Reviewed, UniProtKB/Swiss-Prot Q9UNS2 (CSN3_HUMAN)

Names and origin

Protein names

Recommended name:
    COP9 signalosome complex subunit 3
      Short name=Signalosome subunit 3
      Short name=SGN3
Alternative name(s):
    JAB1-containing signalosome subunit 3

Gene names

Name:	COPS3
Synonyms:	CSN3

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

Protein attributes

Sequence length	423 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	Component 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 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/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. Ref.5 Ref.6 Ref.8 Ref.10 Ref.11
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, COPS4 and COPS8. Interacts with CK2 and PKD. Interacts with the translation initiation factor EIF3S6 and IKBKG. Ref.11 Ref.7 Ref.9
Subcellular location	Cytoplasm. Nucleus. Ref.5
Tissue specificity	Widely expressed. Expressed at high level in heart and skeletal muscle. Ref.1
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.14 Ref.15 Ref.16
Miscellaneous	Amplified and overexpressed in some osteosarcomas (OS), suggesting that it may participate in TP53 degradation in OS.
Sequence similarities	Belongs to the CSN3 family. Contains 1 PCI domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Signalosome
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	response to light stimulus Ref.5 Traceable author statement. Source: ProtInc signal transduction Ref.5 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.5 Traceable author statement. Source: ProtInc signalosome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.7 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-350590,EBI-365961
IKBKG	Q9Y6K9	1	EBI-350590,EBI-81279
PHYH	O14832	1	EBI-350590,EBI-721853
RAF1	P04049	2	EBI-350590,EBI-365996
WDR8	Q9P2S5	1	EBI-350590,EBI-1054904

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3 Ref.4
	Chain	2 – 423	422	COP9 signalosome complex subunit 3		PRO_0000120978
Regions
	Domain	195 – 362	168	PCI
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.15 Ref.4
	Modified residue	410	1	Phosphoserine Ref.14 Ref.16
	Modified residue	423	1	Phosphoserine Ref.15

Sequences

	Sequence		Length	Mass (Da)
	Q9UNS2-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 1D371050C7D7BF8D	FASTA	423	47,873
	10 20 30 40 50 60 MASALEQFVN SVRQLSAQGQ MTQLCELINK SGELLAKNLS HLDTVLGALD VQEHSLGVLA 70 80 90 100 110 120 VLFVKFSMPS VPDFETLFSQ VQLFISTCNG EHIRYATDTF AGLCHQLTNA LVERKQPLRG 130 140 150 160 170 180 IGILKQAIDK MQMNTNQLTS IHADLCQLCL LAKCFKPALP YLDVDMMDIC KENGAYDAKH 190 200 210 220 230 240 FLCYYYYGGM IYTGLKNFER ALYFYEQAIT TPAMAVSHIM LESYKKYILV SLILLGKVQQ 250 260 270 280 290 300 LPKYTSQIVG RFIKPLSNAY HELAQVYSTN NPSELRNLVN KHSETFTRDN NMGLVKQCLS 310 320 330 340 350 360 SLYKKNIQRL TKTFLTLSLQ DMASRVQLSG PQEAEKYVLH MIEDGEIFAS INQKDGMVSF 370 380 390 400 410 420 HDNPEKYNNP AMLHNIDQEM LKCIELDERL KAMDQEITVN PQFVQKSMGS QEDDSGNKPS SYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Subunit 3 of the COP9 signal transduction complex is conserved from plants to humans and maps within the smith-magenis syndrome critical region in 17p11.2." Potocki L., Chen K.-S., Lupski J.R. Genomics 57:180-182(1999) [PubMed: 10191102] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[2]	"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: Lung.
[3]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-13. Tissue: Platelet.
[4]	Bienvenut W.V., Quadroni M. Submitted (OCT-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 31-37; 244-251 AND 313-336, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Cervix carcinoma and Platelet.
[5]	"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: NUCLEOTIDE SEQUENCE [MRNA] OF 5-423, PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION. Tissue: Cervix carcinoma.
[6]	"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.
[7]	"CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation." Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B. FEBS Lett. 499:133-136(2001) [PubMed: 11418127] [Abstract] Cited for: INTERACTION WITH IKBKG.
[8]	"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.
[9]	"Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome." Hoareau Alves K., Bochard V., Rety S., Jalinot P. FEBS Lett. 527:15-21(2002) [PubMed: 12220626] [Abstract] Cited for: INTERACTION WITH EIF3S6.
[10]	"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.
[11]	"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, INTERACTION WITH CK2 AND PKD.
[12]	"Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation." Henriksen J., Aagesen T.H., Maelandsmo G.M., Lothe R.A., Myklebost O., Forus A. Oncogene 22:5358-5361(2003) [PubMed: 12917637] [Abstract] Cited for: OVEREXPRESSION IN OSTEOSARCOMA.
[13]	"Amplification and overexpression of genes in 17p11.2 approximately p12 in osteosarcoma." Van Dartel M., Hulsebos T.J.M. Cancer Genet. Cytogenet. 153:77-80(2004) [PubMed: 15325100] [Abstract] Cited for: OVEREXPRESSION IN OSTEOSARCOMA.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410, MASS SPECTROMETRY.
[15]	"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: INITIATOR METHIONINE REMOVAL, ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-423.
[16]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410, MASS SPECTROMETRY.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF098109 mRNA. Translation: AAD41247.1. BC001891 mRNA. Translation: AAH01891.1. AF031647 mRNA. Translation: AAC14197.1. Different initiation.
IPI	IPI00025721.
RefSeq	NP_003644.2.
UniGene	Hs.6076
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UNS2. 7 interactions.
PTM databases
PhosphoSite	Q9UNS2.
Proteomic databases
PeptideAtlas	Q9UNS2.
PRIDE	Q9UNS2.
Genome annotation databases
Ensembl	ENSG00000141030. Homo sapiens. [Contig view]
GeneID	8533.
KEGG	hsa:8533.
UCSC	uc002grd.1. human.
Organism-specific databases
GeneCards	GC17M017090.
H-InvDB	HIX0013583.
HGNC	HGNC:2239. COPS3.
MIM	604665. gene.
PharmGKB	PA26755.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UNS2.
HOVERGEN	Q9UNS2.
OMA	Q9UNS2. ALYFFEV.
Gene expression databases
ArrayExpress	Q9UNS2.
Bgee	Q9UNS2.
CleanEx	HS_COPS3. HS_CSN3.
GermOnline	ENSG00000141030. Homo sapiens.
Family and domain databases
InterPro	IPR000717. PCI. IPR011991. Wing_hlx_DNA_bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
Pfam	PF01399. PCI. 1 hit. [Graphical view]
SMART	SM00088. PINT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31960.
SOURCE	Search...

Entry information

Entry name

CSN3_HUMAN

Accession

Primary (citable) accession number: Q9UNS2
Secondary accession number(s): O43191, Q7LDR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 71 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)