COP9 signalosome complex subunit 5 (COPS5)

The protein contains 334 amino acids for an estimated molecular weight of 37579 Da.

 

Probable protease subunit 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 the 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. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 604850

Cop9 signalosome, subunit 5; cops5
Csn5
Jun activation domain-binding protein; jab1
Sgn5
Mov34 family, 38-kd member

DESCRIPTION

COPS5 is a subunit of the COP9 signalosome (CSN), which phosphorylates target proteins, leading to their ubiquitination and degradation by the 26S proteasome. COPS5 functions as a receptor within the COP9 signalosome and binds substrate proteins (Bech-Otschir et al., 2001).

CLONING

Using the more variable activation domain of JUN (165160) as bait in a yeast 2-hybrid system, Claret et al. (1996) identified JAB1. The JAB1 gene encodes a protein of 334 amino acids with a relative molecular mass of 37.5 kD. The N-terminal region of JAB1 shows 57% identity to the products of the open reading frame F37A4.5 of C. elegans and the S. pombe pad1+ gene, which was identified genetically as a coactivator of a subset of AP1 target genes. The JAB1 and pad1+ proteins are functionally interchangeable. They define a new group of coactivators that increase the specificity of target gene activation by AP1 proteins. The 1.5-kb JAB1 transcript was widely expressed. Immunofluorescence analysis indicated that JAB1 is a nuclear protein.

GENE FAMILY

Asano et al. (1997) identified JAB1 as a member of the MOV34 (PSMD7; 157970) family. They referred to JAB1 as the 38-kD MOV34 homolog.

GENE FUNCTION

Using the yeast 2-hybrid system, Claret et al. (1996) found that JAB1 interacted with JUN and JUND (165162), but not with JUNB (165161) or v-jun. As a result, JAB1 selectively potentiated transactivation by only JUN or JUND. In vitro, JAB1 specifically stabilized complexes of JUN or JUND with AP1 sites and did not affect binding of either JUNB or v-jun. Amino acids 31 to 57 of JUN, which are absent in v-jun, contained the JAB1 interaction surface. JAB1 interacted with JUN and stimulated its activity in mammalian cells. Although JAB1 did not form a heterodimer with JUN or JUND, its effect on their DNA binding and transactivation abilities was analogous to the effect of the Extradenticle coactivator on homeodomain proteins of the Bithorax complex in Drosophila. Bianchi et al. (2000) found that JAB1 interacts with the cytoplasmic domain of the beta-2 subunit of the alpha-L/beta-2 integrin LFA1 (155370/600065). Bianchi et al. (2000) found that JAB1 is present both in the nucleus and in the cytoplasm of cells and that a fraction of JAB1 colocalizes with LFA1 at the cell membrane. LFA1 engagement is followed by an increase of the nuclear pool of JAB1, paralleled by enhanced binding of c-Jun-containing AP1 complexes to their DNA consensus site and increased transactivation of an AP1-dependent promoter. Bianchi et al. (2000) suggested that signaling through the LFA1 integrin may affect JUN-driven transcription by regulating JAB1 nuclear localization. This represented a new pathway for integrin-dependent modulation of gene expression. Using full-length macrophage migration inhibitory factor (MIF; 153620) as bait in a yeast 2-hybrid screen of a brain cDNA library, Kleemann et al. (2000) captured JAB1 as an interacting partner of MIF. By coimmunoprecipitation and pull-down experiments, Kleemann et al. (2000) confirmed the specific MIF-JAB1 association. Confocal microscopic analysis demonstrated that the MIF-JAB1 complex is localized in the cytosol near the peripheral plasma membrane, suggesting a potential connection between MIF and the integrin signaling pathways. Luciferase reporter and gel shift analyses showed that endogenous and exogenous MIF inhibited JAB1-induced AP1 transcriptional activity but did not interfere with n ... More on the omim web site

Subscribe to this protein entry history

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 604850 was added.