COPS5 (18q13.1), CSN5, SGN5, JAB1, MOV-34 , JAMM-motiivi; stabiloi surviviinia

https://www.ncbi.nlm.nih.gov/gene/10987

Official Symbol

COPS5provided by HGNC

Official Full Name

COP9 signalosome subunit 5provided by HGNC

Also known as

CSN5; JAB1; SGN5; MOV-34

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 is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be an coactivator that increases the specificity of JUN/AP1 transcription factors. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in testis (RPKM 37.3), heart (RPKM 32.6) and 25 other tissues See more

Orthologs

mouse all

Preferred Names

COP9 signalosome complex subunit 5

Names

38 kDa Mov34 homolog

COP9 constitutive photomorphogenic homolog subunit 5

jun activation domain-binding protein 1

signalosome subunit 5

testis secretory sperm-binding protein Li 231m

 

mRNA and Protein(s)

1. NM_006837.3 → NP_006828.2  COP9 signalosome complex subunit 5
   See identical proteins and their annotated locations for NP_006828.2
   ,

   Conserved Domains (1) summary

   cd08069
   Location:44 → 314

   MPN_RPN11_CSN5; Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit CSN5

   This family contains proteasomal regulatory protein Rpn11 (26S proteasome regulatory subunit rpn11; PAD1; POH1; RPN11; PSMD14; Rpn11 subunit of the 19S-proteasome; regulatory particle number 11) and signalosomal CSN5 (COP9 signalosome complex subunit 5; COP9 complex homolog subunit 5; c-Jun activation domain-binding protein-1; CSN5/JAB1; JAB1). COP9 signalosome (CSN) and the proteasome lid are paralogous complexes and their respective subunits CSN5 and Rpn11 are most closely related between the two complexes, both containing the conserved JAMM (JAB1/MPN/Mov34 metalloenzyme) motif involved in zinc ion coordination and providing the active site for isopeptidase activity. Rpn11 is responsible for substrate deubiquitination during proteasomal degradation. It is essential for maintaining a correct cell cycle and normal mitochondrial morphology and physiology; mutations in Rpn11 cause cell cycle and mitochondrial defects, temperature sensitivity and sensitivity to DNA damaging reagents such as UV. It has been shown that the C-terminal region of Rpn11 is involved in the regulation of the mitochondrial fission and tubulation processes. CSN5, one of the eight subunits of CSN, is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Its MPN+ domain is critical for the physical interaction of RUNX3 and Jab1. It has been suggested that the direct interaction of CSN5/JAB1 with p27 provides p27 with a leucine-rich nuclear export signal (NES), which is required for binding to chromosomal region maintenance 1 (CRM1), and facilitates nuclear export. The over-expression of CSN5/JAB1 also has been implicated in cancer initiation and progression, including cancer of the lung, pancreas, mouth, thyroid, and breast, suggesting that the oncogenic activity of CSN5 is associated with the down-regulation of RUNX3.

            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..334
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8q13.1"
     Protein         1..334
                     /product="COP9 signalosome complex subunit 5"
                     /note="38 kDa Mov34 homolog; signalosome subunit 5; jun
                     activation domain-binding protein 1; COP9 constitutive
                     photomorphogenic homolog subunit 5; testis secretory
                     sperm-binding protein Li 231m"
                     /calculated_mol_wt=37448
     Site            2
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N-acetylalanine. {ECO:0000269|PubMed:18850735,
                     ECO:0000269|Ref.6}; propagated from UniProtKB/Swiss-Prot
                     (Q92905.4)"
     Region          44..314
                     /region_name="MPN_RPN11_CSN5"
                     /note="Mov34/MPN/PAD-1 family: proteasomal regulatory
                     protein Rpn11 and signalosome complex subunit CSN5;
                     cd08069"
                     /db_xref="CDD:163700"
     Site            order(76,138,140,148,151)
                     /site_type="other"
                     /note="MPN+ (JAMM) motif"
                     /db_xref="CDD:163700"
     Region          138..151
                     /region_name="JAMM motif.
                     {ECO:0000255|PROSITE-ProRule:PRU01182}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q92905.4)"
     Site            order(138,140,151)
                     /site_type="other"
                     /note="Zinc-binding site [ion binding]"
                     /db_xref="CDD:163700"
     CDS             1..334
                     /gene="COPS5"
                     /gene_synonym="CSN5; JAB1; MOV-34; SGN5"
                     /coded_by="NM_006837.3:138..1142"
                     /db_xref="CCDS:CCDS6198.1"
                     /db_xref="GeneID:10987"
                     /db_xref="HGNC:HGNC:2240"
                     /db_xref="MIM:604850"
ORIGIN      
        1 maasgsgmaq ktwelannmq eaqsideiyk ydkkqqqeil aakpwtkdhh yfkyckisal
       61 allkmvmhar sggnlevmgl mlgkvdgetm iimdsfalpv egtetrvnaq aaayeymaay
      121 ienakqvgrl enaigwyhsh pgygcwlsgi dvstqmlnqq fqepfvavvi dptrtisagk
      181 vnlgafrtyp kgykppdegp seyqtiplnk iedfgvhckq yyalevsyfk ssldrkllel
      241 lwnkywvntl sssslltnad yttgqvfdls ekleqseaql grgsfmlgle thdrksedkl
      301 akatrdsckt tieaihglms qvikdklfnq inis
//

Related articles in PubMed

1. CSN5/JAB1 suppresses the WNT inhibitor DKK1 in colorectal cancer cells. Jumpertz S, et al. Cell Signal, 2017 Jun. PMID 28229932
2. Oxidized LDL-induced JAB1 influences NF-κB independent inflammatory signaling in human macrophages during foam cell formation. Schwarz A, et al. J Biomed Sci, 2017 Feb 7. PMID 28173800, Free PMC Article
3. Jab1 promotes glioma cell proliferation by regulating Siah1/β-catenin pathway. Zhu Y, et al. J Neurooncol, 2017 Jan. PMID 27640199
4. JAB1 accelerates odontogenic differentiation of dental pulp stem cells. Lian M, et al. J Mol Histol, 2016 Jun. PMID 26989054
5. Suppression of CSN5 promotes the apoptosis of gastric cancer cells through regulating p53-related apoptotic pathways. Sang MM, et al. Bioorg Med Chem Lett, 2015 Aug 1. PMID 26048783

See all (249) citations in PubMed

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

GeneRIFs: Gene References Into Functions

1. A positive correlation was found between the expression of LASP1 and COPS5 while a negative correlation existed between 14-3-3sigma and COPS5/LASP1 in most CRC samples.
2. CSN5 directly bound survivin and decreased its ubiquitination to enhance the protein stability of survivin.
3. overexpression of COPS5, through its isopeptidase activity, leads to ubiquitination and proteasome-mediated degradation of NCoR, a key corepressor for ERalpha and tamoxifen-mediated suppression of ERalpha target genes.
4. These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.
5. We identified a novel Jab1-Trx axis that is a key cellular process in the pathobiologic characteristics of acute myeloid leukemia (AML-M5). Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5
6. These data identified CSN5 as a critical oncoprotein involved in progression of hepatocellular carcinoma (HCC) cells, which could serve as a potential therapeutic target in HCC patients.
7. The authors find that UCHL3 regulates COPS5-dependent deneddylation of Cullin1, which is an essential component of SCF(beta-TrCP) complex and associated with SCF(beta-TrCP) activities. The authors further demonstrate that UCHL3 upregulates the levels of SCF(beta-TrCP) substrates including IFN-I receptor IFNAR1, which enhances IFN-I mediated signaling pathway and antiviral activity.
8. Collectively, our findings suggest that JAB1 activates the neuronal differentiation ability of CPNE1 through the binding of C2A domain in CPNE1 with MPN domain in JAB1.
9. data suggests that Jab1-mediated phosphorylation of p53 at Thr155 residue mediates nuclear export of p53
10. CSN5 is contributed to colorectal cancer development by actively driving aberrant WNT signaling through repression of the WNT antagonist DKK1.

Submit: New GeneRIF Correction See all GeneRIFs (105)