Full text data of COPS2
COPS2
(CSN2, TRIP15)
[Confidence: high (present in two of the MS resources)]
COP9 signalosome complex subunit 2; SGN2; Signalosome subunit 2 (Alien homolog; JAB1-containing signalosome subunit 2; Thyroid receptor-interacting protein 15; TR-interacting protein 15; TRIP-15)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
COP9 signalosome complex subunit 2; SGN2; Signalosome subunit 2 (Alien homolog; JAB1-containing signalosome subunit 2; Thyroid receptor-interacting protein 15; TR-interacting protein 15; TRIP-15)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00018813
IPI00018813 Splice Isoform 1 Of COP9 signalosome complex subunit 2 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 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic isoform 1 or 2 found at its expected molecular weight found at molecular weight
IPI00018813 Splice Isoform 1 Of COP9 signalosome complex subunit 2 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 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic isoform 1 or 2 found at its expected molecular weight found at molecular weight
UniProt
P61201
ID CSN2_HUMAN Reviewed; 443 AA.
AC P61201; O88950; Q15647; Q6FGP4; Q9BY54; Q9R249; Q9UNI2; Q9UNQ5;
read moreDT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=COP9 signalosome complex subunit 2;
DE Short=SGN2;
DE Short=Signalosome subunit 2;
DE AltName: Full=Alien homolog;
DE AltName: Full=JAB1-containing signalosome subunit 2;
DE AltName: Full=Thyroid receptor-interacting protein 15;
DE Short=TR-interacting protein 15;
DE Short=TRIP-15;
GN Name=COPS2; Synonyms=CSN2, TRIP15;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Dumdey R., Bech-Otschir D., Ferrell K., Dubiel W.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Pituitary;
RA Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-236 (ISOFORM 1).
RX PubMed=7776974; DOI=10.1210/me.9.2.243;
RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.;
RT "Two classes of proteins dependent on either the presence or absence
RT of thyroid hormone for interaction with the thyroid hormone
RT receptor.";
RL Mol. Endocrinol. 9:243-254(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-443 (ISOFORM 1), SUBCELLULAR LOCATION,
RP AND INTERACTION WITH NR2F1.
RX PubMed=10207062;
RA Dressel U., Thormeyer D., Altincicek B., Paululat A., Eggert M.,
RA Schneider S., Tenbaum S.P., Renkawitz R., Baniahmad A.;
RT "Alien, a highly conserved protein with characteristics of a
RT corepressor for members of the nuclear hormone receptor superfamily.";
RL Mol. Cell. Biol. 19:3383-3394(1999).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9535219;
RA Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R.,
RA Schade R., Gordon C., Naumann M., Dubiel W.;
RT "A novel protein complex involved in signal transduction possessing
RT similarities to 26S proteasome subunits.";
RL FASEB J. 12:469-478(1998).
RN [9]
RP INTERACTION WITH NR0B1.
RX PubMed=10713076; DOI=10.1074/jbc.275.11.7662;
RA Altincicek B., Tenbaum S.P., Dressel U., Thormeyer D., Renkawitz R.,
RA Baniahmad A.;
RT "Interaction of the corepressor Alien with DAX-1 is abrogated by
RT mutations of DAX-1 involved in adrenal hypoplasia congenita.";
RL J. Biol. Chem. 275:7662-7667(2000).
RN [10]
RP INTERACTION WITH IRF8/ICSBP1.
RX PubMed=10991940; DOI=10.1074/jbc.M004900200;
RA Cohen H., Azriel A., Cohen T., Meraro D., Hashmueli S.,
RA Bech-Otschir D., Kraft R., Dubiel W., Levi B.Z.;
RT "Interaction between interferon consensus sequence-binding protein and
RT COP9/signalosome subunit CSN2 (Trip15). A possible link between
RT interferon regulatory factor signaling and the COP9/signalosome.";
RL J. Biol. Chem. 275:39081-39089(2000).
RN [11]
RP FUNCTION.
RX PubMed=11285227; DOI=10.1093/emboj/20.7.1630;
RA Bech-Otschir D., Kraft R., Huang X., Henklein P., Kapelari B.,
RA Pollmann C., Dubiel W.;
RT "COP9 signalosome-specific phosphorylation targets p53 to degradation
RT by the ubiquitin system.";
RL EMBO J. 20:1630-1639(2001).
RN [12]
RP FUNCTION, COMPOSITION OF THE CSN COMPLEX, AND INTERACTION WITH CUL1.
RX PubMed=11337588; DOI=10.1126/science.1059780;
RA Lyapina S., Cope G., Shevchenko A., Serino G., Tsuge T., Zhou C.,
RA Wolf D.A., Wei N., Shevchenko A., Deshaies R.J.;
RT "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.";
RL Science 292:1382-1385(2001).
RN [13]
RP FUNCTION.
RX PubMed=12732143; DOI=10.1016/S0092-8674(03)00316-7;
RA Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M.,
RA Drapkin R., Kisselev A.F., Tanaka K., Nakatani Y.;
RT "The ubiquitin ligase activity in the DDB2 and CSA complexes is
RT differentially regulated by the COP9 signalosome in response to DNA
RT damage.";
RL Cell 113:357-367(2003).
RN [14]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=12628923; DOI=10.1093/emboj/cdg127;
RA Uhle S., Medalia O., Waldron R., Dumdey R., Henklein P.,
RA Bech-Otschir D., Huang X., Berse M., Sperling J., Schade R.,
RA Dubiel W.;
RT "Protein kinase CK2 and protein kinase D are associated with the COP9
RT signalosome.";
RL EMBO J. 22:1302-1312(2003).
RN [15]
RP IDENTIFICATION IN THE CSN COMPLEX.
RX PubMed=18850735; DOI=10.1021/pr800574c;
RA Fang L., Wang X., Yamoah K., Chen P.L., Pan Z.Q., Huang L.;
RT "Characterization of the human COP9 signalosome complex using affinity
RT purification and mass spectrometry.";
RL J. Proteome Res. 7:4914-4925(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Essential component of the COP9 signalosome complex
CC (CSN), a complex involved in various cellular and developmental
CC processes. The CSN complex is an essential regulator of the
CC ubiquitin (Ubl) conjugation pathway by mediating the deneddylation
CC of the cullin subunits of SCF-type E3 ligase complexes, leading to
CC decrease the Ubl ligase activity of SCF-type complexes such as
CC SCF, CSA or DDB2. The complex is also involved in phosphorylation
CC of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP,
CC possibly via its association with CK2 and PKD kinases. CSN-
CC dependent phosphorylation of TP53 and JUN promotes and protects
CC degradation by the Ubl system, respectively. Involved in early
CC stage of neuronal differentiation via its interaction with NIF3L1.
CC -!- SUBUNIT: Interacts with NIF3L1 (By similarity). Component of the
CC CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5,
CC COP6, COPS7 (COPS7A or COPS7B) and COPS8. In the complex, it
CC probably interacts directly with COPS1, COPS4, COPS5 COPS6 and
CC COPS7 (COPS7A or COPS7B). Interacts with CUL1 and CUL2.
CC Specifically interacts with the ligand binding domain of the
CC thyroid receptor (TR). Does not require the presence of thyroid
CC hormone for its interaction. Interacts with IRF8/ICSBP1 and with
CC nuclear receptors NR2F1 and NR0B1.
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=3; IntAct=EBI-1050386, EBI-8869494;
CC Q92793:CREBBP; NbExp=3; IntAct=EBI-1050386, EBI-81215;
CC P45481:Crebbp (xeno); NbExp=2; IntAct=EBI-1050386, EBI-296306;
CC Q09472:EP300; NbExp=2; IntAct=EBI-1050386, EBI-447295;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61201-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61201-2; Sequence=VSP_011884;
CC -!- PTM: Phosphorylated by CK2 and PKD kinases.
CC -!- SIMILARITY: Belongs to the CSN2 family.
CC -!- SIMILARITY: Contains 1 PCI domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD30269.1; Type=Frameshift; Positions=304;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/COPS2ID47362ch15q21.html";
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DR EMBL; AF084260; AAC34122.1; -; mRNA.
DR EMBL; AF100762; AAD43026.1; -; mRNA.
DR EMBL; AF212227; AAK26250.1; -; mRNA.
DR EMBL; CR542063; CAG46860.1; -; mRNA.
DR EMBL; BC012629; AAH12629.1; -; mRNA.
DR EMBL; L40388; AAC41734.1; -; mRNA.
DR EMBL; AF120268; AAD30269.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001137359.1; NM_001143887.1.
DR RefSeq; NP_004227.1; NM_004236.3.
DR UniGene; Hs.369614; -.
DR ProteinModelPortal; P61201; -.
DR SMR; P61201; 101-409.
DR DIP; DIP-42076N; -.
DR IntAct; P61201; 17.
DR MINT; MINT-1204035; -.
DR STRING; 9606.ENSP00000299259; -.
DR PhosphoSite; P61201; -.
DR DMDM; 47117681; -.
DR PaxDb; P61201; -.
DR PRIDE; P61201; -.
DR DNASU; 9318; -.
DR Ensembl; ENST00000299259; ENSP00000299259; ENSG00000166200.
DR Ensembl; ENST00000388901; ENSP00000373553; ENSG00000166200.
DR GeneID; 9318; -.
DR KEGG; hsa:9318; -.
DR UCSC; uc001zxf.3; human.
DR CTD; 9318; -.
DR GeneCards; GC15M049417; -.
DR HGNC; HGNC:30747; COPS2.
DR HPA; HPA016867; -.
DR HPA; HPA018271; -.
DR MIM; 604508; gene.
DR neXtProt; NX_P61201; -.
DR PharmGKB; PA134952445; -.
DR eggNOG; COG5159; -.
DR HOVERGEN; HBG003924; -.
DR KO; K12176; -.
DR OMA; YGLEYSE; -.
DR SignaLink; P61201; -.
DR GeneWiki; COPS2; -.
DR GenomeRNAi; 9318; -.
DR NextBio; 34905; -.
DR PRO; PR:P61201; -.
DR ArrayExpress; P61201; -.
DR Bgee; P61201; -.
DR CleanEx; HS_COPS2; -.
DR CleanEx; HS_CSN2; -.
DR Genevestigator; P61201; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0004871; F:signal transducer activity; NAS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR013143; PAM.
DR InterPro; IPR000717; PCI_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF01399; PCI; 1.
DR SMART; SM00753; PAM; 1.
DR SMART; SM00088; PINT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Signalosome.
FT CHAIN 1 443 COP9 signalosome complex subunit 2.
FT /FTId=PRO_0000120968.
FT DOMAIN 248 413 PCI.
FT VAR_SEQ 124 124 Q -> QNSDFLCQ (in isoform 2).
FT /FTId=VSP_011884.
FT CONFLICT 36 36 Y -> N (in Ref. 3; CAG46860).
FT CONFLICT 151 151 T -> A (in Ref. 2; AAD43026).
FT CONFLICT 211 211 N -> T (in Ref. 3; CAG46860).
FT CONFLICT 352 352 R -> Q (in Ref. 7).
FT CONFLICT 392 392 C -> S (in Ref. 7).
SQ SEQUENCE 443 AA; 51597 MW; 1DB6FA774C13BC59 CRC64;
MSDMEDDFMC DDEEDYDLEY SEDSNSEPNV DLENQYYNSK ALKEDDPKAA LSSFQKVLEL
EGEKGEWGFK ALKQMIKINF KLTNFPEMMN RYKQLLTYIR SAVTRNYSEK SINSILDYIS
TSKQMDLLQE FYETTLEALK DAKNDRLWFK TNTKLGKLYL EREEYGKLQK ILRQLHQSCQ
TDDGEDDLKK GTQLLEIYAL EIQMYTAQKN NKKLKALYEQ SLHIKSAIPH PLIMGVIREC
GGKMHLREGE FEKAHTDFFE AFKNYDESGS PRRTTCLKYL VLANMLMKSG INPFDSQEAK
PYKNDPEILA MTNLVSAYQN NDITEFEKIL KTNHSNIMDD PFIREHIEEL LRNIRTQVLI
KLIKPYTRIH IPFISKELNI DVADVESLLV QCILDNTIHG RIDQVNQLLE LDHQKRGGAR
YTALDKWTNQ LNSLNQAVVS KLA
//
ID CSN2_HUMAN Reviewed; 443 AA.
AC P61201; O88950; Q15647; Q6FGP4; Q9BY54; Q9R249; Q9UNI2; Q9UNQ5;
read moreDT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=COP9 signalosome complex subunit 2;
DE Short=SGN2;
DE Short=Signalosome subunit 2;
DE AltName: Full=Alien homolog;
DE AltName: Full=JAB1-containing signalosome subunit 2;
DE AltName: Full=Thyroid receptor-interacting protein 15;
DE Short=TR-interacting protein 15;
DE Short=TRIP-15;
GN Name=COPS2; Synonyms=CSN2, TRIP15;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Dumdey R., Bech-Otschir D., Ferrell K., Dubiel W.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Pituitary;
RA Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-236 (ISOFORM 1).
RX PubMed=7776974; DOI=10.1210/me.9.2.243;
RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.;
RT "Two classes of proteins dependent on either the presence or absence
RT of thyroid hormone for interaction with the thyroid hormone
RT receptor.";
RL Mol. Endocrinol. 9:243-254(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-443 (ISOFORM 1), SUBCELLULAR LOCATION,
RP AND INTERACTION WITH NR2F1.
RX PubMed=10207062;
RA Dressel U., Thormeyer D., Altincicek B., Paululat A., Eggert M.,
RA Schneider S., Tenbaum S.P., Renkawitz R., Baniahmad A.;
RT "Alien, a highly conserved protein with characteristics of a
RT corepressor for members of the nuclear hormone receptor superfamily.";
RL Mol. Cell. Biol. 19:3383-3394(1999).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9535219;
RA Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R.,
RA Schade R., Gordon C., Naumann M., Dubiel W.;
RT "A novel protein complex involved in signal transduction possessing
RT similarities to 26S proteasome subunits.";
RL FASEB J. 12:469-478(1998).
RN [9]
RP INTERACTION WITH NR0B1.
RX PubMed=10713076; DOI=10.1074/jbc.275.11.7662;
RA Altincicek B., Tenbaum S.P., Dressel U., Thormeyer D., Renkawitz R.,
RA Baniahmad A.;
RT "Interaction of the corepressor Alien with DAX-1 is abrogated by
RT mutations of DAX-1 involved in adrenal hypoplasia congenita.";
RL J. Biol. Chem. 275:7662-7667(2000).
RN [10]
RP INTERACTION WITH IRF8/ICSBP1.
RX PubMed=10991940; DOI=10.1074/jbc.M004900200;
RA Cohen H., Azriel A., Cohen T., Meraro D., Hashmueli S.,
RA Bech-Otschir D., Kraft R., Dubiel W., Levi B.Z.;
RT "Interaction between interferon consensus sequence-binding protein and
RT COP9/signalosome subunit CSN2 (Trip15). A possible link between
RT interferon regulatory factor signaling and the COP9/signalosome.";
RL J. Biol. Chem. 275:39081-39089(2000).
RN [11]
RP FUNCTION.
RX PubMed=11285227; DOI=10.1093/emboj/20.7.1630;
RA Bech-Otschir D., Kraft R., Huang X., Henklein P., Kapelari B.,
RA Pollmann C., Dubiel W.;
RT "COP9 signalosome-specific phosphorylation targets p53 to degradation
RT by the ubiquitin system.";
RL EMBO J. 20:1630-1639(2001).
RN [12]
RP FUNCTION, COMPOSITION OF THE CSN COMPLEX, AND INTERACTION WITH CUL1.
RX PubMed=11337588; DOI=10.1126/science.1059780;
RA Lyapina S., Cope G., Shevchenko A., Serino G., Tsuge T., Zhou C.,
RA Wolf D.A., Wei N., Shevchenko A., Deshaies R.J.;
RT "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.";
RL Science 292:1382-1385(2001).
RN [13]
RP FUNCTION.
RX PubMed=12732143; DOI=10.1016/S0092-8674(03)00316-7;
RA Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M.,
RA Drapkin R., Kisselev A.F., Tanaka K., Nakatani Y.;
RT "The ubiquitin ligase activity in the DDB2 and CSA complexes is
RT differentially regulated by the COP9 signalosome in response to DNA
RT damage.";
RL Cell 113:357-367(2003).
RN [14]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=12628923; DOI=10.1093/emboj/cdg127;
RA Uhle S., Medalia O., Waldron R., Dumdey R., Henklein P.,
RA Bech-Otschir D., Huang X., Berse M., Sperling J., Schade R.,
RA Dubiel W.;
RT "Protein kinase CK2 and protein kinase D are associated with the COP9
RT signalosome.";
RL EMBO J. 22:1302-1312(2003).
RN [15]
RP IDENTIFICATION IN THE CSN COMPLEX.
RX PubMed=18850735; DOI=10.1021/pr800574c;
RA Fang L., Wang X., Yamoah K., Chen P.L., Pan Z.Q., Huang L.;
RT "Characterization of the human COP9 signalosome complex using affinity
RT purification and mass spectrometry.";
RL J. Proteome Res. 7:4914-4925(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Essential component of the COP9 signalosome complex
CC (CSN), a complex involved in various cellular and developmental
CC processes. The CSN complex is an essential regulator of the
CC ubiquitin (Ubl) conjugation pathway by mediating the deneddylation
CC of the cullin subunits of SCF-type E3 ligase complexes, leading to
CC decrease the Ubl ligase activity of SCF-type complexes such as
CC SCF, CSA or DDB2. The complex is also involved in phosphorylation
CC of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP,
CC possibly via its association with CK2 and PKD kinases. CSN-
CC dependent phosphorylation of TP53 and JUN promotes and protects
CC degradation by the Ubl system, respectively. Involved in early
CC stage of neuronal differentiation via its interaction with NIF3L1.
CC -!- SUBUNIT: Interacts with NIF3L1 (By similarity). Component of the
CC CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5,
CC COP6, COPS7 (COPS7A or COPS7B) and COPS8. In the complex, it
CC probably interacts directly with COPS1, COPS4, COPS5 COPS6 and
CC COPS7 (COPS7A or COPS7B). Interacts with CUL1 and CUL2.
CC Specifically interacts with the ligand binding domain of the
CC thyroid receptor (TR). Does not require the presence of thyroid
CC hormone for its interaction. Interacts with IRF8/ICSBP1 and with
CC nuclear receptors NR2F1 and NR0B1.
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=3; IntAct=EBI-1050386, EBI-8869494;
CC Q92793:CREBBP; NbExp=3; IntAct=EBI-1050386, EBI-81215;
CC P45481:Crebbp (xeno); NbExp=2; IntAct=EBI-1050386, EBI-296306;
CC Q09472:EP300; NbExp=2; IntAct=EBI-1050386, EBI-447295;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61201-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61201-2; Sequence=VSP_011884;
CC -!- PTM: Phosphorylated by CK2 and PKD kinases.
CC -!- SIMILARITY: Belongs to the CSN2 family.
CC -!- SIMILARITY: Contains 1 PCI domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD30269.1; Type=Frameshift; Positions=304;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/COPS2ID47362ch15q21.html";
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DR EMBL; AF084260; AAC34122.1; -; mRNA.
DR EMBL; AF100762; AAD43026.1; -; mRNA.
DR EMBL; AF212227; AAK26250.1; -; mRNA.
DR EMBL; CR542063; CAG46860.1; -; mRNA.
DR EMBL; BC012629; AAH12629.1; -; mRNA.
DR EMBL; L40388; AAC41734.1; -; mRNA.
DR EMBL; AF120268; AAD30269.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001137359.1; NM_001143887.1.
DR RefSeq; NP_004227.1; NM_004236.3.
DR UniGene; Hs.369614; -.
DR ProteinModelPortal; P61201; -.
DR SMR; P61201; 101-409.
DR DIP; DIP-42076N; -.
DR IntAct; P61201; 17.
DR MINT; MINT-1204035; -.
DR STRING; 9606.ENSP00000299259; -.
DR PhosphoSite; P61201; -.
DR DMDM; 47117681; -.
DR PaxDb; P61201; -.
DR PRIDE; P61201; -.
DR DNASU; 9318; -.
DR Ensembl; ENST00000299259; ENSP00000299259; ENSG00000166200.
DR Ensembl; ENST00000388901; ENSP00000373553; ENSG00000166200.
DR GeneID; 9318; -.
DR KEGG; hsa:9318; -.
DR UCSC; uc001zxf.3; human.
DR CTD; 9318; -.
DR GeneCards; GC15M049417; -.
DR HGNC; HGNC:30747; COPS2.
DR HPA; HPA016867; -.
DR HPA; HPA018271; -.
DR MIM; 604508; gene.
DR neXtProt; NX_P61201; -.
DR PharmGKB; PA134952445; -.
DR eggNOG; COG5159; -.
DR HOVERGEN; HBG003924; -.
DR KO; K12176; -.
DR OMA; YGLEYSE; -.
DR SignaLink; P61201; -.
DR GeneWiki; COPS2; -.
DR GenomeRNAi; 9318; -.
DR NextBio; 34905; -.
DR PRO; PR:P61201; -.
DR ArrayExpress; P61201; -.
DR Bgee; P61201; -.
DR CleanEx; HS_COPS2; -.
DR CleanEx; HS_CSN2; -.
DR Genevestigator; P61201; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0004871; F:signal transducer activity; NAS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR013143; PAM.
DR InterPro; IPR000717; PCI_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF01399; PCI; 1.
DR SMART; SM00753; PAM; 1.
DR SMART; SM00088; PINT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Signalosome.
FT CHAIN 1 443 COP9 signalosome complex subunit 2.
FT /FTId=PRO_0000120968.
FT DOMAIN 248 413 PCI.
FT VAR_SEQ 124 124 Q -> QNSDFLCQ (in isoform 2).
FT /FTId=VSP_011884.
FT CONFLICT 36 36 Y -> N (in Ref. 3; CAG46860).
FT CONFLICT 151 151 T -> A (in Ref. 2; AAD43026).
FT CONFLICT 211 211 N -> T (in Ref. 3; CAG46860).
FT CONFLICT 352 352 R -> Q (in Ref. 7).
FT CONFLICT 392 392 C -> S (in Ref. 7).
SQ SEQUENCE 443 AA; 51597 MW; 1DB6FA774C13BC59 CRC64;
MSDMEDDFMC DDEEDYDLEY SEDSNSEPNV DLENQYYNSK ALKEDDPKAA LSSFQKVLEL
EGEKGEWGFK ALKQMIKINF KLTNFPEMMN RYKQLLTYIR SAVTRNYSEK SINSILDYIS
TSKQMDLLQE FYETTLEALK DAKNDRLWFK TNTKLGKLYL EREEYGKLQK ILRQLHQSCQ
TDDGEDDLKK GTQLLEIYAL EIQMYTAQKN NKKLKALYEQ SLHIKSAIPH PLIMGVIREC
GGKMHLREGE FEKAHTDFFE AFKNYDESGS PRRTTCLKYL VLANMLMKSG INPFDSQEAK
PYKNDPEILA MTNLVSAYQN NDITEFEKIL KTNHSNIMDD PFIREHIEEL LRNIRTQVLI
KLIKPYTRIH IPFISKELNI DVADVESLLV QCILDNTIHG RIDQVNQLLE LDHQKRGGAR
YTALDKWTNQ LNSLNQAVVS KLA
//
MIM
604508
*RECORD*
*FIELD* NO
604508
*FIELD* TI
*604508 COP9, SUBUNIT 2; COPS2
;;THYROID HORMONE RECEPTOR INTERACTOR 15; TRIP15;;
SGN2;;
read moreALIEN, DROSOPHILA, HOMOLOG OF
*FIELD* TX
CLONING
The thyroid hormone receptors (TRs) are hormone-dependent transcription
factors that regulate expression of a variety of specific target genes.
They must specifically interact with a number of proteins as they
progress from their initial translation and nuclear translocation to
heterodimerization with retinoid X receptors (RXRs), functional
interactions with other transcription factors and the basic
transcriptional apparatus, and eventually, degradation. To help
elucidate the mechanisms that underlie the transcriptional effects and
other potential functions of TRs, Lee et al. (1995) used the yeast
interaction trap, a version of the yeast 2-hybrid system, to identify
proteins that specifically interact with the ligand-binding domain of
rat TR-beta (THRB; 190160). They isolated HeLa cell cDNAs encoding
several different TR-interacting proteins (TRIPs), including TRIP15.
TRIP15 interacted with rat Thrb only in the absence of thyroid hormone.
In contrast, it interacted with RXR-alpha (RXRA; 180245) only in the
presence of 9-cis-retinoic acid. TRIP15 did not interact with the
glucocorticoid receptor (NR3C1; 138040) under any condition.
Some nuclear hormone receptors (NHRs) silence gene expression in the
absence of hormone. Corepressors, which are bound to the silencing
domain of NHRs and are involved in the repression of gene expression,
dissociate upon hormone binding, leading to the binding of coactivators
that mediate gene activation. TR is a transcriptional silencer in the
absence of hormone as well as a hormone-dependent trans-activator, with
its silencing domain localized in the C terminus. Dressel et al. (1999)
obtained a full-length HeLa cell cDNA encoding TRIP15, the human homolog
of the Drosophila corepressor 'Alien.' Sequence analysis predicted that
the 305-amino acid TRIP15 protein, which is 90% identical and 95%
similar to Drosophila Alien, contains an acidic region in the N
terminus, a putative zinc finger in the C terminus, and a central
hydrophobic core region flanked by 2 putative alpha-helical structures
and a nuclear localization signal. Western blot analysis determined that
TRIP15 is expressed as a 41-kD protein. Yeast 2-hybrid, GST pull-down,
and coimmunoprecipitation analyses showed that TRIP15 interacts with the
C terminus of TR, but not with intact RAR (180240), only in the absence
of hormone. Immunofluorescence microscopy demonstrated that TRIP15 is
localized in the nucleus. Reporter assays indicated that TRIP15
increases receptor-mediated silencing and harbors an autonomous
silencing function, which correlates with the ability of TRIP15 to
interact with TR in both the hinge region and the C-terminal end of the
TR silencing domain.
Schaefer et al. (1999) obtained a mouse cDNA encoding Cops2, which is
homologous to Drosophila Alien. The mouse gene encodes a larger protein
than human TRIP15.
GENE FUNCTION
TRIP15, or SGN2, is part of a 450-kD signalosome complex that includes
COPS3 (604665), COPS5 (604850), GPS1 (601934), and at least 4 other
subunits. By autoradiographic analysis, Seeger et al. (1998) showed that
the complex phosphorylates JUN (165160), IKBA (164008), and the
C-terminal part of the p105 precursor of NFKB (164011). The 26S
proteasome is not a phosphorylation target, although immunofluorescence
microscopy demonstrated that the 450-kD complex has a cytosolic
localization, concentrated around the nucleus.
GENE STRUCTURE
Schaefer et al. (1999) determined that the mouse Trip15 gene contains 12
exons spanning 30 kb.
MAPPING
Schaefer et al. (1999) mapped the mouse Trip15 gene to the central part
of chromosome 2.
Scott (2000) mapped the TRIP15 gene to 15q21.2 based on sequence
similarity between the TRIP15 sequence (GenBank GENBANK AF120268) and
the chromosome 15 clone RP11-325E5 (GenBank GENBANK AC013452).
*FIELD* RF
1. Dressel, U.; Thormeyer, D.; Altincicek, B.; Paululat, A.; Eggert,
M.; Schneider, S.; Tenbaum, S. P.; Renkawitz, R.; Baniahmad, A.:
Alien, a highly conserved protein with characteristics of a corepressor
for members of the nuclear hormone receptor superfamily. Molec. Cell.
Biol. 19: 3383-3394, 1999.
2. Lee, J. W.; Choi, H.-S.; Gyuris, J.; Brent, R.; Moore, D. D.:
Two classes of proteins dependent on either the presence or absence
of thyroid hormone for interaction with the thyroid hormone receptor. Molec.
Endocr. 9: 243-254, 1995.
3. Schaefer, L.; Beermann, M. L.; Miller, J. B.: Coding sequence,
genomic organization, chromosomal localization, and expression pattern
of the signalosome component Cops2: the mouse homologue of Drosophila
alien. Genomics 56: 310-316, 1999.
4. Scott, A. F.: Personal Communication. Baltimore, Md. 11/8/2000.
5. Seeger, M.; Kraft, R.; Ferrell, K.; Dawadschargal, B.-O.; Dumdey,
R.; Schade, R.; Gordon, C.; Naumann, M.; Dubiel, W.: A novel protein
complex involved in signal transduction possessing similarities to
26S proteasome subunits. FASEB J. 12: 469-478, 1998.
*FIELD* CN
Paul J. Converse - updated: 11/8/2000
*FIELD* CD
Patti M. Sherman: 2/4/2000
*FIELD* ED
alopez: 04/25/2005
mgross: 11/8/2000
mgross: 2/8/2000
psherman: 2/7/2000
*RECORD*
*FIELD* NO
604508
*FIELD* TI
*604508 COP9, SUBUNIT 2; COPS2
;;THYROID HORMONE RECEPTOR INTERACTOR 15; TRIP15;;
SGN2;;
read moreALIEN, DROSOPHILA, HOMOLOG OF
*FIELD* TX
CLONING
The thyroid hormone receptors (TRs) are hormone-dependent transcription
factors that regulate expression of a variety of specific target genes.
They must specifically interact with a number of proteins as they
progress from their initial translation and nuclear translocation to
heterodimerization with retinoid X receptors (RXRs), functional
interactions with other transcription factors and the basic
transcriptional apparatus, and eventually, degradation. To help
elucidate the mechanisms that underlie the transcriptional effects and
other potential functions of TRs, Lee et al. (1995) used the yeast
interaction trap, a version of the yeast 2-hybrid system, to identify
proteins that specifically interact with the ligand-binding domain of
rat TR-beta (THRB; 190160). They isolated HeLa cell cDNAs encoding
several different TR-interacting proteins (TRIPs), including TRIP15.
TRIP15 interacted with rat Thrb only in the absence of thyroid hormone.
In contrast, it interacted with RXR-alpha (RXRA; 180245) only in the
presence of 9-cis-retinoic acid. TRIP15 did not interact with the
glucocorticoid receptor (NR3C1; 138040) under any condition.
Some nuclear hormone receptors (NHRs) silence gene expression in the
absence of hormone. Corepressors, which are bound to the silencing
domain of NHRs and are involved in the repression of gene expression,
dissociate upon hormone binding, leading to the binding of coactivators
that mediate gene activation. TR is a transcriptional silencer in the
absence of hormone as well as a hormone-dependent trans-activator, with
its silencing domain localized in the C terminus. Dressel et al. (1999)
obtained a full-length HeLa cell cDNA encoding TRIP15, the human homolog
of the Drosophila corepressor 'Alien.' Sequence analysis predicted that
the 305-amino acid TRIP15 protein, which is 90% identical and 95%
similar to Drosophila Alien, contains an acidic region in the N
terminus, a putative zinc finger in the C terminus, and a central
hydrophobic core region flanked by 2 putative alpha-helical structures
and a nuclear localization signal. Western blot analysis determined that
TRIP15 is expressed as a 41-kD protein. Yeast 2-hybrid, GST pull-down,
and coimmunoprecipitation analyses showed that TRIP15 interacts with the
C terminus of TR, but not with intact RAR (180240), only in the absence
of hormone. Immunofluorescence microscopy demonstrated that TRIP15 is
localized in the nucleus. Reporter assays indicated that TRIP15
increases receptor-mediated silencing and harbors an autonomous
silencing function, which correlates with the ability of TRIP15 to
interact with TR in both the hinge region and the C-terminal end of the
TR silencing domain.
Schaefer et al. (1999) obtained a mouse cDNA encoding Cops2, which is
homologous to Drosophila Alien. The mouse gene encodes a larger protein
than human TRIP15.
GENE FUNCTION
TRIP15, or SGN2, is part of a 450-kD signalosome complex that includes
COPS3 (604665), COPS5 (604850), GPS1 (601934), and at least 4 other
subunits. By autoradiographic analysis, Seeger et al. (1998) showed that
the complex phosphorylates JUN (165160), IKBA (164008), and the
C-terminal part of the p105 precursor of NFKB (164011). The 26S
proteasome is not a phosphorylation target, although immunofluorescence
microscopy demonstrated that the 450-kD complex has a cytosolic
localization, concentrated around the nucleus.
GENE STRUCTURE
Schaefer et al. (1999) determined that the mouse Trip15 gene contains 12
exons spanning 30 kb.
MAPPING
Schaefer et al. (1999) mapped the mouse Trip15 gene to the central part
of chromosome 2.
Scott (2000) mapped the TRIP15 gene to 15q21.2 based on sequence
similarity between the TRIP15 sequence (GenBank GENBANK AF120268) and
the chromosome 15 clone RP11-325E5 (GenBank GENBANK AC013452).
*FIELD* RF
1. Dressel, U.; Thormeyer, D.; Altincicek, B.; Paululat, A.; Eggert,
M.; Schneider, S.; Tenbaum, S. P.; Renkawitz, R.; Baniahmad, A.:
Alien, a highly conserved protein with characteristics of a corepressor
for members of the nuclear hormone receptor superfamily. Molec. Cell.
Biol. 19: 3383-3394, 1999.
2. Lee, J. W.; Choi, H.-S.; Gyuris, J.; Brent, R.; Moore, D. D.:
Two classes of proteins dependent on either the presence or absence
of thyroid hormone for interaction with the thyroid hormone receptor. Molec.
Endocr. 9: 243-254, 1995.
3. Schaefer, L.; Beermann, M. L.; Miller, J. B.: Coding sequence,
genomic organization, chromosomal localization, and expression pattern
of the signalosome component Cops2: the mouse homologue of Drosophila
alien. Genomics 56: 310-316, 1999.
4. Scott, A. F.: Personal Communication. Baltimore, Md. 11/8/2000.
5. Seeger, M.; Kraft, R.; Ferrell, K.; Dawadschargal, B.-O.; Dumdey,
R.; Schade, R.; Gordon, C.; Naumann, M.; Dubiel, W.: A novel protein
complex involved in signal transduction possessing similarities to
26S proteasome subunits. FASEB J. 12: 469-478, 1998.
*FIELD* CN
Paul J. Converse - updated: 11/8/2000
*FIELD* CD
Patti M. Sherman: 2/4/2000
*FIELD* ED
alopez: 04/25/2005
mgross: 11/8/2000
mgross: 2/8/2000
psherman: 2/7/2000