COP9 signalosome complex subunit 6 (COPS6)
The protein contains 327 amino acids for an estimated molecular weight of 36163 Da.
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, 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. Has some glucocorticoid receptor-responsive activity. Stabilizes COP1 through reducing COP1 auto-ubiquitination and decelerating COP1 turnover rate, hence regulates the ubiquitination of COP1 targets. (updated: April 25, 2018)
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.
- 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.
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.
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Biological Process
Cullin deneddylation
Nucleotide-excision repair, DNA damage recognition
Post-translational protein modification
Protein deneddylation
Transcription-coupled nucleotide-excision repair
Viral process
Cellular Component
COP9 signalosome
Cytoplasm
Cytosol
Extracellular exosome
Nucleoplasm
Perinuclear region of cytoplasm
The reference OMIM entry for this protein is 614729
Cop9 signalosome, subunit 6; cops6
Csn6
Mov34 family, 34-kd member
DESCRIPTION
COPS6 is a subunit of the highly conserved COP9 signalosome (CSN) complex, which is involved in checkpoint control, signal transduction, development, and the cell cycle. The COP9 signalosome complex has a major role in controlling protein stability via the ubiquitin-proteasome system (review by Kato and Yoneda-Kato, 2009).CLONING
By searching EST databases using the sequence of the p47 subunit of EIF3 (EIF3F; 603914) as probe to identify proteins related to MOV34 (PSMD7; 1579770), Asano et al. (1997) identified mouse and human COPS6, which they called the 34-kD MOV34 homolog. The deduced human protein contains 297 amino acids and has a calculated molecular mass of 33.6 kD. In their review, Kato and Yoneda-Kato (2009) noted that CSN6 contains an MPN domain, which is also found in subunits of the proteasome lid complex (e.g., RPN8, or PSMD7) and in some subunits of the eIF3 complex (e.g., EIF3F).GENE FUNCTION
The 14-3-3-sigma (SFN; 601290) gene, which is upregulated by p53 (TP53; 191170) in response to DNA damage, exists in a positive-feedback loop with p53 to prevent mitotic checkpoint dysfunction. Choi et al. (2011) showed that COPS6 contributed to degradation of 14-3-3-sigma in human cell lines by stabilizing the ubiquitin ligase COP1 (RFWD2; 608067). COPS6 function did not require expression of p53. Gel-filtration and Western blot analyses revealed that COPS6 interacted directly with COP1 and 14-3-3-sigma in a large COP9 molecular complex. Coimmunoprecipitation and protein pull-down assays revealed that the N-terminal region of COPS6 interacted directly with the C-terminal region of COP1. Overexpression of COPS6 resulted in stabilization of COP1 and increased 14-3-3-sigma polyubiquitination and degradation, which in turn relieved 14-3-3-sigma-mediated inhibition of the downstream prosurvival kinase AKT (164730) and facilitated cell growth. Conversely, knockdown of COPS6 via short hairpin RNA reduced 14-3-3-sigma ubiquitination, suppressed AKT phosphorylation and activity, and increased cell sensitivity to apoptotic stress. Choi et al. (2011) concluded that COPS6 is involved in a signaling network that regulates cell growth.BIOCHEMICAL FEATURES
- Crystal Structure Lingaraju et al. (2014) presented the crystal structure of the entire 350-kD human CSN holoenzyme at 3.8-angstrom resolution, detailing the molecular architecture of the complex. CSN has 2 organizational centers: a horseshoe-shaped ring created by its 6 proteasome lid-CSN-initiation factor-3 domain proteins, and a large bundle formed by the carboxy-terminal alpha-helices of every subunit. CSN5 (COPS5; 604850) and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. Lingaraju et al. (2014) found that neddylated cullin-RING E3 ubiquitin ligase binding to CSN is sensed by CSN4 (COPS4; 616008), and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase.MAPPING
Hartz (2012) mapped the COPS6 gene to chromosome 7q22.1 based on an alignment of the COPS6 sequence (GenBank GENBANK BC002520) with the genomic sequence (GRCh37). ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
April 27, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614729 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed