COG5 is a noncatalytic subunit of the conserved oligomeric Golgi complex. It helps assemble and stabilize the complex's lobe B, cooperating with COG7 to incorporate COG6. Cytosolic and peripheral Golgi-associated COG5 pools support the organization of trafficking machinery that recycles Golgi components and maintains Golgi architecture. Disruption of this machinery alters glycosylation indirectly by disturbing the distribution and stability of Golgi proteins. Biallelic COG5 variants cause a congenital disorder of glycosylation with variable neurological and systemic manifestations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: COG5 is a peripheral Golgi-membrane component. Reason: The UniProt location mapping agrees with the Golgi-associated pool of GTC-90/COG5 and Golgi localization of replacement COG5 in human cells. Membrane association does not imply a transmembrane protein. |
| GO:0000139 Golgi membrane | NAS PMID:27066481 COG Complex Complexities: Detailed Characterization of a Com... | ACCEPT | Summary: Human COG5 associates with the Golgi. Reason: The human HEK293T knockout/rescue study observes replacement COG5 at the Golgi. The NAS location is consistent with the earlier biochemical and microscopy evidence, without assigning the Golgi lumen to this peripheral subunit. Supporting Evidence: PMID:27066481 each replacement COG subunit was observed on the Golgi |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809006 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: This tethering event places the octameric COG complex at the cis-Golgi membrane alongside golgins and vesicle-associated factors. It supports the location of the COG5 subunit; it does not establish an isolated COG5 tethering reaction. Supporting Evidence: Reactome:R-HSA-6809006 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809010 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: The uncoating event retains the COG complex on the Golgi membrane while coat components are released. This supports the cellular-component annotation, not a claim that COG5 catalyses COPI coat removal. Supporting Evidence: Reactome:R-HSA-6809010 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809011 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: The cis-Golgi SNARE event represents membrane-associated COG in a tethered-vesicle assembly. Its location supports this annotation; SNARE zippering itself is performed by the SNARE machinery, not demonstrated for COG5. Supporting Evidence: Reactome:R-HSA-6809011 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811433 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: The curated event places the COG complex and associated SNARE assemblies at the Golgi membrane. Retain COG5 location through complex membership; specific contacts demonstrated for other COG subunits are not reassigned to COG5. Supporting Evidence: Reactome:R-HSA-6811433 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-8847544 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: This intra-Golgi tethering event represents COG with CUX1 and GOLGA5 at the Golgi membrane. It supports the location and integrated machinery context without assigning the golgins’ individual activities to COG5. Supporting Evidence: Reactome:R-HSA-8847544 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-8847635 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: The intra-Golgi fusion event includes membrane-associated COG as the tethering assembly is recycled. Retain the location; neither autonomous membrane fusion nor SNARE-complex catalysis is inferred for COG5. Supporting Evidence: Reactome:R-HSA-8847635 |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-8849748 | ACCEPT | Summary: The COG5-containing COG complex occupies Golgi membranes. Reason: The RAB-interaction event localizes the COG complex to the Golgi membrane. This is a complex-level location premise, not a target-specific demonstration of every listed RAB–COG5 contact. Supporting Evidence: Reactome:R-HSA-8849748 |
| GO:0000301 retrograde transport, vesicle recycling within Golgi | IMP PMID:27066481 COG Complex Complexities: Detailed Characterization of a Com... | ACCEPT | Summary: COG5 assembly activity supports intra-Golgi retrograde recycling. Reason: The human knockout source supports COG5-dependent complex stability, Golgi architecture and rescue. Together with cooperative complex assembly and the original intra-Golgi assay, this supports the inherited recycling process. Clinical PMID:19690088 reports delayed BFA-induced Golgi-to-ER redistribution rescued by wild-type COG5 cDNA; PMID:23228021 independently measures delayed GalT-GFP redistribution. These corroborate retrograde trafficking dysfunction, not a direct intra-Golgi cargo-flux measurement. No glycosylation catalysis is assigned to COG5. |
| GO:0005515 protein binding | IPI PMID:15047703 The binary interacting network of the conserved oligomeric G... | MODIFY | Summary: COG5 provides structural assembly activity within the COG complex. Reason: The source reports a weak but specific reciprocal COG5–COG7 association. More decisively, COG5 and COG7 together incorporate COG6, whereas neither alone does; this performed assembly work supports the integral-complex scaffold refinement. COG4–COG5 association is stronger, but pairwise strength is not the scaffold criterion. Human subunits were translated in rabbit reticulocyte lysate; the authors reserve conclusive binary directness for purified proteins. No isolated tethering or COG4-specific Sly1/STX5 bridging is assigned to COG5. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:15047703 Incorporation of COG6 into the complex depends on the concerted interaction of both COG5 and COG7 |
| GO:0005515 protein binding | IPI PMID:15047703 The binary interacting network of the conserved oligomeric G... | KEEP AS NON CORE | Summary: Positive COG5–COG4 assembly association. Reason: Reciprocal co-immunoprecipitation supports this stronger COG5–COG4 association. The authors call such lysate interactions direct in a relative sense, explicitly awaiting purified-protein confirmation. Retain the distinct positive pair alongside the cooperative-assembly scaffold refinement; COG4-specific Sly1/STX5 recruitment is not transferred to COG5. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex detects COG5 association with COG7. Reason: Two exact anti-tag co-immunoprecipitation records support this pair across HEK293T and HCT116 contexts. The mapped bait/prey roles and tags are preserved in the evidence index. AP-MS establishes co-purification, not necessarily an isolated direct interface; it independently corroborates the COG assembly context. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex detects COG5 association with COG4. Reason: Two exact anti-tag co-immunoprecipitation records support this pair across HEK293T and HCT116 contexts. The mapped bait/prey roles and tags are preserved in the evidence index. AP-MS establishes co-purification, not necessarily an isolated direct interface; it independently corroborates the COG assembly context. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: COG5 is located at the Golgi apparatus. Reason: The curated immunofluorescence location is consistent with independent COG5 Golgi localization. The underlying source images for GO_REF:0000052 were not independently inspected; no narrower compartment is inferred from that mapping alone. |
| GO:0005794 Golgi apparatus | IDA PMID:11980916 Characterization of a mammalian Golgi-localized protein comp... | ACCEPT | Summary: COG5 is a Golgi-associated complex component. Reason: The paper identifies COG5 in the purified complex and cites its established Golgi localization. Its new microscopy chiefly examines COG1 and COG7, so those images are not relabeled as COG5 assays. The original GTC-90 work and later human replacement-localization study independently substantiate the location. |
| GO:0005794 Golgi apparatus | IDA PMID:9792665 Purification and characterization of a novel 13 S hetero-oli... | ACCEPT | Summary: GTC-90/COG5 has a Golgi-associated pool. Reason: Original rat NRK microscopy and bovine fractionation support Golgi association, alongside human cDNA characterization. Retain the curated human annotation with this cross-species source scope; the cloning result does not make the localization experiment a human assay. Supporting Evidence: |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: COG5 also occurs in cytosolic complexes. Reason: Biochemical fractionation identifies a cytosolic GTC-90-containing complex as well as membrane-associated material. Cytosol and Golgi association describe complementary pools, not competing exclusive localizations. |
| GO:0006891 intra-Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved COG5 assembly supports intra-Golgi vesicle transport. Reason: Current yeast and human same-term records provide extant grounding, and the primary assembly and transport evidence supports the target role. The historical PAINT tree and IBD placement were not inspected; the target in WITH/FROM is legitimate descendant evidence, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000325596 UNRESOLVED Historical IBD placement and alignment were not inspected. Positive current descendant records and target evidence are assessed separately and support the retained biological assertion. |
| GO:0006891 intra-Golgi vesicle-mediated transport | IEA GO_REF:0000002 | ACCEPT | Summary: The COG5-family mapping agrees with intra-Golgi transport participation. Reason: The electronic family annotation is consistent with experimentally supported COG5 assembly in the transport complex. This retains a noncatalytic structural contribution to the transport machinery, without assigning isolated fusogenic activity. |
| GO:0006891 intra-Golgi vesicle-mediated transport | NAS PMID:9792665 Purification and characterization of a novel 13 S hetero-oli... | ACCEPT | Summary: GTC-90-containing complexes participate in intra-Golgi transport. Reason: The original complex purification and antibody-inhibition experiment supports transport participation. It does not isolate COG5 activity from the other subunits or resolve docking from fusion; the later positive assembly study provides a concrete structural contribution. |
| GO:0007030 Golgi organization | IMP PMID:27066481 COG Complex Complexities: Detailed Characterization of a Com... | ACCEPT | Summary: COG5-dependent assembly helps maintain Golgi organization. Reason: COG5 loss in human HEK293T cells destabilizes COG7 and reduces COG6, with dilated Golgi mini-stacks. COG5 has the least severe ultrastructural phenotype in this comparison, so it is not equated with COG4. Positive subcomplex reconstruction supplies the performed structural role behind the phenotype. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: The broad membrane location is biologically consistent. Reason: The membrane definition includes proteins attached to a lipid bilayer; it does not require an integral membrane protein. Independent fractionation and Golgi localization support peripheral COG5 membrane association, so retain the broad location as non-core. The exact COG5 row in the YTS proteomics supplement remains unverified; that source-link uncertainty is recorded separately. Neither plasma-membrane localization nor a verified YTS target detection is asserted. |
| GO:0017119 COG complex | IBA GO_REF:0000033 | ACCEPT | Summary: COG5 is a conserved COG-complex component. Reason: Current fly, yeast and human records support the same complex membership, which is independently established by primary biochemistry. The extant record set does not reconstruct the historical PAINT ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000325596 UNRESOLVED Historical IBD placement and alignment were not inspected. Positive current descendant records and target evidence are assessed separately and support the retained biological assertion. |
| GO:0017119 COG complex | IDA PMID:15047703 The binary interacting network of the conserved oligomeric G... | ACCEPT | Summary: Human COG5 contributes to the assembled COG complex. Reason: The original human-subunit reconstruction demonstrates COG5-containing assemblies. This supports integral complex membership while retaining the distinction between cooperative incorporation and a purified binary interface. Supporting Evidence: |
| GO:0017119 COG complex | IEA GO_REF:0000002 | ACCEPT | Summary: The COG5 family is correctly mapped to the COG complex. Reason: The family-based membership agrees with COG5 identification in the purified mammalian complex and the human assembly experiments. |
| GO:0017119 COG complex | NAS PMID:27066481 COG Complex Complexities: Detailed Characterization of a Com... | ACCEPT | Summary: COG5 is the lobe-B subunit tested in the knockout panel. Reason: The source explicitly deletes COG5 and measures interdependence of COG5, COG7 and COG6. Complex membership is independently supported by the original assembly and purification studies, not only by similar loss phenotypes. |
| GO:0017119 COG complex | NAS PMID:9792665 Purification and characterization of a novel 13 S hetero-oli... | ACCEPT | Summary: GTC-90 was identified as a component of the Golgi transport complex. Reason: The original purification identifies GTC-90 in a transport-stimulating heterooligomer. Later work unifies this material with the eight-subunit COG complex; preserve the original nomenclature and source identity. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-6811431 | ACCEPT | Summary: The modeled COG complex occupies the trans-Golgi network membrane. Reason: The RAB6/endosome-derived-vesicle event places a COG-containing assembly at the trans-Golgi network membrane. It supports the location. Reactome explicitly leaves joint GARP–COG capture of one vesicle unestablished; no such simultaneous mechanism is inferred. Supporting Evidence: Reactome:R-HSA-6811431 |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-6814682 | ACCEPT | Summary: The modeled COG complex occupies the trans-Golgi network membrane. Reason: The early-endosome-vesicle fusion event represents COG in the trans-Golgi membrane context. It supports this location while the precise fusion mechanism remains incompletely established; it does not assign autonomous fusion activity to COG5. Supporting Evidence: Reactome:R-HSA-6814682 |
| GO:0048219 inter-Golgi cisterna vesicle-mediated transport | IDA PMID:9792665 Purification and characterization of a novel 13 S hetero-oli... | ACCEPT | Summary: COG5-containing GTC supports inter-cisternal Golgi transport. Reason: The original bovine complex stimulates a CHO donor/acceptor Golgi assay, and anti-GTC-90 IgG inhibits it while preimmune IgG does not. Fab fragments are noninhibitory. The glycosylation readout leaves the precise transport step and direction unresolved; it is not purified human COG5 catalysis. |
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Download this section (compressed HTML)Q: Which COG5 product-specific regions control COG7 association and cooperative COG6 incorporation?
Q: Does COG5 directly stabilize or recycle ATP7A, and can that effect be separated from loss of the larger COG complex?
Experiment: Compare sequence-verified COG5 products at matched expression in deficient human cells, measuring COG7/COG6 assembly and defined retrograde cargo flux alongside Golgi morphology.
Hypothesis: Product-specific sequence changes can alter cooperative assembly without uniformly abolishing every COG5 interaction.
Experiment: Measure ATP7A localization and recycling kinetics after acute COG5 perturbation, with assembly-preserving separation-of-function variants and protein-turnover controls.
Hypothesis: The ATP7A stability phenotype reflects a separable trafficking step rather than an intrinsic copper-transport activity of COG5.
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