Reviewed, UniProtKB/Swiss-Prot P61201 (CSN2_HUMAN)

Names and origin

Protein names

Recommended name:
    COP9 signalosome complex subunit 2
      Short name=Signalosome subunit 2
      Short name=SGN2
Alternative name(s):
    JAB1-containing signalosome subunit 2
    Thyroid receptor-interacting protein 15
      Short name=TRIP-15
    Alien homolog

Gene names

Name:	COPS2
Synonyms:	CSN2, TRIP15

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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.
Subcellular location	Cytoplasm. Nucleus.
Post-translational modification	Phosphorylated by CK2 and PKD kinases.
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	Direct protein sequencing
Gene Ontology (GO)
Biological process	signal transduction Ref.8 Non-traceable author statement. Source: UniProtKB transcription from RNA polymerase II promoter Ref.6 Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Ref.8 Inferred from direct assay. Source: UniProtKB signalosome Ref.8 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB signal transducer activity Ref.8 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
WDR8	Q9P2S5	1	EBI-1050386,EBI-1054904

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		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: 10931946] [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: 15489334] [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: 7776974] [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: 10207062] [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: 9535219] [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: 10713076] [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: 10991940] [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: 11285227] [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: 11337588] [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: 12732143] [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: 12628923] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
RefSeq	NP_004227.1.
UniGene	Hs.369614
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P61201.
PTM databases
PhosphoSite	P61201.
Genome annotation databases
Ensembl	ENSG00000166200. Homo sapiens. [Contig view]
GeneID	9318.
KEGG	hsa:9318.
Organism-specific databases
H-InvDB	HIX0012224.
HGNC	HGNC:30747. COPS2.
HPA	HPA016867.
MIM	604508. gene.
PharmGKB	PA134952445.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P61201.
Gene expression databases
ArrayExpress	P61201.
CleanEx	HS_COPS2. HS_CSN2.
GermOnline	ENSG00000166200. Homo sapiens.
Family and domain databases
InterPro	IPR013143. PAM. 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	SM00753. PAM. 1 hit. SM00088. PINT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	P61201.
NextBio	34905.
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 4, 2008
This is version 52 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)