id: P61201
gene_symbol: COPS2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  COPS2 (COP9 signalosome complex subunit 2, also known as TRIP15/Alien) is a core
  PCI-domain scaffold subunit of the COP9 signalosome (CSN), an eight-subunit protein
  complex essential for regulating the ubiquitin-proteasome pathway. COPS2 is a
  non-catalytic structural component that organizes the CSN complex and engages
  cullin-RING E3 ligases (CRLs) to enable CSN5-mediated deneddylation of cullins,
  thereby controlling CRL ubiquitin ligase activity and downstream proteostasis.
  COPS2 also functions independently as a nuclear receptor corepressor (Alien/TRIP15),
  interacting with thyroid hormone receptor, DAX-1, and other nuclear receptors to
  repress transcription. The protein localizes to both cytoplasm and nucleus,
  consistent with its roles in both CRL regulation and transcriptional regulation.
alternative_products:
- id: P61201-1
  name: '1'
- id: P61201-2
  name: '2'
existing_annotations:
- term:
    id: GO:0008180
    label: COP9 signalosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Core annotation. COPS2/CSN2 is an integral subunit of the COP9 signalosome
      as demonstrated by multiple structural and biochemical studies. The CSN
      complex consists of COPS1-8/9 subunits, and COPS2 is part of the
      Csn1/2/3/8 module [PMID:19141280]. Crystal structure confirms COPS2 as a
      core subunit [PMID:25043011].
    action: ACCEPT
    reason: >-
      COPS2 is a well-established core subunit of the COP9 signalosome. IBA
      annotation based on phylogenetic inference is fully supported by
      extensive experimental evidence in mammals and other eukaryotes.
    supported_by:
    - reference_id: PMID:19141280
      supporting_text: >-
        Our results indicate that the catalytically active human complex,
        reconstituted in vitro, is composed of a single copy of each of the
        eight subunits. By forming a total of 35 subcomplexes, we are able to
        build a comprehensive interaction map that shows two symmetrical
        modules, Csn1/2/3/8 and Csn4/5/6/7, connected by interactions between
        Csn1-Csn6.
    - reference_id: PMID:25043011
      supporting_text: >-
        Here we present the crystal structure of the entire ∼350-kDa human CSN
        holoenzyme at 3.8 Å resolution, detailing the molecular architecture
        of the complex.
- term:
    id: GO:0000338
    label: protein deneddylation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Core annotation. COPS2 is essential for CSN complex integrity and
      deneddylase function. Mouse knockout studies show that Csn2 disruption
      leads to loss of CSN function and accumulation of neddylated cullins
      [PMID:12628923]. The deneddylation is catalyzed by CSN5, but requires
      the intact complex including COPS2 for activity.
    action: ACCEPT
    reason: >-
      COPS2 is required for CSN-mediated deneddylation. While COPS2 itself
      lacks catalytic activity (CSN5 is the isopeptidase), COPS2 is essential
      for CSN complex assembly and function. The IBA annotation appropriately
      captures the role of CSN2 in the deneddylation process.
    supported_by:
    - reference_id: PMID:25043011
      supporting_text: >-
        CSN inactivates CRLs by removing their covalently attached activator,
        NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn(2+)-dependent
        isopeptidase that is inactive in isolation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Supported by experimental evidence. CSN complex including COPS2 shows
      nuclear localization by fluorescence microscopy [PMID:24421388]. COPS2
      as Alien/TRIP15 also functions in the nucleus as a corepressor for
      nuclear receptors [PMID:10207062].
    action: ACCEPT
    reason: >-
      IEA annotation is consistent with direct experimental evidence from
      multiple studies showing nuclear localization of COPS2 and the CSN complex.
    additional_reference_ids: [PMID:24421388, PMID:10207062]
    supported_by:
    - reference_id: PMID:24421388
      supporting_text: >-
        Through biochemical and fluorescence microscopy analyses, we
        determined that the complex is localized in the cytoplasm,
        nucleoplasm, and chromatin-bound fractions, each differing in the
        composition of posttranslationally modified subunits, depending on
        its location within the cell
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Supported by experimental evidence. The CSN complex shows cytoplasmic
      localization [PMID:9535219, PMID:24421388]. Immunofluorescence staining
      reveals subcellular distribution similar to 26S proteasome.
    action: ACCEPT
    reason: >-
      IEA annotation is consistent with direct experimental evidence showing
      cytoplasmic localization of COPS2/CSN2 and the CSN complex.
    additional_reference_ids: [PMID:9535219, PMID:24421388]
    supported_by:
    - reference_id: PMID:9535219
      supporting_text: >-
        Immunofluorescence staining reveals that the new complex shows a
        subcellular distribution similar to that of the 26S proteasome.
- term:
    id: GO:0008180
    label: COP9 signalosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Duplicate of IBA annotation above for same term. Both annotations are
      valid as they represent different evidence sources.
    action: ACCEPT
    reason: >-
      IEA annotation consistent with extensive experimental data confirming
      COPS2 as a core subunit of the COP9 signalosome.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Very general term. COPS2 is part of the COP9 signalosome complex,
      which is a more specific term already annotated.
    action: ACCEPT
    reason: >-
      While GO:0008180 (COP9 signalosome) is more informative, this general
      complex annotation is not incorrect. COPS2 is indeed part of a
      protein-containing complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15304329
  review:
    summary: >-
      Generic protein binding term. This annotation refers to hepatopoietin
      interaction with the COP9 signalosome. Too generic to be informative
      about COPS2 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague and uninformative. COPS2 has specific
      molecular functions as a scaffold protein and corepressor that are
      better captured by other terms.
    supported_by:
    - reference_id: PMID:15304329
      supporting_text: >-
        Hepatopoietin interacts directly with COP9 signalosome and regulates
        AP-1 activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18850735
  review:
    summary: >-
      Generic protein binding from CSN complex characterization study.
      Identified protein-protein interactions via affinity purification
      and mass spectrometry.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While the study confirms COPS2 interacts with other proteins within
      the CSN complex, the protein binding term is too generic. More
      specific scaffold or complex assembly terms would be more informative.
    supported_by:
    - reference_id: PMID:18850735
      supporting_text: >-
        Characterization of the human COP9 signalosome complex using
        affinity purification and mass spectrometry.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19615732
  review:
    summary: >-
      Generic protein binding from deubiquitinating enzyme interaction
      landscape study - high-throughput study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome study. Protein binding is too generic
      to be informative about COPS2 function.
    supported_by:
    - reference_id: PMID:19615732
      supporting_text: >-
        Defining the human deubiquitinating enzyme interaction landscape.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20399188
  review:
    summary: >-
      Generic protein binding from structural study showing CSN
      architecture. This study provides important structural insights.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While this study provides valuable structural information about CSN
      architecture, the protein binding annotation is too generic.
    supported_by:
    - reference_id: PMID:20399188
      supporting_text: >-
        Structural insights into the COP9 signalosome and its common
        architecture with the 26S proteasome lid and eIF3.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21145461
  review:
    summary: >-
      Generic protein binding from cullin-RING ligase network proteomics
      study - demonstrates COPS2/CSN interaction with CRL network.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput proteomics study. Protein binding is uninformative
      as a molecular function annotation.
    supported_by:
    - reference_id: PMID:21145461
      supporting_text: >-
        Dynamics of cullin-RING ubiquitin ligase network revealed by
        systematic quantitative proteomics.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21911577
  review:
    summary: >-
      Generic protein binding from dengue virus-human protein interaction
      network study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Viral interactome study. Protein binding is too generic and this
      interaction may represent viral hijacking rather than normal function.
    supported_by:
    - reference_id: PMID:21911577
      supporting_text: >-
        A physical interaction network of dengue virus and human proteins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23441852
  review:
    summary: >-
      Protein binding documenting interaction between Alien/COPS2 and
      CREB-binding protein (CBP)/p300. This interaction controls corepressor
      activity through acetylation.
    action: MODIFY
    reason: >-
      This specific interaction with CBP/p300 relates to COPS2's corepressor
      function. A more informative term would capture the regulatory
      relationship between corepressor and coactivator.
    proposed_replacement_terms:
    - id: GO:0003714
      label: transcription corepressor activity
    supported_by:
    - reference_id: PMID:23441852
      supporting_text: >-
        The corepressor Alien interacts with the CREB-binding protein (CBP)
        coactivator. This interaction was further confirmed by
        coimmunoprecipitation and glutathione S-transferase pull-down
        experiments, suggesting that Alien interacts in vivo and in vitro
        with the histone acetyltransferase (HAT) coactivators CBP and its
        paralog p300.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24421388
  review:
    summary: >-
      Generic protein binding from CSN DNA damage response study. Study
      focuses on CSN complex dynamics rather than specific COPS2 interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput proteomics study. Protein binding is too generic.
    supported_by:
    - reference_id: PMID:24421388
      supporting_text: >-
        Dynamic regulation of the COP9 signalosome in response to DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25043011
  review:
    summary: >-
      Generic protein binding from CSN crystal structure study. This landmark
      study provides detailed structural information about CSN subunit
      interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While the structural study is highly valuable, protein binding is
      too generic as an MF annotation. COPS2's role as a structural scaffold
      is better captured by CC annotations.
    supported_by:
    - reference_id: PMID:25043011
      supporting_text: >-
        Crystal structure of the human COP9 signalosome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  review:
    summary: >-
      Generic protein binding from organelle-specific protein landscape study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput proteomics study. Protein binding is uninformative.
    supported_by:
    - reference_id: PMID:27173435
      supporting_text: >-
        An organelle-specific protein landscape identifies novel diseases
        and molecular mechanisms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      Generic protein binding from human binary protein interactome reference
      map - large-scale interactome study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome mapping. Protein binding is too generic.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: >-
        A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      Generic protein binding from neurodegenerative disease interactome
      mapping study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome study focused on neurodegeneration.
      Protein binding is uninformative.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: >-
        Interactome Mapping Provides a Network of Neurodegenerative Disease
        Proteins and Uncovers Widespread Protein Aggregation in Affected
        Brains.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      Generic protein binding from dual proteome-scale network study on
      human interactome remodeling.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput proteomics study. Protein binding is uninformative.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Dual proteome-scale networks reveal cell-specific remodeling of
        the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      Generic protein binding from multimodal cell maps study on structural
      and functional genomics.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput multimodal study. Protein binding is too generic.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: >-
        Multimodal cell maps as a foundation for structural and functional
        genomics.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      COPS2/Alien functions as a corepressor for nuclear hormone receptors
      including thyroid hormone receptor [PMID:10207062] and DAX-1
      [PMID:10713076]. The corepressor activity is documented experimentally.
    action: ACCEPT
    reason: >-
      IEA annotation consistent with experimental evidence. COPS2 as
      Alien/TRIP15 is a well-established corepressor for nuclear receptors,
      mediating transcriptional repression.
    additional_reference_ids: [PMID:10207062, PMID:10713076]
    supported_by:
    - reference_id: PMID:10207062
      supporting_text: >-
        Alien, a highly conserved protein with characteristics of a
        corepressor for members of the nuclear hormone receptor superfamily.
- term:
    id: GO:0003714
    label: transcription corepressor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Core annotation for COPS2's Alien/TRIP15 function. Well-documented
      corepressor activity for nuclear hormone receptors including thyroid
      hormone receptor, DAX-1, and others [PMID:10207062, PMID:10713076,
      PMID:23441852].
    action: ACCEPT
    reason: >-
      IEA annotation consistent with extensive experimental evidence. COPS2
      as Alien is a bona fide corepressor with documented ability to repress
      transcription in conjunction with nuclear receptors.
    additional_reference_ids:
    - PMID:10207062
    - PMID:10713076
    - PMID:23441852
    supported_by:
    - reference_id: PMID:23441852
      supporting_text: >-
        The regulation of gene repression by corepressors is a controlled
        process... the corepressor Alien interacts with the CREB-binding
        protein (CBP) coactivator.
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      UniProt notes involvement in early stage of neuronal differentiation
      via interaction with NIF3L1. This is a downstream effect of CSN
      function or corepressor activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      While COPS2 may play a role in neuronal differentiation (possibly
      through its corepressor function or CSN activity), this is a
      downstream developmental effect rather than a core molecular function.
- term:
    id: GO:0045171
    label: intercellular bridge
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      This annotation from immunofluorescence data seems questionable for
      COPS2's known functions. The primary localization is nucleus and
      cytoplasm, not intercellular bridges.
    action: UNDECIDED
    reason: >-
      The evidence source GO_REF:0000052 refers to curation of
      immunofluorescence data, but intercellular bridge localization is not
      a well-characterized aspect of COPS2 function. Unable to access
      underlying data to verify.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:24421388
  review:
    summary: >-
      Direct evidence for nuclear localization from fluorescence microscopy
      analyses showing CSN complex in nucleoplasm and chromatin-bound fractions.
    action: ACCEPT
    reason: >-
      Well-supported by direct experimental evidence in the cited publication.
    supported_by:
    - reference_id: PMID:24421388
      supporting_text: >-
        Through biochemical and fluorescence microscopy analyses, we
        determined that the complex is localized in the cytoplasm,
        nucleoplasm, and chromatin-bound fractions, each differing in the
        composition of posttranslationally modified subunits, depending on
        its location within the cell
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24421388
  review:
    summary: >-
      Direct evidence for cytoplasmic localization from fluorescence microscopy
      and biochemical analyses.
    action: ACCEPT
    reason: >-
      Well-supported by direct experimental evidence in the cited publication.
    supported_by:
    - reference_id: PMID:24421388
      supporting_text: >-
        Through biochemical and fluorescence microscopy analyses, we
        determined that the complex is localized in the cytoplasm,
        nucleoplasm, and chromatin-bound fractions, each differing in the
        composition of posttranslationally modified subunits, depending on
        its location within the cell
- term:
    id: GO:0045116
    label: protein neddylation
  evidence_type: NAS
  original_reference_id: PMID:24421388
  review:
    summary: >-
      The CSN complex primarily performs deneddylation (removal of NEDD8),
      not neddylation (addition of NEDD8). This annotation appears to be
      an error or misunderstanding of CSN function.
    action: MODIFY
    reason: >-
      The CSN complex, including COPS2, is involved in deneddylation,
      the opposite of neddylation. The term should be changed to reflect
      the regulatory role or the correct process.
    proposed_replacement_terms:
    - id: GO:0000338
      label: protein deneddylation
    supported_by:
    - reference_id: PMID:25043011
      supporting_text: >-
        CSN inactivates CRLs by removing their covalently attached
        activator, NEDD8.
- term:
    id: GO:2000434
    label: regulation of protein neddylation
  evidence_type: NAS
  original_reference_id: PMID:24421388
  review:
    summary: >-
      CSN regulates the neddylation/deneddylation cycle by performing
      deneddylation, thereby controlling CRL activity. This annotation
      captures the regulatory aspect appropriately.
    action: ACCEPT
    reason: >-
      The CSN complex does regulate protein neddylation levels by
      catalyzing deneddylation. This annotation appropriately captures
      the regulatory role of the complex in the neddylation cycle.
    supported_by:
    - reference_id: PMID:25043011
      supporting_text: >-
        CSN inactivates CRLs by removing their covalently attached
        activator, NEDD8.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Duplicate of IEA annotation for same term. ISS evidence from
      sequence similarity supports the corepressor function.
    action: ACCEPT
    reason: >-
      Consistent with COPS2/Alien's documented corepressor function.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:9535219
  review:
    summary: >-
      OVER-ANNOTATION: COPS2 is a PCI-domain scaffold subunit of the COP9
      signalosome (CSN). PMID:9535219 shows the CSN complex has kinase
      activity, but UniProt notes this is "possibly via its association
      with CK2 and PKD kinases". COPS2 itself lacks kinase catalytic
      activity - it is a structural scaffold. The kinase activity comes
      from associated kinases, not COPS2.
    action: MODIFY
    reason: >-
      COPS2 does not have intrinsic kinase activity. The phosphorylation
      activity is due to associated kinases (CK2, PKD) that interact with
      the CSN complex. The annotation should reflect the regulatory role
      rather than direct catalytic phosphorylation.
    proposed_replacement_terms:
    - id: GO:0045859
      label: regulation of protein kinase activity
    supported_by:
    - reference_id: PMID:9535219
      supporting_text: >-
        The isolated JAB1-containing particle has kinase activity that
        phosphorylates IkappaBalpha, the carboxy terminus of p105, and
        Ser63 and/or Ser73 of the amino-terminal activation domain of c-Jun.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8863721
  review:
    summary: >-
      Reactome annotation for CSN involvement in TOR1/STON deneddylation
      pathway. Cytosolic localization is consistent with biochemical
      evidence.
    action: ACCEPT
    reason: >-
      Consistent with experimental evidence showing cytoplasmic/cytosolic
      localization of the CSN complex.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8863723
  review:
    summary: >-
      Reactome annotation for COP9 and TOR1 deneddylation activity.
      Duplicate localization annotation for same compartment.
    action: ACCEPT
    reason: >-
      Consistent with known cytosolic localization of CSN complex.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956040
  review:
    summary: >-
      Reactome annotation for CSN deneddylation of cytosolic CRL E3
      ubiquitin ligase complexes.
    action: ACCEPT
    reason: >-
      Appropriate annotation reflecting cytosolic location of CSN-CRL
      deneddylation activity.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5691006
  review:
    summary: >-
      Reactome annotation for XPC:RAD23:CETN2 and UV-DDB binding to
      distorted DNA in nucleotide excision repair context.
    action: ACCEPT
    reason: >-
      CSN complex has documented nucleoplasmic localization and role
      in DNA damage response [PMID:24421388].
    additional_reference_ids: [PMID:24421388]
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6781833
  review:
    summary: >-
      Reactome annotation for ERCC8 (CSA) binding stalled RNA Pol II,
      relevant to transcription-coupled repair.
    action: ACCEPT
    reason: >-
      CSN complex localizes to nucleoplasm and participates in DNA
      damage response pathways.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956045
  review:
    summary: >-
      Reactome annotation for CSN deneddylation of nuclear CRL4 E3
      ubiquitin ligase complex.
    action: ACCEPT
    reason: >-
      Appropriate annotation reflecting nucleoplasmic location of
      CSN-CRL4 deneddylation activity in DNA repair contexts.
- term:
    id: GO:0000338
    label: protein deneddylation
  evidence_type: IDA
  original_reference_id: PMID:19141280
  review:
    summary: >-
      Direct evidence for deneddylation function. Study reconstituted
      catalytically active CSN complex in vitro and demonstrated
      deneddylation activity.
    action: ACCEPT
    reason: >-
      Well-supported by direct experimental evidence. COPS2 as part
      of the reconstituted CSN complex is essential for deneddylation.
    supported_by:
    - reference_id: PMID:19141280
      supporting_text: >-
        Our results indicate that the catalytically active human complex,
        reconstituted in vitro, is composed of a single copy of each of
        the eight subunits.
- term:
    id: GO:0008180
    label: COP9 signalosome
  evidence_type: IDA
  original_reference_id: PMID:18850735
  review:
    summary: >-
      Direct identification of COPS2 as CSN subunit by affinity
      purification and mass spectrometry.
    action: ACCEPT
    reason: >-
      Strong experimental evidence confirming COPS2 as a component of
      the CSN complex.
    supported_by:
    - reference_id: PMID:18850735
      supporting_text: >-
        Mass spectrometric analysis of the purified CSN complex has
        revealed the identity of its composition as well as N-terminal
        modification and phosphorylation of the CSN subunits
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17438371
  review:
    summary: >-
      Study identified transcription factors as interaction partners of
      Alien/COPS2 including nucleophosmin, ERCC3, TRIP11, and CRSP3.
      These interactions relate to COPS2's role in transcriptional
      regulation and DNA repair.
    action: MODIFY
    reason: >-
      The interactions identified are more informative than generic
      protein binding. The interactions with transcription factors
      support the corepressor activity annotation.
    proposed_replacement_terms:
    - id: GO:0003714
      label: transcription corepressor activity
    supported_by:
    - reference_id: PMID:17438371
      supporting_text: >-
        In this way we detected protein interactions of Alien involving
        nucleophosmin, ERCC3, TRIP11, as well as CRSP3
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:9535219
  review:
    summary: >-
      Early characterization of CSN showing cytoplasmic distribution
      by immunofluorescence.
    action: ACCEPT
    reason: >-
      Well-supported by direct experimental evidence.
    supported_by:
    - reference_id: PMID:9535219
      supporting_text: >-
        Immunofluorescence staining reveals that the new complex shows
        a subcellular distribution similar to that of the 26S proteasome.
- term:
    id: GO:0006366
    label: transcription by RNA polymerase II
  evidence_type: TAS
  original_reference_id: PMID:7776974
  review:
    summary: >-
      Early study identified TRIP15/COPS2 as thyroid hormone receptor-
      interacting protein, implying role in transcription. The general
      transcription term is broader than the specific corepressor role.
    action: MODIFY
    reason: >-
      COPS2/TRIP15's role in transcription is specifically as a
      corepressor, not a general transcription factor. A more specific
      term is appropriate.
    proposed_replacement_terms:
    - id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: PMID:7776974
      supporting_text: >-
        Several such proteins, called Trips (TR-interacting proteins),
        were isolated from independent selections carried out either in
        the presence or absence of T3.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: NAS
  original_reference_id: PMID:9535219
  review:
    summary: >-
      The original CSN characterization paper proposed signaling roles
      based on kinase activity and substrate phosphorylation. This is
      a very broad term.
    action: KEEP_AS_NON_CORE
    reason: >-
      Signal transduction is a downstream effect of CSN function in
      regulating CRL-mediated proteolysis and associated kinase activity.
      Not a core molecular function of COPS2.
    supported_by:
    - reference_id: PMID:9535219
      supporting_text: >-
        Considering the putative role of the complex in signal
        transduction and its widespread occurrence, we suggest the
        name JAB1-containing signalosome.
- term:
    id: GO:0008180
    label: COP9 signalosome
  evidence_type: IDA
  original_reference_id: PMID:9535219
  review:
    summary: >-
      Original characterization study identifying COPS2/TRIP15 as a
      subunit of the novel CSN complex.
    action: ACCEPT
    reason: >-
      Foundational experimental evidence establishing COPS2 as a
      CSN subunit.
    supported_by:
    - reference_id: PMID:9535219
      supporting_text: >-
        It consists of at least eight different subunits including
        JAB1, the Jun activation-domain binding protein 1, and Trip15,
        the thyroid hormone receptor-interacting protein 15.
references:
- id: GO_REF:0000024
  title: >-
    Manual transfer of experimentally-verified manual GO annotation data
    to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: >-
    Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
    Location vocabulary mapping, accompanied by conservative changes to
    GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: >-
    Automatic transfer of experimentally verified manual GO annotation
    data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: >-
    Electronic Gene Ontology annotations created by ARBA machine learning
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:7776974
  title: >-
    Two classes of proteins dependent on either the presence or absence
    of thyroid hormone for interaction with the thyroid hormone receptor.
  findings:
  - statement: Identified TRIP15 as a thyroid hormone receptor-interacting 
      protein
- id: PMID:9535219
  title: >-
    A novel protein complex involved in signal transduction possessing
    similarities to 26S proteasome subunits.
  findings:
  - statement: Characterized CSN complex including TRIP15/COPS2
  - statement: Demonstrated associated kinase activity
  - statement: Showed cytoplasmic localization
- id: PMID:10207062
  title: >-
    Alien, a highly conserved protein with characteristics of a corepressor
    for members of the nuclear hormone receptor superfamily.
  findings:
  - statement: Characterized Alien/COPS2 as nuclear receptor corepressor
  - statement: Showed nuclear localization
- id: PMID:10713076
  title: >-
    Interaction of the corepressor Alien with DAX-1 is abrogated by
    mutations of DAX-1 involved in adrenal hypoplasia congenita.
  findings:
  - statement: Documented Alien/COPS2 interaction with DAX-1
- id: PMID:15304329
  title: >-
    Hepatopoietin interacts directly with COP9 signalosome and regulates
    AP-1 activity.
  findings: []
- id: PMID:17438371
  title: >-
    Detection and identification of transcription factors as interaction
    partners of alien in vivo.
  findings:
  - statement: Identified Alien interactions with nucleophosmin, ERCC3, TRIP11, 
      CRSP3
- id: PMID:18850735
  title: >-
    Characterization of the human COP9 signalosome complex using affinity
    purification and mass spectrometry.
  findings:
  - statement: Confirmed COPS2 as CSN subunit by mass spectrometry
- id: PMID:19141280
  title: >-
    Symmetrical modularity of the COP9 signalosome complex suggests its
    multifunctionality.
  findings:
  - statement: Demonstrated CSN complex structure with two symmetrical modules
  - statement: COPS2 in Csn1/2/3/8 module
  - statement: Reconstituted catalytically active complex
- id: PMID:19615732
  title: Defining the human deubiquitinating enzyme interaction landscape.
  findings: []
- id: PMID:20399188
  title: >-
    Structural insights into the COP9 signalosome and its common
    architecture with the 26S proteasome lid and eIF3.
  findings: []
- id: PMID:21145461
  title: >-
    Dynamics of cullin-RING ubiquitin ligase network revealed by
    systematic quantitative proteomics.
  findings: []
- id: PMID:21911577
  title: A physical interaction network of dengue virus and human proteins.
  findings: []
- id: PMID:23441852
  title: The corepressor activity of Alien is controlled by CREB-binding 
    protein/p300.
  findings:
  - statement: Demonstrated Alien/COPS2 interaction with CBP/p300
  - statement: Showed acetylation regulates corepressor activity
- id: PMID:24421388
  title: Dynamic regulation of the COP9 signalosome in response to DNA damage.
  findings:
  - statement: Showed CSN localization in cytoplasm, nucleoplasm, chromatin
  - statement: Documented UV-induced nuclear shuttling
- id: PMID:25043011
  title: Crystal structure of the human COP9 signalosome.
  findings:
  - statement: Solved 3.8A crystal structure of CSN
  - statement: Revealed molecular architecture including COPS2
- id: PMID:27173435
  title: >-
    An organelle-specific protein landscape identifies novel diseases and
    molecular mechanisms.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: >-
    Interactome Mapping Provides a Network of Neurodegenerative Disease
    Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: >-
    Dual proteome-scale networks reveal cell-specific remodeling of the
    human interactome.
  findings: []
- id: PMID:40205054
  title: >-
    Multimodal cell maps as a foundation for structural and functional
    genomics.
  findings: []
- id: Reactome:R-HSA-5691006
  title: XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site
  findings: []
- id: Reactome:R-HSA-6781833
  title: ERCC8 (CSA) binds stalled RNA Pol II
  findings: []
- id: Reactome:R-HSA-8863721
  title: NEDD8-STON binds TOR1 hexamer and COP9 complex
  findings: []
- id: Reactome:R-HSA-8863723
  title: COP9 and TOR1 deneddylate STON2
  findings: []
- id: Reactome:R-HSA-8956040
  title: COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase 
    complexes
  findings: []
- id: Reactome:R-HSA-8956045
  title: COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex
  findings: []
core_functions:
- description: >-
    PCI-domain scaffold subunit of the COP9 signalosome complex, essential
    for CSN complex integrity and CSN5-mediated deneddylation of cullins
  in_complex:
    id: GO:0008180
    label: COP9 signalosome
  directly_involved_in:
  - id: GO:0000338
    label: protein deneddylation
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005654
    label: nucleoplasm
  supported_by:
  - reference_id: PMID:19141280
    supporting_text: >-
      Our results indicate that the catalytically active human complex,
      reconstituted in vitro, is composed of a single copy of each of the
      eight subunits.
  - reference_id: PMID:25043011
    supporting_text: >-
      Here we present the crystal structure of the entire ~350-kDa human CSN
      holoenzyme at 3.8 A resolution.
    full_text_unavailable: true
- molecular_function:
    id: GO:0003714
    label: transcription corepressor activity
  description: >-
    Transcription corepressor (as Alien/TRIP15) for nuclear hormone receptors
    including thyroid hormone receptor, DAX-1, and NR2F1
  directly_involved_in:
  - id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:10207062
    supporting_text: >-
      Alien, a highly conserved protein with characteristics of a corepressor
      for members of the nuclear hormone receptor superfamily.
  - reference_id: PMID:23441852
    supporting_text: >-
      The corepressor Alien interacts with the CREB-binding protein (CBP)
      coactivator.