Full text data of COPS6
COPS6
(CSN6, HVIP)
[Confidence: low (only semi-automatic identification from reviews)]
COP9 signalosome complex subunit 6; SGN6; Signalosome subunit 6 (JAB1-containing signalosome subunit 6; MOV34 homolog; Vpr-interacting protein; hVIP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
COP9 signalosome complex subunit 6; SGN6; Signalosome subunit 6 (JAB1-containing signalosome subunit 6; MOV34 homolog; Vpr-interacting protein; hVIP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q7L5N1
ID CSN6_HUMAN Reviewed; 327 AA.
AC Q7L5N1; A4D2A3; O15387;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 95.
DE RecName: Full=COP9 signalosome complex subunit 6;
DE Short=SGN6;
DE Short=Signalosome subunit 6;
DE AltName: Full=JAB1-containing signalosome subunit 6;
DE AltName: Full=MOV34 homolog;
DE AltName: Full=Vpr-interacting protein;
DE Short=hVIP;
GN Name=COPS6; Synonyms=CSN6, HVIP;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-327.
RX PubMed=9341143; DOI=10.1074/jbc.272.43.27042;
RA Asano K., Vornlocher H.-P., Richter-Cook N.J., Merrick W.C.,
RA Hinnebusch A.G., Hershey J.W.B.;
RT "Structure of cDNAs encoding human eukaryotic initiation factor 3
RT subunits. Possible roles in RNA binding and macromolecular assembly.";
RL J. Biol. Chem. 272:27042-27052(1997).
RN [5]
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 [6]
RP INTERACTION WITH HIV-1 VPR.
RX PubMed=8195203;
RA Zhao L.-J., Mukherjee S., Narayan O.;
RT "Biochemical mechanism of HIV-I Vpr function. Specific interaction
RT with a cellular protein.";
RL J. Biol. Chem. 269:15577-15582(1994).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH HUMAN
RP VPR.
RX PubMed=9520381; DOI=10.1073/pnas.95.7.3419;
RA Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Kao G.D.,
RA Muschel R.J., Weiner D.B.;
RT "HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular
RT factor linked to the G2/M phase transition of the mammalian cell
RT cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3419-3424(1998).
RN [8]
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 [9]
RP FUNCTION, COMPOSITION OF THE CSN COMPLEX, AND INTERACTION WITH RBX1.
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 [10]
RP INTERACTION WITH EIF3S6.
RX PubMed=12220626; DOI=10.1016/S0014-5793(02)03147-2;
RA Hoareau Alves K., Bochard V., Rety S., Jalinot P.;
RT "Association of the mammalian proto-oncoprotein Int-6 with the three
RT protein complexes eIF3, COP9 signalosome and 26S proteasome.";
RL FEBS Lett. 527:15-21(2002).
RN [11]
RP INTERACTION WITH VPR.
RX PubMed=12237292; DOI=10.1074/jbc.M203905200;
RA Ramanathan M.P., Curley E. III, Su M., Chambers J.A., Weiner D.B.;
RT "Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction
RT and glucocorticoid-mediated signaling.";
RL J. Biol. Chem. 277:47854-47860(2002).
RN [12]
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 [13]
RP FUNCTION.
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 [14]
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 [15]
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).
RN [16]
RP FUNCTION, AND INTERACTION WITH RFWD2 AND SFN.
RX PubMed=21625211; DOI=10.1038/onc.2011.192;
RA Choi H.H., Gully C., Su C.H., Velazquez-Torres G., Chou P.C.,
RA Tseng C., Zhao R., Phan L., Shaiken T., Chen J., Yeung S.C., Lee M.H.;
RT "COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3
RT ubiquitin ligase for 14-3-3sigma.";
RL Oncogene 30:4791-4801(2011).
CC -!- FUNCTION: Component of the COP9 signalosome complex (CSN), a
CC complex involved in various cellular and developmental processes.
CC The CSN complex is an essential regulator of the ubiquitin (Ubl)
CC conjugation pathway by mediating the deneddylation of the cullin
CC subunits of SCF-type E3 ligase complexes, leading to decrease the
CC Ubl ligase activity of SCF-type complexes such as SCF, CSA or
CC DDB2. The complex is also involved in phosphorylation of p53/TP53,
CC c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its
CC association with CK2 and PKD kinases. CSN-dependent
CC phosphorylation of TP53 and JUN promotes and protects degradation
CC by the Ubl system, respectively. Has some glucocorticoid receptor-
CC responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2
CC auto-ubiquitination and decelerating RFWD2 turnover rate, hence
CC regulates the ubiquitination of RFWD2 targets.
CC -!- SUBUNIT: Component of the CSN complex, composed of COPS1/GPS1,
CC COPS2, COPS3, COPS4, COPS5, COP6, COPS7 (COPS7A or COPS7B) and
CC COPS8. In the complex, it probably interacts directly with COPS2,
CC COPS4, COPS5 and COPS7 (COPS7A or COPS7B). Interacts with the
CC translation initiation factor EIF3S6. Interacts weakly with RBX1.
CC Interacts with the HIV-1 protein Vpr. Directly interacts with
CC RFWD2 and 14-3-3 protein sigma/SFN.
CC -!- INTERACTION:
CC Q9BX70:BTBD2; NbExp=2; IntAct=EBI-486838, EBI-710091;
CC Q8NHY2:RFWD2; NbExp=3; IntAct=EBI-486838, EBI-1176214;
CC P31947:SFN; NbExp=7; IntAct=EBI-486838, EBI-476295;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The interaction
CC with HIV-1 Vpr protein possibly leads its translocation to a
CC perinuclear region.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. CSN6 subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- CAUTION: Although related to the peptidase M67A family, it lacks
CC the JAMM motif that probably constitutes the catalytic center and
CC therefore it probably does not have a protease activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD03469.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; CH236956; EAL23857.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76601.1; -; Genomic_DNA.
DR EMBL; BC002520; AAH02520.2; -; mRNA.
DR EMBL; U70735; AAD03469.1; ALT_INIT; mRNA.
DR RefSeq; NP_006824.2; NM_006833.4.
DR UniGene; Hs.15591; -.
DR ProteinModelPortal; Q7L5N1; -.
DR SMR; Q7L5N1; 38-242.
DR DIP; DIP-32655N; -.
DR IntAct; Q7L5N1; 131.
DR MINT; MINT-5005311; -.
DR STRING; 9606.ENSP00000304102; -.
DR MEROPS; M67.972; -.
DR PhosphoSite; Q7L5N1; -.
DR DMDM; 55976470; -.
DR PaxDb; Q7L5N1; -.
DR PeptideAtlas; Q7L5N1; -.
DR PRIDE; Q7L5N1; -.
DR DNASU; 10980; -.
DR Ensembl; ENST00000303904; ENSP00000304102; ENSG00000168090.
DR GeneID; 10980; -.
DR KEGG; hsa:10980; -.
DR UCSC; uc003usu.3; human.
DR CTD; 10980; -.
DR GeneCards; GC07P099686; -.
DR HGNC; HGNC:21749; COPS6.
DR HPA; HPA044315; -.
DR MIM; 614729; gene.
DR neXtProt; NX_Q7L5N1; -.
DR PharmGKB; PA134919933; -.
DR eggNOG; COG1310; -.
DR HOGENOM; HOG000253002; -.
DR HOVERGEN; HBG107770; -.
DR InParanoid; Q7L5N1; -.
DR KO; K12179; -.
DR OMA; IGKQKGR; -.
DR OrthoDB; EOG7WT41Q; -.
DR PhylomeDB; Q7L5N1; -.
DR ChiTaRS; COPS6; human.
DR GeneWiki; COPS6; -.
DR GenomeRNAi; 10980; -.
DR NextBio; 41718; -.
DR PRO; PR:Q7L5N1; -.
DR ArrayExpress; Q7L5N1; -.
DR Bgee; Q7L5N1; -.
DR CleanEx; HS_COPS6; -.
DR Genevestigator; Q7L5N1; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR InterPro; IPR000555; JAB_MPN_dom.
DR InterPro; IPR024969; Rpn11/EIF3F_C.
DR Pfam; PF01398; JAB; 1.
DR Pfam; PF13012; MitMem_reg; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Host-virus interaction; Nucleus; Reference proteome; Signalosome.
FT CHAIN 1 327 COP9 signalosome complex subunit 6.
FT /FTId=PRO_0000194860.
FT DOMAIN 39 148 MPN.
FT REGION 211 327 Interaction with Vpr.
SQ SEQUENCE 327 AA; 36163 MW; E33CAC6ADF799A8D CRC64;
MAAAAAAAAA TNGTGGSSGM EVDAAVVPSV MACGVTGSVS VALHPLVILN ISDHWIRMRS
QEGRPVQVIG ALIGKQEGRN IEVMNSFELL SHTVEEKIII DKEYYYTKEE QFKQVFKELE
FLGWYTTGGP PDPSDIHVHK QVCEIIESPL FLKLNPMTKH TDLPVSVFES VIDIINGEAT
MLFAELTYTL ATEEAERIGV DHVARMTATG SGENSTVAEH LIAQHSAIKM LHSRVKLILE
YVKASEAGEV PFNHEILREA YALCHCLPVL STDKFKTDFY DQCNDVGLMA YLGTITKTCN
TMNQFVNKFN VLYDRQGIGR RMRGLFF
//
ID CSN6_HUMAN Reviewed; 327 AA.
AC Q7L5N1; A4D2A3; O15387;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 95.
DE RecName: Full=COP9 signalosome complex subunit 6;
DE Short=SGN6;
DE Short=Signalosome subunit 6;
DE AltName: Full=JAB1-containing signalosome subunit 6;
DE AltName: Full=MOV34 homolog;
DE AltName: Full=Vpr-interacting protein;
DE Short=hVIP;
GN Name=COPS6; Synonyms=CSN6, HVIP;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-327.
RX PubMed=9341143; DOI=10.1074/jbc.272.43.27042;
RA Asano K., Vornlocher H.-P., Richter-Cook N.J., Merrick W.C.,
RA Hinnebusch A.G., Hershey J.W.B.;
RT "Structure of cDNAs encoding human eukaryotic initiation factor 3
RT subunits. Possible roles in RNA binding and macromolecular assembly.";
RL J. Biol. Chem. 272:27042-27052(1997).
RN [5]
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 [6]
RP INTERACTION WITH HIV-1 VPR.
RX PubMed=8195203;
RA Zhao L.-J., Mukherjee S., Narayan O.;
RT "Biochemical mechanism of HIV-I Vpr function. Specific interaction
RT with a cellular protein.";
RL J. Biol. Chem. 269:15577-15582(1994).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH HUMAN
RP VPR.
RX PubMed=9520381; DOI=10.1073/pnas.95.7.3419;
RA Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Kao G.D.,
RA Muschel R.J., Weiner D.B.;
RT "HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular
RT factor linked to the G2/M phase transition of the mammalian cell
RT cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3419-3424(1998).
RN [8]
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 [9]
RP FUNCTION, COMPOSITION OF THE CSN COMPLEX, AND INTERACTION WITH RBX1.
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 [10]
RP INTERACTION WITH EIF3S6.
RX PubMed=12220626; DOI=10.1016/S0014-5793(02)03147-2;
RA Hoareau Alves K., Bochard V., Rety S., Jalinot P.;
RT "Association of the mammalian proto-oncoprotein Int-6 with the three
RT protein complexes eIF3, COP9 signalosome and 26S proteasome.";
RL FEBS Lett. 527:15-21(2002).
RN [11]
RP INTERACTION WITH VPR.
RX PubMed=12237292; DOI=10.1074/jbc.M203905200;
RA Ramanathan M.P., Curley E. III, Su M., Chambers J.A., Weiner D.B.;
RT "Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction
RT and glucocorticoid-mediated signaling.";
RL J. Biol. Chem. 277:47854-47860(2002).
RN [12]
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 [13]
RP FUNCTION.
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 [14]
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 [15]
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).
RN [16]
RP FUNCTION, AND INTERACTION WITH RFWD2 AND SFN.
RX PubMed=21625211; DOI=10.1038/onc.2011.192;
RA Choi H.H., Gully C., Su C.H., Velazquez-Torres G., Chou P.C.,
RA Tseng C., Zhao R., Phan L., Shaiken T., Chen J., Yeung S.C., Lee M.H.;
RT "COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3
RT ubiquitin ligase for 14-3-3sigma.";
RL Oncogene 30:4791-4801(2011).
CC -!- FUNCTION: Component of the COP9 signalosome complex (CSN), a
CC complex involved in various cellular and developmental processes.
CC The CSN complex is an essential regulator of the ubiquitin (Ubl)
CC conjugation pathway by mediating the deneddylation of the cullin
CC subunits of SCF-type E3 ligase complexes, leading to decrease the
CC Ubl ligase activity of SCF-type complexes such as SCF, CSA or
CC DDB2. The complex is also involved in phosphorylation of p53/TP53,
CC c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its
CC association with CK2 and PKD kinases. CSN-dependent
CC phosphorylation of TP53 and JUN promotes and protects degradation
CC by the Ubl system, respectively. Has some glucocorticoid receptor-
CC responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2
CC auto-ubiquitination and decelerating RFWD2 turnover rate, hence
CC regulates the ubiquitination of RFWD2 targets.
CC -!- SUBUNIT: Component of the CSN complex, composed of COPS1/GPS1,
CC COPS2, COPS3, COPS4, COPS5, COP6, COPS7 (COPS7A or COPS7B) and
CC COPS8. In the complex, it probably interacts directly with COPS2,
CC COPS4, COPS5 and COPS7 (COPS7A or COPS7B). Interacts with the
CC translation initiation factor EIF3S6. Interacts weakly with RBX1.
CC Interacts with the HIV-1 protein Vpr. Directly interacts with
CC RFWD2 and 14-3-3 protein sigma/SFN.
CC -!- INTERACTION:
CC Q9BX70:BTBD2; NbExp=2; IntAct=EBI-486838, EBI-710091;
CC Q8NHY2:RFWD2; NbExp=3; IntAct=EBI-486838, EBI-1176214;
CC P31947:SFN; NbExp=7; IntAct=EBI-486838, EBI-476295;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The interaction
CC with HIV-1 Vpr protein possibly leads its translocation to a
CC perinuclear region.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. CSN6 subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- CAUTION: Although related to the peptidase M67A family, it lacks
CC the JAMM motif that probably constitutes the catalytic center and
CC therefore it probably does not have a protease activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD03469.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; CH236956; EAL23857.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76601.1; -; Genomic_DNA.
DR EMBL; BC002520; AAH02520.2; -; mRNA.
DR EMBL; U70735; AAD03469.1; ALT_INIT; mRNA.
DR RefSeq; NP_006824.2; NM_006833.4.
DR UniGene; Hs.15591; -.
DR ProteinModelPortal; Q7L5N1; -.
DR SMR; Q7L5N1; 38-242.
DR DIP; DIP-32655N; -.
DR IntAct; Q7L5N1; 131.
DR MINT; MINT-5005311; -.
DR STRING; 9606.ENSP00000304102; -.
DR MEROPS; M67.972; -.
DR PhosphoSite; Q7L5N1; -.
DR DMDM; 55976470; -.
DR PaxDb; Q7L5N1; -.
DR PeptideAtlas; Q7L5N1; -.
DR PRIDE; Q7L5N1; -.
DR DNASU; 10980; -.
DR Ensembl; ENST00000303904; ENSP00000304102; ENSG00000168090.
DR GeneID; 10980; -.
DR KEGG; hsa:10980; -.
DR UCSC; uc003usu.3; human.
DR CTD; 10980; -.
DR GeneCards; GC07P099686; -.
DR HGNC; HGNC:21749; COPS6.
DR HPA; HPA044315; -.
DR MIM; 614729; gene.
DR neXtProt; NX_Q7L5N1; -.
DR PharmGKB; PA134919933; -.
DR eggNOG; COG1310; -.
DR HOGENOM; HOG000253002; -.
DR HOVERGEN; HBG107770; -.
DR InParanoid; Q7L5N1; -.
DR KO; K12179; -.
DR OMA; IGKQKGR; -.
DR OrthoDB; EOG7WT41Q; -.
DR PhylomeDB; Q7L5N1; -.
DR ChiTaRS; COPS6; human.
DR GeneWiki; COPS6; -.
DR GenomeRNAi; 10980; -.
DR NextBio; 41718; -.
DR PRO; PR:Q7L5N1; -.
DR ArrayExpress; Q7L5N1; -.
DR Bgee; Q7L5N1; -.
DR CleanEx; HS_COPS6; -.
DR Genevestigator; Q7L5N1; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR InterPro; IPR000555; JAB_MPN_dom.
DR InterPro; IPR024969; Rpn11/EIF3F_C.
DR Pfam; PF01398; JAB; 1.
DR Pfam; PF13012; MitMem_reg; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Host-virus interaction; Nucleus; Reference proteome; Signalosome.
FT CHAIN 1 327 COP9 signalosome complex subunit 6.
FT /FTId=PRO_0000194860.
FT DOMAIN 39 148 MPN.
FT REGION 211 327 Interaction with Vpr.
SQ SEQUENCE 327 AA; 36163 MW; E33CAC6ADF799A8D CRC64;
MAAAAAAAAA TNGTGGSSGM EVDAAVVPSV MACGVTGSVS VALHPLVILN ISDHWIRMRS
QEGRPVQVIG ALIGKQEGRN IEVMNSFELL SHTVEEKIII DKEYYYTKEE QFKQVFKELE
FLGWYTTGGP PDPSDIHVHK QVCEIIESPL FLKLNPMTKH TDLPVSVFES VIDIINGEAT
MLFAELTYTL ATEEAERIGV DHVARMTATG SGENSTVAEH LIAQHSAIKM LHSRVKLILE
YVKASEAGEV PFNHEILREA YALCHCLPVL STDKFKTDFY DQCNDVGLMA YLGTITKTCN
TMNQFVNKFN VLYDRQGIGR RMRGLFF
//
MIM
614729
*RECORD*
*FIELD* NO
614729
*FIELD* TI
*614729 COP9, SUBUNIT 6; COPS6
;;CSN6;;
MOV34 FAMILY, 34-KD MEMBER
*FIELD* TX
DESCRIPTION
read more
COPS6 is a subunit of the highly conserved COP9 signalosome complex,
which is involved in checkpoint control, signal transduction,
development, and the cell cycle. The COP9 signalosome complex has a
major role in controlling protein stability via the ubiquitin-proteasome
system (review by Kato and Yoneda-Kato, 2009).
CLONING
By searching EST databases using the sequence of the p47 subunit of EIF3
(EIF3F; 603914) as probe to identify proteins related to MOV34 (PSMD7;
1579770), Asano et al. (1997) identified mouse and human COPS6, which
they called the 34-kD MOV34 homolog. The deduced human protein contains
297 amino acids and has a calculated molecular mass of 33.6 kD.
In their review, Kato and Yoneda-Kato (2009) noted that CSN6 contains an
MPN domain, which is also found in subunits of the proteasome lid
complex (e.g., RPN8, or PSMD7) and in some subunits of the eIF3 complex
(e.g., EIF3F).
GENE FUNCTION
The 14-3-3-sigma (SFN; 601290) gene, which is upregulated by p53 (TP53;
191170) in response to DNA damage, exists in a positive-feedback loop
with p53 to prevent mitotic checkpoint dysfunction. Choi et al. (2011)
showed that COPS6 contributed to degradation of 14-3-3-sigma in human
cell lines by stabilizing the ubiquitin ligase COP1 (RFWD2; 608067).
COPS6 function did not require expression of p53. Gel-filtration and
Western blot analyses revealed that COPS6 interacted directly with COP1
and 14-3-3-sigma in a large COP9 molecular complex.
Coimmunoprecipitation and protein pull-down assays revealed that the
N-terminal region of COPS6 interacted directly with the C-terminal
region of COP1. Overexpression of COPS6 resulted in stabilization of
COP1 and increased 14-3-3-sigma polyubiquitination and degradation,
which in turn relieved 14-3-3-sigma-mediated inhibition of the
downstream prosurvival kinase AKT (164730) and facilitated cell growth.
Conversely, knockdown of COPS6 via short hairpin RNA reduced
14-3-3-sigma ubiquitination, suppressed AKT phosphorylation and
activity, and increased cell sensitivity to apoptotic stress. Choi et
al. (2011) concluded that COPS6 is involved in a signaling network that
regulates cell growth.
MAPPING
Hartz (2012) mapped the COPS6 gene to chromosome 7q22.1 based on an
alignment of the COPS6 sequence (GenBank GENBANK BC002520) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Asano, K.; Vornlocher, H.-P.; Richter-Cook, N. J.; Merrick, W.
C.; Hinnebusch, A. G.; Hershey, J. W. B.: Structure of cDNAs encoding
human eukaryotic initiation factor 3 subunits: possible roles in DNA
binding and macromolecular assembly. J. Biol. Chem. 272: 27042-27052,
1997.
2. Choi, H. H.; Gully, C.; Su, C.-H.; Velazquez-Torres, G.; Chou,
P.-C.; Tseng, C.; Zhao, R.; Phan, L.; Shaiken, T.; Chen, J.; Yeung,
S. C.; Lee, M.-H.: COP9 signalosome subunit 6 stabilizes COP1, which
functions as an E3 ubiquitin ligase for 14-3-3-sigma. Oncogene 30:
4791-4801, 2011.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/11/2012.
4. Kato, J.; Yoneda-Kato, N.: Mammalian COP9 signalosome. Genes
Cells 14: 1209-1225, 2009.
*FIELD* CD
Patricia A. Hartz: 7/18/2012
*FIELD* ED
mgross: 07/18/2012
*RECORD*
*FIELD* NO
614729
*FIELD* TI
*614729 COP9, SUBUNIT 6; COPS6
;;CSN6;;
MOV34 FAMILY, 34-KD MEMBER
*FIELD* TX
DESCRIPTION
read more
COPS6 is a subunit of the highly conserved COP9 signalosome complex,
which is involved in checkpoint control, signal transduction,
development, and the cell cycle. The COP9 signalosome complex has a
major role in controlling protein stability via the ubiquitin-proteasome
system (review by Kato and Yoneda-Kato, 2009).
CLONING
By searching EST databases using the sequence of the p47 subunit of EIF3
(EIF3F; 603914) as probe to identify proteins related to MOV34 (PSMD7;
1579770), Asano et al. (1997) identified mouse and human COPS6, which
they called the 34-kD MOV34 homolog. The deduced human protein contains
297 amino acids and has a calculated molecular mass of 33.6 kD.
In their review, Kato and Yoneda-Kato (2009) noted that CSN6 contains an
MPN domain, which is also found in subunits of the proteasome lid
complex (e.g., RPN8, or PSMD7) and in some subunits of the eIF3 complex
(e.g., EIF3F).
GENE FUNCTION
The 14-3-3-sigma (SFN; 601290) gene, which is upregulated by p53 (TP53;
191170) in response to DNA damage, exists in a positive-feedback loop
with p53 to prevent mitotic checkpoint dysfunction. Choi et al. (2011)
showed that COPS6 contributed to degradation of 14-3-3-sigma in human
cell lines by stabilizing the ubiquitin ligase COP1 (RFWD2; 608067).
COPS6 function did not require expression of p53. Gel-filtration and
Western blot analyses revealed that COPS6 interacted directly with COP1
and 14-3-3-sigma in a large COP9 molecular complex.
Coimmunoprecipitation and protein pull-down assays revealed that the
N-terminal region of COPS6 interacted directly with the C-terminal
region of COP1. Overexpression of COPS6 resulted in stabilization of
COP1 and increased 14-3-3-sigma polyubiquitination and degradation,
which in turn relieved 14-3-3-sigma-mediated inhibition of the
downstream prosurvival kinase AKT (164730) and facilitated cell growth.
Conversely, knockdown of COPS6 via short hairpin RNA reduced
14-3-3-sigma ubiquitination, suppressed AKT phosphorylation and
activity, and increased cell sensitivity to apoptotic stress. Choi et
al. (2011) concluded that COPS6 is involved in a signaling network that
regulates cell growth.
MAPPING
Hartz (2012) mapped the COPS6 gene to chromosome 7q22.1 based on an
alignment of the COPS6 sequence (GenBank GENBANK BC002520) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Asano, K.; Vornlocher, H.-P.; Richter-Cook, N. J.; Merrick, W.
C.; Hinnebusch, A. G.; Hershey, J. W. B.: Structure of cDNAs encoding
human eukaryotic initiation factor 3 subunits: possible roles in DNA
binding and macromolecular assembly. J. Biol. Chem. 272: 27042-27052,
1997.
2. Choi, H. H.; Gully, C.; Su, C.-H.; Velazquez-Torres, G.; Chou,
P.-C.; Tseng, C.; Zhao, R.; Phan, L.; Shaiken, T.; Chen, J.; Yeung,
S. C.; Lee, M.-H.: COP9 signalosome subunit 6 stabilizes COP1, which
functions as an E3 ubiquitin ligase for 14-3-3-sigma. Oncogene 30:
4791-4801, 2011.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/11/2012.
4. Kato, J.; Yoneda-Kato, N.: Mammalian COP9 signalosome. Genes
Cells 14: 1209-1225, 2009.
*FIELD* CD
Patricia A. Hartz: 7/18/2012
*FIELD* ED
mgross: 07/18/2012