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:
  - molecular_function:
      id: GO:0003674
      label: molecular_function
    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.
  - 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.