrial inner membrane	EXP PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	ACCEPT	Summary: Experimental localisation of COX18 to the mitochondrial inner membrane, consistent with its insertase function on inner-membrane substrates. Reason: Directly determined inner-membrane localisation; this is the anatomical location where COX18 acts. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0032977 membrane insertase activity	IGI PMID:16911509 The COX18 gene, involved in mitochondrial biogenesis, is fun...	ACCEPT	Summary: Genetic-interaction evidence supporting membrane insertase activity for COX18, from cross-species complementation studies (human/fission-yeast) placing it in the Oxa1/Cox18 insertase family. Reason: The functional conservation and genetic interaction data support the insertase molecular function; consistent with the multiple experimental lines for the core MF. Supporting Evidence: PMID:16911509 facilitate the membrane insertion of various hydrophobic PMID:16911509 Oxa1 and Cox18, which play successive roles
GO:0005515 protein binding	IPI PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	REMOVE	Summary: Physical-interaction annotation (with/from SCO1/O75880, MT-CO2/P00403 and COX20/Q5RI15) recording COX18's partners within the MT-CO2 maturation module. As a bare "protein binding" term it is uninformative about molecular function. Reason: Bare GO:0005515 protein binding conveys no specific molecular function. The interactions are real (COX18 transiently engages its substrate MT-CO2 and the COX20/SCO1 maturation module), and their functional content is already captured by the insertase MF (GO:0032977) and the complex IV assembly BP (GO:0033617). Removal does not imply the interactions are false. Supporting Evidence: file:human/COX18/COX18-uniprot.txt Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX20, PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0032977 membrane insertase activity	IDA PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	ACCEPT	Summary: Direct-assay evidence that COX18 has membrane insertase activity in the MT-CO2 maturation module. Reason: Direct experimental demonstration of the core insertase molecular function; duplicates the EXP/IBA/IEA/IGI/IMP support for GO:0032977. Supporting Evidence: PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0032979 protein insertion into mitochondrial inner membrane from matrix	IDA PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	ACCEPT	Summary: Direct-assay evidence that COX18 mediates insertion of protein (the MT-CO2 C-tail) into the mitochondrial inner membrane from the matrix side. Reason: The mechanism (translocation of the MT-CO2 C-terminus across the inner membrane) is directly demonstrated; this is a core biological process. Supporting Evidence: PMID:28330871 transiently interacts with COX2 to promote translocation across the inner
GO:0033617 mitochondrial respiratory chain complex IV assembly	IMP PMID:28330871 Human mitochondrial cytochrome c oxidase assembly factor COX...	ACCEPT	Summary: Mutant-phenotype evidence that COX18 is required for complex IV assembly; a COX18 knockout HEK293T line displays isolated complete complex IV deficiency. Reason: Direct knockout phenotype establishes COX18's requirement for complex IV assembly; core biological process, duplicating the IBA/TAS/IMP support. Supporting Evidence: PMID:28330871 COX18 is an additional COX2 assembly factor that belongs to the
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9902096	ACCEPT	Summary: Reactome traceable-author-statement annotation of inner-membrane localisation, from the pathway describing COX18 inserting nascent MT-CO2 in the COX20:TMEM77 module. Reason: Concordant with the experimentally determined inner-membrane localisation; correct anatomical location. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0008535 respiratory chain complex IV assembly	IGI PMID:16911509 The COX18 gene, involved in mitochondrial biogenesis, is fun...	MODIFY	Summary: Genetic-interaction evidence that COX18 is involved in cytochrome c oxidase assembly. The term used (GO:0008535) is the general, bacteria-inclusive complex IV assembly term rather than the mitochondria-specific one. Reason: GO:0008535 (respiratory chain complex IV assembly) is a sibling/general term that also covers bacterial cytochrome c oxidase; for a mitochondrial human protein the specific GO:0033617 (mitochondrial respiratory chain complex IV assembly) is more appropriate. Modify to the mitochondria-specific term. Proposed replacements: mitochondrial respiratory chain complex IV assembly Supporting Evidence: PMID:16911509 Oxa1 and Cox18, which play successive roles
GO:0051204 protein insertion into mitochondrial membrane	IGI PMID:16911509 The COX18 gene, involved in mitochondrial biogenesis, is fun...	MODIFY	Summary: Genetic-interaction evidence that COX18 mediates protein insertion into the mitochondrial membrane. The term is a broad parent of the specific inner-membrane-from-matrix insertion process. Reason: COX18 specifically inserts the MT-CO2 C-tail into the mitochondrial inner membrane from the matrix side; the more specific GO:0032979 better captures the established mechanism than the generic "mitochondrial membrane" parent. Proposed replacements: protein insertion into mitochondrial inner membrane from matrix Supporting Evidence: PMID:16911509 facilitate the membrane insertion of various hydrophobic PMID:16212937 Cox18p catalyses the insertion of Cox2p COOH-tail into the
GO:0005743 mitochondrial inner membrane	IDA PMID:16212937 hCOX18 and hCOX19: two human genes involved in cytochrome c ...	ACCEPT	Summary: Direct-assay localisation of human COX18 to the mitochondrial inner membrane, analogous to the yeast Cox18p localisation. Reason: Direct experimental determination of inner-membrane localisation; the correct anatomical location where COX18 functions. Supporting Evidence: file:human/COX18/COX18-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:16212937 Cox18p catalyses the insertion of Cox2p COOH-tail into the

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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