Affinage

COG7

Conserved oligomeric Golgi complex subunit 7 · UniProt P83436

Length
770 aa
Mass
86.3 kDa
Annotated
2026-04-28
34 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COG7 is a subunit of lobe B (Cog5–8) of the conserved oligomeric Golgi (COG) complex, a multisubunit tethering factor that mediates retrograde vesicle trafficking within the Golgi apparatus and is essential for maintaining Golgi architecture and glycosylation homeostasis. COG7 directly binds COG5 through a conserved CATCHR-fold interface whose disruption impairs trafficking and glycosylation (PMID:25331899, PMID:38987656), and it physically associates with the golgin-84 tether to capture COPI vesicles for intra-Golgi retrograde transport (PMID:20874812). Loss of COG7 causes mislocalization of medial-Golgi glycosyltransferases into COG complex-dependent vesicles, slowed retrograde Golgi-to-ER trafficking, reduced steady-state levels of vesicular SNAREs GS15 and GS28, and combined N- and O-glycosylation defects, as demonstrated in patient fibroblasts, knockout cell lines, and Drosophila mutants (PMID:15107842, PMID:16420527, PMID:16510524, PMID:22946051). Biallelic loss-of-function mutations in COG7 cause a congenital disorder of glycosylation (CDG) with combined N- and O-glycosylation abnormalities (PMID:15107842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2002 High

    Identification of COG7 as a previously unrecognized subunit of the eight-subunit COG complex established the complete molecular composition of this Golgi-associated tethering factor and revealed its bilobed architecture.

    Evidence Biochemical purification, co-immunoprecipitation, gel filtration, deep-etch EM of bovine brain COG complex

    PMID:11980916

    Open questions at the time
    • No individual function assigned to COG7 within the complex
    • No intersubunit interaction map resolved
    • Mechanism of Golgi membrane association unknown
  2. 2004 High

    Discovery that COG7 mutation underlies a human congenital disorder of glycosylation demonstrated that COG7 is essential for both N- and O-glycosylation pathways and for maintaining integrity of the entire COG complex in vivo.

    Evidence Patient fibroblast analysis with glycosylation assays, Western blot, and complementation

    PMID:15107842

    Open questions at the time
    • Precise trafficking step disrupted by COG7 loss not defined
    • Contribution of COG7 versus other subunits to glycosylation unclear
  3. 2005 High

    Establishing that Cog5–7 form a stable subcomplex (lobe B) bridged to lobe A (Cog1–4) by Cog8 resolved the internal architecture of the COG complex and showed that different lobes have partially distinct effects on Golgi membrane proteins.

    Evidence Gel filtration and immunoblotting of COG7-deficient patient fibroblasts combined with siRNA knockdown

    PMID:16051600

    Open questions at the time
    • Direct binary interactions within lobe B not structurally mapped
    • Functional non-redundancy of lobes not fully tested
  4. 2006 High

    Demonstration that COG7 knockdown mislocalizes medial-Golgi glycosyltransferases into COG complex-dependent (CCD) vesicles and slows retrograde Golgi-to-ER transport pinpointed the specific trafficking step — retrograde recycling of Golgi-resident enzymes — that COG7 controls.

    Evidence siRNA knockdown, in vitro CCD vesicle docking reconstitution, brefeldin A retrograde transport assays, and complementation rescue in patient fibroblasts

    PMID:16420527 PMID:16510524

    Open questions at the time
    • Mechanism by which COG7 promotes vesicle docking not resolved at molecular level
    • Identity of SNARE complexes assembled by COG7-containing tethering events unknown
  5. 2010 High

    Identification of golgin-84 as a direct binding partner of COG7 revealed how the COG complex is linked to the golgin tethering machinery on COPI vesicles, providing a molecular bridge for intra-Golgi retrograde vesicle capture.

    Evidence Reciprocal co-immunoprecipitation, siRNA knockdown of COG7, and vesicle composition analysis

    PMID:20874812

    Open questions at the time
    • Binding interface between COG7 and golgin-84 not structurally defined
    • Whether COG7–golgin-84 interaction is regulated is unknown
  6. 2012 High

    Drosophila Cog7 mutant analysis extended the functional repertoire of COG7 to acroblast assembly and meiotic cytokinesis, showing it acts upstream of Rab11 and the phosphatidylinositol transfer protein Giotto in membrane addition at the cleavage furrow.

    Evidence Loss-of-function genetics, co-immunoprecipitation with Giotto and Rab11, EM, and immunofluorescence in Drosophila testes

    PMID:22946051

    Open questions at the time
    • Whether Cog7–Giotto interaction is direct or bridged unknown
    • Relevance of cytokinesis role to mammalian cell division not tested
  7. 2014 High

    The crystal structure of the Cog5–Cog7 complex revealed a CATCHR-fold interface conserved from yeast to humans, providing the first atomic-resolution view of subunit contacts within the COG complex and validating this interface as functionally required.

    Evidence X-ray crystallography, mutagenesis, and functional complementation in human cells

    PMID:25331899

    Open questions at the time
    • Structure of full lobe B (Cog5–Cog7–Cog6–Cog8) not solved
    • Conformational dynamics during vesicle tethering unknown
  8. 2017 Medium

    Genetic epistasis in Drosophila showed that Rab1 overexpression rescues Cog7-loss phenotypes, positioning Rab1 as a downstream effector and linking COG complex function to Rab1-dependent Golgi trafficking.

    Evidence Overexpression rescue, 3D-SIM co-localization, and N-glycome profiling in Drosophila

    PMID:28883096

    Open questions at the time
    • Direct physical interaction between Cog7 and Rab1 not demonstrated
    • Mechanism of Rab1 rescue not molecularly defined
  9. 2021 Medium

    COG7 knockout in human cells revealed a specific role in glycosaminoglycan biosynthesis and proteoglycan turnover, broadening the glycosylation defects beyond N- and O-glycans to GAG chains.

    Evidence CRISPR knockout in HEK293T cells with proteoglycan metabolic labeling and GAG chain analysis

    PMID:34053170

    Open questions at the time
    • Specific glycosyltransferases or sulfotransferases affected not identified
    • In vivo significance of altered GAG chains not assessed
  10. 2024 Medium

    A disease-causing COG5 missense mutation that abrogates the COG5–COG7 interaction in patient cells confirmed that the crystallographically defined interface is essential in human physiology.

    Evidence Co-immunoprecipitation from patient-derived cells with in silico stability analysis

    PMID:38987656

    Open questions at the time
    • Effect of interface disruption on full COG complex assembly not assessed
    • Structural basis of disruption by L100F not experimentally determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of COG7–golgin-84 interaction, how the COG complex coordinates SNARE complex assembly during vesicle fusion, and whether COG7 has functions independent of the holocomplex.
  • No structure of full COG complex or lobe B tetramer available
  • SNARE assembly mechanism during COG-mediated tethering not reconstituted
  • Potential COG7 functions outside the octameric complex not explored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Localization
GO:0005794 Golgi apparatus 6
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
COG5COG6COG8GOLGA5GOLPH3RAB1RAB11
Complex memberships
COG complex (lobe B, Cog5-8)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 COG7 was identified as a previously unidentified subunit of the conserved oligomeric Golgi (COG) complex, which localizes to the Golgi and is required for normal Golgi morphology and function. EM of purified COG revealed an ~37-nm-long structure comprising two globular domains, and COG1/COG2 mutants showed dilated Golgi cisternae, establishing the complex's structural role. Biochemical purification, co-immunoprecipitation, gel filtration, immunofluorescence, deep-etch electron microscopy The Journal of cell biology High 11980916
2004 Mutation of COG7 impairs integrity of the entire COG complex and disrupts multiple glycosylation pathways (both N- and O-linked), establishing COG7 as required for Golgi trafficking and glycosylation machinery function. Patient fibroblast analysis, Western blot, glycosylation assays, complementation Nature medicine High 15107842
2005 COG7 deficiency studies in patient fibroblasts established that Cog5-7 form a stable subcomplex (lobe B), and Cog8 bridges lobe A (Cog1-4) and lobe B (Cog5-7) subcomplexes into the complete COG complex. Only one or two of the Golgi membrane proteins (GEARs) sensitive to Cog1/Cog2 deficiency are also sensitive to Cog7 deficiency, indicating distinctive subunit roles. Immunoblotting, gel filtration, immunofluorescence, siRNA knockdown in Cog7-deficient patient fibroblasts The Journal of biological chemistry High 16051600
2006 COG7 knockdown (like COG3 knockdown) causes mislocalization of medial-Golgi glycosyltransferases into COG complex-dependent (CCD) vesicles, and double COG3/COG7 KD caused similar defects, demonstrating that the entire COG complex orchestrates retrograde recycling of Golgi-resident glycosyltransferases. In vitro reconstitution of CCD vesicle docking supports their role as functional trafficking intermediates. siRNA knockdown, immunofluorescence, in vitro vesicle docking reconstitution, glycosylation assays Traffic (Copenhagen, Denmark) High 16420527
2006 In COG7-deficient human fibroblasts, retrograde transport of multiple Golgi proteins to the ER (via brefeldin A-induced tubules) is significantly slower than normal, while anterograde trafficking is much less affected. The vesicular SNAREs GS15 and GS28 showed abnormal staining and GS15 steady-state levels were reduced. All defects were normalized in COG7-corrected fibroblasts. Immunofluorescence, brefeldin A treatment, live imaging, complementation with COG7 cDNA in patient fibroblasts Molecular biology of the cell High 16510524
2010 Golgin-84 physically interacts with the COG complex through its subunit COG7, and this interaction mediates tethering of COPI vesicles for intra-Golgi retrograde transport. CCD vesicles accumulating in COG7 KD cells carry golgin-84, and the interaction between golgin-84 and CASP decreases in COG3 KD cells. Co-immunoprecipitation, siRNA knockdown (COG7 KD), immunofluorescence, vesicle analysis Traffic (Copenhagen, Denmark) High 20874812
2012 In Drosophila, Cog7 is enriched at Golgi stacks throughout spermatogenesis; loss of Cog7 disrupts Golgi architecture, reduces Golgi stack numbers, impairs assembly of the Golgi-derived acroblast, and causes furrow ingression failure during meiotic cytokinesis. Rab11 and Giotto (phosphatidylinositol transfer protein) recruitment to the cleavage site requires Cog7. Giotto co-immunoprecipitates with Cog7 and Rab11 in testes, placing Cog7 upstream in a Gio-Rab11 pathway for membrane addition during cytokinesis. Loss-of-function mutant analysis, co-immunoprecipitation, immunofluorescence, electron microscopy in Drosophila spermatogenesis Journal of cell science High 22946051
2014 Crystal structure of the Cog5-Cog7 complex revealed that Cog5 adopts a CATCHR (complexes associated with tethering containing helical rods) fold, homologous to subunits of other multisubunit tethering complexes (Dsl1, exocyst, GARP). Biochemical and functional studies validated that the Cog5-Cog7 interface is conserved from yeast to humans, and its disruption causes trafficking and glycosylation defects in human cells. X-ray crystallography, biochemical binding assays, mutagenesis, functional complementation in human cells Proceedings of the National Academy of Sciences of the United States of America High 25331899
2014 Assembled COG complex does not diffuse from the Golgi periphery in live HeLa cells (shown by FRAP and FLIP). COG subunits remain membrane-associated even in COG4- or COG7-depleted cells where Golgi architecture is severely affected. Different COG sub-complexes preferentially bind different Golgi membrane partners (β-COP, p115, STX5), indicating multipronged membrane attachment. FRAP, FLIP, knock-sideways depletion, overexpression of myc-tagged COG sub-complexes in HeLa cells Cellular logistics Medium 24649395
2017 In Drosophila, Cog7 colocalizes with Rab1 and GOLPH3 at Golgi stacks. The COG complex cooperates with Rab1 and GOLPH3 to regulate Golgi trafficking. Overexpression of Rab1 rescues both cytokinesis defects and locomotor defects caused by loss of Cog7, establishing Rab1 as a downstream functional effector in the COG7 pathway. Co-localization imaging (3D-SIM), epistasis by overexpression rescue, Drosophila loss-of-function genetics, N-glycome profiling Journal of cell science Medium 28883096
2008 The COG complex (including COG7) is organized into two lobes: Lobe A (Cog1-4) and Lobe B (Cog5-8). Deletion of Lobe A subunits in yeast causes severe growth defects; mutations in COG1, COG7, and COG8 in humans cause congenital disorders of glycosylation. Down-regulation of COG function causes mislocalization or degradation of resident Golgi glycosyltransferases/glycosidases. Genetic analysis in yeast, patient cell biochemistry, immunofluorescence, Western blotting Carbohydrate research Medium 18353293
2021 Glycosaminoglycan (GAG) modification of proteoglycans is significantly reduced in COG7 knockout HEK293T cells, and COG7 KO cells show longer cell-associated GAG chains than wild-type, implicating COG7 in cellular turnover of proteoglycans. CRISPR/siRNA knockout, proteoglycan metabolic labeling, GAG chain analysis in HEK293T cells Traffic (Copenhagen, Denmark) Medium 34053170
2014 Silencing of COG7 (and other lobe B COG subunits: COG5, COG6, COG8) inhibited HIV-1 replication at a step preceding late reverse transcription but not affecting viral fusion, implicating COG7-mediated Golgi/TGN function in early HIV-1 life cycle steps. siRNA knockdown, HIV-1 infectivity assays, RT product quantification Virus research Low 25179963
2024 In patient-derived cells, a COG5 missense variant (p.Leu100Phe) abrogates the COG5-COG7 protein-protein interaction as shown by co-immunoprecipitation, confirming that the COG5-COG7 interface identified in the crystal structure is functionally required in human cells. Co-immunoprecipitation from patient-derived cells, in silico stability analysis Journal of human genetics Medium 38987656

Source papers

Stage 0 corpus · 34 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 238 11980916
2006 COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation. Traffic (Copenhagen, Denmark) 137 16420527
2008 Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydrate research 101 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 42 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 34 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
2008 EMBRYO YELLOW gene, encoding a subunit of the conserved oligomeric Golgi complex, is required for appropriate cell expansion and meristem organization in Arabidopsis thaliana. Genes to cells : devoted to molecular & cellular mechanisms 24 18422605
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 19 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 19 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
2014 Wrinkled skin and fat pads in patients with ALG8-CDG: revisiting skin manifestations in congenital disorders of glycosylation. Pediatric dermatology 7 24555185
2023 Discovery and bioinspired total syntheses of unprecedented sesquiterpenoid dimers unveiled bifurcating [4 + 2] cycloaddition and target differentiation of enantiomers. Chemical science 6 38274075
2025 Machine learning in Alzheimer's disease genetics. Nature communications 5 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