Q92905 (CSN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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

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. Cytoplasm › perinuclear 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 component	Cytoplasm Nucleus Signalosome
Ligand	Metal-binding
Molecular function	Hydrolase Metalloprotease Protease
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cullin 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 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: Compara transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc
Cellular_component	eukaryotic translation initiation factor 3 complex Traceable author statement Ref.2. Source: ProtInc perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell signalosome Inferred from direct assay Ref.24Ref.26. Source: UniProtKB
Molecular_function	metal 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCNDBP1	O95273	5	EBI-594661,EBI-748961
CDKN1B	P46527	3	EBI-594661,EBI-519280
F2RL1	P55085	8	EBI-594661,EBI-4303189
FAM188A	Q9H8M7	3	EBI-594661,EBI-724928
SMAD7	O15105	10	EBI-594661,EBI-3861591
TXN	P10599	8	EBI-594661,EBI-594644
UCHL1	P09936	3	EBI-594661,EBI-714860

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6 Ref.24

Chain

2 – 334

333

COP9 signalosome complex subunit 5

PRO_0000194835

Regions

Domain

53 – 164

112

MPN

Motif

138 – 151

14

JAMM motif

Sites

Metal binding

138

1

Zinc; catalytic Probable

Metal binding

140

1

Zinc; catalytic By similarity

Metal binding

151

1

Zinc; catalytic By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6 Ref.24

Experimental info

Mutagenesis

138

1

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

3

KPW → NLG in AAD03468. Ref.2

Sequence conflict

129

1

R → H in AAB16847. Ref.1

Secondary structure

1

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334

Helix Strand Turn

Details...

Helix

6 – 16

11

Helix

33 – 42

10

Turn

45 – 47

3

Beta strand

54 – 58

5

Helix

59 – 71

13

Turn

72 – 74

3

Beta strand

78 – 86

9

Beta strand

89 – 97

9

Helix

104 – 107

4

Helix

112 – 124

13

Beta strand

125 – 127

3

Beta strand

133 – 139

7

Turn

141 – 143

3

Helix

149 – 161

13

Beta strand

167 – 170

4

Beta strand

183 – 188

6

Beta strand

221 – 223

3

Beta strand

225 – 231

7

Helix

235 – 250

16

Sequences

	Sequence		Length	Mass (Da)
	Q92905 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: B5742F4AAD03A1CF	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

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] [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, 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.

IPI

IPI00009958.

PIR

S71820.

RefSeq

NP_006828.2. NM_006837.2.

UniGene

Hs.491912.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F7O	X-ray	2.60	A/B	1-257	[»]

ProteinModelPortal

Q92905.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34546N.

IntAct

Q92905. 113 interactions.

MINT

MINT-1188008.

STRING

9606.ENSP00000350512.

Protein family/group databases

MEROPS

M67.002.

PTM databases

PhosphoSite

Q92905.

Polymorphism databases

DMDM

55976562.

2D gel databases

REPRODUCTION-2DPAGE

IPI00009958.

Proteomic databases

PaxDb

Q92905.

PRIDE

Q92905.

Protocols and materials databases

DNASU

10987.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000357849; ENSP00000350512; ENSG00000121022.

GeneID

10987.

KEGG

hsa:10987.

UCSC

uc003xxd.3. human.

Organism-specific databases

CTD

10987.

GeneCards

GC08M068005.

HGNC

HGNC:2240. COPS5.

HPA

CAB004242.
HPA004845.

MIM

604850. gene.

neXtProt

NX_Q92905.

PharmGKB

PA26757.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1310.

HOGENOM

HOG000116528.

HOVERGEN

HBG051137.

InParanoid

Q92905.

KO

K09613.

OMA

SAGKVCL.

OrthoDB

EOG41NTMD.

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. JAB1_Mov34_MPN_PAD1.
[Graphical view]

Pfam

PF01398. JAB. 1 hit.
[Graphical view]

SMART

SM00232. JAB_MPN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

COPS5. human.

GenomeRNAi

10987.

NextBio

41743.

SOURCE

Search...

Entry information

Entry name

CSN5_HUMAN

Accession

Primary (citable) accession number: Q92905
Secondary accession number(s): O15386 , Q6AW95, Q86WQ4, Q9BQ17

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 121 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.