Affinage

COG3

Conserved oligomeric Golgi complex subunit 3 · UniProt Q96JB2

Length
828 aa
Mass
94.1 kDa
Annotated
2026-04-28
41 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COG3 is a core subunit of the conserved oligomeric Golgi (COG) complex, an eight-subunit vesicle tethering machine that maintains Golgi glycosylation enzyme homeostasis by mediating the capture and docking of COPI-coated retrograde intra-Golgi transport vesicles at cis/medial-Golgi cisternae (PMID:10562277, PMID:12011112, PMID:16420527). COG3 functions as an effector of the Rab GTPase Ypt1/Rab1, which directs its recruitment to Golgi membranes, and cooperates with intra-Golgi SNAREs and the vesicle tether golgin-84 to complete vesicle docking prior to fusion (PMID:10562277, PMID:34453710, PMID:20874812). Loss of COG3 causes mislocalization of medial- and trans-Golgi glycosyltransferases, defective N-glycosylation, O-glycosylation, and glycosaminoglycan chain elongation on proteoglycans, and Golgi fragmentation that is suppressed by Rab6 pathway perturbation (PMID:21421995, PMID:34053170, PMID:31428608). COG3 subunit stoichiometry within the complex is controlled by an Ac/N-degron whose exposure is shielded by direct binding partners COG1 and COG2 (PMID:23603116).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 High

    Identification of Sec34p (COG3 ortholog) as a component of an ~750 kDa complex required for vesicle tethering to the Golgi established its fundamental role in ER-to-Golgi and intra-Golgi membrane traffic and placed it functionally downstream of the Rab GTPase Ypt1p.

    Evidence In vitro vesicle tethering assay, genetic suppressor analysis, cytosol fractionation, and co-precipitation in S. cerevisiae

    PMID:10512869 PMID:10562277

    Open questions at the time
    • Direct physical interaction between Sec34p and Ypt1p not demonstrated at this stage
    • Subunit composition of the full complex unknown
  2. 2001 High

    Characterization of the full eight-subunit COG complex and localization of human COG3 to cis/medial-Golgi membranes defined COG3 as a peripheral Golgi-associated protein within a conserved tethering complex family.

    Evidence Immunofluorescence, BFA sensitivity, glycerol gradient fractionation in human cells; affinity purification and sequence homology in yeast

    PMID:11292827 PMID:11703943

    Open questions at the time
    • Structural organization of the eight-subunit complex at atomic resolution unknown
    • Whether COG3 contacts membranes directly or via other subunits not resolved
  3. 2002 High

    Demonstration that the COG complex interacts physically with COPI coat, intra-Golgi SNAREs, and Ypt1p, and that anti-COG3 antibodies block ER-to-Golgi transport, established COG3 as a nexus connecting vesicle coat recognition, Rab signaling, and SNARE-mediated fusion.

    Evidence Co-immunoprecipitation, two-hybrid, genetic interaction analysis, semi-intact cell transport assay, and deep-etch EM of purified complex

    PMID:11929878 PMID:11980916 PMID:12011112

    Open questions at the time
    • Whether COG3 directly binds COPI or SNAREs versus acting through other subunits not distinguished
    • Mechanism of coupling between tethering and SNARE complex assembly unknown
  4. 2004 High

    A COG3 temperature-sensitive allele revealed that COG3 acts at the level of sorting glycosyltransferases into retrograde vesicles rather than at the fusion step, refining the mechanistic step at which COG3 operates in intra-Golgi recycling.

    Evidence Temperature-shift analysis with density gradient fractionation in yeast, epistatic comparison with SNARE ts mutants

    PMID:15229219

    Open questions at the time
    • Molecular mechanism by which COG3 influences cargo sorting into vesicles not identified
    • Single allele study—allele-specific effects not excluded
  5. 2006 High

    In vitro reconstitution of COG-dependent vesicle docking and identification of CCD vesicles carrying Golgi enzymes upon COG3 knockdown proved that COG3 is required for tethering of retrograde intra-Golgi transport intermediates, with direct consequences for glycoprotein processing.

    Evidence siRNA knockdown in HeLa, in vitro vesicle docking reconstitution, lectin staining and glycoprotein analysis

    PMID:16420527

    Open questions at the time
    • Identity of all cargo on CCD vesicles incomplete
    • Whether tethering defect is solely due to COG3 loss or reflects destabilization of other COG subunits not fully resolved
  6. 2010 High

    The discovery that golgin-84 on COPI vesicles engages COG (via COG7) before SNARE assembly, and that COG3 depletion disrupts the golgin-84/CASP interaction, established a temporal order: golgin-84–COG tethering precedes SNARE-mediated fusion in retrograde Golgi traffic.

    Evidence Co-immunoprecipitation, siRNA knockdown, vesicle content analysis in HeLa cells

    PMID:20874812

    Open questions at the time
    • Whether golgin-84 engages COG3 directly or exclusively through COG7 not resolved
    • Structural basis of golgin-84–COG interaction unknown
  7. 2013 High

    Identification of an Ac/N-degron on COG subunits (including Cog1) that is shielded by COG2 and COG3 binding revealed a quality-control mechanism ensuring proper COG complex stoichiometry, explaining how orphan subunits are selectively degraded.

    Evidence Subunit decoy technique, pulse-chase stability assays, genetic manipulation in yeast

    PMID:23603116

    Open questions at the time
    • Ubiquitin ligase responsible for Ac/N-degron-mediated degradation of COG subunits not identified
    • Whether this regulatory mechanism operates identically in mammalian cells unknown
  8. 2019 High

    A systematic epistatic siRNA screen placed COG3 within a Rab6/minus-end kinesin-regulated Golgi organization pathway, identifying Rab6A, Rab27A, Rab39A, KIFC3, and KIF25 as upstream regulators whose depletion suppresses COG3 loss-induced Golgi fragmentation.

    Evidence Combinatorial siRNA screen (19 Rabs × 44 kinesins), fluorescence microscopy, EM validation in HeLa cells

    PMID:31428608

    Open questions at the time
    • Direct physical interaction between COG3 and Rab6 not shown
    • Mechanism by which minus-end kinesins contribute to COG3-dependent Golgi organization uncharacterized
  9. 2021 Medium

    COG3 was shown to be a direct Ypt1/Rab1 effector recruited to Golgi membranes in a Ypt1-dependent manner, and COG3 knockout was found to specifically impair glycosaminoglycan chain elongation on proteoglycans, revealing a subunit-specific role in GAG biosynthesis.

    Evidence Chimeric Rab localization assay in yeast; CRISPR KO of individual COG subunits with GAG chain biochemical analysis in HEK293T

    PMID:34053170 PMID:34453710

    Open questions at the time
    • Structural basis for Ypt1–COG3 effector interaction not resolved
    • Whether COG3's specific GAG elongation phenotype reflects a direct interaction with GAG biosynthetic enzymes or indirect tethering effects is unknown
    • GAG elongation phenotype from single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic-resolution structure of COG3 within the assembled COG complex, the precise mechanism by which COG3 bridges vesicle coat recognition and SNARE complex assembly, and the identity of the E3 ligase mediating Ac/N-degron-dependent COG subunit turnover remain unresolved.
  • No high-resolution structure of COG3 in the context of the full octameric COG complex
  • Mechanism coupling COG3-mediated tethering to SNARE priming/zippering not defined
  • Pathways controlling COG3 expression and degradation in mammalian cells largely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3
Localization
GO:0005794 Golgi apparatus 5 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
COG1COG2COG7GOLGA5RAB6AYPT1
Complex memberships
COG complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Sec34p (yeast COG3 ortholog) forms an ~750 kDa protein complex with Sec35p in yeast cytosol, is required in vitro for vesicle tethering to the Golgi, and its temperature-sensitive phenotype is suppressed by the Rab GTPase Ypt1p and the SNARE-associated protein Sly1-20p, placing Sec34p in the ER-to-Golgi vesicle tethering pathway. Genetic suppressor analysis, two-hybrid interaction, cytosol fractionation, in vitro vesicle tethering assay The Journal of cell biology High 10562277
1999 Sec34p (yeast COG3 ortholog) physically associates with Sec35p to form a ~480 kDa multiprotein complex; overexpression of SEC34 specifically suppresses the sec35-1 mutation, confirming a functional partnership in ER-to-Golgi vesicular traffic. Co-precipitation, high-copy suppressor screen, gel filtration Molecular biology of the cell High 10512869
2001 Human Sec34p (COG3) is a peripheral membrane protein that localizes to cis/medial Golgi cisternae, migrates as part of an ~300 kDa complex in cytosol, and its Golgi association is sensitive to Brefeldin A, consistent with a role in tethering intra-Golgi transport vesicles. Immunofluorescence microscopy, glycerol velocity gradient fractionation, GFP live imaging, BFA treatment The Journal of biological chemistry High 11292827
2001 Dor1p and seven associated proteins in yeast (including Sec34p/COG3 and Sec35p) constitute the Sec34/35 complex; several subunits show distant homology to exocyst and Vps52/53/54 complex components, defining a conserved family of tethering complexes involved in multiple membrane traffic steps. Affinity purification, sequence homology analysis, co-purification Developmental cell High 11703943
2002 Human COG complex (comprising COG3/Sec34 along with COG1–8) is required for normal Golgi morphology; EM of ldlB and ldlC mutants showed Golgi morphology defects, and deep-etch EM of purified COG revealed an ~37-nm two-domain structure. EM of mutant CHO cells, deep-etch EM of purified complex, biochemical subunit identification The Journal of cell biology High 11980916
2002 The yeast Sec34/35 complex (containing COG3 ortholog Sec34p) interacts genetically and physically with the Rab protein Ypt1p, intra-Golgi SNARE molecules, and COPI vesicle coat proteins, supporting its role as a tether connecting cis-Golgi membranes with COPI-coated retrograde intra-Golgi vesicles. Genetic interaction analysis, co-immunoprecipitation, two-hybrid The Journal of cell biology High 12011112
2002 Mammalian COG3 (Sec34) directly interacts with COG1 (ldlBp) and COG2 (ldlCp) in vitro and co-immunoprecipitates with GTC-90 and ldlBp from rat liver cytosol; anti-Sec34 antibodies inhibit ER-to-Golgi transport in a semi-intact cell assay in a dose-dependent manner. Co-immunoprecipitation from rat liver cytosol, in vitro binding assay, semi-intact cell ER-to-Golgi transport assay The Journal of biological chemistry High 11929878
2004 A COG3 temperature-sensitive allele (cog3-202) in yeast causes mislocalization of Golgi mannosyltransferases Och1p and Mnn1p without accumulating them in retrograde vesicles, consistent with COG3 playing a role in sorting Och1p into retrograde vesicles for intra-Golgi recycling rather than in vesicle fusion. Temperature-sensitive allele analysis, density gradient fractionation, genetic comparison with sed5(ts) and sft1(ts) strains The Journal of biological chemistry High 15229219
2005 C. elegans COGC-3 (COG3 ortholog) is required for the glycosylation and gonadal basement membrane localization of the ADAM protease MIG-17; cogc-3 mutants display misdirected distal tip cell migration phenocopying mig-17 mutants, and COGC-3 requires MIG-17 activity for its effect on organ morphogenesis. Genetic loss-of-function analysis, RNAi of all 8 COG subunits, epistasis, MIG-17 glycosylation and localization assay Development (Cambridge, England) High 16354716
2006 Acute siRNA knockdown of COG3 in mammalian cells causes accumulation of COG complex-dependent (CCD) vesicles containing medial-Golgi glycosylation enzymes, resulting in defective glycosylation of CD44 and Lamp2; in vitro reconstitution showed COG complex-dependent docking of isolated CCD vesicles, supporting their identity as functional retrograde trafficking intermediates. siRNA knockdown, vesicle accumulation assay, in vitro vesicle docking reconstitution, lectin/antibody staining of glycoproteins Traffic (Copenhagen, Denmark) High 16420527
2007 Epistasis analysis shows that COG3 and ZW10/RINT-1 act in separate Golgi trafficking pathways both regulated upstream by Rab6; co-depletion of ZW10 with COG3 did not alter vesicle formation caused by COG3 knockdown, and dominant-negative Rab6 suppressed COG3 KD-induced Golgi fragmentation, whereas dominant-negative Bicaudal-D (Rab6-dynein linker) suppressed ZW10 but not COG3 KD effects. siRNA epistasis, dominant-negative expression, fluorescence microscopy Molecular biology of the cell High 17699596
2010 Golgin-84 interacts with the COG complex through its subunit COG7, and CCD vesicles accumulating in COG3 knockdown cells carry golgin-84; COG3 depletion also reduces the golgin-84/CASP interaction, indicating that golgin-84 on COPI vesicles engages COG before SNARE assembly in intra-Golgi retrograde tethering. Co-immunoprecipitation, siRNA knockdown, vesicle content analysis, immunofluorescence Traffic (Copenhagen, Denmark) High 20874812
2011 COG3 knockdown in HeLa cells causes mislocalization of multiple Golgi glycosyltransferases (MAN2A1, MGAT1, B4GALT1, ST6GAL1) and blocks Brefeldin A– and Sar1-DN–induced retrograde redistribution of Golgi residents to the ER, with lobe B subunits (COG6, COG8) found on glycosyltransferase-carrying trafficking intermediates. siRNA knockdown, immunofluorescence, BFA/Sar1-DN redistribution assays, MALDI-TOF glycan analysis Glycobiology High 21421995
2013 COG3 (Cog3), a subunit of the Golgi-associated COG complex, contains an Ac/N-degron (N-terminal acetylation degradation signal) that is repressed by direct ligands Cog2 and Cog3 themselves; when the total level of Cog1 increases in the cell, its Ac/N-degron is exposed and Cog1 is destabilized, providing a mechanism for regulating COG complex subunit stoichiometry. Subunit decoy technique, pulse-chase protein stability assay, genetic manipulation of subunit levels in yeast Molecular cell High 23603116
2019 Epistatic siRNA screen identified that co-depletion of Rab6A, Rab6A', Rab27A, Rab39A, KIFC3, and KIF25 suppressed COG3 depletion-induced Golgi fragmentation, while no Rabs or Kifs selectively suppressed only COG3-depletion effects, placing COG3 in a Rab6/minus-end kinesin-regulated Golgi organization pathway. Systematic siRNA epistasis screen (19 Rabs, 44 Kifs), fluorescence microscopy scoring, EM validation Frontiers in cell and developmental biology High 31428608
2021 COG3 knockout in HEK293T cells particularly reduces the ability to polymerize glycosaminoglycan chains on proteoglycans, while all COG subunit KOs reduce GAG modification, indicating COG3 has a specific role in GAG chain elongation within the Golgi. CRISPR KO of individual COG subunits, biochemical analysis of proteoglycan GAG chains Traffic (Copenhagen, Denmark) Medium 34053170
2021 In yeast, Cog3-GFP is recruited to Golgi membranes in an Ypt1-dependent manner; a chimeric Rab (Ypt1-SW1Sec4) with altered GEF specificity changes Cog3-GFP localization, demonstrating that Cog3 is a direct effector of the Rab GTPase Ypt1p. Fluorescent protein localization, chimeric Rab analysis, live imaging Methods in molecular biology Medium 34453710
2024 siRNA-mediated knockdown of COG3 in ovarian cancer cell lines disrupts Golgi morphology, reduces MT1-MMP and YKL40 expression, suppresses SNAP23-mediated angiogenesis, and decreases cell proliferation and migration; COG3 knockdown suppresses tumor growth in a mouse xenograft model. siRNA knockdown, immunofluorescence (Golgi morphology), RT-PCR, western blot, MTT assay, TUNEL assay, tube-formation angiogenesis assay, in vivo tumor xenograft MicroRNA (Shariqah, United Arab Emirates) Medium 38243930

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 863 19812674
2013 Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Molecular cell 252 23603116
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
2001 The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic. Developmental cell 214 11703943
2002 The Sec34/Sec35p complex, a Ypt1p effector required for retrograde intra-Golgi trafficking, interacts with Golgi SNAREs and COPI vesicle coat proteins. The Journal of cell biology 180 12011112
2006 COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation. Traffic (Copenhagen, Denmark) 137 16420527
1999 Sec34p, a protein required for vesicle tethering to the yeast Golgi apparatus, is in a complex with Sec35p. The Journal of cell biology 110 10562277
2011 Conserved oligomeric Golgi complex specifically regulates the maintenance of Golgi glycosylation machinery. Glycobiology 89 21421995
2007 Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis. Molecular biology of the cell 79 17699596
1999 High-copy suppressor analysis reveals a physical interaction between Sec34p and Sec35p, a protein implicated in vesicle docking. Molecular biology of the cell 69 10512869
2010 Interaction of Golgin-84 with the COG complex mediates the intra-Golgi retrograde transport. Traffic (Copenhagen, Denmark) 62 20874812
2019 Dynamic inosinome profiles reveal novel patient stratification and gender-specific differences in glioblastoma. Genome biology 56 30760294
2001 Identification of a human orthologue of Sec34p as a component of the cis-Golgi vesicle tethering machinery. The Journal of biological chemistry 55 11292827
2005 The conserved oligomeric Golgi complex acts in organ morphogenesis via glycosylation of an ADAM protease in C. elegans. Development (Cambridge, England) 51 16354716
2015 Endocytic pathway mediates refractoriness of insect Bactrocera dorsalis to RNA interference. Scientific reports 50 25731667
2014 Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation. Clinical genetics 47 24784932
2004 Retrograde transport of the mannosyltransferase Och1p to the early Golgi requires a component of the COG transport complex. The Journal of biological chemistry 41 15229219
2002 YOS9, the putative yeast homolog of a gene amplified in osteosarcomas, is involved in the endoplasmic reticulum (ER)-Golgi transport of GPI-anchored proteins. The Journal of biological chemistry 40 12077121
2016 Arabidopsis COG Complex Subunits COG3 and COG8 Modulate Golgi Morphology, Vesicle Trafficking Homeostasis and Are Essential for Pollen Tube Growth. PLoS genetics 37 27448097
2001 Sgf1p, a new component of the Sec34p/Sec35p complex. Traffic (Copenhagen, Denmark) 33 11733049
2016 Using RNA-Seq SNP data to reveal potential causal mutations related to pig production traits and RNA editing. Animal genetics 25 27642173
2024 COG3 confers the chilling tolerance to mediate OsFtsH2-D1 module in rice. The New phytologist 24 38173177
2002 Sec34 is implicated in traffic from the endoplasmic reticulum to the Golgi and exists in a complex with GTC-90 and ldlBp. The Journal of biological chemistry 23 11929878
2021 Syntaxin of plants31 (SYP31) and SYP32 is essential for Golgi morphology maintenance and pollen development. Plant physiology 20 33576796
2003 Molecular heterogeneity in human osteosarcoma demonstrated by enriched mRNAs isolated by directional tag PCR subtraction cloning. Anticancer research 17 12894494
2003 Characterization of Grp1p, a novel cis-Golgi matrix protein. Biochemical and biophysical research communications 16 12646213
2017 Testicular adenosine to inosine RNA editing in the mouse is mediated by ADARB1. Biology of reproduction 13 28395340
2013 A-to-I RNA editing does not change with age in the healthy male rat brain. Biogerontology 13 23708854
2015 The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3. G3 (Bethesda, Md.) 11 26637431
2021 Proteoglycan synthesis in conserved oligomeric Golgi subunit deficient HEK293T cells is affected differently, depending on the lacking subunit. Traffic (Copenhagen, Denmark) 9 34053170
2014 Mutations in proteins of the Conserved Oligomeric Golgi Complex affect polarity, cell wall structure, and glycosylation in the filamentous fungus Aspergillus nidulans. Fungal genetics and biology : FG & B 9 25312861
2021 Where all the Roads Meet? A Crossover Perspective on Host Factors Regulating SARS-CoV-2 infection. Journal of molecular biology 7 34914966
2019 Epistatic Analysis of the Contribution of Rabs and Kifs to CATCHR Family Dependent Golgi Organization. Frontiers in cell and developmental biology 6 31428608
2021 COG1-congenital disorders of glycosylation: Milder presentation and review. Clinical genetics 5 33960418
2019 Landscape of RNA editing reveals new insights into the dynamic gene regulation of spermatogenesis. Cell cycle (Georgetown, Tex.) 5 31594448
2021 Conservation of A-to-I RNA editing in bowhead whale and pig. PloS one 4 34882682
2020 Proteomic Signatures of Corals from Thermodynamic Reefs. Microorganisms 4 32752238
2023 Meta-Analysis of Keratoconus Transcriptomic Data Revealed Altered RNA Editing Levels Impacting Keratin Genomic Clusters. Investigative ophthalmology & visual science 3 37279397
2024 Tumor Targeting via siRNA-COG3 to Suppress Tumor Progression in Mice and Inhibit Cancer Metastasis and Angiogenesis in Ovarian Cancer Cell Lines. MicroRNA (Shariqah, United Arab Emirates) 1 38243930
2025 The COG3 subunit interacts with SNX1 to enhance salt tolerance in Arabidopsis. Plant physiology and biochemistry : PPB 0 41448066
2021 Testing the Phenotypic Effects of a Rab Chimera that Resolves Exchange Factor Specificity from Effector Specificity. Methods in molecular biology (Clifton, N.J.) 0 34453710