Q9UNS2 (CSN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
COP9 signalosome complex subunit 3
Short name=SGN3
Short name=Signalosome subunit 3

Alternative name(s):
JAB1-containing signalosome subunit 3

Gene names

Name:	COPS3
Synonyms:	CSN3

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	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.1 Ref.9 Ref.11 Ref.13 Ref.14
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.10 Ref.12 Ref.14 Ref.18
Subcellular location	Cytoplasm. Nucleus Ref.1.
Tissue specificity	Widely expressed. Expressed at high level in heart and skeletal muscle. Ref.2
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.
Sequence caution	The sequence AAC14197.1 differs from that shown. Reason: Frameshift at position 5.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Signalosome
Coding sequence diversity	Alternative splicing
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cullin deneddylation Inferred from direct assay PubMed 19141280. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara response to light stimulus Traceable author statement Ref.1. Source: ProtInc signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA signalosome Inferred from direct assay Ref.18. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-350590,EBI-365961
IKBKG	Q9Y6K9	2	EBI-350590,EBI-81279

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UNS2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UNS2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7 Ref.8 Ref.18
	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.8 Ref.18
	Modified residue	410	1	Phosphoserine Ref.19
	Modified residue	423	1	Phosphoserine Ref.18 Ref.19 Ref.20 Ref.22
Natural variations
	Alternative sequence	1 – 20	20	Missing in isoform 2.		VSP_044271

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: C835D56B8A9DFA4A	FASTA	403	45,727
	10 20 30 40 50 60 MTQLCELINK SGELLAKNLS HLDTVLGALD VQEHSLGVLA VLFVKFSMPS VPDFETLFSQ 70 80 90 100 110 120 VQLFISTCNG EHIRYATDTF AGLCHQLTNA LVERKQPLRG IGILKQAIDK MQMNTNQLTS 130 140 150 160 170 180 IHADLCQLCL LAKCFKPALP YLDVDMMDIC KENGAYDAKH FLCYYYYGGM IYTGLKNFER 190 200 210 220 230 240 ALYFYEQAIT TPAMAVSHIM LESYKKYILV SLILLGKVQQ LPKYTSQIVG RFIKPLSNAY 250 260 270 280 290 300 HELAQVYSTN NPSELRNLVN KHSETFTRDN NMGLVKQCLS SLYKKNIQRL TKTFLTLSLQ 310 320 330 340 350 360 DMASRVQLSG PQEAEKYVLH MIEDGEIFAS INQKDGMVSF HDNPEKYNNP AMLHNIDQEM 370 380 390 400 LKCIELDERL KAMDQEITVN PQFVQKSMGS QEDDSGNKPS SYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION. Tissue: Cervix carcinoma.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Hippocampus.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Lung.
[7]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-13 (ISOFORM 1). Tissue: Platelet.
[8]	Bienvenut W.V., Quadroni M. Submitted (OCT-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 31-37; 244-251 AND 313-336 (ISOFORM 1), CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Cervix carcinoma and Platelet.
[9]	"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.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IKBKG.
[11]	"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.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF3S6.
[13]	"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.
[14]	"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, INTERACTION WITH CK2 AND PKD.
[15]	"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] [Europe PMC] [Abstract] Cited for: OVEREXPRESSION IN OSTEOSARCOMA.
[16]	"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] [Europe PMC] [Abstract] Cited for: OVEREXPRESSION IN OSTEOSARCOMA.
[17]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[18]	"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, PHOSPHORYLATION AT SER-423.
[19]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410 AND SER-423, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-423, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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].
[22]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-423, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF031647 mRNA. Translation: AAC14197.1. Frameshift. AF098109 mRNA. Translation: AAD41247.1. AK312476 mRNA. Translation: BAG35380.1. AK302304 mRNA. Translation: BAG63643.1. AK316400 mRNA. Translation: BAH14771.1. AC055811 Genomic DNA. No translation available. CH471196 Genomic DNA. Translation: EAW55712.1. BC001891 mRNA. Translation: AAH01891.1.
IPI	IPI00025721.
RefSeq	NP_001186054.1. NM_001199125.1. NP_003644.2. NM_003653.3.
UniGene	Hs.6076.
3D structure databases
ProteinModelPortal	Q9UNS2.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32478N.
IntAct	Q9UNS2. 9 interactions.
MINT	MINT-129190.
STRING	9606.ENSP00000268717.
PTM databases
PhosphoSite	Q9UNS2.
Polymorphism databases
DMDM	55976621.
Proteomic databases
PaxDb	Q9UNS2.
PeptideAtlas	Q9UNS2.
PRIDE	Q9UNS2.
Protocols and materials databases
DNASU	8533.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268717; ENSP00000268717; ENSG00000141030. ENST00000539941; ENSP00000437606; ENSG00000141030.
GeneID	8533.
KEGG	hsa:8533.
UCSC	uc002grd.3. human.
Organism-specific databases
CTD	8533.
GeneCards	GC17M017151.
HGNC	HGNC:2239. COPS3.
HPA	HPA021997.
MIM	604665. gene.
neXtProt	NX_Q9UNS2.
PharmGKB	PA26755.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG249849.
HOGENOM	HOG000030451.
HOVERGEN	HBG051135.
InParanoid	Q9UNS2.
KO	K12177.
OMA	DRALYFF.
OrthoDB	EOG49KFQJ.
PhylomeDB	Q9UNS2.
Gene expression databases
ArrayExpress	Q9UNS2.
Bgee	Q9UNS2.
CleanEx	HS_COPS3. HS_CSN3.
Genevestigator	Q9UNS2.
GermOnline	ENSG00000141030. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR000717. PCI_dom. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF01399. PCI. 1 hit. [Graphical view]
SMART	SM00088. PINT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	COPS3. human.
GenomeRNAi	8533.
NextBio	31960.
SOURCE	Search...

Entry information

Entry name

CSN3_HUMAN

Accession

Primary (citable) accession number: Q9UNS2
Secondary accession number(s): B2R683 , B4DY81, O43191, Q7LDR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 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.