Affinage

COPB2

Coatomer subunit beta' · UniProt P35606

Length
906 aa
Mass
102.5 kDa
Annotated
2026-04-28
67 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COPB2 (β'-COP/RACK2) is a WD40-repeat-containing stoichiometric subunit of the heptameric COPI coatomer complex that is essential for vesicular trafficking in the early secretory pathway, functioning in both retrograde Golgi-to-ER retrieval and anterograde ER-to-Golgi transport. COPI coat assembly on Golgi membranes requires ARF-GTP, and COPB2's WD40 domain directly recognizes di-lysine (KKXX) retrieval signals on cargo proteins to mediate their retrograde recycling (PMID:1631136, PMID:14699056). Beyond its coatomer role, COPB2 serves as RACK2—a receptor for activated PKCε—recruiting PKCε to Golgi membranes, and it regulates plasma membrane delivery of multiple ion channels and transporters (TREK1, TREK2, ANO1, TTYH2, Na,K-ATPase) by controlling their retention in or exit from the early secretory pathway (PMID:9360998, PMID:20801885, PMID:20362547, PMID:27207835). Homozygous Copb2 knockout is embryonic lethal in mice, and hypomorphic WD40-domain mutations cause cortical neuron loss and increased apoptosis, establishing a specific requirement for COPB2 in corticogenesis (PMID:29036432).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 High

    Establishing that β-COP is a peripheral Golgi membrane protein existing in cytosolic and membrane-bound pools on non-clathrin-coated vesicles resolved the identity of the major coat protein of COPI-coated Golgi vesicles.

    Evidence Cloning, immunofluorescence, immunoelectron microscopy, and biochemical fractionation of CHO/HeLa cells and Golgi fractions

    PMID:1840503

    Open questions at the time
    • β'-COP (COPB2) not yet distinguished from β-COP at this stage
    • coat stoichiometry undefined
  2. 1992 High

    Demonstrating that ARF-GTP is the obligate upstream signal for coatomer recruitment to Golgi membranes—and that brefeldin A blocks this step—established the GTPase-driven coat assembly mechanism for COPI.

    Evidence In vitro reconstitution with recombinant ARF, ARF depletion, GTPγS and BFA treatments on Golgi membranes

    PMID:1631136 PMID:1957170

    Open questions at the time
    • Which coatomer subunit directly contacts ARF was unknown
    • role of heterotrimeric G proteins in coat regulation not resolved
  3. 1993 High

    Identification of β'-COP (COPB2) as a distinct stoichiometric coatomer subunit with WD40 repeats and G-protein β-subunit homology, combined with evidence that β-COP antibodies block ER-to-Golgi transport, established that the complete coatomer is required for bidirectional early secretory traffic.

    Evidence Protein purification and N-terminal sequencing of coatomer subunits; antibody microinjection blocking VSV-G transport; immunoEM localizing coat to cis-Golgi vesicles

    PMID:8334707 PMID:8334999 PMID:8376457 PMID:8458872

    Open questions at the time
    • Specific cargo-binding function of the β'-COP WD40 domain not yet tested
    • whether β'-COP has functions separate from the heptameric complex was unknown
  4. 1997 High

    Discovery that β'-COP functions as RACK2—a selective receptor for activated PKCε at Golgi membranes—revealed an unexpected signaling role for a coat subunit outside vesicle budding.

    Evidence cDNA library screen, direct binding assays, co-IP, co-localization in cardiac myocytes, Golgi membrane recruitment of PKCε

    PMID:9360998

    Open questions at the time
    • Functional consequence of PKCε-COPB2 interaction on coat dynamics unknown
    • whether RACK2 function is separable from coatomer function not tested
  5. 1999 High

    Mapping HIV-1 Nef's interaction with β-COP through diacidic and RXR motifs showed how a viral protein hijacks COPI machinery to route CD4 and MHC-I for lysosomal degradation, broadening COPI's role to endosomal sorting.

    Evidence Mutagenesis of Nef motifs, co-IP from infected cells, CD4/MHC-I degradation assays, Rab7 co-localization

    PMID:10199403 PMID:18725938

    Open questions at the time
    • Precise structural basis of Nef–β-COP interaction unresolved
    • whether endogenous cargoes use the same diacidic route unknown
  6. 2003 High

    Genetic dissection in yeast showed that the β'-COP WD40 domain directly recognizes di-lysine retrieval signals on cargo, is functionally overlapping with α-COP's WD40 domain, and is essential for retrograde Golgi-to-ER transport.

    Evidence Yeast point mutations and domain deletions in sec27 (β'-COP), Emp47p turnover and invertase maturation assays

    PMID:14699056

    Open questions at the time
    • Structural model of WD40–KKXX interaction lacking
    • whether mammalian β'-COP has identical cargo selectivity not directly tested
  7. 2010 High

    Identification of β-COP as a direct regulator of ion channel and transporter surface expression—promoting TREK1 forward trafficking while retaining unassembled Na,K-ATPase α-subunit via a dibasic motif—extended COPB2's role from general coat function to selective quality control of plasma membrane proteins.

    Evidence Yeast two-hybrid, mutagenesis of Na,K-ATPase Lys54, surface biotinylation, electrophysiology for TREK1

    PMID:20362547 PMID:20801885

    Open questions at the time
    • Whether β-COP versus β'-COP mediates these effects not always distinguished
    • mechanism by which β-COP differentially promotes or retains channels unclear
  8. 2016 Medium

    Extension to ANO1 and cholesterol efflux showed that COPB2 negatively regulates ANO1 surface delivery and participates in apoA-I-mediated cholesterol export, indicating broad roles in controlling plasma membrane composition.

    Evidence siRNA knockdown with electrophysiology (ANO1 in glioblastoma cells); shRNA knockdown with cholesterol efflux assay and immunogold EM in macrophages

    PMID:26986486 PMID:27207835

    Open questions at the time
    • Direct versus indirect effects on cholesterol trafficking not fully separated from general secretory disruption
    • ANO1 interaction domain on COPB2 not mapped
  9. 2017 High

    Mouse genetic studies established that COPB2 is essential for embryogenesis and that its WD40 domain is specifically required for cortical neuron survival, linking secretory pathway integrity to brain development.

    Evidence CRISPR-generated null and hypomorphic (R254C) Copb2 alleles in mice, CTIP2+ neuron counts, neurosphere assays

    PMID:29036432

    Open questions at the time
    • Which COPB2-dependent cargo(es) are critical for cortical neurons not identified
    • whether the R254C mutation selectively disrupts di-lysine binding versus overall coatomer assembly unclear
  10. 2022 Medium

    Demonstration that β-COP differentially regulates TREK2 (suppresses surface expression) versus TREK1 (promotes surface expression and TWIK1/TREK1 heterodimer delivery in astrocytes) revealed subunit-selective and channel-specific trafficking logic.

    Evidence Yeast two-hybrid, C-terminal deletion/point mutations of TREK2, electrophysiology in astrocytes

    PMID:36291187 PMID:37296621

    Open questions at the time
    • Structural basis for opposite effects on TREK1 versus TREK2 unknown
    • in vivo significance for astrocyte K+ conductance not validated
  11. 2025 Medium

    Discovery that COPB2 interacts with the ERAD glycosidase EDEM3 to maintain ER homeostasis, and that inhibitory peptides targeting the PKCε–RACK2 interface use a KxKxx motif, refined the molecular logic of COPB2's two distinct functional surfaces.

    Evidence Co-IP and glycoproteomic analysis of COPB2-EDEM3 in ovarian cancer cells; alanine-scanning mutagenesis of KIKIC peptide blocking PKCε–RACK2 binding

    PMID:40736660 PMID:41115472

    Open questions at the time
    • Whether EDEM3 interaction is mediated through the WD40 domain or a separate surface not determined
    • therapeutic utility of RACK2-blocking peptides not established in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of full-length COPB2 bound to di-lysine cargo and to PKCε, and identification of the critical neuronal cargoes whose mistrafficking causes cortical defects, remain central open questions.
  • No crystal or cryo-EM structure of β'-COP WD40 domain in complex with KKXX peptide
  • neuronal cargo(es) whose missorting causes cortical apoptosis unidentified
  • mechanism discriminating positive versus negative regulation of different ion channels not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0038024 cargo receptor activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005794 Golgi apparatus 4 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-9609507 Protein localization 6 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 1 R-HSA-1430728 Metabolism 1
Partners
ARF1ATP1A1COPAEDEM3KCNK10KCNK2PRKCERAB1B
Complex memberships
COPI coatomer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Beta-COP (COPB2) was identified as a peripheral 110 kDa Golgi membrane protein that exists in a membrane-bound form and in a cytosolic ~550 kDa complex (~13-14S). By immunofluorescence and immunoelectron microscopy, beta-COP localizes to non-clathrin-coated vesicles and cisternae of the Golgi complex, and these coated vesicles accumulate in GTPγS-treated Golgi fractions. Cloning/sequencing, immunofluorescence, immunoelectron microscopy, biochemical fractionation Cell High 1840503
1991 ARF (ADP-ribosylation factor) and beta-COP both reversibly associate with the Golgi apparatus in energy-, GTP-, and brefeldin A-sensitive manners. Addition of Gβγ subunits of heterotrimeric G proteins inhibited the GTPγS-stimulated association of both ARF and beta-COP with Golgi membranes, indicating that heterotrimeric G proteins regulate COPI coat assembly. Cell fractionation, membrane binding assays, pharmacological treatments (BFA, GTPγS, Gβγ) Science High 1957170
1992 ARF is required for the binding of beta-COP (as part of the coatomer) to Golgi membranes. A coatomer fraction resolved from ARF cannot bind Golgi membranes; binding is reconstituted by addition of recombinant ARF. Brefeldin A inhibits beta-COP membrane association by blocking the initial ARF-membrane interaction step. In vitro reconstitution, recombinant protein addition, ARF depletion, GTPγS and AlF treatments Proceedings of the National Academy of Sciences of the United States of America High 1631136
1993 Beta-COP is essential for biosynthetic membrane transport from the ER to the Golgi in vivo. Microinjection of anti-beta-COP antibodies blocks transport of VSV-G glycoprotein and arrests it in tubular membrane structures at the ER-Golgi interface; secretion of endogenous proteins and cathepsin D maturation are also inhibited. Antibody microinjection, pulse-chase transport assays, endoglycosidase H resistance assay, immunofluorescence Cell High 8334707
1993 Beta-COP is a component of the coatomer complex and is essential for ER-to-cis-Golgi vesicle budding in vitro. A novel high molecular weight (>1,000 kDa) form of beta-COP distinct from coatomer mediates efficient vesicle budding from the ER, and Rab1B co-precipitates with this beta-COP-containing complex and is also required for function. In vitro ER-to-Golgi transport assay, antibody inhibition with F(ab) fragments, rat liver cytosol fractionation, co-immunoprecipitation The Journal of cell biology High 8376457
1993 Beta'-COP (COPB2) is a novel stoichiometric subunit of the coatomer complex, distinct from beta-COP, present in amounts stoichiometric with the other COP subunits in both cytosolic coatomer and non-clathrin-coated vesicles. It shows homology to the beta-subunits of trimeric G proteins. Protein purification, SDS-PAGE, N-terminal sequencing, sequence homology analysis The EMBO journal High 8334999
1993 Beta-COP localizes predominantly to the cis-Golgi side in exocrine pancreatic cells (68% of Golgi-associated label on cis-side), associated with ~50 nm vesicles with a ~10 nm coat. Energy depletion causes beta-COP to form spherical aggregates at the cis-Golgi side, and BFA treatment releases beta-COP from membranes to the cytoplasm, suggesting a specific role in cis-Golgi membrane transport. Immunogold cytochemistry, quantitative electron microscopy, pharmacological treatments (BFA, energy depletion, AlF) The Journal of cell biology High 8458872
1993 Yeast coatomer contains a subunit homologous to mammalian beta'-COP (COPB2), identified by cross-reactivity with anti-beta'-COP antibody and N-terminal sequencing, establishing evolutionary conservation of the coatomer complex. Protein purification, urea-SDS-PAGE, Western blot with anti-peptide antibody, N-terminal sequencing FEBS letters Medium 8405452
1994 HIV-1 Nef physically interacts with beta-COP (COPB2), identified by yeast two-hybrid screening. Nef and beta-COP interact in vitro and are co-immunoprecipitated from HIV-1-infected cells, suggesting beta-COP may mediate Nef's effects on membrane trafficking. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation from HIV-1-infected cells The Journal of biological chemistry Medium 7982906
1995 Beta-COP accumulates on vesicular profiles and buds in the intermediate compartment (IC) at 15°C temperature block, co-localizing with VSV-G ts-O45-G passenger protein in transit between the ER/IC and the cis-Golgi, supporting a role for COP-coated vesicles in anterograde IC-to-Golgi transport. Immunoelectron microscopy, quantitative immunofluorescence, temperature block experiments Journal of cell science High 7593324
1997 Beta'-COP (COPB2) functions as a receptor for activated protein kinase C epsilon (PKCε) — a RACK (RACK2). Beta'-COP contains seven WD40 repeats, selectively binds activated PKCε via its V1 region, co-localizes with PKCε in cardiac myocytes, and recruits PKCε to Golgi membranes in a beta'-COP-dependent manner. cDNA library screening, direct protein binding assays, co-immunoprecipitation, co-localization in cardiac myocytes, Golgi membrane binding assay The Journal of biological chemistry High 9360998
1999 HIV-1 Nef connects CD4 to beta-COP (the beta subunit of COPI coatomers) in endosomes via a diacidic sequence (acidic dipeptide) in Nef, routing internalized CD4 molecules for lysosomal degradation. Beta-COP was identified as the downstream partner for this novel endosomal sorting motif. Mutagenesis of Nef diacidic motif, co-immunoprecipitation, subcellular fractionation, CD4 degradation assay Cell Medium 10199403
2000 Rab2 requires PKC iota/lambda to recruit beta-COP to pre-Golgi intermediate membranes for vesicle budding. PKC iota/lambda translocates to membranes in a Rab2-dependent, dose-dependent manner; inhibition of PKC iota/lambda blocks beta-COP recruitment and vesicle formation, though PKC iota/lambda kinase activity is not required for beta-COP binding but is necessary for Rab2-mediated vesicle budding. Quantitative membrane binding assays, Western blot for PKC isoforms, anti-PKC antibody treatment, kinase-dead mutant and pseudosubstrate peptide inhibition, vesicle budding assay Traffic Medium 11208158
2003 The WD40 domain of beta'-COP (COPB2) is required for recycling of the KTKLL-tagged Golgi protein Emp47p back to the ER. Point mutation in the WD40 domain (sec27-95) or deletion of the domain causes accelerated Emp47p degradation. The two WD40 domains of alpha-COP and beta'-COP bind distinct but overlapping sets of di-lysine signals, with both contributing to retrograde retrieval of KKXX-motif proteins. Absence of both WD40 domains is lethal in yeast. Yeast genetics (point mutations, domain deletions), protein turnover assay, two-hybrid studies, invertase maturation assay Molecular biology of the cell High 14699056
2006 The stomach-specific calpain nCL-2 (calpain-8a) proteolyzes beta-COP near its linker region in a Ca2+-dependent manner. Beta-COP and nCL-2 co-localize at the Golgi in COS7 cells; Ca2+-ionophore stimulation causes nCL-2-mediated proteolysis of beta-COP, resulting in its dissociation from the Golgi. This suggests beta-COP cleavage by nCL-2 regulates membrane trafficking in mucus-secreting cells. Yeast two-hybrid identification, in vitro proteolysis assay, co-expression and co-localization in COS7 cells, Ca2+-ionophore stimulation The Journal of biological chemistry Medium 16476741
2008 HIV-1 Nef contains two separable beta-COP binding sites that mediate degradation of distinct cargo: an RXR motif in the N-terminal alpha-helical domain required for maximal MHC-I degradation, and a di-acidic motif in the C-terminal loop needed for efficient CD4 degradation. Both MHC-I and CD4 are ultimately found in Rab7+ vesicles and degraded via beta-COP activity. Site-directed mutagenesis of Nef motifs, co-immunoprecipitation, confocal microscopy (Rab7 co-localization), flow cytometry (surface expression), degradation assays PLoS pathogens High 18725938
2008 siRNA-mediated depletion of beta-COP disrupts compartmentalization of ERGIC, Golgi, TGN, and recycling endosomes into large globular compartments, arrests anterograde trafficking of VSV-G and soluble cargoes, perturbs transferrin recycling, and blocks biosynthetic transport of caveolin-1 (Cav1). Cav1 co-precipitates with the gamma-subunit of COP-I, suggesting Cav1 is a COP-I cargo. siRNA knockdown, immunofluorescence co-localization, VSV-G transport assay, transferrin recycling assay, co-immunoprecipitation American journal of physiology. Cell physiology High 18385291
2010 Beta-COP directly interacts with the N-terminal region of the TREK1 K2P potassium channel, identified by yeast two-hybrid. Co-expression of beta-COP with TREK1 in COS-7 cells increases surface expression and channel activity of TREK1, while beta-COP shRNA reduces TREK1 surface expression, indicating beta-COP promotes forward trafficking of TREK1 to the plasma membrane. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, surface expression assay, electrophysiology, shRNA knockdown Biochemical and biophysical research communications Medium 20362547
2010 Beta-COP interacts with the Na,K-ATPase alpha-subunit via a dibasic motif at Lys54. When expressed without the Na,K-ATPase beta-subunit, the alpha-subunit interacts with beta-COP, is retained in the ER, and is degraded. Upon beta-subunit co-expression, the alpha-subunit no longer interacts with beta-COP and traffics to the plasma membrane. Mutation of Lys54 abolishes beta-COP interaction and allows cell surface delivery of the alpha-subunit even without the beta-subunit. Novel labeling technique for partner protein identification, co-immunoprecipitation, pulse-chase experiments, mutagenesis, surface biotinylation The Journal of biological chemistry High 20801885
2016 Beta-COP directly interacts with the Ca2+-activated chloride channel ANO1, identified by yeast two-hybrid. Co-transfection of beta-COP with ANO1 in HEK293T cells decreases ANO1 surface expression and channel activity. Silencing of endogenous beta-COP in U251 glioblastoma cells enhances ANO1 surface expression and whole-cell currents, indicating beta-COP negatively regulates ANO1 plasma membrane trafficking. Yeast two-hybrid, in vitro and in vivo binding assays, co-immunoprecipitation, surface expression assay, electrophysiology, siRNA knockdown Biochemical and biophysical research communications Medium 27207835
2017 Copb2 is essential for early embryogenesis in mice (two independent null alleles are lethal). Hypomorphic compound heterozygous mice (Copb2R254C/Zfn) show severe perinatal phenotype with increased apoptosis in the brain, reduced layer V (CTIP2+) neurons, and reduced neurosphere growth, establishing a specific role for COPB2 in corticogenesis. The R254C mutation lies in the WD40 domain. CRISPR-Cas9 genome editing to generate allelic series, immunostaining, neurosphere assay, mouse genetics Human molecular genetics High 29036432
2017 The O. tsutsugamushi effector Ank9 binds COPB2 (host protein mediating Golgi-to-ER retrograde transport) via a GRIP-like Golgi localization domain, uses retrograde Golgi-to-ER trafficking, and destabilizes the Golgi and ER. COPB2 siRNA treatment also destabilizes the Golgi, and reduction of COPB2 benefits Orientia replication. Co-immunoprecipitation, siRNA knockdown, confocal microscopy, transport assays Cellular microbiology Medium 28103630
2019 Beta-COP directly interacts with the C-terminus of TTYH2 anion channel (identified by yeast two-hybrid). Co-expression of beta-COP with TTYH2 decreases its surface expression and channel activity, and overexpression of beta-COP in LoVo colon cancer cells reduces endogenous TTYH2 surface expression, indicating beta-COP suppresses TTYH2 plasma membrane trafficking. Yeast two-hybrid, in vitro and in vivo binding assays, surface expression assay, electrophysiology, co-immunoprecipitation BMB reports Medium 30670146
2021 COPB2 knockdown in mutant EGFR NSCLC cells alters the post-translational processing of receptor tyrosine kinases (RTKs), alters subcellular localization of EGFR and COPB2 within the early secretory pathway, and induces ER stress response pathway changes. A small molecule (EMI66) that alters COPB2 electrophoretic mobility reproduces these effects. siRNA knockdown, Western blot, immunofluorescence, small molecule treatment, organoid growth assay Journal of molecular biology Medium 34662547
2022 Beta-COP binds directly to the C-terminus of TREK2 (but not TRAAK) and reduces TREK2 cell surface expression. Deletion or point mutations in the TREK2 C-terminus abolish beta-COP binding and prevent surface expression suppression. Beta-COP also enhances surface expression of the TWIK1/TREK1 heterodimeric channel in a TREK1-dependent manner (binding TREK1 but not TWIK1), thereby regulating passive K+ conductance in astrocytes. Yeast two-hybrid, co-immunoprecipitation, surface expression assay, electrophysiology in astrocytes, C-terminal deletion and point mutation analysis Cells Medium 36291187 37296621
2004 ADIP (afadin DIL domain-interacting protein) directly binds beta'-COP (COPB2) and co-localizes with beta'-COP at the Golgi complex in MDCK and NRK cells, suggesting ADIP links cell-cell adhesion machinery to COPI vesicle trafficking. Yeast two-hybrid (implied), direct binding assay, co-localization by immunofluorescence Biochemical and biophysical research communications Low 15358183
2016 Beta-COP knockdown in THP-1 macrophages reduces apoA-1-mediated cholesterol efflux, increases intracellular cholesterol accumulation, and is associated with beta-COP appearing on membrane protrusion complexes during apolipoprotein-mediated cholesterol exocytosis. ApoA-1 promotes beta-COP translocation to the cell membrane. Lentiviral shRNA knockdown, confocal microscopy, immunogold electron microscopy, cholesterol efflux assay, proteomics of secreted particles PloS one Medium 26986486
2024 Beta'-COP (COPB2) directly interacts with PPARγ in trophoblasts, mediating its sorting into early endosomes and multivesicular bodies for incorporation into extracellular vesicles. Knockout of beta'-COP impairs PPARγ loading into EVs. Molecular dynamics simulations identified critical binding sites; mutation of these sites weakens the interaction and reduces PPARγ EV levels. Co-immunoprecipitation, proteomic analysis, lentiviral knockout/overexpression, molecular dynamics simulation, mutagenesis Cellular and molecular life sciences Medium 39601826
2025 COPB2 interacts with EDEM3 (a key ERAD enzyme) in ovarian cancer cells, enhancing EDEM3's ER localization and mannose-trimming function. COPB2 depletion impairs EDEM3 activity, causes glycan processing defects, and leads to ER stress accumulation, revealing a COPB2-EDEM3 axis that maintains ER homeostasis. Co-immunoprecipitation, glycoproteomic analysis, COPB2 knockdown/overexpression, in vitro and in vivo functional assays Cellular oncology Medium 40736660
2025 Inhibitory peptides derived from PKCε (with KxKxx motif and C-terminal carboxylate) block the interaction of activated PKCε with RACK2/COPB2. Alanine scanning of the KIKIC peptide revealed that the two Lys residues and the C-terminal carboxylate are critical for inhibitory activity. KIKIC penetrates cells and modifies PKCε translocation in response to lipid treatment. Proximity-based chemiluminescent binding assay, alanine scan mutagenesis of peptides, RACK2 pulldown with liver lysate, cell-penetration assay, PKCε translocation assay Biochimica et biophysica acta. Molecular cell research Medium 41115472
2025 Knockdown of COPB2 in Huh-7 hepatocarcinoma cells (identified in a genome-wide RNAi screen) decreases uptake of HDL holoparticles, reduces cell surface abundance of SR-BI (interfering with its glycosylation), decreases APOA1 expression and apoA-I secretion, and increases ABCA1 cell surface abundance and ABCA1-mediated cholesterol efflux, demonstrating COPB2 regulates multiple steps of HDL metabolism in hepatocytes. Genome-wide RNAi screen, targeted siRNA knockdown, fluorescent HDL uptake assay, flow cytometry (SR-BI, ABCA1 surface abundance), apoA-I secretion assay, cholesterol efflux assay bioRxivpreprint Medium bio_10.1101_2025.08.21.25332476

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Beta-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the Golgi complex, shows homology to beta-adaptin. Cell 473 1840503
1992 ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes. Proceedings of the National Academy of Sciences of the United States of America 438 1631136
1991 Binding of ARF and beta-COP to Golgi membranes: possible regulation by a trimeric G protein. Science (New York, N.Y.) 346 1957170
1993 Beta-COP is essential for biosynthetic membrane transport from the endoplasmic reticulum to the Golgi complex in vivo. Cell 306 8334707
1999 Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 243 10199403
1997 The coatomer protein beta'-COP, a selective binding protein (RACK) for protein kinase Cepsilon. The Journal of biological chemistry 212 9360998
1993 Beta-COP localizes mainly to the cis-Golgi side in exocrine pancreas. The Journal of cell biology 185 8458872
1994 Physical interaction of the HIV-1 Nef protein with beta-COP, a component of non-clathrin-coated vesicles essential for membrane traffic. The Journal of biological chemistry 151 7982906
1993 Beta-COP is essential for transport of protein from the endoplasmic reticulum to the Golgi in vitro. The Journal of cell biology 132 8376457
2008 HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS pathogens 126 18725938
1995 Immunocytochemical localization of beta-COP to the ER-Golgi boundary and the TGN. Journal of cell science 114 7593324
1993 beta'-COP, a novel subunit of coatomer. The EMBO journal 102 8334999
2003 The alpha- and beta'-COP WD40 domains mediate cargo-selective interactions with distinct di-lysine motifs. Molecular biology of the cell 85 14699056
2017 Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly. Human molecular genetics 52 29036432
2008 Depletion of beta-COP reveals a role for COP-I in compartmentalization of secretory compartments and in biosynthetic transport of caveolin-1. American journal of physiology. Cell physiology 50 18385291
2001 Nef-induced CD4 downregulation: a diacidic sequence in human immunodeficiency virus type 1 Nef does not function as a protein sorting motif through direct binding to beta-COP. Journal of virology 48 11264386
1991 Involvement of beta-COP in membrane traffic through the Golgi complex. Trends in cell biology 48 14731804
2019 COPB2 is up-regulated in breast cancer and plays a vital role in the metastasis via N-cadherin and Vimentin. Journal of cellular and molecular medicine 47 31119859
2019 MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer. Bioscience, biotechnology, and biochemistry 47 31631786
2000 Rab2 requires PKC iota/lambda to recruit beta-COP for vesicle formation. Traffic (Copenhagen, Denmark) 42 11208158
2018 COPB2 promotes cell proliferation and tumorigenesis through up-regulating YAP1 expression in lung adenocarcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 40 29674272
2017 Orientia tsutsugamushi Ank9 is a multifunctional effector that utilizes a novel GRIP-like Golgi localization domain for Golgi-to-endoplasmic reticulum trafficking and interacts with host COPB2. Cellular microbiology 39 28103630
2021 Early prediction of COVID-19 severity using extracellular vesicle COPB2. Journal of extracellular vesicles 38 34122778
2003 Identification and localization of a beta-COP-like protein involved in the morphodynamics of the plant Golgi apparatus. Journal of experimental botany 37 12885863
2016 COPB2 Is Upregulated in Prostate Cancer and Regulates PC-3 Cell Proliferation, Cell Cycle, and Apoptosis. Archives of medical research 32 27986120
2019 Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway. International journal of oncology 29 30968146
2013 RNA interference mediated knockdown of the KDEL receptor and COPB2 inhibits digestion and reproduction in the parasitic copepod Lepeophtheirus salmonis. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 27 24382395
2010 Enhancement of TREK1 channel surface expression by protein-protein interaction with beta-COP. Biochemical and biophysical research communications 27 20362547
1999 Closing in on the BPES gene on 3q23: mapping of a de Novo reciprocal translocation t(3;4)(q23;p15.2) breakpoint within a 45-kb cosmid and mapping of three candidate genes, RBP1, RBP2, and beta'-COP, distal to the breakpoint. Genomics 27 10191085
2020 COPB2 gene silencing inhibits colorectal cancer cell proliferation and induces apoptosis via the JNK/c-Jun signaling pathway. PloS one 25 33211699
2017 COPB2 suppresses cell proliferation and induces cell cycle arrest in human colon cancer by regulating cell cycle-related proteins. Experimental and therapeutic medicine 25 29399086
2021 Chrysin Induced Cell Apoptosis Through H19/let-7a/COPB2 Axis in Gastric Cancer Cells and Inhibited Tumor Growth. Frontiers in oncology 24 34150620
2006 Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the beta-subunit of coatomer complex, beta-COP. The Journal of biological chemistry 24 16476741
2016 Surface expression of the Anoctamin-1 (ANO1) channel is suppressed by protein-protein interactions with β-COP. Biochemical and biophysical research communications 21 27207835
2020 Loss of Arabidopsis β-COP Function Affects Golgi Structure, Plant Growth and Tolerance to Salt Stress. Frontiers in plant science 20 32351533
1993 Yeast coatomer contains a subunit homologous to mammalian beta'-COP. FEBS letters 20 8405452
2021 COPB2: a transport protein with multifaceted roles in cancer development and progression. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 18 34101128
2011 Biochemical and localization analyses of putative type III secretion translocator proteins CopB and CopB2 of Chlamydia trachomatis reveal significant distinctions. Infection and immunity 18 21606186
2020 MiR-216a-3p regulates the proliferation, apoptosis, migration, and invasion of lung cancer cells via targeting COPB2. Bioscience, biotechnology, and biochemistry 16 32619135
2018 Downregulation of COPB2 by RNAi inhibits growth of human cholangiocellular carcinoma cells. European review for medical and pharmacological sciences 16 29509246
2017 Coatomer subunit beta 2 (COPB2), identified by label-free quantitative proteomics, regulates cell proliferation and apoptosis in human prostate carcinoma cells. Biochemical and biophysical research communications 16 29129687
2019 High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma. CNS neuroscience & therapeutics 15 31710183
2010 Association with {beta}-COP regulates the trafficking of the newly synthesized Na,K-ATPase. The Journal of biological chemistry 14 20801885
2021 Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells. Journal of molecular biology 10 34662547
2004 Afadin- and alpha-actinin-binding protein ADIP directly binds beta'-COP, a subunit of the coatomer complex. Biochemical and biophysical research communications 10 15358183
2000 Cloning and characterization of beta-COP from Dictyostelium discoideum. European journal of cell biology 10 10887966
2022 β-COP Regulates TWIK1/TREK1 Heterodimeric Channel-Mediated Passive Conductance in Astrocytes. Cells 9 36291187
2019 Surface expression of TTYH2 is attenuated by direct interaction with β-COP. BMB reports 9 30670146
2016 β-COP as a Component of Transport Vesicles for HDL Apolipoprotein-Mediated Cholesterol Exocytosis. PloS one 9 26986486
2020 Upregulation of the Coatomer Protein Complex Subunit beta 2 (COPB2) Gene Targets microRNA-335-3p in NCI-H1975 Lung Adenocarcinoma Cells to Promote Cell Proliferation and Migration. Medical science monitor : international medical journal of experimental and clinical research 8 32004259
2022 Implication of COPB2 Expression on Cutaneous Squamous Cell Carcinoma Pathogenesis. Cancers 7 35454945
2022 Upregulation of COPB2 Promotes Prostate Cancer Proliferation and Invasion Through the MAPK/TGF-β Signaling Pathway. Frontiers in oncology 7 35600351
2021 An Integrative Pan-Cancer Analysis of the Oncogenic Role of COPB2 in Human Tumors. BioMed research international 7 34676262
2022 Lysine demethylase 5A promotes prostate adenocarcinoma progression by suppressing microRNA-330-3p expression and activating the COPB2/PI3K/AKT axis in an ETS1-dependent manner. Journal of cell communication and signaling 6 35581421
2017 Detection of COPB2 as a KRAS synthetic lethal partner through integration of functional genomics screens. Oncotarget 6 28415695
2021 Silencing the COPB2 gene decreases the proliferation, migration and invasion of human triple-negative breast cancer cells. Experimental and therapeutic medicine 5 34093748
2020 COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p. Translational cancer research 5 35117624
1999 Identification of the mouse beta'-COP Golgi component as a spermatocyte autoantigen in scleroderma and mapping of its gene Copb2 to mouse chromosome 9. Cytogenetics and cell genetics 4 10702668
2025 COPB2 promotes hepatocellular carcinoma progression through regulation of YAP1 nuclear translocation. Oncology research 3 40191726
2023 β-COP Suppresses the Surface Expression of the TREK2. Cells 3 37296621
2022 Differential Involvement of Arabidopsis β'-COP Isoforms in Plant Development. Cells 3 35326389
2022 Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma. BMC cancer 2 35715770
2024 β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles. Cellular and molecular life sciences : CMLS 1 39601826
2023 Novel insight into the phenotype of microcephaly 19 in the patient with missense COPB2 mutation. European journal of medical genetics 1 37734708
2026 COPB2 drives gastric cancer progression via PI3K/AKT/NF-κB signaling: a multi-omics and functional study. Cell adhesion & migration 0 41618837
2025 COPB2 facilitates EDEM3-mediated mannose trimming to sustain ER homeostasis in ovarian cancer. Cellular oncology (Dordrecht, Netherlands) 0 40736660
2025 Cell-penetrant peptides as novel inhibitors of the interaction of coatomer protein COPB2/RACK2 with protein kinase Cε and cargo proteins. Biochimica et biophysica acta. Molecular cell research 0 41115472