Affinage

COG7

Conserved oligomeric Golgi complex subunit 7 · UniProt P83436

Length
770 aa
Mass
86.3 kDa
Annotated
2026-06-09
33 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COG7 is a subunit of the conserved oligomeric Golgi (COG) complex, an eight-subunit peripheral membrane assembly required for normal Golgi morphology and glycosylation (PMID:11980916). Within the complex, COG7 belongs to the lobe B subcomplex, forming a stable association with COG5 and COG6, while COG8 bridges lobe B to the lobe A subcomplex (COG1-4) (PMID:16051600); the COG5-COG7 interface is built from a CATCHR helical-rod fold shared with other tethering complexes and is conserved from yeast to humans (PMID:25331899). Functionally, COG7 mediates retrograde tethering of intra-Golgi COPI vesicles: its depletion causes accumulation of COG complex-dependent vesicles carrying medial-Golgi glycosyltransferases, and isolated such vesicles dock in a COG-dependent manner in vitro (PMID:16420527). COG7 directly binds golgin-84 on COPI vesicles prior to SNARE assembly, and supports SNARE function, since COG7-deficient cells show mislocalized v-SNAREs GS15 and GS28 and reduced retrograde transport to the ER (PMID:20874812, PMID:16510524). Through this tethering and recycling activity, COG7 maintains both N- and O-linked glycosylation as well as glycosaminoglycan modification of proteoglycans (PMID:15107842, PMID:34053170), and loss-of-function mutations in COG7 underlie a congenital disorder of glycosylation that disrupts COG complex integrity and Golgi trafficking (PMID:15107842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established COG7 as a bona fide subunit of the COG complex, defining the molecular context in which all later mechanism would be interpreted.

    Evidence Biochemical purification, deep-etch EM of the native complex, and analysis of CHO Golgi mutants

    PMID:11980916

    Open questions at the time
    • Did not resolve COG7's position within the complex architecture
    • No functional role for COG7 specifically assigned
  2. 2004 High

    Connected COG7 to human disease, showing that a splice-site mutation destabilizes the COG complex and broadly disrupts glycosylation, establishing COG7 as a glycosylation-maintaining factor.

    Evidence Patient fibroblast analysis with COG subunit immunoblotting and N-/O-glycosylation assays

    PMID:15107842

    Open questions at the time
    • Did not define the trafficking step COG7 controls
    • Mechanism linking complex disassembly to glycan defects not resolved
  3. 2005 High

    Resolved the subcomplex organization, placing COG7 in lobe B (COG5-7) bridged to lobe A by COG8, and showed COG subunits have distinctive, non-redundant roles.

    Evidence Gel filtration, immunoblotting, and immunofluorescence in COG7-patient fibroblasts and RNAi cells

    PMID:16051600

    Open questions at the time
    • Did not determine atomic-level interface geometry
    • Functional differences between subunits not mechanistically explained
  4. 2006 High

    Defined COG7's molecular activity as retrograde vesicle tethering, showing depletion accumulates glycosyltransferase-bearing CCD vesicles and reconstituting COG-dependent docking in vitro.

    Evidence siRNA knockdown, immunofluorescence, in vitro vesicle docking reconstitution, and glycosylation assays

    PMID:16420527

    Open questions at the time
    • Direct vesicle-binding partner of COG7 not yet identified
    • Order of tethering relative to SNARE assembly unresolved
  5. 2006 High

    Linked COG7 loss to specific SNARE/retrograde-transport defects, showing slowed retrograde transport to the ER and destabilized v-SNAREs GS15/GS28, with rescue upon complementation.

    Evidence Brefeldin A retrograde assay, immunofluorescence, Western blotting, and wild-type COG7 complementation in patient fibroblasts

    PMID:16510524

    Open questions at the time
    • Whether COG7 binds SNAREs directly not shown
    • Anterograde-versus-retrograde selectivity mechanism unexplained
  6. 2010 Medium

    Identified a direct vesicle-side binding partner, golgin-84, showing COG7 engages golgin-84 on COPI vesicles before SNARE assembly to tether retrograde carriers.

    Evidence Co-immunoprecipitation/interaction analyses, COG3/COG7 knockdown, and vesicle cargo characterization

    PMID:20874812

    Open questions at the time
    • Single-lab interaction without structural mapping
    • Stoichiometry and regulation of the COG7-golgin-84 contact unknown
  7. 2012 Medium

    Extended COG7 function beyond glycosylation into cytokinesis, placing it upstream of a Giotto-Rab11 membrane-addition pathway in Drosophila.

    Evidence Drosophila loss-of-function genetics, immunofluorescence, co-immunoprecipitation, and EM

    PMID:22946051

    Open questions at the time
    • Ortholog-based; human relevance of cytokinesis role not established
    • Direct versus indirect Cog7-Gio interaction not dissected
  8. 2014 High

    Provided the atomic basis of the COG5-COG7 interface, revealing a CATCHR fold shared with Dsl1/exocyst/GARP tethers and confirming the interface is functionally required.

    Evidence X-ray crystallography of Cog5-Cog7, mutagenesis, and trafficking/glycosylation assays in human cells

    PMID:25331899

    Open questions at the time
    • No structure of the full assembled complex
    • How CATCHR rods engage membranes/vesicles not visualized
  9. 2014 Medium

    Characterized the membrane-attachment behavior of COG complexes, showing stable membrane association and that distinct subassemblies bind distinct partners (β-COP, p115, STX5).

    Evidence Knock-sideways depletion, FRAP, FLIP in live HeLa cells, and co-immunoprecipitation of tagged subcomplexes

    PMID:24649395

    Open questions at the time
    • Which partner COG7 specifically anchors not isolated
    • Single-lab interaction set
  10. 2014 Low

    Implicated COG7-dependent trafficking in HIV-1 replication at an early pre-reverse-transcription step.

    Evidence siRNA knockdown in human cells with HIV-1 RT-product and fusion assays

    PMID:25179963

    Open questions at the time
    • No mechanistic pathway placement beyond general COG function
    • Single lab, single phenotypic readout, indirect effect not excluded
  11. 2017 Medium

    Connected COG7 to Rab1/GOLPH3-regulated Golgi trafficking, showing GTP-Rab1 rescues Cog7-loss cytokinesis and neuromuscular defects and that loss alters the N-glycome.

    Evidence Drosophila genetics, colocalization, N-glycome mass spectrometry, and Rab1-overexpression rescue

    PMID:28883096

    Open questions at the time
    • Ortholog-based; direct Cog7-GOLPH3/Rab1 contacts not defined
    • Whether human COG7 acts in the same pathway untested
  12. 2021 Medium

    Demonstrated a subunit-specific glycan role, showing COG7 knockout reduces GAG chain length on secreted proteoglycans and alters cell-associated GAG turnover differently from other COG subunits.

    Evidence CRISPR knockout of COG subunits in HEK293T cells with proteoglycan/GAG chain-length analysis

    PMID:34053170

    Open questions at the time
    • Mechanism linking COG7 loss to differential GAG turnover unresolved
    • Specific glycosyltransferases affected not identified
  13. 2024 Medium

    Confirmed the in vivo requirement of the COG5-COG7 interface for complex integrity by showing a disease COG5 variant abrogates the interaction in patient cells.

    Evidence Co-immunoprecipitation in patient-derived cells plus in silico stability analysis

    PMID:38987656

    Open questions at the time
    • Single co-IP readout in patient cells
    • Quantitative effect on downstream trafficking not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How COG7 selectively coordinates direct partners (golgin-84, SNAREs, β-COP/p115) into a defined tethering reaction, and how this maps onto the substrate-specific glycosylation defects seen in patients, remains unresolved.
  • No structure of the fully assembled human COG complex on membranes
  • Direct COG7-SNARE contact not biochemically proven
  • Rules governing which glycosyltransferases are mislocalized upon COG7 loss unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005794 Golgi apparatus 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-392499 Metabolism of proteins 2
Partners
COG5COG6COG8GOLGIN-84GS15GS28
Complex memberships
COG complexCOG lobe B subcomplex (COG5-COG6-COG7)

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 COG7 was identified as a previously uncharacterized subunit of the conserved oligomeric Golgi (COG) complex, a ~37-nm peripheral membrane complex with two globular domains, required for normal Golgi morphology. The complex also contains Cog1-6 and Cog8, and its disruption (in ldlB/ldlC mutants) impairs Golgi structure. Biochemical purification, deep-etch EM of purified complex, immunofluorescence, analysis of CHO cell mutants The Journal of cell biology High 11980916
2004 A splice-site mutation in COG7 impairs integrity of the COG complex and alters Golgi trafficking, resulting in disruption of multiple glycosylation pathways (both N- and O-linked glycosylation). Patient fibroblast analysis, Western blotting showing reduced COG subunit levels, glycosylation assays Nature medicine High 15107842
2005 COG7-deficient cells show that Cog5-7 form a stable subcomplex (lobe B), and Cog8 helps bridge lobe A (Cog1-4) and lobe B (Cog5-7) subcomplexes into the complete COG complex. Only one or two of the seven Cog1/Cog2-dependent Golgi membrane proteins (GEARs) are also sensitive to Cog7 deficiency, indicating COG subunits play distinctive roles. Immunoblotting, gel filtration, immunofluorescence microscopy of COG-deficient cells (COG7-patient fibroblasts and RNAi knockdown cells) The Journal of biological chemistry High 16051600
2006 COG7 knockdown (like COG3 knockdown) causes accumulation of COG complex-dependent (CCD) vesicles carrying medial-Golgi enzymes (glycosyltransferases), leading to disrupted glycosylation of plasma membrane and lysosomal glycoproteins. In vitro reconstitution showed COG complex-dependent docking of isolated CCD vesicles, supporting the role of the COG complex in retrograde vesicle tethering and recycling of Golgi-resident glycosylation enzymes. siRNA knockdown of COG7, immunofluorescence, in vitro vesicle docking reconstitution assay, glycosylation assays Traffic (Copenhagen, Denmark) High 16420527
2006 COG7-deficient patient fibroblasts show slower retrograde transport of Golgi proteins to the ER (via brefeldin A-induced tubules), abnormal localization of ERGIC-53 and v-SNAREs GS15 and GS28, and greatly decreased steady-state GS15 levels. Anterograde trafficking was much less affected. All abnormalities were normalized in COG7-corrected fibroblasts. Immunofluorescence, brefeldin A retrograde transport assay, Western blotting, complementation with wild-type COG7 Molecular biology of the cell High 16510524
2010 Golgin-84 directly interacts with the COG complex through its subunit Cog7 (by protein interaction analyses). CCD vesicles accumulating in Cog3 or Cog7 KD cells carry golgin-84. Golgin-84 on COPI vesicles interacts with the COG complex prior to SNARE assembly, indicating COG7 participates in tethering of intra-Golgi retrograde COPI vesicles via golgin-84. Co-immunoprecipitation/protein interaction analyses, siRNA knockdown of Cog3/Cog7, immunofluorescence, vesicle characterization Traffic (Copenhagen, Denmark) Medium 20874812
2012 In Drosophila, loss-of-function Cog7 mutations disrupt Golgi architecture, reduce Golgi stack numbers in primary spermatocytes, impair acroblast assembly in spermatids, and cause cytokinesis failure. Rab11 and the phosphatidylinositol transfer protein Giotto (Gio) fail to recruit to the cleavage site in Cog7 mutants; Gio co-immunoprecipitates with Cog7 and Rab11 in testes, placing Cog7 upstream of a Gio-Rab11 pathway controlling membrane addition during cytokinesis. Drosophila genetics (loss-of-function mutants), immunofluorescence, co-immunoprecipitation, electron microscopy Journal of cell science Medium 22946051
2014 Crystal structure of the Cog5-Cog7 complex revealed that Cog5 belongs to the CATCHR (complexes associated with tethering containing helical rods) fold family, with structural homology to subunits of the Dsl1, exocyst, and GARP complexes. Biochemical and functional studies confirmed the physiological relevance of the Cog5-Cog7 interface, showed it is conserved from yeast to humans, and demonstrated that disruption of this interface in human cells causes defects in trafficking and glycosylation. X-ray crystallography, biochemical binding assays, mutagenesis, functional assays in human cells (trafficking and glycosylation) Proceedings of the National Academy of Sciences of the United States of America High 25331899
2014 Multiple complementary approaches (knock-sideways depletion, FRAP, FLIP) showed that the assembled COG complex does not diffuse freely from Golgi periphery in live HeLa cells. COG subunits (including those in COG7-depleted cells) remained membrane-associated even when Golgi architecture was severely disrupted. Different COG assemblies preferentially bind distinct Golgi membrane partners: β-COP, p115, and SNARE STX5 bind to different COG subunit subcomplexes, indicating multipronged membrane attachment. Knock-sideways depletion, FRAP, FLIP in live HeLa cells, overexpression of tagged COG subcomplexes, co-immunoprecipitation Cellular logistics Medium 24649395
2014 Targeted silencing of COG7 (along with other lobe B COG subunits COG5, COG6, COG8) inhibited HIV-1 replication at a step preceding late reverse transcription but did not affect viral fusion, implicating COG7-dependent Golgi/TGN trafficking in an early step of HIV-1 replication. siRNA knockdown of COG7 in human cells, HIV-1 replication assays (RT product formation), viral fusion assay Virus research Low 25179963
2017 In Drosophila, Cog7 colocalizes with GOLPH3 at Golgi stacks. The COG complex cooperates with Rab1 and GOLPH3 to regulate Golgi trafficking; overexpression of GTP-bound Rab1 rescues cytokinesis and locomotor defects caused by loss of Cog7. Cog7 mutants exhibit altered N-glycome profiles and reduced bouton numbers at larval neuromuscular junctions. Drosophila genetics (loss-of-function mutants), immunofluorescence colocalization, N-glycome mass spectrometry, genetic rescue by Rab1 overexpression, NMJ bouton counting Journal of cell science Medium 28883096
2021 Knockout of COG7 in HEK293T cells reduces glycosaminoglycan (GAG) modification of proteoglycans. Unlike cells lacking COG1 or COG8 (which bridge lobes A and B), COG7 KO cells show reduced GAG chain lengths on secreted proteoglycans. COG7 KO cells (unlike COG4 KO) display longer cell-associated GAG chains than wild-type, suggesting a role for COG7 in cellular turnover of proteoglycans. CRISPR/KO of COG subunits in HEK293T cells, proteoglycan and GAG chain length analysis Traffic (Copenhagen, Denmark) Medium 34053170
2024 A COG5 missense variant (p.Leu100Phe) abrogates the COG5-COG7 protein interaction, as confirmed by co-immunoprecipitation in patient-derived cells, demonstrating that this interface is required for COG complex integrity in vivo. Co-immunoprecipitation in patient-derived cells, in silico stability/solubility analysis Journal of human genetics Medium 38987656

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. Nature medicine 246 15107842
2002 Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function. The Journal of cell biology 239 11980916
2006 COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation. Traffic (Copenhagen, Denmark) 138 16420527
2008 Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydrate research 103 18353293
2007 COG8 deficiency causes new congenital disorder of glycosylation type IIh. Human molecular genetics 96 17331980
2009 Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation. Human molecular genetics 94 19690088
2007 A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia. European journal of human genetics : EJHG 82 17356545
2005 Genetic analysis of the subunit organization and function of the conserved oligomeric golgi (COG) complex: studies of COG5- and COG7-deficient mammalian cells. The Journal of biological chemistry 74 16051600
2010 Interaction of Golgin-84 with the COG complex mediates the intra-Golgi retrograde transport. Traffic (Copenhagen, Denmark) 62 20874812
2006 COG-7-deficient Human Fibroblasts Exhibit Altered Recycling of Golgi Proteins. Molecular biology of the cell 58 16510524
2011 Plasma N-glycan profiling by mass spectrometry for congenital disorders of glycosylation type II. Clinical chemistry 57 21273509
2007 Molecular and clinical characterization of a Moroccan Cog7 deficient patient. Molecular genetics and metabolism 45 17395513
2013 Pathway analysis of a genome-wide association study in schizophrenia. Gene 43 23644028
2012 COG5-CDG: expanding the clinical spectrum. Orphanet journal of rare diseases 38 23228021
2017 Rab1 interacts with GOLPH3 and controls Golgi structure and contractile ring constriction during cytokinesis in Drosophila melanogaster. Open biology 37 28100664
2012 Mutations in Cog7 affect Golgi structure, meiotic cytokinesis and sperm development during Drosophila spermatogenesis. Journal of cell science 35 22946051
2009 A new mutation in COG7 extends the spectrum of COG subunit deficiencies. European journal of medical genetics 34 19577670
2017 A Population-Based Study on Congenital Disorders of Protein N- and Combined with O-Glycosylation Experience in Clinical and Genetic Diagnosis. The Journal of pediatrics 29 28139241
2017 Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency. Journal of inherited metabolic disease 27 28409271
2014 Multipronged interaction of the COG complex with intracellular membranes. Cellular logistics 24 24649395
2017 COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes. Journal of cell science 23 28883096
2023 Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review. International journal of molecular sciences 21 37239976
2014 Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex. Proceedings of the National Academy of Sciences of the United States of America 20 25331899
2014 Target silencing of components of the conserved oligomeric Golgi complex impairs HIV-1 replication. Virus research 14 25179963
2021 Proteoglycan synthesis in conserved oligomeric Golgi subunit deficient HEK293T cells is affected differently, depending on the lacking subunit. Traffic (Copenhagen, Denmark) 9 34053170
2023 COG-imposed Golgi functional integrity determines the onset of dark-induced senescence. Nature plants 8 37884654
2023 Discovery and bioinspired total syntheses of unprecedented sesquiterpenoid dimers unveiled bifurcating [4 + 2] cycloaddition and target differentiation of enantiomers. Chemical science 7 38274075
2014 Wrinkled skin and fat pads in patients with ALG8-CDG: revisiting skin manifestations in congenital disorders of glycosylation. Pediatric dermatology 7 24555185
2025 Machine learning in Alzheimer's disease genetics. Nature communications 6 40691194
2021 Conserved oligomeric Golgi (COG) complex genes functioning in defense are expressed in root cells undergoing a defense response to a pathogenic infection and exhibit regulation my MAPKs. PloS one 5 34437620
2021 Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast. BMC ecology and evolution 2 34039270
2024 Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine 0 38489667
2024 Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein. Journal of human genetics 0 38987656

Missed literature

Know a paper Affinage missed for COG7? Flag it for the maintainers and the community.

No submissions yet.