COPS6 (7q22.1).CSN6, MOV-34-34kD,MPN metalloproteaasi ilman JAMM motiivia

https://www.ncbi.nlm.nih.gov/gene/10980

Official Symbol

COPS6 provided by HGNC

Official Full Name

COP9 signalosome subunit 6 provided by HGNC

Also known as

CSN6; MOV34-34KD

Summary

The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in esophagus (RPKM 33.2), testis (RPKM 32.7) and 25 other tissues See more

Orthologs

mouse all 

Preferred Names

COP9 signalosome complex subunit 6

Names

COP9 constitutive photomorphogenic homolog subunit 6

H_NH0506M12.12

JAB1-containing signalosome subunit 6

MOV34 homolog, 34 kD

SGN6

hVIP

vpr-interacting protein

mRNA and Protein(s)

1. NM_006833.5 → NP_006824.2  COP9 signalosome complex subunit 6
   See identical proteins and their annotated locations for NP_006824.2
   
   Status: REVIEWED

   Source sequence(s)

   BC002520, CB990467, CD367717

   Consensus CDS

   CCDS5682.1

   UniProtKB/Swiss-Prot

   Q7L5N1

   Related

   ENSP00000304102.3, ENST00000303904.8

   Conserved Domains (1) summary

   cd08063
   Location:39 → 321

   MPN_CSN6; Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6. CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.

Related articles in PubMed

1. Crystal structure of the human CSN6 MPN domain. Ma XL, et al. Biochem Biophys Res Commun, 2014 Oct 10. PMID 25242525
2. Choice of expression vector alters the localization of a human cellular protein. Ramanathan MP, et al. DNA Cell Biol, 2001 Feb. PMID 11244567
3. [Distribution pattern of rigor mortis in various joint regions]. Mittmeyer HJ. Beitr Gerichtl Med, 1975. PMID 1222062
4. COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer. Gao S, et al. Oncotarget, 2015 Sep 29. PMID 26318036, Free PMC Article
5. CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6. Chen B, et al. Cell Cycle, 2012 Dec 15. PMID 23187808, Free PMC Article

See all (102) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. High CSN6 expression is associated with metastasis of glioblastoma.
2. The overexpression of CSN6 reduced the effect of quercetin treatment on HT29 cells, suggesting that quercetininduced apoptosis may involve the AktCSN6Myc signaling axis in HT29 cells.
3. CSN6 positively regulates c-Jun in a MEKK1-dependent manner
4. our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.
5. CSN6 interacts with p27(Kip1) and facilitates ubiquitin-mediated degradation of p27(Kip1).
6. Findings indicate that the deregulation of beta-catenin by extracellular signal-regulated kinase 2 (ERK2)-activated CSN6 protein is important for colorectal cancer (CRC) development.
7. Analyses of the pseudo metal-binding motif in CSN6 suggest that the loss of two key histidine residues may contribute to the lack of catalytic activity in CSN6.
8. Data suggest that CSN6 is an important negative regulator of p57 (Kip2) , and that overexpression of CSN6 in many types of cancer could lead to decreased expression of p57 (Kip2) and result in promoted cancer cell growth.
9. COPS6 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells.
10. loss of CSN6 enhances p53-mediated tumor suppression in vivo and CSN6 plays an important role in regulating DNA damage-associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway

Submit: New GeneRIF Correction See all GeneRIFs (12)