Affinage

COPS2

COP9 signalosome complex subunit 2 · UniProt P61201

Round 2 corrected
Length
443 aa
Mass
51.6 kDa
Annotated
2026-04-28
130 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COPS2 (Alien/Trip15/CSN2) is an essential, evolutionarily conserved subunit of the COP9 signalosome (CSN) that functions both as a core component of the CSN deneddylase complex regulating cullin-RING ubiquitin ligase activity and as a transcriptional corepressor for select nuclear hormone receptors and other transcription factors (PMID:11337588, PMID:10207062, PMID:10877839). As a corepressor, COPS2 binds thyroid hormone receptor and vitamin D receptor in the absence of ligand, recruits Sin3A/HDAC-dependent and HDAC-independent silencing mechanisms, and enhances NAP1-mediated nucleosome assembly at target promoters such as CYP24 (PMID:15173382, PMID:17339334). Within the CSN, COPS2 contributes to intrinsic kinase activity that phosphorylates substrates including p53, ICSBP, and IκBα, targeting them for regulated degradation or modulating their transcriptional function (PMID:11285227, PMID:10991940, PMID:9535219). In embryonic stem cells, COPS2 stabilizes Nanog protein against proteasomal degradation and promotes G2/M progression by sequestering OCT4 away from CDK1, and its knockout in mice is embryonic lethal (PMID:27226076, PMID:30033083, PMID:18174916).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 Medium

    The initial identification of COPS2 as a thyroid hormone receptor-interacting protein established it as a ligand-sensitive nuclear receptor cofactor, revealing that it binds TR specifically in the absence of hormone.

    Evidence Yeast two-hybrid screen of rat TRβ LBD with and without T3

    PMID:7776974

    Open questions at the time
    • Interaction detected only in yeast two-hybrid; endogenous complex not validated
    • Mechanism of repression not addressed
    • Whether COPS2 interacts with other nuclear receptors unknown
  2. 1998 High

    Biochemical purification of the COP9 signalosome placed COPS2 as an integral subunit of a ~450 kDa complex with intrinsic kinase activity, establishing a second functional identity beyond nuclear receptor corepression.

    Evidence Native complex purification from human cells, SDS-PAGE subunit mapping, in vitro kinase assays on IκBα, p105, and c-Jun

    PMID:9535219

    Open questions at the time
    • Identity of the kinase subunit or associated kinase not resolved
    • Physiological relevance of CSN kinase activity toward IκBα/c-Jun not demonstrated in cells
  3. 1999 High

    Multi-method validation confirmed COPS2/Alien as a bona fide corepressor with autonomous silencing activity, extending the interaction to Drosophila ecdysone receptor and COUP-TF but excluding RAR and RXR, thereby defining receptor selectivity.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, reporter assays, immunofluorescence in mammalian and Drosophila systems

    PMID:10087198 PMID:10207062

    Open questions at the time
    • Molecular basis of receptor selectivity undefined
    • Identity of effector repression complex not known
  4. 2000 High

    Extension of corepressor activity to VDR and demonstration that Alien-mediated repression is only partially HDAC-dependent revealed a dual (HDAC-dependent and HDAC-independent) repression mechanism distinct from classical NCoR/SMRT corepression, while CSN-mediated phosphorylation of ICSBP linked CSN2 to transcription factor regulation via post-translational modification.

    Evidence GST pull-down, co-IP, reporter assays with TSA treatment for VDR; yeast two-hybrid, in vitro phosphorylation mapping for ICSBP

    PMID:10877839 PMID:10991940

    Open questions at the time
    • HDAC-independent repression mechanism uncharacterized
    • Structural basis of COPS2-VDR versus COPS2-NCoR distinction not resolved
  5. 2001 High

    The discovery that the CSN deneddylates CUL1 and that CSN-associated kinase activity phosphorylates p53 at Thr155 to promote its degradation established two core enzymatic functions of the signalosome complex in which COPS2 resides, connecting it to ubiquitin-proteasome regulation and tumor suppressor control.

    Evidence In vitro deneddylation assay in S. pombe, CSN-deficient yeast genetics; EM of p53-CSN complex, site-directed mutagenesis (T155V), reconstituted degradation assay

    PMID:11285227 PMID:11337588

    Open questions at the time
    • Individual contribution of COPS2 subunit to deneddylation catalysis not dissected
    • Physiological relevance of p53 Thr155 phosphorylation in primary cells not shown
  6. 2003 High

    Identification of Sin3A and NAP1 as direct COPS2-interacting effectors, together with CSN incorporation into CUL4A-DDB2/CSA NER complexes, defined two mechanistic arms: chromatin-level gene silencing via HDAC and nucleosome assembly, and DNA repair regulation through deneddylation of CUL4A ubiquitin ligases.

    Evidence ChIP/re-ChIP at CYP24 promoter for Sin3A and NAP1 co-occupancy; affinity purification and RNAi with NER functional readout for CUL4A complexes; neuronal differentiation phenotypes in P19 cells and Nif3l1 synergy

    PMID:12522100 PMID:12524175 PMID:12732143 PMID:15173382

    Open questions at the time
    • Whether COPS2 recruits Sin3A and NAP1 simultaneously or sequentially is unclear
    • Direct structural contacts within the COPS2-Sin3A-NAP1-nucleosome axis not mapped
    • NER defect upon CSN knockdown not attributed specifically to COPS2
  7. 2007 High

    Reconstituted nucleosome assembly assays showed COPS2 enhances NAP1-mediated chromatin compaction and directly binds histones H3/H4, establishing a chromatin remodeling mechanism for HDAC-independent gene silencing at endogenous promoters.

    Evidence In vitro nucleosome assembly assay, histone pull-down, MNase chromatin fractionation, ChIP/re-ChIP at CYP24

    PMID:17339334

    Open questions at the time
    • Genome-wide scope of COPS2-dependent nucleosome remodeling unknown
    • Relative contribution of HDAC-dependent versus nucleosome assembly-dependent repression at individual loci not quantified
  8. 2016 High

    Functional specificity of COPS2 within the CSN was demonstrated in embryonic stem cells: uniquely among CSN subunits, COPS2 knockdown collapsed pluripotency by destabilizing Nanog protein, linking COPS2 to proteasomal regulation of a master pluripotency factor independently of its signalosome deneddylase role.

    Evidence Individual CSN subunit shRNA screen, co-IP of COPS2-Nanog, proteasome inhibitor rescue, pluripotency marker analysis, reprogramming assays

    PMID:27226076

    Open questions at the time
    • Mechanism by which COPS2 shields Nanog from ubiquitination not identified
    • Whether Nanog stabilization is CSN-dependent or a CSN-independent function of COPS2 not resolved
  9. 2017 Medium

    NF-κB-driven transcriptional upregulation of COPS2 in hepatocellular carcinoma was shown to stabilize Snail protein and promote EMT and metastasis, extending COPS2's protein-stabilization function to an oncogenic context.

    Evidence ChIP for p65 on CSN2 promoter, knockdown/overexpression with EMT marker readout, in vivo pulmonary metastasis model, human HCC immunohistochemistry

    PMID:28423737

    Open questions at the time
    • Direct physical interaction between COPS2 and Snail not demonstrated
    • Whether Snail stabilization is CSN-mediated deneddylation of a cullin-Snail ligase or a CSN-independent function is unclear
    • Findings from a single lab
  10. 2018 High

    A cell-cycle mechanism was delineated in which COPS2 sequesters OCT4 away from CDK1, relieving OCT4-mediated inhibition of CDK1/CYCLIN B kinase activity and enabling G2/M progression in ESCs and somatic cells, explaining the G2/M arrest observed upon COPS2 depletion.

    Evidence Co-IP and mass spectrometry of COPS2-OCT4-CDK1 interactions, CDK1 kinase activity assay, overexpression/knockdown with cell-cycle analysis in ESCs and HeLa

    PMID:30033083

    Open questions at the time
    • Whether COPS2-OCT4-CDK1 regulation is relevant outside stem/cancer cells unknown
    • Structural basis of the COPS2-OCT4 sequestration not defined
  11. 2020 Medium

    Proteomic analysis in cancer cachexia identified COPS2 downregulation in skeletal muscle and linked it to actin cytoskeleton dysregulation and altered DR4-mediated transcription, suggesting a tissue-specific role in muscle homeostasis.

    Evidence Unbiased proteomics in tumor-bearing animals, COPS2 knockdown/overexpression in myotubes, F-actin imaging, DR4 reporter assay, exercise training rescue in vivo

    PMID:32408015

    Open questions at the time
    • Molecular mechanism linking COPS2 to actin cytoskeleton regulation not elucidated
    • DR4-mediated transcriptional targets downstream of COPS2 in muscle not identified
    • Single study; findings in muscle not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of COPS2's CSN-independent functions (Nanog stabilization, OCT4 sequestration), the genome-wide scope of COPS2-mediated chromatin remodeling, and whether its protein-stabilization activities operate through a common mechanism or are target-specific.
  • No structural model of COPS2 in complex with Nanog, OCT4, or NAP1
  • CSN-dependent versus CSN-independent functions of COPS2 not systematically dissected
  • In vivo conditional knockout phenotypes in adult tissues beyond embryonic lethality not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 1 R-HSA-4839726 Chromatin organization 1 R-HSA-73894 DNA Repair 1
Partners
CDK1IRF8NANOGNAP1L1POU5F1SIN3ATHRAVDR
Complex memberships
COP9 signalosome (CSN)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 COPS2 (Trip15) was identified as a thyroid hormone receptor (TR)-interacting protein that binds the TR ligand-binding domain specifically in the ABSENCE of thyroid hormone (T3), classifying it as a hormone-dependent TR co-repressor. Yeast two-hybrid screen of rat TRβ ligand-binding domain against cDNA library, performed with and without T3 Molecular endocrinology Medium 7776974
1998 COPS2 (Trip15) was identified as a subunit of a novel ~450 kDa human protein complex (the COP9 signalosome/JAB1-containing signalosome) that has intrinsic kinase activity phosphorylating IκBα, p105 C-terminus, and c-Jun at Ser63/73. Biochemical purification of the native complex, SDS-PAGE subunit identification, in vitro kinase assays, immunofluorescence localization FASEB journal High 9535219
1999 Alien/COPS2 functions as a corepressor for the thyroid hormone receptor (TR): it interacts with TR only in the absence of hormone, and hormone addition causes dissociation. Alien also exhibits autonomous silencing activity and is localized in the cell nucleus. The Drosophila ortholog shows conserved hormone-sensitive interaction with TR and selective interaction with ecdysone receptor and Seven-up (COUP-TF1 homolog) but not with RAR, RXR/USP, or other Drosophila NHRs. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, reporter gene assays, immunofluorescence Molecular and cellular biology High 10207062
1999 The mouse homologue Cops2 encodes a 443-aa (~50 kDa) protein expressed broadly from E7.5 onward; immunostaining localizes the protein to both cytoplasm and nucleus, with predominant nuclear localization in some cells. EST database homology search, genomic mapping, Northern blotting, immunostaining of native and epitope-tagged Cops2 Genomics Medium 10087198
2000 COPS2/Alien interacts directly with the vitamin D receptor (VDR) in a ligand-sensitive, DNA-selective manner, distinct from NCoR. The VDR–Alien interaction is independent of the AF-2 trans-activation domain; higher ligand concentrations are required to dissociate VDR–Alien than VDR–NCoR complexes, indicating a different binding interface. Alien-mediated VDR superrepression is only partially blocked by HDAC inhibitor trichostatin A, suggesting both HDAC-dependent and HDAC-independent repression mechanisms. GST pull-down, co-immunoprecipitation, luciferase reporter assays, HDAC inhibitor treatment FASEB journal High 10877839
2000 COPS2/CSN2 (Trip15) is a component of the COP9 signalosome and physically interacts with ICSBP (IRF-8) via ICSBP's IAD domain. In vitro association of ICSBP with the CSN leads to CSN-mediated phosphorylation of ICSBP at a unique serine within its IAD; this phosphorylation is essential for efficient ICSBP association with IRF-1, thereby modulating ICSBP's repressor activity on IRF-1. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation in COS7 cells, in vitro phosphorylation assay The Journal of biological chemistry High 10991940
2001 The COP9 signalosome (containing CSN2/Trip15) promotes cleavage of NEDD8 from cullin-1 (deneddylation) both in vivo and in vitro in fission yeast; CSN-deficient cells accumulate multiple NEDD8-modified proteins, placing the CSN as a key regulator of SCF/cullin-RING ubiquitin ligase activity through neddylation/deneddylation cycles. Genetic analysis in S. pombe (CSN-deficient strains), in vitro deneddylation assay, immunoblotting Science High 11337588
2001 The COP9 signalosome (containing CSN2) directly phosphorylates p53 at its core domain (including Thr155), targeting p53 for ubiquitin-26S proteasome degradation. p53 binds the native CSN complex with high affinity (visualized by electron microscopy) and interacts via its N-terminus with CSN5/Jab1. A phosphorylation-site mutant (p53-T155V) is stabilized against E6-dependent degradation and accumulates in cells. EM visualization of p53-CSN complex, GST pull-down, far-western blotting, in vitro phosphorylation mapping with phosphopeptide inhibitor, site-directed mutagenesis (T155V), reticulocyte lysate degradation assay, cell-based accumulation assay The EMBO journal High 11285227
2002 Drosophila Alien/CSN2 physically interacts with the 19S regulatory particle lid subunit Rpn6 via Rpn6's PCI domain, as shown by yeast two-hybrid. Rpn6 is essential for Drosophila development, and Rpn6 and alien/CSN2 have overlapping spatial and temporal expression patterns, supporting in vivo interaction. Yeast two-hybrid screen, expression pattern analysis by in situ hybridization, genetic analysis of Rpn6 P-element mutants Gene Medium 12426099
2003 Trip15/CSN2 plays a critical role in neuronal differentiation of P19 embryonal carcinoma cells. Enforced expression of Trip15/CSN2 sense mRNA downregulates Oct-3/4, converts P19 cells to neurons (without RA), and in combination with RA stimulates both neuronal and glial differentiation; antisense mRNA suppresses neuronal commitment. Trip15/CSN2 protein is localized in nuclei of neonatal rat CNS neurons. Overexpression and antisense RNA in P19 cells, RT-PCR for marker genes (Oct-3/4, Brn-2, Mash-1), immunostaining of rat brain sections Brain research. Developmental brain research Medium 12524175
2003 Nif3l1 interacts with Trip15/CSN2 (confirmed by yeast two-hybrid, pull-down, and co-immunoprecipitation). Nif3l1 is mainly cytoplasmic but translocates to the nucleus during retinoic acid-induced neural differentiation of P19 cells, and this translocation is enhanced by enforced Trip15/CSN2 expression. Nif3l1 acts as a transcriptional repressor and synergizes with Trip15/CSN2 to enhance transcriptional repression in reporter assays. Yeast two-hybrid screen (using Trip15/CSN2 as bait), GST pull-down, epitope-tagged co-immunoprecipitation, subcellular fractionation/immunostaining, luciferase reporter assay The Journal of biological chemistry High 12522100
2003 The COP9 signalosome (CSN, containing CSN2) is incorporated into the DDB2 and CSA ubiquitin ligase complexes (each containing DDB1, CUL4A, ROC1) and differentially regulates their ubiquitin ligase activity in response to UV irradiation. CSN deneddylates these CUL4A complexes; RNAi knockdown of CSN leads to NER defects. Affinity purification, co-immunoprecipitation, in vitro ubiquitin ligase assay, RNAi knockdown with NER assay readout Cell High 12732143
2004 The highly conserved region (HCR) of Sin3A (134 aa, >80% identity with Sin3B) directly interacts with the N-terminus of Alien/COPS2 in vitro and in vivo. Sin3A and Alien co-occupy the endogenous CYP24 promoter (containing VDREs) together with the VDR in vivo (ChIP). Co-expression of Sin3A enhances Alien-mediated gene repression; overexpression of HCR alone inhibits Alien-mediated repression and induces the endogenous CYP24 promoter. Co-immunoprecipitation (in vivo), GST pull-down (in vitro), chromatin immunoprecipitation (ChIP) and re-ChIP on CYP24 promoter, luciferase reporter assays Nucleic acids research High 15173382
2007 Alien/COPS2 binds NAP1 (nucleosome assembly protein 1) in vivo and in vitro, and enhances NAP1-mediated nucleosome assembly on DNA. Alien also reduces the accessibility of histones H3 and H4 for the NAP1-promoted assembly reaction. Alien interacts directly with histones H3 and H4, associates with chromatin and micrococcal nuclease-prepared nucleosome fractions, and co-occupies the endogenous CYP24 promoter with NAP1 (ChIP/re-ChIP). Co-immunoprecipitation (in vivo), GST pull-down (in vitro), in vitro nucleosome assembly assay, deletion mutagenesis, micrococcal nuclease chromatin fractionation, ChIP and re-ChIP Molecular and cellular biology High 17339334
2007 Alien/COPS2 acts as a corepressor for selected nuclear hormone receptors and cell cycle/DNA repair transcription factors; repression is partially mediated by HDAC activity; knockout in mice is embryonic lethal at early stages, indicating an essential developmental role. Review integrating prior experimental data; mouse knockout phenotype Nuclear receptor signaling Medium 18174916
2016 COPS2 (but not other individual COP9 subunits) is essential for pluripotency maintenance in mouse embryonic stem cells. COPS2 knockdown reduces pluripotency gene expression, causes G2/M arrest, and compromises embryoid body differentiation. Mechanistically, COPS2 binds Nanog protein and prevents its proteasomal degradation, and also functions as a transcriptional corepressor to facilitate pluripotency maintenance. COPS2 overexpression also facilitates somatic cell reprogramming. Individual COP9 subunit shRNA knockdown, RT-PCR/Western blot for pluripotency markers, cell cycle analysis, embryoid body assay, co-immunoprecipitation (COPS2-Nanog), proteasome inhibitor rescue experiment, transcriptional reporter assay, reprogramming assay Scientific reports High 27226076
2017 RMP activates NF-κB signaling which directly promotes CSN2 expression; elevated CSN2 in turn represses Snail degradation (stabilizes Snail protein), facilitating epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma. Immunohistochemistry in human HCC tissues confirms correlation of RMP with p65, CSN2, and Snail expression. Overexpression and knockdown of RMP in HCC cell lines, migration/invasion assays, Western blot for EMT markers, NF-κB reporter assay, ChIP for p65 on CSN2 promoter, in vivo pulmonary metastasis mouse model, immunohistochemistry in human HCC tissues Oncotarget Medium 28423737
2018 COPS2 interacts with both OCT4 and CDK1 (identified by co-immunoprecipitation and mass spectrometry). COPS2 stimulates CDK1/CYCLIN B kinase activity specifically when OCT4 is present. Mechanistically, COPS2 sequesters OCT4 away from CDK1, attenuating OCT4's inhibitory effect on CDK1 and thereby promoting the G2/M transition in mouse ESCs and HeLa cells. Co-immunoprecipitation, mass spectrometry, CDK1 kinase activity assay, COPS2 overexpression/knockdown with cell cycle (G2/M) readout in ESCs and HeLa cells Stem cell reports High 30033083
2020 COPS2 protein is downregulated in skeletal muscle at early stages of cancer cachexia and in lung cancer patients with low endurance capacity. COPS2 knockdown in human myotubes broadly affects multiple cellular pathways including actin cytoskeleton regulation. In mouse myotubes, COPS2 knockdown partially restores F-actin expression reduced by cancer-conditioned media. COPS2 overexpression decreases DR4 (direct repeat 4) transcriptional activity in mouse myoblasts, and COPS2 knockdown inhibits cancer-conditioned media effects on DR4 activity. Exercise training normalizes muscle COPS2 protein levels in tumor-bearing animals. Unbiased proteomic screening, in vitro COPS2 knockdown/overexpression in human and mouse myotubes, F-actin imaging, DR4 luciferase reporter assay, in vivo exercise training in tumor-bearing rats and mice Molecular metabolism Medium 32408015

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science (New York, N.Y.) 1480 24292625
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 601 12732143
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2006 Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 585 16964240
2001 Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science (New York, N.Y.) 580 11337588
2006 A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Molecular cell 538 16949367
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1995 Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Molecular endocrinology (Baltimore, Md.) 408 7776974
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2001 COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. The EMBO journal 314 11285227
1998 A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 304 9535219
2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 286 21903422
1997 Alien introgression in rice. Plant molecular biology 175 9291958
1999 Alien, a highly conserved protein with characteristics of a corepressor for members of the nuclear hormone receptor superfamily. Molecular and cellular biology 164 10207062
2000 VDR-Alien: a novel, DNA-selective vitamin D(3) receptor-corepressor partnership. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 139 10877839
1992 Genomic in situ hybridization to identify alien chromosomes and chromosome segments in wheat. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 130 24201474
2001 Genetic rescue of remnant tropical trees by an alien pollinator. Proceedings. Biological sciences 85 11703880
1975 Alien histocompatibility determinants on the cell surface of sarcomas induced by methylcholanthrene. I. In vivo studies. International journal of cancer 79 52628
1991 Identification of alien chromatin specifying resistance to wheat streak mosaic and greenbug in wheat germ plasm by C-banding and in situ hybridization. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 65 24221269
2014 SNP Discovery for mapping alien introgressions in wheat. BMC genomics 62 24716476
2001 Highly expressed and alien genes of the Synechocystis genome. Nucleic acids research 54 11266562
2001 Predicted highly expressed and putative alien genes of Deinococcus radiodurans and implications for resistance to ionizing radiation damage. Proceedings of the National Academy of Sciences of the United States of America 52 11296249
2016 What do we really know about alien plant invasion? A review of the invasion mechanism of one of the world's worst weeds. Planta 51 27056056
2011 Crystal structure of clustered regularly interspaced short palindromic repeats (CRISPR)-associated Csn2 protein revealed Ca2+-dependent double-stranded DNA binding activity. The Journal of biological chemistry 44 21697083
2010 Effects of beta-kappa-casein (CSN2-CSN3) haplotypes, beta-lactoglobulin (BLG) genotypes, and detailed protein composition on coagulation properties of individual milk of Simmental cows. Journal of dairy science 44 20655451
2017 How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent. Scientific reports 42 28195155
1990 Identification of Brassica oleracea monosomic alien chromosome addition lines with molecular markers reveals extensive gene duplication. Molecular & general genetics : MGG 36 1979141
2019 Genomic biosurveillance of forest invasive alien enemies: A story written in code. Evolutionary applications 35 31892946
2000 Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome. The Journal of biological chemistry 34 10991940
1991 The cytogenetic and molecular architecture of chromosome 1R--one of the most widely utilized sources of alien chromatin in wheat varieties. Chromosoma 34 1769268
2017 How Can Methanol Dehydrogenase from Methylacidiphilum fumariolicum Work with the Alien CeIII Ion in the Active Center? A Theoretical Study. Chemistry (Weinheim an der Bergstrasse, Germany) 30 28488399
2014 The β-casein in camels: molecular characterization of the CSN2 gene, promoter analysis and genetic variability. Gene 30 24973699
2002 The proteasome regulatory particle subunit Rpn6 is required for Drosophila development and interacts physically with signalosome subunit Alien/CSN2. Gene 30 12426099
2022 The β-casein (CSN2) A2 allelic variant alters milk protein profile and slightly worsens coagulation properties in Holstein cows. Journal of dairy science 29 35248385
2014 Invasion trajectory of alien trees: the role of introduction pathway and planting history. Global change biology 29 24343918
2005 Detection of alien chromatin introgression from Thinopyrum into wheat using S genomic DNA as a probe--a landmark approach for Thinopyrum genome research. Cytogenetic and genome research 29 15753596
2020 Monitoring of alien mosquitoes in Western Austria (Tyrol, Austria, 2018). PLoS neglected tropical diseases 28 32574163
2007 The nucleosome assembly activity of NAP1 is enhanced by Alien. Molecular and cellular biology 28 17339334
2020 Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/TRIP15/ALIEN. Molecular metabolism 27 32408015
2014 Construction of a complete set of alien chromosome addition lines from Gossypium australe in Gossypium hirsutum: morphological, cytological, and genotypic characterization. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 27 24553965
2010 Production and identification of wheat - Agropyron cristatum (1.4P) alien translocation lines. Genome 27 20555436
2004 The highly conserved region of the co-repressor Sin3A functionally interacts with the co-repressor Alien. Nucleic acids research 27 15173382
2003 The role of transcriptional corepressor Nif3l1 in early stage of neural differentiation via cooperation with Trip15/CSN2. The Journal of biological chemistry 27 12522100
2007 Aquaculture and transport in a changing environment: overlap and links in the spread of alien biota. Marine pollution bulletin 26 17223137
2012 Identification, structural, and biochemical characterization of a group of large Csn2 proteins involved in CRISPR-mediated bacterial immunity. Proteins 25 22753072
2005 Short communication: predominance of beta-casein (CSN2) C allele in goat breeds reared in Italy. Journal of dairy science 25 15829682
2003 Alien genes introgression and development of monosomic alien addition lines from Oryza latifolia Desv. to rice, Oryza sativa L. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 25 12764581
2008 Characterization of a novel fungal chitosanase Csn2 from Gongronella sp. JG. Carbohydrate research 24 18722595
2007 Hybridization and sexual reproduction in the invasive alien Fallopia (Polygonaceae) complex in Belgium. Annals of botany 24 17210609
2018 Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest. Marine drugs 23 30400299
2016 Introgression of chromosome segments from multiple alien species in wheat breeding lines with wheat streak mosaic virus resistance. Heredity 23 27245423
2012 Crystal structure of Streptococcus pyogenes Csn2 reveals calcium-dependent conformational changes in its tertiary and quaternary structure. PloS one 23 22479393
2012 Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity. Chemical communications (Cambridge, England) 23 23104016
2020 Diverse Wheat-Alien Introgression Lines as a Basis for Durable Resistance and Quality Characteristics in Bread Wheat. Frontiers in plant science 22 32765555
2012 The crystal structure of the CRISPR-associated protein Csn2 from Streptococcus agalactiae. Journal of structural biology 22 22531577
2011 Towards more robust methods of alien gene detection. Nucleic acids research 22 21297116
2021 DAMA: the global Distribution of Alien Mammals database. Ecology 21 34273183
2014 Canine distemper outbreak in raccoons suggests pathogen interspecies transmission amongst alien and native carnivores in urban areas from Germany. Veterinary microbiology 21 25258173
2003 Implication of Trip15/CSN2 in early stage of neuronal differentiation of P19 embryonal carcinoma cells. Brain research. Developmental brain research 21 12524175
1999 Coding sequence, genomic organization, chromosomal localization, and expression pattern of the signalosome component Cops2: the mouse homologue of Drosophila alien. Genomics 21 10087198
2015 Molecular Characterization of the Llamas (Lama glama) Casein Cluster Genes Transcripts (CSN1S1, CSN2, CSN1S2, CSN3) and Regulatory Regions. PloS one 20 25923814
2007 An SNP in the goat CSN2 promoter region is associated with the absence of beta-casein in milk. Animal genetics 20 17931404
2024 The promoting effects of soil microplastics on alien plant invasion depend on microplastic shape and concentration. The Science of the total environment 19 38554966
2015 Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System. Structure (London, England : 1993) 19 26671707
2021 Identification and fine mapping of alien fragments associated with enhanced grain weight from Agropyron cristatum chromosome 7P in common wheat backgrounds. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 18 34355268
2016 Analysis of root-knot nematode and fusarium wilt disease resistance in cotton (Gossypium spp.) using chromosome substitution lines from two alien species. Genetica 18 26882892
2016 Cops2 promotes pluripotency maintenance by Stabilizing Nanog Protein and Repressing Transcription. Scientific reports 18 27226076
2014 Members of Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic species and the status of two invasive alien species in the Yunnan Province (China). Journal of insect science (Online) 18 25502045
2017 RMP promotes epithelial-mesenchymal transition through NF-κB/CSN2/Snail pathway in hepatocellular carcinoma. Oncotarget 17 28423737
2005 Production of alien chromosome additions and their utility in plant genetics. Cytogenetic and genome research 17 15753594
2014 Anatomy and transcript profiling of gynoecium development in female sterile Brassica napus mediated by one alien chromosome from Orychophragmus violaceus. BMC genomics 16 24456102
2014 Ecophysiology of native and alien-invasive clams in an ocean warming context. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 16 24835486
2008 Inducement of chromosome translocation with small alien segments by irradiating mature female gametes of the whole arm translocation line. Science in China. Series C, Life sciences 15 18368312
2021 Characterization of chromosome constitution in three wheat - Thinopyrum intermedium amphiploids revealed frequent rearrangement of alien and wheat chromosomes. BMC plant biology 14 33663390
2021 Alien plants of Europe: introduction pathways, gateways and time trends. PeerJ 14 34141463
2020 Genome-wide impacts of alien chromatin introgression on wheat gene transcriptions. Scientific reports 14 32179864
2020 Spillover of an alien parasite reduces expression of costly behaviour in native host species. The Journal of animal ecology 14 32291765
2009 Wheat-alien metaphase I pairing of individual wheat genomes and D genome chromosomes in interspecific hybrids between Triticum aestivum L. and Aegilops geniculata Roth. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 14 19557382
2003 The use of multiple alien chromosome addition aneuploids facilitates genetic linkage mapping of the Gossypium G genome. Genome 14 14608394
2023 Global spatial distribution of Chromolaena odorata habitat under climate change: random forest modeling of one of the 100 worst invasive alien species. Scientific reports 13 37328479
2021 Predominant wheat-alien chromosome translocations in newly developed wheat of China. Molecular breeding : new strategies in plant improvement 13 37309352
2020 Deletion of csn2 gene affects acid tolerance and exopolysaccharide synthesis in Streptococcus mutans. Molecular oral microbiology 13 32794605
2018 Monosomic alien addition lines (MAALs) of Oryza rhizomatis in Oryza sativa: production, cytology, alien trait introgression, molecular analysis and breeding application. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 13 30032316
2012 Introduction pathway and climate trump ecology and life history as predictors of establishment success in alien frogs and toads. Ecology and evolution 13 22957152
2004 Construction of a binary BAC library for an apomictic monosomic addition line of Beta corolliflora in sugar beet and identification of the clones derived from the alien chromosome. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 13 14749846
2003 Cucumis monosomic alien addition lines: morphological, cytological, and genotypic analyses. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 13 14666371
2019 Nuclear Disposition of Alien Chromosome Introgressions into Wheat and Rye Using 3D-FISH. International journal of molecular sciences 12 31450653
2018 Efficient anchoring of alien chromosome segments introgressed into bread wheat by new Leymus racemosus genome-based markers. BMC genetics 12 29587653
2016 Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306. Gene 12 27265028
2010 Centromere targeting of alien CENH3s in Arabidopsis and tobacco cells. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 12 20084454
2005 Cloning of resistance gene analogs located on the alien chromosome in an addition line of wheat-Thinopyrum intermedium. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 12 16044269
1991 Cytological analysis on the distribution and origin of the alien chromosome pair conferring blue aleurone color in several European common wheat (Triticum aestivum L.) strains. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 12 24221323
2021 Optimization and validation of a cost-effective protocol for biosurveillance of invasive alien species. Ecology and evolution 11 33717437
2019 Development of PCR markers specific to Dasypyrum villosum genome based on transcriptome data and their application in breeding Triticum aestivum-D. villosum#4 alien chromosome lines. BMC genomics 11 30987602
2015 Distribution and molecular phylogeny of biliary trematodes (Opisthorchiidae) infecting native Lutra lutra and alien Neovison vison across Europe. Parasitology international 11 26620805
1981 Alien-driven diversity and alien-selected escape: a rationale for allogeneic cancer immunotherapy. Transplantation proceedings 11 7036482
2023 Nutrient enrichment promotes invasion success of alien plants via increased growth and suppression of chemical defenses. Ecological applications : a publication of the Ecological Society of America 10 36482783
2022 Role of CSN2, CSN3, and BLG genes and the polygenic background in the cattle milk protein profile. Journal of dairy science 10 35525618
2021 The invasive alien red-eared slider turtle, Trachemys scripta, as a carrier of STEF-disease pathogens. Fungal biology 10 35078582
2018 COPS2 Antagonizes OCT4 to Accelerate the G2/M Transition of Mouse Embryonic Stem Cells. Stem cell reports 10 30033083
2012 Physiological response of the sea urchin Paracentrotus lividus fed with the seagrass Posidonia oceanica and the alien algae Caulerpa racemosa and Lophocladia lallemandii. Marine environmental research 10 23158497
2007 The coregulator Alien. Nuclear receptor signaling 10 18174916
2023 Transferring a new Fusarium head blight resistance locus FhbRc1 from Roegneria ciliaris into wheat by developing alien translocation lines. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 9 36897377
2017 Drought-associated absence of alien invasive anchorworm, Lernaea cyprinacea (Copepoda: Lernaeidae), is related to changes in fish health. International journal for parasitology. Parasites and wildlife 9 30951570
2008 Short communication: the beta-casein (CSN2) silent allele C1 is highly spread in goat breeds. Journal of dairy science 9 18946150
2007 Frequency and fidelity of alien chromosome transmission in Gossypium hexaploid bridging populations. Genome 9 17612617
2005 Detection and characterization by high-performance liquid chromatography and mass spectrometry of a goat beta-casein associated with a CSN2 null allele. Rapid communications in mass spectrometry : RCM 9 16178051
2001 Detection of alien chromosomes from S-genome species in the addition/substitution lines of bread wheat and visualization of A-, B- and D-genomes by GISH. Hereditas 9 12152324
1992 Regional localization of human beta-casein gene (CSN2) to 4pter-q21. Genomics 9 1577486
2023 The effect of temperature and invasive alien predator on genetic and phenotypic variation in the damselfly Ischnura elegans: cross-latitude comparison. Frontiers in zoology 8 37032330
2016 DDA1 promotes stage IIB-IIC colon cancer progression by activating NFκB/CSN2/GSK-3β signaling. Oncotarget 8 26942699
2004 Effect of single alien chromosome from shallot (Allium cepa L. Aggregatum group) on carbohydrate production in leaf blade of bunching onion (A. fistulosum L.). Genes & genetic systems 8 15729002