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P61201 (CSN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P299913EBI-1050386,EBI-8826488From a different organism.
CREBBPQ927933EBI-1050386,EBI-81215
CrebbpP454812EBI-1050386,EBI-296306From a different organism.
EP300Q094722EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 443443COP9 signalosome complex subunit 2
PRO_0000120968

Regions

Domain248 – 413166PCI

Natural variations

Alternative sequence1241Q → QNSDFLCQ in isoform 2.
VSP_011884

Experimental info

Sequence conflict361Y → N in CAG46860. Ref.3
Sequence conflict1511T → A in AAD43026. Ref.2
Sequence conflict2111N → T in CAG46860. Ref.3
Sequence conflict3521R → Q Ref.7
Sequence conflict3921C → S Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 10, 2004. Version 1.
Checksum: 1DB6FA774C13BC59

FASTA44351,597
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 581DE764677E90C0
Show »

FASTA45052,405

References

« Hide '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. expand/collapse author list , 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.

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.
RefSeqNP_001137359.1. NM_001143887.1.
NP_004227.1. NM_004236.3.
UniGeneHs.369614.

3D structure databases

ProteinModelPortalP61201.
SMRP61201. Positions 65-413.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114729. 91 interactions.
DIPDIP-42076N.
IntActP61201. 17 interactions.
MINTMINT-1204035.
STRING9606.ENSP00000299259.

PTM databases

PhosphoSiteP61201.

Polymorphism databases

DMDM47117681.

Proteomic databases

PaxDbP61201.
PRIDEP61201.

Protocols and materials databases

DNASU9318.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299259; ENSP00000299259; ENSG00000166200. [P61201-2]
ENST00000388901; ENSP00000373553; ENSG00000166200. [P61201-1]
GeneID9318.
KEGGhsa:9318.
UCSCuc001zxf.3. human. [P61201-1]
uc001zxh.3. human. [P61201-2]

Organism-specific databases

CTD9318.
GeneCardsGC15M049417.
HGNCHGNC:30747. COPS2.
HPAHPA016867.
HPA018271.
MIM604508. gene.
neXtProtNX_P61201.
PharmGKBPA134952445.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5159.
HOVERGENHBG003924.
KOK12176.
OMAYGLEYSE.
PhylomeDBP61201.
TreeFamTF105738.

Enzyme and pathway databases

SignaLinkP61201.

Gene expression databases

ArrayExpressP61201.
BgeeP61201.
CleanExHS_COPS2.
HS_CSN2.
GenevestigatorP61201.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
1.25.40.10. 1 hit.
InterProIPR013143. PAM.
IPR000717. PCI_dom.
IPR011990. TPR-like_helical.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF01399. PCI. 1 hit.
[Graphical view]
SMARTSM00753. PAM. 1 hit.
SM00088. PINT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCOPS2.
GenomeRNAi9318.
NextBio34905.
PROP61201.
SOURCESearch...

Entry information

Entry nameCSN2_HUMAN
AccessionPrimary (citable) accession number: P61201
Secondary accession number(s): O88950 expand/collapse secondary AC list , Q15647, Q6FGP4, Q9BY54, Q9R249, Q9UNI2, Q9UNQ5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: April 16, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM