COP9 signalosome complex subunit 4 (COPS4)
The protein contains 406 amino acids for an estimated molecular weight of 46269 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. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, 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. (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
Cullin deneddylation
Nucleotide-excision repair, DNA damage recognition
Post-translational protein modification
Protein deneddylation
Transcription-coupled nucleotide-excision repair
Cellular Component
Cell junction
COP9 signalosome
Cytosol
Extracellular exosome
Nuclear speck
Nucleoplasm
Nucleus
Synaptic vesicle
The reference OMIM entry for this protein is 616008
Cop9 signalosome, subunit 4; cops4
Csn4
DESCRIPTION
COPS4 is a subunit of the conserved COP9 signalosome (Min et al., 2005).CLONING
Wei et al. (1998) purified COP9 complexes from pig spleen and mouse brain, liver, and spleen extracts. Sequencing revealed that the highly conserved 406-amino acid mammalian S4 subunit has a C-terminal proteasome (see 604449)-COP9-initiation factor-3 (see 602039) (PCI) domain.GENE FUNCTION
SKP1 (601434)/CUL1 (603134)/F-box protein (see 605648) (SCF) complexes are ubiquitin ligases that regulate diverse cellular functions by ubiquitinating key regulatory proteins. SCF activity requires conjugation of NEDD8 (603171) to the cullin subunit, and the COP9 signalosome (CSN) inactivates SCF by catalyzing deconjugation of NEDD8. Min et al. (2005) found that CSN interacted with CUL1 irrespective of its neddylation state. Addition of CAND1 (607727), which bound only unneddylated CUL1, inhibited binding of CUL1 to CSN and enhanced the deneddylase activity of CSN in vitro. Coexpression of specific CSN subunits revealed that CSN1 (GPS1; 601934), CSN2 (604508), CSN4, and CSN5 (604850) provided the minimal core CUL1-binding unit.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 and its dimerization partner, CSN6 (COPS6; 614729), 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, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase.MAPPING
Hartz (2014) mapped the COPS4 gene to chromosome 4q21.22 based on an alignment of the COPS4 sequence (GenBank GENBANK AF100757) with the genomic sequence (GRCh38). ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 616008 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed