COP9 signalosome complex subunit 2 (COPS2)
The protein contains 443 amino acids for an estimated molecular weight of 51597 Da.
Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Involved in early stage of neuronal differentiation via its interaction with NIF3L1. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Cell population proliferation
Cullin deneddylation
Inner cell mass cell proliferation
Negative regulation of nucleic acid-templated transcription
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription, DNA-templated
Neurogenesis
Neuron differentiation
Nucleotide-excision repair, DNA damage recognition
Post-translational protein modification
Protein deneddylation
Protein phosphorylation
Signal transduction
Skeletal muscle cell differentiation
Transcription by RNA polymerase II
Transcription-coupled nucleotide-excision repair
The reference OMIM entry for this protein is 604508
Cop9 signalosome, subunit 2; cops2
Thyroid hormone receptor interactor 15; trip15
Sgn2
Alien, drosophila, homolog of
Csn2
DESCRIPTION
COPS2 is a subunit of the conserved COP9 signalosome (Min et al., 2005).CLONING
Thyroid hormone receptors (TRs) are hormone-dependent transcription factors that regulate expression of a variety of specific target genes. They must specifically interact with a number of proteins as they progress from their initial translation and nuclear translocation to heterodimerization with retinoid X receptors (RXRs), functional interactions with other transcription factors and the basic transcriptional apparatus, and eventually, degradation. To help elucidate the mechanisms that underlie the transcriptional effects and other potential functions of TRs, Lee et al. (1995) used the yeast interaction trap, a version of the yeast 2-hybrid system, to identify proteins that specifically interact with the ligand-binding domain of rat TR-beta (THRB; 190160). They isolated HeLa cell cDNAs encoding several different TR-interacting proteins (TRIPs), including TRIP15. Some nuclear hormone receptors (NHRs) silence gene expression in the absence of hormone. Corepressors, which are bound to the silencing domain of NHRs and are involved in the repression of gene expression, dissociate upon hormone binding, leading to the binding of coactivators that mediate gene activation. Dressel et al. (1999) obtained a full-length HeLa cell cDNA encoding TRIP15, the human homolog of the Drosophila corepressor Alien. The predicted 305-amino acid TRIP15 protein, which is 90% identical to Drosophila Alien, contains an acidic region in the N terminus, a putative zinc finger in the C terminus, and a central hydrophobic core region flanked by 2 putative alpha-helical structures and a nuclear localization signal. Western blot analysis determined that TRIP15 is expressed as a 41-kD protein. Immunofluorescence microscopy demonstrated that TRIP15 localized in the nucleus. Schaefer et al. (1999) obtained a mouse cDNA encoding Cops2, which is homologous to Drosophila Alien. The mouse gene encodes a larger protein than human TRIP15.GENE FUNCTION
Lee et al. (1995) found that human TRIP15 interacted with rat Thrb only in the absence of thyroid hormone. In contrast, it interacted with RXR-alpha (RXRA; 180245) only in the presence of 9-cis-retinoic acid. TRIP15 did not interact with the glucocorticoid receptor (NR3C1; 138040) under any condition. TR is a transcriptional silencer in the absence of hormone, as well as a hormone-dependent trans-activator, with its silencing domain localized in the C terminus. Yeast 2-hybrid, GST pull-down, and coimmunoprecipitation analyses showed that TRIP15 interacted with the C terminus of TR, but not with intact RAR (180240), only in the absence of hormone. Reporter assays indicated that TRIP15 increased receptor-mediated silencing and harbored an autonomous silencing function, which correlated with the ability of TRIP15 to interact with TR in both the hinge region and the C-terminal end of the TR silencing domain. TRIP15, or SGN2, is part of a 450-kD signalosome complex that includes COPS3 (604665), COPS5 (604850), GPS1 (601934), and at least 4 other subunits. By autoradiographic analysis, Seeger et al. (1998) showed that the complex phosphorylates JUN (165160), IKBA (164008), and the C-terminal part of the p105 precursor of NFKB (164011). The 26S proteasome is not a phosphorylation target, although immunofluorescence microscopy demonstrated that the 450-kD complex has a cytosolic localization, concentrated around ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604508 was added.