COP9 signalosome complex subunit 5 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q92905 (CSN5_HUMAN)

Last modified January 19, 2010. Version 84. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    COP9 signalosome complex subunit 5
      Short name=Signalosome subunit 5
      Short name=SGN5
    EC=3.4.-.-
Alternative name(s):
    Jun activation domain-binding protein 1

Gene names

Name:	COPS5
Synonyms:	CSN5, JAB1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	334 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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 ICSBP, 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. Ref.8 Ref.13 Ref.14 Ref.18 Ref.19 Ref.26
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. Ref.13 Ref.26 Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.16 Ref.17 Ref.21 Ref.22
Subcellular location	Cytoplasm. Nucleus Ref.8.
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.

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Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Signalosome
Ligand	Metal-binding
Molecular function	Hydrolase Metalloprotease Protease
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	protein deneddylation Ref.26 Inferred from mutant phenotype. Source: UniProtKB transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc translation Ref.2 Traceable author statement. Source: ProtInc
Cellular component	eukaryotic translation initiation factor 3 complex Ref.2 Traceable author statement. Source: ProtInc signalosome Ref.26 Inferred from direct assay. Source: UniProtKB
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Ref.26 Inferred from mutant phenotype. Source: UniProtKB transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc translation initiation factor activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
CCNDBP1	O95273	1	EBI-594661,EBI-748961
CDKN1B	P46527	1	EBI-594661,EBI-519280
TXN	P10599	5	EBI-594661,EBI-594644
UCHL1	P09936	1	EBI-594661,EBI-714860
VHL	P40337	1	EBI-594661,EBI-301246

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.6 Ref.23

Chain

2 – 334

333

COP9 signalosome complex subunit 5

PRO_0000194835

Regions

Domain

53 – 164

112

MPN

Motif

138 – 151

JAMM motif

Sites

Metal binding

138

Zinc; catalytic Probable

Metal binding

140

Zinc; catalytic By similarity

Metal binding

151

Zinc; catalytic By similarity

Amino acid modifications

Modified residue

N-acetylalanine Ref.6 Ref.23 Ref.25

Modified residue

N6-acetyllysine Ref.27

Experimental info

Mutagenesis

138

H → Q: Abolishes ability to deneddylate cullins, without affecting the 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex. Ref.26

Sequence conflict

43 – 45

KPW → NLG in AAD03468. Ref.2

Sequence conflict

129

R → H in AAB16847. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q92905-1 [UniParc].

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

334

37,579

        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

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References

	« Hide 'large scale' referencesShow '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: 8837781] [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: 9341143] [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: 15489334] [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: 17974005] [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, 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: 9535219] [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: 10362352] [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: 10722692] [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: 11089976] [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: 10766246] [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: 11285227] [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: 11337588] [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: 11818334] [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: 11709497] [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: 12082530] [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: 12732143] [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: 12628923] [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: 14500717] [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: 15126503] [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: 14993265] [Abstract] Cited for: INTERACTION WITH SMAD7.
[23]	"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: 18850735] [Abstract] Cited for: IDENTIFICATION IN THE CSN COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2.
[24]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[25]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[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: 19214193] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE SIGNALOSOME COMPLEX, INTERACTION WITH THE BRISC COMPLEX, MUTAGENESIS OF HIS-138.
[27]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-47, MASS SPECTROMETRY.
+	Additional computationally mapped references.

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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.
IPI	IPI00009958.
PIR	S71820.
RefSeq	NP_006828.2.
UniGene	Hs.491912
3D structure databases
SMR	Q92905. Positions 52-188.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92905. 18 interactions.
STRING	Q92905.
Protein family/group databases
MEROPS	M67.002.
PTM databases
PhosphoSite	Q92905.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00009958.
Proteomic databases
PRIDE	Q92905.
Genome annotation databases
Ensembl	ENST00000357849; ENSP00000350512; ENSG00000121022; Homo sapiens. [Genome view]
GeneID	10987.
KEGG	hsa:10987.
UCSC	uc003xxe.1. human.
Organism-specific databases
CTD	10987.
GeneCards	GC08M068117.
H-InvDB	HIX0007560.
HGNC	HGNC:2240. COPS5.
HPA	CAB004242. HPA004845.
MIM	604850. gene.
PharmGKB	PA26757.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17635.
HOGENOM	HBG499867.
HOVERGEN	Q92905.
InParanoid	Q92905.
OMA	EVQSIDE.
OrthoDB	EOG90VZ84.
PhylomeDB	Q92905.
Enzyme and pathway databases
Pathway_Interaction_DB	hif1_tfpathway. HIF-1-alpha transcription factor network. hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
Gene expression databases
ArrayExpress	Q92905.
Bgee	Q92905.
CleanEx	HS_COPS5.
Genevestigator	Q92905.
GermOnline	ENSG00000121022. Homo sapiens.
Family and domain databases
InterPro	IPR000555. Mov34_MPN_PAD1. [Graphical view]
Pfam	PF01398. Mov34. 1 hit. [Graphical view]
SMART	SM00232. JAB_MPN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	41743.
SOURCE	Search...

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Entry information

Entry name

CSN5_HUMAN

Accession

Primary (citable) accession number: Q92905
Secondary accession number(s): O15386

Q9BQ17

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	January 23, 2007
Last modified:	January 19, 2010
This is version 84 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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

MIM cross-references

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

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents