Affinage

COPA

Coatomer subunit alpha · UniProt P53621

Length
1224 aa
Mass
138.3 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COPA encodes the α-COP cargo-recognition subunit of the COPI coatomer, which mediates retrograde Golgi-to-ER transport by selectively binding di-lysine sorting signals through its N-terminal WD40 domain (PMID:9811561, PMID:7490292, PMID:8647451). α-COP discriminates among distinct di-lysine signals and acts as a selective gate for retrograde cargo retrieval, a function dependent on the integrity of the coatomer complex (PMID:9811561, PMID:7490292). Within coatomer, the α-COP C-terminal domain interlocks with ε-COP through a TPR–β-hairpin interface, and this heterodimer engages the Dsl1 tethering complex; ε-COP in turn stabilizes α-COP against degradation (PMID:20534429, PMID:9463377). Disease-causing heterozygous missense mutations in the WD40 domain impair cargo binding and trigger ER stress and TH17-skewed cytokine priming, the basis of COPA syndrome (PMID:25894502). Mechanistically, α-COP physically interacts with STING, and the SURF4 adapter facilitates COPA-mediated retrieval of STING from the Golgi to the ER; mutant or depleted COPA causes STING to accumulate at the Golgi, driving ligand-independent, STING-dependent type I interferon signaling that is genetically rescued by STING deletion in CopaE241K/+ mice (PMID:32725128, PMID:32725126). The autoimmune disease is propagated by T cells: mutant Copa in thymic epithelial cells disrupts thymic selection, expanding autoreactive T cells whose adoptive transfer causes interstitial lung disease (PMID:32198142), while the HAQ STING allele dominantly dampens COPA-dependent STING signaling and modifies disease penetrance (PMID:40014299). Distinct C-terminal domain mutations disrupt coatomer integrity to impair both anterograde and retrograde trafficking, converging on cGAS/STING-dependent interferon and ER stress (PMID:38175705). Beyond vesicular transport, α-COP binds di-lysine motifs in the SMN protein, an interaction separable from its COPI trafficking role and required for neuronal process outgrowth (PMID:23727837, PMID:26464491).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Established that α-COP is functionally required for retrograde retrieval of canonical di-lysine cargo to the ER, defining its role in COPI-mediated transport.

    Evidence ret1-1 α-COP mutant analysis with di-lysine-tagged hybrid cargo and retrograde transport assays in yeast

    PMID:7490292

    Open questions at the time
    • Did not resolve which coatomer subunit directly contacts the di-lysine signal
    • No structural basis for cargo recognition
  2. 1998 High

    Defined α-COP as a selective gate that discriminates between distinct di-lysine signals, showing cargo recognition is allele-specific yet dependent on the broader coatomer complex.

    Evidence In vitro GST-fusion binding assays with ret1 coatomer alleles plus in vivo localization in yeast

    PMID:9811561

    Open questions at the time
    • Direct binding site on α-COP not mapped
    • Mammalian cargo repertoire unaddressed
  3. 1998 High

    Showed ε-COP stabilizes α-COP, revealing an interdependence within coatomer that protects α-COP from degradation.

    Evidence Yeast high-copy suppressor screen, temperature-sensitive mutants, and α-COP Western blots

    PMID:9463377

    Open questions at the time
    • Structural basis of the α-COP–ε-COP interaction not yet defined
    • Mechanism of α-COP degradation unknown
  4. 1998 Medium

    Identified α-COP as the unique coatomer subunit that binds PtdIns(3,4,5)P3, implicating phosphoinositide lipids in COPI trafficking.

    Evidence Photoaffinity labeling and competitive displacement across COPI subunits

    PMID:9525943

    Open questions at the time
    • Single method without reconstitution
    • Functional consequence of lipid binding in trafficking not demonstrated
  5. 2010 High

    Provided the structural basis for the α-COP/ε-COP interlock and linked the heterodimer to the Dsl1 tethering machinery.

    Evidence X-ray crystallography of α-COP CTD–ε-COP at 2.9 Å with Dsl1 binding assays

    PMID:20534429

    Open questions at the time
    • Structure of the full coatomer not resolved
    • Functional role of Dsl1 contact in vivo not tested here
  6. 2013 Medium

    Extended α-COP function beyond classical trafficking by showing it binds SMN di-lysine motifs to support neurite outgrowth.

    Evidence Co-IP, SMN di-lysine mutagenesis, and neurite length measurement in NSC-34 cells

    PMID:23727837

    Open questions at the time
    • Whether SMN binding requires COPI trafficking not separated here
    • In vivo relevance not tested
  7. 2015 High

    Established COPA as the genetic cause of an autoimmune disorder, linking WD40-domain cargo-binding defects to ER stress and TH17 priming.

    Evidence Whole-exome sequencing, cargo binding assays, ER stress assays, and patient CD4+ T cell phenotyping

    PMID:25894502

    Open questions at the time
    • Specific cargo whose mishandling triggers inflammation not yet identified
    • Mechanism linking ER stress to TH17 skewing unresolved
  8. 2015 High

    Separated α-COP's SMN-binding neuronal function from its COPI trafficking role using point mutants that abolish SMN binding while preserving Golgi-ER transport.

    Evidence Site-directed mutagenesis, Co-IP, trafficking assays, and neurite outgrowth in NSC-34 cells and zebrafish motor neurons

    PMID:26464491

    Open questions at the time
    • Molecular role of α-COP–SMN complex in axon biology unresolved
    • Relevance to human motor neuron disease not established
  9. 2020 High

    Identified STING as the pathogenic cargo of COPA, showing mutant COPA fails to retrieve STING from the Golgi, driving type I interferon signaling.

    Evidence Co-IP of COPA–STING, mutant overexpression, siRNA knockdown, ISG quantification, and STING immunofluorescence

    PMID:32725128

    Open questions at the time
    • Adapter mediating STING recognition not defined in this study
    • How Golgi STING activates IFN signaling not detailed
  10. 2020 High

    Provided in vivo proof that STING is the disease driver and identified SURF4 as the adapter facilitating COPA-mediated STING retrieval.

    Evidence CopaE241K/+ × STING-/- genetic epistasis in mice, SURF4 pulldown, and STING transport assays

    PMID:32725126

    Open questions at the time
    • Stoichiometry and structure of COPA–SURF4–STING complex unknown
    • Whether SURF4 mediates other COPA cargo unaddressed
  11. 2020 High

    Localized the pathogenic mechanism to T cells, showing mutant Copa in thymic epithelium disrupts thymic selection to generate disease-causing autoreactive T cells.

    Evidence Germline Copa knock-in mouse, thymocyte selection analysis, and adoptive transfer causing interstitial lung disease

    PMID:32198142

    Open questions at the time
    • Link between thymic selection defect and STING pathway not integrated
    • Cell-intrinsic vs stromal contributions partially resolved
  12. 2021 Medium

    Refined the STING activation model, showing disease COPA variants augment stimulus-induced rather than constitutive STING/IFN signaling and cause STING-dependent lung disease in vivo.

    Evidence IFN promoter reporter assays and CopaV242G/+ knock-in mouse with dendritic cell STING activation readouts

    PMID:33982886

    Open questions at the time
    • Why activation is inducible rather than constitutive not mechanistically explained
    • Single lab, two approaches
  13. 2024 High

    Revealed that C-terminal domain mutations act by a mechanism distinct from WD40 mutations, disrupting coatomer integrity and impairing bidirectional trafficking to drive cGAS/STING and ER stress responses.

    Evidence Patient-derived fibroblast trafficking, cGAS/STING and ER stress assays, and electron microscopy of COPI vesicles

    PMID:38175705

    Open questions at the time
    • How loss of coatomer integrity engages cGAS specifically unclear
    • Genotype-phenotype correlation across domains not fully mapped
  14. 2025 High

    Confirmed STING as the critical mediator of COPA syndrome and identified the HAQ STING allele as a dominant penetrance modifier that rescues the molecular phenotype.

    Evidence Carrier sequencing, exome analysis, and functional rescue expressing HAQ STING in patient cells

    PMID:40014299

    Open questions at the time
    • Mechanism by which HAQ STING dampens signaling not detailed
    • Other genetic modifiers unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how COPA mutations mechanistically connect impaired cargo trafficking to the distinct downstream outcomes of STING-driven interferon, ER stress, TH17 skewing, and thymic selection defects within a single unified pathway.
  • No structural model of COPA cargo recognition in mammalian cells
  • Full repertoire of COPA-dependent cargo beyond STING and SMN undefined
  • Integration of T-cell and STING mechanisms incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 1
Localization
GO:0005794 Golgi apparatus 3 GO:0005783 endoplasmic reticulum 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
COPEDSL1SMN1STING1SURF4
Complex memberships
COPI coatomer

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 COPA (coatomer subunit α) variants in the WD40 domain impair binding to proteins targeted for retrograde Golgi-to-ER transport; expression of mutant COPA results in ER stress and upregulation of cytokines priming for a TH17 response, and patient-derived CD4+ T cells show skewing toward TH17 phenotype. Whole-exome sequencing, binding assays showing impaired cargo binding, ER stress assays, cytokine profiling, T cell phenotyping Nature genetics High 25894502
2020 COPA physically interacts with STING; mutant COPA (and COPA silencing) causes accumulation of ER-resident STING at the Golgi, consistent with failure of Golgi-to-ER STING retrieval, leading to STING-dependent IFN signaling. Co-immunoprecipitation (COPA–STING interaction), overexpression of mutant COPA, siRNA knockdown, ISG/IFN-α quantification, subcellular localization of STING by immunofluorescence The Journal of experimental medicine High 32725128
2020 Pathogenic COPA variants cause defective COPI-mediated Golgi-to-ER transport, leading to ligand-independent activation of STING and type I interferon-driven inflammation; SURF4 was identified as an adapter molecule that facilitates COPA-mediated retrieval of STING at the Golgi; activated STING contributes to immune dysregulation rescued in STING-deficient CopaE241K/+ mice. Genetic epistasis (CopaE241K/+ × STING-/- mice), SURF4 identification as COPA–STING adapter (pulldown/Co-IP), STING transport assays, knock-in mouse model with IFN readout The Journal of experimental medicine High 32725126
2010 Crystal structure of the C-terminal domain (CTD) of α-COP in complex with full-length ε-COP at 2.9 Å resolution reveals that ε-COP adopts a TPR fold that wraps around a β-hairpin of the α-COP CTD, interlocking the two proteins; the α-COP CTD–ε-COP heterodimer directly interacts with the Dsl1 tethering complex. X-ray crystallography, solution biochemistry (heterodimer formation), direct binding assay with Dsl1 tethering complex Proceedings of the National Academy of Sciences of the United States of America High 20534429
1998 ε-COP (Sec28p) functions to stabilize α-COP; loss of ε-COP causes rapid degradation of α-COP at restrictive temperature and ER trafficking defects; overproduction of ε-COP suppresses α-COP mutant defects by stabilizing α-COP levels. Yeast genetics (high-copy suppressor screen), temperature-sensitive mutant analysis, Western blotting for α-COP levels, carboxypeptidase Y trafficking assay, gel filtration of coatomer The EMBO journal High 9463377
1998 α-COP can discriminate between distinct di-lysine signals: ret1-1 mutant α-COP fails to bind the Wbp1p di-lysine signal in vitro but retains binding to the Emp47p di-lysine signal; other coatomer subunits (β'-, γ-, δ-, ζ-COP) are required for binding both di-lysine signals, placing α-COP in a regulatory gating role for selective retrograde transport. In vitro GST-fusion binding assay with coatomer from ret1 alleles, sucrose gradient fractionation, immunofluorescence, epistasis with multiple COP subunit mutants Journal of cell science High 9811561
1995 α-COP is required for ER localization of di-lysine-tagged proteins: a hybrid Ste2p–Emp47p tail protein bearing the Emp47p di-lysine signal is mislocalized to the cell surface in the ret1-1 α-COP mutant; Emp47p cycles between Golgi and ER in a di-lysine-dependent but α-COP-independent manner, establishing that α-COP is needed for retrograde transport of canonical di-lysine cargo. Yeast genetics (ret1-1 mutant), immunofluorescence, retrograde transport assay in sec12 block, subcellular fractionation The Journal of cell biology High 7490292
1998 α-COP specifically binds phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] among coatomer subunits; both D-3 and D-5 phosphates are critical for this interaction, suggesting a role for PtdIns(3,4,5)P3 in COPI vesicular trafficking. Photoaffinity labeling with [3H]BZDC-PtdIns(3,4,5)P3 and competitive displacement assays across COPI subunits The Journal of biological chemistry Medium 9525943
2013 Dilysine motifs in exon 2b of SMN protein mediate binding to α-COP (COPA); mutagenesis of the canonical dilysine motifs in SMN abrogates α-COP binding and eliminates the ability of SMN to restore neurite outgrowth in SMN-depleted NSC-34 cells. Co-immunoprecipitation, mutagenesis of SMN dilysine motifs, inducible knockdown cell system, neurite length measurement Human molecular genetics Medium 23727837
2015 α-COP binding to SMN is required for neuronal process outgrowth: single amino acid mutants of α-COP that selectively abrogate SMN binding while retaining COPI-mediated Golgi-ER trafficking fail to support neurite outgrowth in NSC-34 cells and zebrafish motor neurons. Site-directed mutagenesis of α-COP, Co-IP to confirm loss of SMN binding, Golgi-ER trafficking assay, neurite length in NSC-34 cells, in vivo zebrafish motor neuron imaging Human molecular genetics High 26464491
2020 Mutant Copa in thymic epithelial cells impairs thymic selection of T cells, resulting in an increase in autoreactive T cells and decrease in regulatory T cells in peripheral tissues; adoptive transfer of Copa mutant T cells causes interstitial lung disease, establishing T cells as the pathogenic effector population. Germline Copa knock-in mouse model, thymocyte selection analysis, flow cytometry, adoptive transfer experiment Journal of immunology High 32198142
2021 COPA V242G (and other disease-causing COPA variants) augments STING-induced type I IFN promoter activity; in CopaV242G/+ dendritic cells the STING pathway is hyperactivated upon stimulation rather than constitutively, leading to increased type I IFN production; interstitial lung disease in CopaV242G/+ mice is STING-dependent. In vitro IFN promoter reporter assay, CopaV242G/+ knock-in mouse model, STING pathway activation assays in dendritic cells, ISG expression analysis Arthritis & rheumatology Medium 33982886
2024 Heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, p.R1142X) disrupt COPI integrity and cause both anterograde ER-to-Golgi and retrograde Golgi-to-ER trafficking defects, leading to cGAS/STING-dependent upregulation of type I IFN signaling and ER stress/NF-κB activation, via a distinct mechanism from WD40-domain mutations. Patient-derived fibroblast trafficking assays, cGAS/STING pathway analysis, ER stress and NF-κB signaling assays in patient-derived primary cell lines, electron microscopy of COPI vesicles The Journal of clinical investigation High 38175705
2025 The common HAQ STING allele acts dominantly to dampen COPA-dependent STING signaling; expressing HAQ STING in patient cells rescues the molecular phenotype of COPA syndrome, establishing STING as a critical pathway mediator and HAQ STING as a modifier of COPA syndrome penetrance. Sequencing of COPA mutation carriers (affected vs. unaffected), exome sequencing, functional rescue experiments expressing HAQ STING in patient cells, STING signaling assays The Journal of experimental medicine High 40014299
1999 The Aspergillus nidulans sodVIC gene encodes an α-COP ortholog (COPA homolog) that is essential for establishing and maintaining polarized hyphal growth; molecular disruption is lethal, and conditional mutants show defects in nuclear division and hyphal extension. Gene cloning from cosmid library, molecular disruption (lethality), conditional mutant analysis, sequence homology to α-COP Fungal genetics and biology Medium 10361037
2004 C-terminal truncation of α-COP in Hansenula polymorpha causes defects in retrograde ER retrieval and intra-Golgi transport, altered trafficking of GPI-anchored protein Gas1p, enhanced secretion of abnormal urokinase forms, and reduction of Golgi Ca2+-ATPase Pmr1p levels; Ca2+ homeostasis defects are suppressed by Pmr1p overexpression, linking COPA-dependent transport to calcium homeostasis. Truncation mutant analysis, secretion assays, Gas1p trafficking, Pmr1p overexpression suppression, Ca2+ growth requirement assay Eukaryotic cell Medium 14871936
1996 The human COPA (HEP-COP) gene encodes a 1224-amino-acid protein with striking homology to yeast α-COP (Ret1p), containing six WD-40 repeats in the N-terminal region, consistent with a role in ER-Golgi membrane transport. cDNA isolation by RACE, sequence analysis, Northern blot demonstrating ubiquitous expression Gene Medium 8647451
2007 Aspergillus nidulans α-COP (CopA) tagged with GFP localizes to putative Golgi equivalents concentrated at hyphal tips; this localization is disrupted by brefeldin A and is independent of the microtubule cytoskeleton. Live-cell GFP imaging, brefeldin A treatment, dynein mutant and nocodazole (microtubule disruption) experiments FEMS microbiology letters Medium 17986089
2020 ADAR2-mediated A-to-I RNA editing of COPA pre-mRNA causes an isoleucine-to-valine substitution at residue 164 (COPAI164V); edited COPAI164V undergoes conformational change making it less stable than wild-type COPAWT; COPAI164V deactivates the PI3K/AKT/mTOR pathway through downregulation of caveolin-1 (CAV1), switching COPA from a tumor-promoting to a tumor-suppressive function. CRISPR/Cas9 deletion of editing complementary sequence, protein stability assays (cycloheximide chase), PI3K/AKT/mTOR pathway readout, CAV1 expression analysis, cell and mouse xenograft models Journal of hepatology Medium 32693003
2014 COPA is required for cellular entry of arginine-rich cell-penetrating peptides; siRNA knockdown of COPA impairs endosomal entry of poly-arginine peptides, implicating COPA in early endosome maturation. siRNA library screening, microscopic observation of fluorescent peptide entry, COPA knockdown validation PloS one Low 24489756
2016 A missense mutation in COPA (arginine-to-cysteine substitution at a completely conserved residue in the WD40 domain) is associated with dominant red coat color in Holstein cattle by disrupting retrograde/cis-Golgi transport, likely causing aberrant MC1R protein or mRNA trafficking within melanocytes, mimicking MC1R loss-of-function. Genetic association (complete association of COPA variant with Dominant Red phenotype), hair pigment composition analysis, RNA-seq PloS one Low 26042826
2010 COPA knockdown induces apoptosis in mesothelioma cells and suppresses tumor growth in a mesothelioma mouse xenograft model, indicating an anti-apoptotic function for COPA in these cancer cells. Genome-wide siRNA screen, COPA knockdown validation, apoptosis assays, mouse xenograft tumor growth assay Genomics Low 20153416

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 CopA: An Escherichia coli Cu(I)-translocating P-type ATPase. Proceedings of the National Academy of Sciences of the United States of America 424 10639134
2015 COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nature genetics 303 25894502
2020 Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling. The Journal of experimental medicine 189 32725128
2001 CueR (YbbI) of Escherichia coli is a MerR family regulator controlling expression of the copper exporter CopA. Molecular microbiology 183 11136469
1990 Control of replication of plasmid R1: the duplex between the antisense RNA, CopA, and its target, CopT, is processed specifically in vivo and in vitro by RNase III. The EMBO journal 174 1694128
2020 A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome. The Journal of experimental medicine 171 32725126
1995 The Golgi-localization of yeast Emp47p depends on its di-lysine motif but is not affected by the ret1-1 mutation in alpha-COP. The Journal of cell biology 158 7490292
2016 Copa Syndrome: a Novel Autosomal Dominant Immune Dysregulatory Disease. Journal of clinical immunology 152 27048656
2011 Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. Mucosal immunology 151 21525866
1988 Control of replication of plasmid R1: kinetics of in vitro interaction between the antisense RNA, CopA, and its target, CopT. The EMBO journal 112 2460339
1992 Replication control of plasmid R1: RepA synthesis is regulated by CopA RNA through inhibition of leader peptide translation. The EMBO journal 101 1378398
1990 Control of replication of plasmid R1: structures and sequences of the antisense RNA, CopA, required for its binding to the target RNA, CopT. The EMBO journal 92 1698621
2017 Type I interferon pathway activation in COPA syndrome. Clinical immunology (Orlando, Fla.) 91 29030294
2003 Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu(+)-ATPase CopA. Biochemistry 90 12974640
2006 COPA--cancer outlier profile analysis. Bioinformatics (Oxford, England) 86 16895932
2018 Analysis of pulmonary features and treatment approaches in the COPA syndrome. ERJ open research 79 29977900
2000 Control of copper homeostasis in Escherichia coli by a P-type ATPase, CopA, and a MerR-like transcriptional activator, CopR. Gene 79 11167016
2003 CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA. FEMS microbiology letters 77 12644235
2011 The combined actions of the copper-responsive repressor CsoR and copper-metallochaperone CopZ modulate CopA-mediated copper efflux in the intracellular pathogen Listeria monocytogenes. Molecular microbiology 74 21564342
2002 The Escherichia coli copper-responsive copA promoter is activated by gold. The Journal of biological chemistry 72 12446701
1998 epsilon-COP is a structural component of coatomer that functions to stabilize alpha-COP. The EMBO journal 72 9463377
2003 Understanding copper trafficking in bacteria: interaction between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis. Biochemistry 66 12590580
2014 Mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones: the interaction of Escherichia coli CopA and CusF. The Journal of biological chemistry 65 24917681
2010 Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse model. Genomics 59 20153416
2001 Interaction of the CopZ copper chaperone with the CopA copper ATPase of Enterococcus hirae assessed by surface plasmon resonance. Biochemical and biophysical research communications 57 11594769
2006 Flavonoids from Artemisia copa with anti-inflammatory activity. Planta medica 54 16450301
1997 Regulation of plasmid R1 replication: PcnB and RNase E expedite the decay of the antisense RNA, CopA. Molecular microbiology 54 9402020
2020 RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis. Journal of hepatology 50 32693003
2003 Measurement of cytoplasmic copper, silver, and gold with a lux biosensor shows copper and silver, but not gold, efflux by the CopA ATPase of Escherichia coli. FEBS letters 47 12832075
2018 Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features. Journal of medical genetics 46 30385646
2013 Abundance and diversity of copper resistance genes cusA and copA in microbial communities in relation to the impact of copper on Chilean marine sediments. Marine pollution bulletin 45 23298430
1998 Alpha-COP can discriminate between distinct, functional di-lysine signals in vitro and regulates access into retrograde transport. Journal of cell science 45 9811561
2017 COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA. BMC medical genetics 44 29137621
1984 Copy mutants of plasmid R1: effects of base pair substitutions in the copA gene on the replication control system. Molecular & general genetics : MGG 44 6203014
2020 COPA syndrome, 5 years after: Where are we? Joint bone spine 43 32919065
2018 Type II toxin/antitoxin system ParESO /CopASO stabilizes prophage CP4So in Shewanella oneidensis. Environmental microbiology 43 29411516
2011 Phenotypic characterization of a copA mutant of Neisseria gonorrhoeae identifies a link between copper and nitrosative stress. Infection and immunity 43 22184419
1992 Replication control in plasmid R1: duplex formation between the antisense RNA, CopA, and its target, CopT, is not required for inhibition of RepA synthesis. The EMBO journal 43 1372249
2013 Coproporphyrin III excretion identifies the anaerobic coproporphyrinogen III oxidase HemN as a copper target in the Cu⁺-ATPase mutant copA⁻ of Rubrivivax gelatinosus. Molecular microbiology 42 23448658
2010 Crystal structure of alpha-COP in complex with epsilon-COP provides insight into the architecture of the COPI vesicular coat. Proceedings of the National Academy of Sciences of the United States of America 42 20534429
2020 Baricitinib in therapy of COPA syndrome in a 15-year-old girl. European journal of rheumatology 41 31449490
2019 Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage. Thorax 41 31666386
2012 The ATPases CopA and CopB both contribute to copper resistance of the thermoacidophilic archaeon Sulfolobus solfataricus. Microbiology (Reading, England) 39 22361944
2008 A Multicopper oxidase (Cj1516) and a CopA homologue (Cj1161) are major components of the copper homeostasis system of Campylobacter jejuni. Journal of bacteriology 36 18931123
2007 Fingerprinting and diversity of bacterial copA genes in response to soil types, soil organic status and copper contamination. FEMS microbiology ecology 36 17696885
1982 Convergent transcription interferes with expression of the copy number control gene, copA, from plasmid R1. The EMBO journal 36 16453418
2020 A Defect in Thymic Tolerance Causes T Cell-Mediated Autoimmunity in a Murine Model of COPA Syndrome. Journal of immunology (Baltimore, Md. : 1950) 35 32198142
2013 Dilysine motifs in exon 2b of SMN protein mediate binding to the COPI vesicle protein α-COP and neurite outgrowth in a cell culture model of spinal muscular atrophy. Human molecular genetics 35 23727837
2018 Characterization of multicopper oxidase CopA from Pseudomonas putida KT2440 and Pseudomonas fluorescens Pf-5: Involvement in bacterial lignin oxidation. Archives of biochemistry and biophysics 33 30347180
2008 Expression of copA and cusA in Shewanella during copper stress. Microbiology (Reading, England) 33 18757804
2021 Augmentation of Stimulator of Interferon Genes-Induced Type I Interferon Production in COPA Syndrome. Arthritis & rheumatology (Hoboken, N.J.) 32 33982886
2015 Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene. PloS one 32 26042826
2009 Nucleotide recognition by CopA, a Cu+-transporting P-type ATPase. The EMBO journal 32 19478797
1998 Degradation pathway of CopA, the antisense RNA that controls replication of plasmid R1. Microbiology (Reading, England) 32 9695924
2017 Imaging findings of Copa syndrome in a 12-year-old boy. Pediatric radiology 31 28956095
2015 α-COP binding to the survival motor neuron protein SMN is required for neuronal process outgrowth. Human molecular genetics 31 26464491
2008 Intermediate phosphorylation reactions in the mechanism of ATP utilization by the copper ATPase (CopA) of Thermotoga maritima. The Journal of biological chemistry 31 18562314
2001 Purification and functional analysis of the copper ATPase CopA of Enterococcus hirae. Biochemical and biophysical research communications 31 11162579
1987 Control of replication of plasmid R1: translation of the 7k reading frame in the RepA mRNA leader region counteracts the interaction between CopA RNA and CopT RNA. The EMBO journal 31 3556167
2019 An unprecedented COPA gene mutation in two patients in the same family: comparative clinical analysis of newly reported patients with other known COPA gene mutations. Pediatric rheumatology online journal 29 31455335
2015 Distinct functions of serial metal-binding domains in the Escherichia coli P1 B -ATPase CopA. Molecular microbiology 29 25899340
2008 Structure and Cu(I)-binding properties of the N-terminal soluble domains of Bacillus subtilis CopA. The Biochemical journal 29 18215122
2007 CopA:GFP localizes to putative Golgi equivalents in Aspergillus nidulans. FEMS microbiology letters 28 17986089
2003 A core mutation affecting the folding properties of a soluble domain of the ATPase protein CopA from Bacillus subtilis. Journal of molecular biology 28 12888353
2016 M-COPA, a Golgi Disruptor, Inhibits Cell Surface Expression of MET Protein and Exhibits Antitumor Activity against MET-Addicted Gastric Cancers. Cancer research 27 27197184
2011 Functional characterization of copA gene encoding multicopper oxidase in Xanthomonas campestris pv. campestris. Journal of agricultural and food chemistry 26 21790191
2006 Activation of Archaeoglobus fulgidus Cu(+)-ATPase CopA by cysteine. Biochimica et biophysica acta 25 17064659
2012 Periplasmic proteins encoded by VCA0261-0260 and VC2216 genes together with copA and cueR products are required for copper tolerance but not for virulence in Vibrio cholerae. Microbiology (Reading, England) 24 22653946
1996 HEP-COP, a novel human gene whose product is highly homologous to the alpha-subunit of the yeast coatomer protein complex. Gene 24 8647451
2015 Assessing the genetic diversity of Cu resistance in mine tailings through high-throughput recovery of full-length copA genes. Scientific reports 23 26286020
1998 Specific interaction of Golgi coatomer protein alpha-COP with phosphatidylinositol 3,4,5-trisphosphate. The Journal of biological chemistry 23 9525943
2005 Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin. Journal of industrial microbiology & biotechnology 22 16187093
2009 Mechanistic insights into Cu(I) cluster transfer between the chaperone CopZ and its cognate Cu(I)-transporting P-type ATPase, CopA. The Biochemical journal 21 19751213
1999 sodVIC is an alpha-COP-related gene which is essential for establishing and maintaining polarized growth in Aspergillus nidulans. Fungal genetics and biology : FG & B 20 10361037
2024 Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome. The Journal of clinical investigation 19 38175705
2008 Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 19 18979168
2022 COPA A-to-I RNA editing hijacks endoplasmic reticulum stress to promote metastasis in colorectal cancer. Cancer letters 18 36336148
2019 Genetics of COPA syndrome. The application of clinical genetics 18 30804679
2017 Oncogenic Kit signalling on the Golgi is suppressed by blocking secretory trafficking with M-COPA in gastrointestinal stromal tumours. Cancer letters 18 29196126
2011 The architecture of CopA from Archeaoglobus fulgidus studied by cryo-electron microscopy and computational docking. Structure (London, England : 1993) 18 21820315
2018 Manganese(II) oxidation by the multi-copper oxidase CopA from Brevibacillus panacihumi MK-8. Enzyme and microbial technology 17 30037555
2007 Thermal stability of CopA, a polytopic membrane protein from the hyperthermophile Archaeoglobus fulgidus. Archives of biochemistry and biophysics 17 18187034
2023 Imaging findings of COPA Syndrome. Pediatric radiology 16 36746811
2016 Expression of genes involved in lipid droplet formation (BSCL2, SNAP23 and COPA) during porcine in vitro adipogenesis. Journal of applied genetics 16 27108337
2019 CopA Protects Streptococcus suis against Copper Toxicity. International journal of molecular sciences 15 31216645
2009 The N-terminal soluble domains of Bacillus subtilis CopA exhibit a high affinity and capacity for Cu(I) ions. Dalton transactions (Cambridge, England : 2003) 15 19378562
1997 Genomic organization and mapping of the human HEP-COP gene (COPA) to 1q. Cytogenetics and cell genetics 14 9186507
1997 Alpha coat protein COPA (HEP-COP): presence of an Alu repeat in cDNA and identity of the amino terminus to xenin. Annals of human genetics 14 9365789
2017 Copper ATPase CopA from Escherichia coli: Quantitative Correlation between ATPase Activity and Vectorial Copper Transport. Journal of the American Chemical Society 13 28272878
2017 M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells. PloS one 13 28403213
2021 A Novel Mutation c.841C>T in COPA Syndrome of an 11-Year-Old Boy: A Case Report and Short Literature Review. Frontiers in pediatrics 12 34900872
2017 Transcriptional response of Erwinia amylovora to copper shock: in vivo role of the copA gene. Molecular plant pathology 12 27862834
2014 COPA and SLC4A4 are required for cellular entry of arginine-rich peptides. PloS one 12 24489756
2025 The common HAQ STING allele prevents clinical penetrance of COPA syndrome. The Journal of experimental medicine 11 40014299
2022 Sequence-based Functional Metagenomics Reveals Novel Natural Diversity of Functional CopA in Environmental Microbiomes. Genomics, proteomics & bioinformatics 11 36089219
1991 Regulation of replication of plasmid R1: an analysis of the intergenic region between copA and repA. Molecular & general genetics : MGG 11 1720863
2021 IL-6 receptor blockade for allograft dysfunction after lung transplantation in a patient with COPA syndrome. Clinical & translational immunology 10 33537146
2016 The relationship between adipocyte size and the transcript levels of SNAP23, BSCL2 and COPA genes in pigs. Meat science 10 27232380
2011 Cu(I)- and proton-binding properties of the first N-terminal soluble domain of Bacillus subtilis CopA. The FEBS journal 10 22077885
2004 C-terminal truncation of alpha-COP affects functioning of secretory organelles and calcium homeostasis in Hansenula polymorpha. Eukaryotic cell 10 14871936

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