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Gene Review

COPS2  -  COP9 signalosome subunit 2

Homo sapiens

Synonyms: ALIEN, Alien homolog, COP9 signalosome complex subunit 2, CSN2, JAB1-containing signalosome subunit 2, ...
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Disease relevance of COPS2


High impact information on COPS2

  • Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase [2].
  • CK2 phosphorylates CSN2 and CSN7, and PKD modifies CSN7 [3].
  • In both cases the Alien Antigens are also artefacts, resulting from genetic heterogeneity in either mice or cell lines [4].
  • It is also unlikely that the successive experimental plagues that created the Alien Antigens are unique to this corner of tumour immunology [4].
  • Functional assays indicated that Alien, but not NCoR, displays selectivity for different VDRE structures for transferring these repressive effects into gene regulatory activities [5].

Biological context of COPS2


Anatomical context of COPS2

  • The Drosophila alien gene is highly homologous to the human thyroid receptor interacting protein, TRIP15/COPS2, which is a component of the recently identified signalosome protein complex [11].
  • Furthermore, Northern experiments demonstrate that Alien is expressed in the adrenal gland and testis in tissues where DAX-1 is specifically expressed [12].
  • However, it has been shown that the CSN2 gene, and this gene only, can be induced in certain mammary cell lines, such as HC11 [7].

Associations of COPS2 with chemical compounds

  • We have previously characterized a novel corepressor, termed Alien, which interacts with TR and the ecdysone receptor but not with the retinoic acid receptors RAR or RXR [12].
  • Functional analyses revealed that Alien, DAX-1 and thyroid hormone receptor mediated transcriptional silencing is strongly enhanced in the presence of active MLK2 [13].
  • Moreover, superrepression via Alien was found to be affected only in part by HDAC inhibitors such as trichostatin A [5].
  • In this study, we report the relationship between uric acid and various cardiovascular risk factors in 1,027 healthy Taiwanese adults living in Alien, an agricultural town in subtropical South Taiwan. Serum uric acid levels increased in proportion to age in women, but not in men [14].

Physical interactions of COPS2

  • Naturally occurring mutants of the DAX-1 gene fail to interact with Alien and have lost silencing function [12].
  • Here, we isolated the mixed lineage kinase 2 (MLK2) as an interacting partner for the corepressor Alien using a yeast two hybrid screen [13].

Other interactions of COPS2

  • The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4 [15].
  • Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita [12].
  • Functionally, co-expression of Sin3A enhances Alien-mediated gene repression and overexpression of the HCR alone leads to the inhibition of Alien-mediated repression and to the induction of the endogenous CYP24 promoter [8].

Analytical, diagnostic and therapeutic context of COPS2

  • Surprisingly, using both Western blotting and MALDI-analyses, we revealed that these bands are composed of the GST-Alien protein itself [16].


  1. ECG of the month. Alien intruders. Ventricular parasystole. Martinez-Lopez, J.I. The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society. (1996) [Pubmed]
  2. Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms. Liu, C., Powell, K.A., Mundt, K., Wu, L., Carr, A.M., Caspari, T. Genes Dev. (2003) [Pubmed]
  3. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. Uhle, S., Medalia, O., Waldron, R., Dumdey, R., Henklein, P., Bech-Otschir, D., Huang, X., Berse, M., Sperling, J., Schade, R., Dubiel, W. EMBO J. (2003) [Pubmed]
  4. Alien antigens return to the fold. Parham, P. Immunol. Today (1989) [Pubmed]
  5. VDR-Alien: a novel, DNA-selective vitamin D(3) receptor-corepressor partnership. Polly, P., Herdick, M., Moehren, U., Baniahmad, A., Heinzel, T., Carlberg, C. FASEB J. (2000) [Pubmed]
  6. Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9 signalosome. Berse, M., Bounpheng, M., Huang, X., Christy, B., Pollmann, C., Dubiel, W. J. Mol. Biol. (2004) [Pubmed]
  7. Structure of the rabbit alphas1- and beta-casein gene cluster, assignment to chromosome 15 and expression of the alphas1-casein gene in HC11 cells. Pauloin, A., Rogel-Gaillard, C., Piumi, F., Hayes, H., Fontaine, M.L., Chanat, E., Chardon, P., Devinoy, E. Gene (2002) [Pubmed]
  8. The highly conserved region of the co-repressor Sin3A functionally interacts with the co-repressor Alien. Moehren, U., Dressel, U., Reeb, C.A., Väisänen, S., Dunlop, T.W., Carlberg, C., Baniahmad, A. Nucleic Acids Res. (2004) [Pubmed]
  9. Nonautonomous inverted repeat Alien transposable elements are associated with genes of both monocotyledonous and dicotyledonous plants. Pozueta-Romero, J., Houlné, G., Schantz, R. Gene (1996) [Pubmed]
  10. Characterization of a family of genes encoding a fruit-specific wound-stimulated protein of bell pepper (Capsicum annuum): identification of a new family of transposable elements. Pozueta-Romero, J., Klein, M., Houlné, G., Schantz, M.L., Meyer, B., Schantz, R. Plant Mol. Biol. (1995) [Pubmed]
  11. Coding sequence, genomic organization, chromosomal localization, and expression pattern of the signalosome component Cops2: the mouse homologue of Drosophila alien. Schaefer, L., Beermann, M.L., Miller, J.B. Genomics (1999) [Pubmed]
  12. Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita. Altincicek, B., Tenbaum, S.P., Dressel, U., Thormeyer, D., Renkawitz, R., Baniahmad, A. J. Biol. Chem. (2000) [Pubmed]
  13. Mixed lineage kinase 2 enhances trans-repression of Alien and nuclear receptors. Eckey, M., Tenbaum, S.P., Muñoz, A., Baniahmad, A. Mol. Cell. Endocrinol. (2003) [Pubmed]
  14. The serum uric acid and related cardiovascular risk factors in south Taiwan. Huang, C.C., Peng, M.C., Tsai, W.C., Chang, Y.Y., Chen, W.H., Chen, S.S., Liu, J.S. Southeast Asian J. Trop. Med. Public Health (2005) [Pubmed]
  15. COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK. Naumann, M., Bech-Otschir, D., Huang, X., Ferrell, K., Dubiel, W. J. Biol. Chem. (1999) [Pubmed]
  16. Protein-protein cross-linking in the use of the eukaryotic eGST-fusion system. Papaioannou, M., Ruppert, T., Dotzlaw, H., Dressel, U., Baniahmad, A. Protein Expr. Purif. (2002) [Pubmed]
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