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Q92905 (CSN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
COP9 signalosome complex subunit 5

Short name=SGN5
Short name=Signalosome subunit 5
EC=3.4.-.-
Alternative name(s):
Jun activation domain-binding protein 1
Gene names
Name:COPS5
Synonyms:CSN5, JAB1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length334 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.13 Ref.14 Ref.18 Ref.19 Ref.26 Ref.28

Cofactor

Divalent metal ions By similarity.

Subunit structure

Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COP6, COPS7 (COPS7A or COPS7B) and COPS8. In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B). The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.28

Subcellular location

Cytoplasm. Nucleus. Cytoplasmperinuclear region. Note: Nuclear localization is diminished in the presence of IFIT3. Ref.8 Ref.23 Ref.28

Domain

The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex By similarity.

Miscellaneous

The CSN complex is associated with some 'Lys-63'-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.

Sequence similarities

Belongs to the peptidase M67A family. CSN5 subfamily.

Contains 1 MPN (JAB/Mov34) domain.

Sequence caution

The sequence AAL82571.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
Signalosome
   LigandMetal-binding
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcullin deneddylation

Inferred from direct assay PubMed 19141280. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16410250. Source: UniProtKB

protein deneddylation

Inferred from mutant phenotype Ref.26. Source: UniProtKB

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of JNK cascade

Inferred from direct assay PubMed 16410250. Source: UniProtKB

regulation of cell cycle

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

translation

Traceable author statement Ref.2. Source: ProtInc

translational initiation

Traceable author statement Ref.2. Source: GOC

   Cellular_componentCOP9 signalosome

Inferred from direct assay Ref.24Ref.26. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.23. Source: UniProtKB

eukaryotic translation initiation factor 3 complex

Traceable author statement Ref.2. Source: ProtInc

nucleus

Inferred from direct assay Ref.23. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metallopeptidase activity

Inferred from mutant phenotype Ref.26. Source: UniProtKB

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

translation initiation factor activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6 Ref.24
Chain2 – 334333COP9 signalosome complex subunit 5
PRO_0000194835

Regions

Domain53 – 164112MPN
Motif138 – 15114JAMM motif

Sites

Metal binding1381Zinc; catalytic Probable
Metal binding1401Zinc; catalytic By similarity
Metal binding1511Zinc; catalytic By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.6 Ref.24

Experimental info

Mutagenesis1381H → Q: Abolishes ability to deneddylate cullins, without affecting the 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex. Ref.26
Sequence conflict43 – 453KPW → NLG in AAD03468. Ref.2
Sequence conflict1291R → H in AAB16847. Ref.1

Secondary structure

.................................... 334
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q92905 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: B5742F4AAD03A1CF

FASTA33437,579
        10         20         30         40         50         60 
MAASGSGMAQ KTWELANNMQ EAQSIDEIYK YDKKQQQEIL AAKPWTKDHH YFKYCKISAL 

        70         80         90        100        110        120 
ALLKMVMHAR SGGNLEVMGL MLGKVDGETM IIMDSFALPV EGTETRVNAQ AAAYEYMAAY 

       130        140        150        160        170        180 
IENAKQVGRL ENAIGWYHSH PGYGCWLSGI DVSTQMLNQQ FQEPFVAVVI DPTRTISAGK 

       190        200        210        220        230        240 
VNLGAFRTYP KGYKPPDEGP SEYQTIPLNK IEDFGVHCKQ YYALEVSYFK SSLDRKLLEL 

       250        260        270        280        290        300 
LWNKYWVNTL SSSSLLTNAD YTTGQVFDLS EKLEQSEAQL GRGSFMLGLE THDRKSEDKL 

       310        320        330 
AKATRDSCKT TIEAIHGLMS QVIKDKLFNQ INIS 

« Hide

References

« Hide 'large scale' references
[1]"A new group of conserved coactivators that increase the specificity of AP-1 transcription factors."
Claret F.-X., Hibi M., Dhut S., Toda T., Karin M.
Nature 383:453-457(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH JUN.
[2]"Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly."
Asano K., Vornlocher H.-P., Richter-Cook N.J., Merrick W.C., Hinnebusch A.G., Hershey J.W.B.
J. Biol. Chem. 272:27042-27052(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Eye and Muscle.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-47.
Tissue: Liver.
[6]Bienvenut W.V., Quadroni M.
Submitted (OCT-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-11; 57-64; 181-187; 237-244 AND 273-282, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[7]"The fusion gene of human Jun activation domain binding protein and membrane cofactor protein which cloned from multiple myeloma cell line ARH-77."
Hu W., Tian J.
Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 146-334.
[8]"A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits."
Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R., Schade R., Gordon C., Naumann M., Dubiel W.
FASEB J. 12:469-478(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION.
[9]"The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators."
Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., Wulczyn F.G., Scheidereit C., Leutz A.
Oncogene 18:3316-3323(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCL3.
[10]"JAB1 interacts with both the progesterone receptor and SRC-1."
Chauchereau A., Georgiakaki M., Perrin-Wolff M., Milgrom E., Loosfelt H.
J. Biol. Chem. 275:8540-8548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA1 AND PGR.
[11]"Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1."
Kleemann R., Hausser A., Geiger G., Mischke R., Burger-Kentischer A., Flieger O., Johannes F.-J., Roger T., Calandra T., Kapurniotu A., Grell M., Finkelmeier D., Brunner H., Bernhagen J.
Nature 408:211-216(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MIF.
[12]"Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity."
Bianchi E., Denti S., Granata A., Bossi G., Geginat J., Villa A., Rogge L., Pardi R.
Nature 404:617-621(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGB2.
[13]"COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system."
Bech-Otschir D., Kraft R., Huang X., Henklein P., Kapelari B., Pollmann C., Dubiel W.
EMBO J. 20:1630-1639(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53.
[14]"Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome."
Lyapina S., Cope G., Shevchenko A., Serino G., Tsuge T., Zhou C., Wolf D.A., Wei N., Shevchenko A., Deshaies R.J.
Science 292:1382-1385(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COMPOSITION OF THE CSN COMPLEX.
[15]"Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation."
Wan M., Cao X., Wu Y., Bai S., Wu L., Shi X., Wang N., Cao X.
EMBO Rep. 3:171-176(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMAD4.
[16]"Intracrine hepatopoietin potentiates AP-1 activity through JAB1 independent of MAPK pathway."
Lu C., Li Y., Zhao Y., Xing G., Tang F., Wang Q., Sun Y., Wei H., Yang X., Wu C., Chen J., Guan K.-L., Zhang C., Chen H., He F.
FASEB J. 16:90-92(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GFER.
[17]"Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)."
Caballero O.L., Resto V., Patturajan M., Meerzaman D., Guo M.Z., Engles J., Yochem R., Ratovitski E., Sidransky D., Jen J.
Oncogene 21:3003-3010(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UCHL1.
[18]"The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage."
Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R., Kisselev A.F., Tanaka K., Nakatani Y.
Cell 113:357-367(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome."
Uhle S., Medalia O., Waldron R., Dumdey R., Henklein P., Bech-Otschir D., Huang X., Berse M., Sperling J., Schade R., Dubiel W.
EMBO J. 22:1302-1312(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M."
Zou Y., Lim S., Lee K., Deng X., Friedman E.
J. Biol. Chem. 278:49573-49581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH RAN; RANBP9 AND DYRK1B.
[21]"Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5."
Yun J., Tomida A., Andoh T., Tsuruo T.
J. Biol. Chem. 279:31296-31303(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TOP2A.
[22]"Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation."
Kim B.-C., Lee H.-J., Park S.H., Lee S.R., Karpova T.S., McNally J.G., Felici A., Lee D.K., Kim S.-J.
Mol. Cell. Biol. 24:2251-2262(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMAD7.
[23]"RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins."
Xiao S., Li D., Zhu H.Q., Song M.G., Pan X.R., Jia P.M., Peng L.L., Dou A.X., Chen G.Q., Chen S.J., Chen Z., Tong J.H.
Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH IFIT3.
[24]"Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry."
Fang L., Wang X., Yamoah K., Chen P.L., Pan Z.Q., Huang L.
J. Proteome Res. 7:4914-4925(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE CSN COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2.
[25]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1."
Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M., Cohen R.E.
EMBO J. 28:621-631(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE SIGNALOSOME COMPLEX, INTERACTION WITH THE BRISC COMPLEX, MUTAGENESIS OF HIS-138.
[27]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its degradation in the ubiquitin-proteasome pathway."
Zhou J., Wan B., Li R., Gu X., Zhong Z., Wang Y., Yu L.
Biochem. Biophys. Res. Commun. 422:647-652(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRSK2, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U65928 mRNA. Translation: AAB16847.1.
U70734 mRNA. Translation: AAD03468.1.
CR541678 mRNA. Translation: CAG46479.1.
BC001187 mRNA. Translation: AAH01187.1.
BC001859 mRNA. Translation: AAH01859.1.
BC007272 mRNA. Translation: AAH07272.1.
BX648542 mRNA. Translation: CAH10375.1.
AY078082 mRNA. Translation: AAL82571.1. Different initiation.
PIRS71820.
RefSeqNP_006828.2. NM_006837.2.
UniGeneHs.491912.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4F7OX-ray2.60A/B1-257[»]
ProteinModelPortalQ92905.
SMRQ92905. Positions 2-333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116183. 777 interactions.
DIPDIP-34546N.
IntActQ92905. 124 interactions.
MINTMINT-1188008.
STRING9606.ENSP00000350512.

Protein family/group databases

MEROPSM67.002.

PTM databases

PhosphoSiteQ92905.

Polymorphism databases

DMDM55976562.

2D gel databases

REPRODUCTION-2DPAGEIPI00009958.

Proteomic databases

PaxDbQ92905.
PRIDEQ92905.

Protocols and materials databases

DNASU10987.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357849; ENSP00000350512; ENSG00000121022.
GeneID10987.
KEGGhsa:10987.
UCSCuc003xxd.3. human.

Organism-specific databases

CTD10987.
GeneCardsGC08M068005.
HGNCHGNC:2240. COPS5.
HPACAB004242.
HPA004845.
MIM604850. gene.
neXtProtNX_Q92905.
PharmGKBPA26757.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1310.
HOGENOMHOG000116528.
HOVERGENHBG051137.
InParanoidQ92905.
KOK09613.
OMAMQEVQSI.
OrthoDBEOG72NRQC.
PhylomeDBQ92905.
TreeFamTF105601.

Gene expression databases

ArrayExpressQ92905.
BgeeQ92905.
CleanExHS_COPS5.
GenevestigatorQ92905.

Family and domain databases

InterProIPR000555. JAMM/MPN+_dom.
[Graphical view]
PfamPF01398. JAB. 1 hit.
[Graphical view]
SMARTSM00232. JAB_MPN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCOPS5. human.
GenomeRNAi10987.
NextBio41743.
PROQ92905.
SOURCESearch...

Entry information

Entry nameCSN5_HUMAN
AccessionPrimary (citable) accession number: Q92905
Secondary accession number(s): O15386 expand/collapse secondary AC list , Q6AW95, Q86WQ4, Q9BQ17
Entry history
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 129 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM