CSN5_HUMAN
ID CSN5_HUMAN Reviewed; 334 AA.
AC Q92905; O15386; Q6AW95; Q86WQ4; Q9BQ17;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=COP9 signalosome complex subunit 5;
DE Short=SGN5;
DE Short=Signalosome subunit 5;
DE EC=3.4.-.-;
DE AltName: Full=Jun activation domain-binding protein 1;
GN Name=COPS5; Synonyms=CSN5, JAB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH JUN.
RX PubMed=8837781; DOI=10.1038/383453a0;
RA Claret F.-X., Hibi M., Dhut S., Toda T., Karin M.;
RT "A new group of conserved coactivators that increase the specificity of AP-
RT 1 transcription factors.";
RL Nature 383:453-457(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 subunits.
RT Possible roles in RNA binding and macromolecular assembly.";
RL J. Biol. Chem. 272:27042-27052(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, and 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-47.
RC TISSUE=Liver;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP PROTEIN SEQUENCE OF 2-11; 57-64; 181-187; 237-244 AND 273-282, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Quadroni M.;
RL Submitted (OCT-2005) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 146-334.
RA Hu W., Tian J.;
RT "The fusion gene of human Jun activation domain binding protein and
RT membrane cofactor protein which cloned from multiple myeloma cell line ARH-
RT 77.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9535219; DOI=10.1096/fasebj.12.6.469;
RA Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R., Schade R.,
RA 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 BCL3.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., Wulczyn F.G.,
RA Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and
RT nuclear co-regulators.";
RL Oncogene 18:3316-3323(1999).
RN [10]
RP INTERACTION WITH NCOA1 AND PGR.
RX PubMed=10722692; DOI=10.1074/jbc.275.12.8540;
RA Chauchereau A., Georgiakaki M., Perrin-Wolff M., Milgrom E., Loosfelt H.;
RT "JAB1 interacts with both the progesterone receptor and SRC-1.";
RL J. Biol. Chem. 275:8540-8548(2000).
RN [11]
RP INTERACTION WITH MIF.
RX PubMed=11089976; DOI=10.1038/35041591;
RA Kleemann R., Hausser A., Geiger G., Mischke R., Burger-Kentischer A.,
RA Flieger O., Johannes F.-J., Roger T., Calandra T., Kapurniotu A., Grell M.,
RA Finkelmeier D., Brunner H., Bernhagen J.;
RT "Intracellular action of the cytokine MIF to modulate AP-1 activity and the
RT cell cycle through Jab1.";
RL Nature 408:211-216(2000).
RN [12]
RP INTERACTION WITH ITGB2.
RX PubMed=10766246; DOI=10.1038/35007098;
RA Bianchi E., Denti S., Granata A., Bossi G., Geginat J., Villa A., Rogge L.,
RA Pardi R.;
RT "Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to
RT modulate AP-1 activity.";
RL Nature 404:617-621(2000).
RN [13]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=11285227; DOI=10.1093/emboj/20.7.1630;
RA Bech-Otschir D., Kraft R., Huang X., Henklein P., Kapelari B., Pollmann C.,
RA Dubiel W.;
RT "COP9 signalosome-specific phosphorylation targets p53 to degradation by
RT the ubiquitin system.";
RL EMBO J. 20:1630-1639(2001).
RN [14]
RP FUNCTION, AND COMPOSITION OF THE CSN COMPLEX.
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 [15]
RP INTERACTION WITH SMAD4.
RX PubMed=11818334; DOI=10.1093/embo-reports/kvf024;
RA Wan M., Cao X., Wu Y., Bai S., Wu L., Shi X., Wang N., Cao X.;
RT "Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation.";
RL EMBO Rep. 3:171-176(2002).
RN [16]
RP INTERACTION WITH GFER.
RX PubMed=11709497; DOI=10.1096/fj.01-0506fje;
RA Lu C., Li Y., Zhao Y., Xing G., Tang F., Wang Q., Sun Y., Wei H., Yang X.,
RA Wu C., Chen J., Guan K.-L., Zhang C., Chen H., He F.;
RT "Intracrine hepatopoietin potentiates AP-1 activity through JAB1
RT independent of MAPK pathway.";
RL FASEB J. 16:90-92(2002).
RN [17]
RP INTERACTION WITH UCHL1.
RX PubMed=12082530; DOI=10.1038/sj.onc.1205390;
RA Caballero O.L., Resto V., Patturajan M., Meerzaman D., Guo M.Z., Engles J.,
RA Yochem R., Ratovitski E., Sidransky D., Jen J.;
RT "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1).";
RL Oncogene 21:3003-3010(2002).
RN [18]
RP FUNCTION.
RX PubMed=12732143; DOI=10.1016/s0092-8674(03)00316-7;
RA Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R.,
RA 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 [19]
RP FUNCTION.
RX PubMed=12628923; DOI=10.1093/emboj/cdg127;
RA Uhle S., Medalia O., Waldron R., Dumdey R., Henklein P., Bech-Otschir D.,
RA Huang X., Berse M., Sperling J., Schade R., 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 [20]
RP IDENTIFICATION IN A COMPLEX WITH RAN; RANBP9 AND DYRK1B.
RX PubMed=14500717; DOI=10.1074/jbc.m307556200;
RA Zou Y., Lim S., Lee K., Deng X., Friedman E.;
RT "Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell
RT migration and is negatively regulated by the Met adaptor Ran-binding
RT protein M.";
RL J. Biol. Chem. 278:49573-49581(2003).
RN [21]
RP INTERACTION WITH TOP2A.
RX PubMed=15126503; DOI=10.1074/jbc.m401411200;
RA Yun J., Tomida A., Andoh T., Tsuruo T.;
RT "Interaction between glucose-regulated destruction domain of DNA
RT topoisomerase IIalpha and MPN domain of Jab1/CSN5.";
RL J. Biol. Chem. 279:31296-31303(2004).
RN [22]
RP INTERACTION WITH SMAD7.
RX PubMed=14993265; DOI=10.1128/mcb.24.6.2251-2262.2004;
RA Kim B.-C., Lee H.-J., Park S.H., Lee S.R., Karpova T.S., McNally J.G.,
RA Felici A., Lee D.K., Kim S.-J.;
RT "Jab1/CSN5, a component of the COP9 signalosome, regulates transforming
RT growth factor beta signaling by binding to Smad7 and promoting its
RT degradation.";
RL Mol. Cell. Biol. 24:2251-2262(2004).
RN [23]
RP INTERACTION WITH NUPR1.
RX PubMed=16300740; DOI=10.1016/j.bbrc.2005.11.018;
RA Malicet C., Hoffmeister A., Moreno S., Closa D., Dagorn J.C., Vasseur S.,
RA Iovanna J.L.;
RT "Interaction of the stress protein p8 with Jab1 is required for Jab1-
RT dependent p27 nuclear-to-cytoplasm translocation.";
RL Biochem. Biophys. Res. Commun. 339:284-289(2006).
RN [24]
RP INTERACTION WITH ZDHHC16.
RC TISSUE=Placenta;
RX PubMed=17123647; DOI=10.1016/j.bbaexp.2006.10.002;
RA Zhang F., Di Y., Li J., Shi Y., Zhang L., Wang C., He X., Liu Y., Wan D.,
RA Huo K., Gu J.;
RT "Molecular cloning and characterization of human Aph2 gene, involved in AP-
RT 1 regulation by interaction with JAB1.";
RL Biochim. Biophys. Acta 1759:514-525(2006).
RN [25]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH IFIT3.
RX PubMed=17050680; DOI=10.1073/pnas.0607830103;
RA Xiao S., Li D., Zhu H.Q., Song M.G., Pan X.R., Jia P.M., Peng L.L.,
RA Dou A.X., Chen G.Q., Chen S.J., Chen Z., Tong J.H.;
RT "RIG-G as a key mediator of the antiproliferative activity of interferon-
RT related pathways through enhancing p21 and p27 proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006).
RN [26]
RP IDENTIFICATION IN THE CSN COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, AND
RP ACETYLATION AT ALA-2.
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 [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [28]
RP FUNCTION, IDENTIFICATION IN THE SIGNALOSOME COMPLEX, INTERACTION WITH THE
RP BRISC COMPLEX, AND MUTAGENESIS OF HIS-138.
RX PubMed=19214193; DOI=10.1038/emboj.2009.27;
RA Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M.,
RA Cohen R.E.;
RT "K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated
RT Brcc36 and proteasomal Poh1.";
RL EMBO J. 28:621-631(2009).
RN [29]
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., Buerckstuemmer T.,
RA 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 [30]
RP FUNCTION, INTERACTION WITH FANK1, AND SUBCELLULAR LOCATION.
RX PubMed=20978819; DOI=10.1007/s00018-010-0559-4;
RA Wang H., Song W., Hu T., Zhang N., Miao S., Zong S., Wang L.;
RT "Fank1 interacts with Jab1 and regulates cell apoptosis via the AP-1
RT pathway.";
RL Cell. Mol. Life Sci. 68:2129-2139(2011).
RN [31]
RP SUBCELLULAR LOCATION.
RX PubMed=21102408; DOI=10.1038/emboj.2010.285;
RA Granata A., Koo S.J., Haucke V., Schiavo G., Warner T.T.;
RT "CSN complex controls the stability of selected synaptic proteins via a
RT torsinA-dependent process.";
RL EMBO J. 30:181-193(2011).
RN [32]
RP INTERACTION WITH MINDY3.
RX PubMed=21499297; DOI=10.1038/onc.2011.116;
RA Shi Y., Chen J., Li Z., Zhang Z., Yu H., Sun K., Wang X., Song X., Wang Y.,
RA Zhen Y., Yang T., Lou K., Zhang Y., Zhang G., Hu Y., Ji J., Hui R.;
RT "C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer
RT and a functional variant of this gene increases the risk of non-small-cell
RT lung cancer.";
RL Oncogene 30:4107-4117(2011).
RN [33]
RP FUNCTION, INTERACTION WITH BRSK2, AND SUBCELLULAR LOCATION.
RX PubMed=22609399; DOI=10.1016/j.bbrc.2012.05.045;
RA Zhou J., Wan B., Li R., Gu X., Zhong Z., Wang Y., Yu L.;
RT "Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its
RT degradation in the ubiquitin-proteasome pathway.";
RL Biochem. Biophys. Res. Commun. 422:647-652(2012).
RN [34]
RP INTERACTION WITH COSP9.
RX PubMed=23776465; DOI=10.1371/journal.pone.0065285;
RA Ebina M., Tsuruta F., Katoh M.C., Kigoshi Y., Someya A., Chiba T.;
RT "Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear localization
RT through Nedd8 modification.";
RL PLoS ONE 8:E65285-E65285(2013).
RN [35]
RP COMPOSITION OF THE CSN COMPLEX, AND INTERACTION WITH COPS9.
RX PubMed=26456823; DOI=10.1016/j.celrep.2015.09.021;
RA Rozen S., Fuezesi-Levi M.G., Ben-Nissan G., Mizrachi L., Gabashvili A.,
RA Levin Y., Ben-Dor S., Eisenstein M., Sharon M.;
RT "CSNAP is a stoichiometric subunit of the COP9 signalosome.";
RL Cell Rep. 13:585-598(2015).
CC -!- FUNCTION: Probable protease subunit 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 ubiquitin
CC (Ubl) conjugation pathway by mediating the deneddylation of the cullin
CC subunits of the SCF-type E3 ligase complexes, leading to decrease the
CC Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The
CC complex is also involved in phosphorylation of p53/TP53, c-jun/JUN,
CC IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with
CC CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN
CC promotes and protects degradation by the Ubl system, respectively. In
CC the complex, it probably acts as the catalytic center that mediates the
CC cleavage of Nedd8 from cullins. It however has no metalloprotease
CC activity by itself and requires the other subunits of the CSN complex.
CC Interacts directly with a large number of proteins that are regulated
CC by the CSN complex, confirming a key role in the complex. Promotes the
CC proteasomal degradation of BRSK2. {ECO:0000269|PubMed:11285227,
CC ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923,
CC ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:19214193,
CC ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399,
CC ECO:0000269|PubMed:9535219}.
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC -!- SUBUNIT: Component of the CSN complex, composed of COPS1/GPS1, COPS2,
CC COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9
CC isoform 1 (PubMed:26456823). In the complex, it probably interacts
CC directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B)
CC and COPS9 isoform 1 (PubMed:26456823). Interacts with COPS9 isoform 2
CC (PubMed:23776465). The CSN complex interacts with the BRISC complex.
CC Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1,
CC NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3,
CC ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B
CC and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with
CC ZDHHC16 (PubMed:17123647). Interacts with MINDY3 (PubMed:21499297).
CC Interacts with FANK1; regulates the phosphorylation of JUN and the
CC transcriptional activity of AP-1 (PubMed:20978819). Interacts with
CC NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to
CC cytoplasm translocation (PubMed:16300740).
CC {ECO:0000269|PubMed:10362352, ECO:0000269|PubMed:10722692,
CC ECO:0000269|PubMed:10766246, ECO:0000269|PubMed:11089976,
CC ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11709497,
CC ECO:0000269|PubMed:11818334, ECO:0000269|PubMed:12082530,
CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14993265,
CC ECO:0000269|PubMed:15126503, ECO:0000269|PubMed:16300740,
CC ECO:0000269|PubMed:17050680, ECO:0000269|PubMed:17123647,
CC ECO:0000269|PubMed:18850735, ECO:0000269|PubMed:19214193,
CC ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:21499297,
CC ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:23776465,
CC ECO:0000269|PubMed:26456823, ECO:0000269|PubMed:8837781}.
CC -!- INTERACTION:
CC Q92905; O95273: CCNDBP1; NbExp=5; IntAct=EBI-594661, EBI-748961;
CC Q92905; P46527: CDKN1B; NbExp=3; IntAct=EBI-594661, EBI-519280;
CC Q92905; Q9UNS2: COPS3; NbExp=17; IntAct=EBI-594661, EBI-350590;
CC Q92905; Q7L5N1: COPS6; NbExp=24; IntAct=EBI-594661, EBI-486838;
CC Q92905; P55085: F2RL1; NbExp=8; IntAct=EBI-594661, EBI-4303189;
CC Q92905; Q13098: GPS1; NbExp=16; IntAct=EBI-594661, EBI-725197;
CC Q92905; Q969Y2: GTPBP3; NbExp=3; IntAct=EBI-594661, EBI-740290;
CC Q92905; O14879: IFIT3; NbExp=4; IntAct=EBI-594661, EBI-745127;
CC Q92905; Q9H8M7: MINDY3; NbExp=3; IntAct=EBI-594661, EBI-724928;
CC Q92905; P35372: OPRM1; NbExp=5; IntAct=EBI-594661, EBI-2624570;
CC Q92905; Q5VTR2: RNF20; NbExp=2; IntAct=EBI-594661, EBI-2372238;
CC Q92905; O15105: SMAD7; NbExp=10; IntAct=EBI-594661, EBI-3861591;
CC Q92905; P10599: TXN; NbExp=9; IntAct=EBI-594661, EBI-594644;
CC Q92905; P09936: UCHL1; NbExp=3; IntAct=EBI-594661, EBI-714860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17050680,
CC ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399,
CC ECO:0000269|PubMed:9535219}. Nucleus {ECO:0000269|PubMed:17050680,
CC ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:9535219}. Cytoplasmic vesicle,
CC secretory vesicle, synaptic vesicle {ECO:0000269|PubMed:21102408}.
CC Note=Nuclear localization is diminished in the presence of IFIT3.
CC {ECO:0000269|PubMed:17050680}.
CC -!- DOMAIN: The JAMM motif is essential for the protease activity of the
CC CSN complex resulting in deneddylation of cullins. It constitutes the
CC catalytic center of the complex (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: The CSN complex is associated with some 'Lys-63'-
CC specific deubiquitination. Such activity is however not mediated by the
CC core CSN complex but by the BRCC3/BRCC36 component of the BRISC
CC complex.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. CSN5 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL82571.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U65928; AAB16847.1; -; mRNA.
DR EMBL; U70734; AAD03468.1; -; mRNA.
DR EMBL; CR541678; CAG46479.1; -; mRNA.
DR EMBL; BC001187; AAH01187.1; -; mRNA.
DR EMBL; BC001859; AAH01859.1; -; mRNA.
DR EMBL; BC007272; AAH07272.1; -; mRNA.
DR EMBL; BX648542; CAH10375.1; -; mRNA.
DR EMBL; AY078082; AAL82571.1; ALT_INIT; mRNA.
DR CCDS; CCDS6198.1; -.
DR PIR; S71820; S71820.
DR RefSeq; NP_006828.2; NM_006837.2.
DR PDB; 4D10; X-ray; 3.80 A; E/M=1-334.
DR PDB; 4D18; X-ray; 4.08 A; E/M=12-334.
DR PDB; 4F7O; X-ray; 2.60 A; A/B=1-257.
DR PDB; 4WSN; X-ray; 5.50 A; E/M/U/c/k/s=14-334.
DR PDB; 5JOG; X-ray; 2.46 A; A=2-257.
DR PDB; 5JOH; X-ray; 1.99 A; A=2-257.
DR PDB; 5M5Q; X-ray; 2.20 A; A=2-257.
DR PDB; 6R6H; EM; 8.40 A; E=1-334.
DR PDB; 6R7F; EM; 8.20 A; E=24-334.
DR PDB; 6R7H; EM; 8.80 A; E=24-334.
DR PDB; 6R7I; EM; 5.90 A; E=1-334.
DR PDBsum; 4D10; -.
DR PDBsum; 4D18; -.
DR PDBsum; 4F7O; -.
DR PDBsum; 4WSN; -.
DR PDBsum; 5JOG; -.
DR PDBsum; 5JOH; -.
DR PDBsum; 5M5Q; -.
DR PDBsum; 6R6H; -.
DR PDBsum; 6R7F; -.
DR PDBsum; 6R7H; -.
DR PDBsum; 6R7I; -.
DR AlphaFoldDB; Q92905; -.
DR SMR; Q92905; -.
DR BioGRID; 116183; 1031.
DR ComplexPortal; CPX-1870; COP9 signalosome variant 1.
DR ComplexPortal; CPX-1871; COP9 signalosome variant 2.
DR CORUM; Q92905; -.
DR DIP; DIP-34546N; -.
DR IntAct; Q92905; 709.
DR MINT; Q92905; -.
DR STRING; 9606.ENSP00000350512; -.
DR BindingDB; Q92905; -.
DR ChEMBL; CHEMBL4105809; -.
DR MEROPS; M67.002; -.
DR GlyGen; Q92905; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92905; -.
DR MetOSite; Q92905; -.
DR PhosphoSitePlus; Q92905; -.
DR SwissPalm; Q92905; -.
DR BioMuta; COPS5; -.
DR DMDM; 55976562; -.
DR REPRODUCTION-2DPAGE; IPI00009958; -.
DR EPD; Q92905; -.
DR jPOST; Q92905; -.
DR MassIVE; Q92905; -.
DR MaxQB; Q92905; -.
DR PaxDb; Q92905; -.
DR PeptideAtlas; Q92905; -.
DR PRIDE; Q92905; -.
DR ProteomicsDB; 75591; -.
DR Antibodypedia; 1439; 540 antibodies from 43 providers.
DR DNASU; 10987; -.
DR Ensembl; ENST00000357849.9; ENSP00000350512.4; ENSG00000121022.14.
DR GeneID; 10987; -.
DR KEGG; hsa:10987; -.
DR MANE-Select; ENST00000357849.9; ENSP00000350512.4; NM_006837.3; NP_006828.2.
DR UCSC; uc003xxe.4; human.
DR CTD; 10987; -.
DR DisGeNET; 10987; -.
DR GeneCards; COPS5; -.
DR HGNC; HGNC:2240; COPS5.
DR HPA; ENSG00000121022; Low tissue specificity.
DR MIM; 604850; gene.
DR neXtProt; NX_Q92905; -.
DR OpenTargets; ENSG00000121022; -.
DR PharmGKB; PA26757; -.
DR VEuPathDB; HostDB:ENSG00000121022; -.
DR eggNOG; KOG1554; Eukaryota.
DR GeneTree; ENSGT00550000074850; -.
DR HOGENOM; CLU_053034_0_1_1; -.
DR InParanoid; Q92905; -.
DR OMA; ALWNKYW; -.
DR OrthoDB; 1031881at2759; -.
DR PhylomeDB; Q92905; -.
DR TreeFam; TF105601; -.
DR PathwayCommons; Q92905; -.
DR Reactome; R-HSA-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q92905; -.
DR SIGNOR; Q92905; -.
DR BioGRID-ORCS; 10987; 763 hits in 1068 CRISPR screens.
DR ChiTaRS; COPS5; human.
DR GenomeRNAi; 10987; -.
DR Pharos; Q92905; Tchem.
DR PRO; PR:Q92905; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q92905; protein.
DR Bgee; ENSG00000121022; Expressed in sperm and 208 other tissues.
DR ExpressionAtlas; Q92905; baseline and differential.
DR Genevisible; Q92905; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005852; C:eukaryotic translation initiation factor 3 complex; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR GO; GO:0019784; F:deNEDDylase activity; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0035718; F:macrophage migration inhibitory factor binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140492; F:metal-dependent deubiquitinase activity; IDA:FlyBase.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0003743; F:translation initiation factor activity; TAS:ProtInc.
DR GO; GO:1990182; P:exosomal secretion; IDA:FlyBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0000338; P:protein deneddylation; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase.
DR GO; GO:0045116; P:protein neddylation; IC:ComplexPortal.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:1903894; P:regulation of IRE1-mediated unfolded protein response; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:2000434; P:regulation of protein neddylation; IC:ComplexPortal.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR DisProt; DP02290; -.
DR InterPro; IPR037740; CSN5.
DR InterPro; IPR040961; CSN5_C.
DR InterPro; IPR000555; JAMM/MPN+_dom.
DR InterPro; IPR037518; MPN.
DR PANTHER; PTHR10410:SF6; PTHR10410:SF6; 1.
DR Pfam; PF18323; CSN5_C; 1.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
DR PROSITE; PS50249; MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Nucleus; Protease; Reference proteome; Signalosome; Synapse; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:18850735, ECO:0000269|Ref.6"
FT CHAIN 2..334
FT /note="COP9 signalosome complex subunit 5"
FT /id="PRO_0000194835"
FT DOMAIN 55..192
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOTIF 138..151
FT /note="JAMM motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:18850735, ECO:0000269|Ref.6"
FT MUTAGEN 138
FT /note="H->Q: Abolishes ability to deneddylate cullins,
FT without affecting the 'Lys-63'-specific deubiquitination
FT associated with the COP9 signalosome complex."
FT /evidence="ECO:0000269|PubMed:19214193"
FT CONFLICT 43..45
FT /note="KPW -> NLG (in Ref. 2; AAD03468)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="R -> H (in Ref. 1; AAB16847)"
FT /evidence="ECO:0000305"
FT HELIX 6..42
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 59..71
FT /evidence="ECO:0007829|PDB:5JOH"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 89..97
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 104..107
FT /evidence="ECO:0007829|PDB:4F7O"
FT HELIX 111..126
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:5JOH"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:5JOH"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 211..217
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5JOH"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5JOH"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:5JOH"
SQ SEQUENCE 334 AA; 37579 MW; B5742F4AAD03A1CF CRC64;
MAASGSGMAQ KTWELANNMQ EAQSIDEIYK YDKKQQQEIL AAKPWTKDHH YFKYCKISAL
ALLKMVMHAR SGGNLEVMGL MLGKVDGETM IIMDSFALPV EGTETRVNAQ AAAYEYMAAY
IENAKQVGRL ENAIGWYHSH PGYGCWLSGI DVSTQMLNQQ FQEPFVAVVI DPTRTISAGK
VNLGAFRTYP KGYKPPDEGP SEYQTIPLNK IEDFGVHCKQ YYALEVSYFK SSLDRKLLEL
LWNKYWVNTL SSSSLLTNAD YTTGQVFDLS EKLEQSEAQL GRGSFMLGLE THDRKSEDKL
AKATRDSCKT TIEAIHGLMS QVIKDKLFNQ INIS
