P61201 (CSN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
COP9 signalosome complex subunit 2
Short name=SGN2
Short name=Signalosome subunit 2

Alternative name(s):
Alien homolog
JAB1-containing signalosome subunit 2
Thyroid receptor-interacting protein 15
Short name=TR-interacting protein 15
Short name=TRIP-15

Gene names

Name:	COPS2
Synonyms:	CSN2, TRIP15

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential 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. Involved in early stage of neuronal differentiation via its interaction with NIF3L1. Ref.8 Ref.11 Ref.12 Ref.13 Ref.14
Subunit structure	Interacts with NIF3L1 By similarity. 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, COPS5 COPS6 and COPS7 (COPS7A or COPS7B). Interacts with CUL1 and CUL2. Specifically interacts with the ligand binding domain of the thyroid receptor (TR). Does not require the presence of thyroid hormone for its interaction. Interacts with IRF8/ICSBP1 and with nuclear receptors NR2F1 and NR0B1. Ref.7 Ref.9 Ref.10 Ref.12 Ref.15
Subcellular location	Cytoplasm. Nucleus Ref.7 Ref.8.
Post-translational modification	Phosphorylated by CK2 and PKD kinases. Ref.14
Sequence similarities	Belongs to the CSN2 family. Contains 1 PCI domain.
Sequence caution	The sequence AAD30269.1 differs from that shown. Reason: Frameshift at position 304.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Signalosome
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Inferred from electronic annotation. Source: Ensembl cullin deneddylation Inferred from direct assay PubMed 19141280. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Ensembl neuron differentiation Inferred from electronic annotation. Source: Ensembl skeletal muscle cell differentiation Inferred from electronic annotation. Source: Ensembl transcription from RNA polymerase II promoter Traceable author statement Ref.6. Source: UniProtKB
Cellular_component	COP9 signalosome Inferred from direct assay Ref.15Ref.8. Source: UniProtKB cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	signal transducer activity Non-traceable author statement Ref.8. Source: UniProtKB transcription corepressor activity Inferred from electronic annotation. Source: Ensembl
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREBBP	Q92793	3	EBI-1050386,EBI-81215
Crebbp	P45481	2	EBI-1050386,EBI-296306	From a different organism.
EP300	Q09472	2	EBI-1050386,EBI-447295

Alternative products

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

Isoform 1 (identifier: P61201-1)

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: P61201-2)

The sequence of this isoform differs from the canonical sequence as follows:
     124-124: Q → QNSDFLCQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 443	443	COP9 signalosome complex subunit 2		PRO_0000120968
Regions
	Domain	248 – 413	166	PCI
Natural variations
	Alternative sequence	124	1	Q → QNSDFLCQ in isoform 2.		VSP_011884
Experimental info
	Sequence conflict	36	1	Y → N in CAG46860. Ref.3
	Sequence conflict	151	1	T → A in AAD43026. Ref.2
	Sequence conflict	211	1	N → T in CAG46860. Ref.3
	Sequence conflict	352	1	R → Q Ref.7
	Sequence conflict	392	1	C → S Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2004. Version 1. Checksum: 1DB6FA774C13BC59	FASTA	443	51,597
	10 20 30 40 50 60 MSDMEDDFMC DDEEDYDLEY SEDSNSEPNV DLENQYYNSK ALKEDDPKAA LSSFQKVLEL 70 80 90 100 110 120 EGEKGEWGFK ALKQMIKINF KLTNFPEMMN RYKQLLTYIR SAVTRNYSEK SINSILDYIS 130 140 150 160 170 180 TSKQMDLLQE FYETTLEALK DAKNDRLWFK TNTKLGKLYL EREEYGKLQK ILRQLHQSCQ 190 200 210 220 230 240 TDDGEDDLKK GTQLLEIYAL EIQMYTAQKN NKKLKALYEQ SLHIKSAIPH PLIMGVIREC 250 260 270 280 290 300 GGKMHLREGE FEKAHTDFFE AFKNYDESGS PRRTTCLKYL VLANMLMKSG INPFDSQEAK 310 320 330 340 350 360 PYKNDPEILA MTNLVSAYQN NDITEFEKIL KTNHSNIMDD PFIREHIEEL LRNIRTQVLI 370 380 390 400 410 420 KLIKPYTRIH IPFISKELNI DVADVESLLV QCILDNTIHG RIDQVNQLLE LDHQKRGGAR 430 440 YTALDKWTNQ LNSLNQAVVS KLA
	Isoform 2 [UniParc]. Checksum: 581DE764677E90C0	FASTA	450	52,405
	10 20 30 40 50 60 MSDMEDDFMC DDEEDYDLEY SEDSNSEPNV DLENQYYNSK ALKEDDPKAA LSSFQKVLEL 70 80 90 100 110 120 EGEKGEWGFK ALKQMIKINF KLTNFPEMMN RYKQLLTYIR SAVTRNYSEK SINSILDYIS 130 140 150 160 170 180 TSKQNSDFLC QMDLLQEFYE TTLEALKDAK NDRLWFKTNT KLGKLYLERE EYGKLQKILR 190 200 210 220 230 240 QLHQSCQTDD GEDDLKKGTQ LLEIYALEIQ MYTAQKNNKK LKALYEQSLH IKSAIPHPLI 250 260 270 280 290 300 MGVIRECGGK MHLREGEFEK AHTDFFEAFK NYDESGSPRR TTCLKYLVLA NMLMKSGINP 310 320 330 340 350 360 FDSQEAKPYK NDPEILAMTN LVSAYQNNDI TEFEKILKTN HSNIMDDPFI REHIEELLRN 370 380 390 400 410 420 IRTQVLIKLI KPYTRIHIPF ISKELNIDVA DVESLLVQCI LDNTIHGRID QVNQLLELDH 430 440 450 QKRGGARYTA LDKWTNQLNS LNQAVVSKLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Dumdey R., Bech-Otschir D., Ferrell K., Dubiel W. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pituitary.
[3]	Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Pituitary.
[4]	"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] (ISOFORM 1).
[5]	"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: Skeletal muscle.
[6]	"Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor." Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D. Mol. Endocrinol. 9:243-254(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-236 (ISOFORM 1).
[7]	"Alien, a highly conserved protein with characteristics of a corepressor for members of the nuclear hormone receptor superfamily." Dressel U., Thormeyer D., Altincicek B., Paululat A., Eggert M., Schneider S., Tenbaum S.P., Renkawitz R., Baniahmad A. Mol. Cell. Biol. 19:3383-3394(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-443 (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH NR2F1.
[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]	"Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita." Altincicek B., Tenbaum S.P., Dressel U., Thormeyer D., Renkawitz R., Baniahmad A. J. Biol. Chem. 275:7662-7667(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NR0B1.
[10]	"Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome." Cohen H., Azriel A., Cohen T., Meraro D., Hashmueli S., Bech-Otschir D., Kraft R., Dubiel W., Levi B.Z. J. Biol. Chem. 275:39081-39089(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IRF8/ICSBP1.
[11]	"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.
[12]	"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, INTERACTION WITH CUL1.
[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, PHOSPHORYLATION.
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CSN COMPLEX.
[16]	"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].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF084260 mRNA. Translation: AAC34122.1. AF100762 mRNA. Translation: AAD43026.1. AF212227 mRNA. Translation: AAK26250.1. CR542063 mRNA. Translation: CAG46860.1. BC012629 mRNA. Translation: AAH12629.1. L40388 mRNA. Translation: AAC41734.1. AF120268 mRNA. Translation: AAD30269.1. Frameshift.
IPI	IPI00018813. IPI00743825.
RefSeq	NP_001137359.1. NM_001143887.1. NP_004227.1. NM_004236.3.
UniGene	Hs.369614.
3D structure databases
ProteinModelPortal	P61201.
SMR	P61201. Positions 101-409.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-42076N.
IntAct	P61201. 15 interactions.
MINT	MINT-1204035.
STRING	9606.ENSP00000299259.
PTM databases
PhosphoSite	P61201.
Polymorphism databases
DMDM	47117681.
Proteomic databases
PaxDb	P61201.
PRIDE	P61201.
Protocols and materials databases
DNASU	9318.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299259; ENSP00000299259; ENSG00000166200. ENST00000388901; ENSP00000373553; ENSG00000166200.
GeneID	9318.
KEGG	hsa:9318.
UCSC	uc001zxf.3. human.
Organism-specific databases
CTD	9318.
GeneCards	GC15M049417.
HGNC	HGNC:30747. COPS2.
HPA	HPA016867. HPA018271.
MIM	604508. gene.
neXtProt	NX_P61201.
PharmGKB	PA134952445.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5159.
HOVERGEN	HBG003924.
KO	K12176.
OMA	YGLEYSE.
Enzyme and pathway databases
SignaLink	P61201.
Gene expression databases
ArrayExpress	P61201.
Bgee	P61201.
CleanEx	HS_COPS2. HS_CSN2.
Genevestigator	P61201.
Family and domain databases
Gene3D	1.10.10.10. 1 hit. 1.25.40.10. 1 hit.
InterPro	IPR013143. PAM. IPR000717. PCI_dom. IPR011990. TPR-like_helical. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF01399. PCI. 1 hit. [Graphical view]
SMART	SM00753. PAM. 1 hit. SM00088. PINT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	COPS2.
GenomeRNAi	9318.
NextBio	34905.
PRO	P61201.
SOURCE	Search...

Entry information

Entry name

CSN2_HUMAN

Accession

Primary (citable) accession number: P61201
Secondary accession number(s): O88950 , Q15647, Q6FGP4, Q9BY54, Q9R249, Q9UNI2, Q9UNQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	November 13, 2013
This is version 98 of the entry and version 1 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.