Full text data of COPS5
COPS5
(CSN5, JAB1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
COP9 signalosome complex subunit 5; SGN5; Signalosome subunit 5; 3.4.-.- (Jun activation domain-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
COP9 signalosome complex subunit 5; SGN5; Signalosome subunit 5; 3.4.-.- (Jun activation domain-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q92905
ID CSN5_HUMAN Reviewed; 334 AA.
AC Q92905; O15386; Q6AW95; Q86WQ4; Q9BQ17;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 126.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT of AP-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
RT subunits. 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.,
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 [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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND 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
RT ARH-77.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
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 BCL3.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S.,
RA Wulczyn F.G., Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel
RT and 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.,
RA 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.,
RA Grell M., Finkelmeier D., Brunner H., Bernhagen J.;
RT "Intracellular action of the cytokine MIF to modulate AP-1 activity
RT and the 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.,
RA Rogge L., Pardi R.;
RT "Integrin LFA-1 interacts with the transcriptional co-activator JAB1
RT to 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.,
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 [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.,
RA Yang X., 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.,
RA Engles J., 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.,
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 [19]
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 [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
RT cell migration and is negatively regulated by the Met adaptor Ran-
RT binding 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
RT transforming growth factor beta signaling by binding to Smad7 and
RT promoting its degradation.";
RL Mol. Cell. Biol. 24:2251-2262(2004).
RN [23]
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
RT interferon-related pathways through enhancing p21 and p27 proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006).
RN [24]
RP IDENTIFICATION IN THE CSN COMPLEX, CLEAVAGE OF INITIATOR METHIONINE,
RP AND 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 [25]
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 [26]
RP FUNCTION, IDENTIFICATION IN THE SIGNALOSOME COMPLEX, INTERACTION WITH
RP THE 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-
RT associated Brcc36 and proteasomal Poh1.";
RL EMBO J. 28:621-631(2009).
RN [27]
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 [28]
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).
CC -!- FUNCTION: Probable protease subunit of the COP9 signalosome
CC complex (CSN), a complex involved in various cellular and
CC developmental processes. The CSN complex is an essential regulator
CC of the ubiquitin (Ubl) conjugation pathway by mediating the
CC deneddylation of the cullin subunits of the SCF-type E3 ligase
CC complexes, leading to decrease the Ubl ligase activity of SCF-type
CC complexes such as SCF, CSA or DDB2. The complex is also involved
CC in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA,
CC ITPK1 and IRF8, possibly via its association with CK2 and PKD
CC kinases. CSN-dependent phosphorylation of TP53 and JUN promotes
CC and protects degradation by the Ubl system, respectively. In the
CC complex, it probably acts as the catalytic center that mediates
CC the cleavage of Nedd8 from cullins. It however has no
CC metalloprotease activity by itself and requires the other subunits
CC of the CSN complex. Interacts directly with a large number of
CC proteins that are regulated by the CSN complex, confirming a key
CC role in the complex. Promotes the proteasomal degradation of
CC BRSK2.
CC -!- COFACTOR: Divalent metal ions (By similarity).
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 COPS1,
CC COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B). The CSN complex
CC interacts with the BRISC complex. Also exists as monomeric form.
CC Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3,
CC GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of
CC a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts
CC with IFIT3. Interacts with BRSK2.
CC -!- INTERACTION:
CC O95273:CCNDBP1; NbExp=5; IntAct=EBI-594661, EBI-748961;
CC P46527:CDKN1B; NbExp=3; IntAct=EBI-594661, EBI-519280;
CC P55085:F2RL1; NbExp=8; IntAct=EBI-594661, EBI-4303189;
CC Q9H8M7:FAM188A; NbExp=3; IntAct=EBI-594661, EBI-724928;
CC Q13098:GPS1; NbExp=3; IntAct=EBI-594661, EBI-725197;
CC P35372:OPRM1; NbExp=5; IntAct=EBI-594661, EBI-2624570;
CC Q5VTR2:RNF20; NbExp=2; IntAct=EBI-594661, EBI-2372238;
CC O15105:SMAD7; NbExp=10; IntAct=EBI-594661, EBI-3861591;
CC P10599:TXN; NbExp=8; IntAct=EBI-594661, EBI-594644;
CC P09936:UCHL1; NbExp=3; IntAct=EBI-594661, EBI-714860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, perinuclear
CC region. Note=Nuclear localization is diminished in the presence of
CC IFIT3.
CC -!- DOMAIN: The JAMM motif is essential for the protease activity of
CC the CSN complex resulting in deneddylation of cullins. It
CC constitutes the catalytic center of the complex (By similarity).
CC -!- MISCELLANEOUS: The CSN complex is associated with some 'Lys-63'-
CC specific deubiquitination. Such activity is however not mediated
CC by the core CSN complex but by the BRCC3/BRCC36 component of the
CC BRISC complex.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. CSN5 subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL82571.1; Type=Erroneous initiation;
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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 PIR; S71820; S71820.
DR RefSeq; NP_006828.2; NM_006837.2.
DR RefSeq; XP_005251195.1; XM_005251138.1.
DR UniGene; Hs.491912; -.
DR PDB; 4F7O; X-ray; 2.60 A; A/B=1-257.
DR PDBsum; 4F7O; -.
DR ProteinModelPortal; Q92905; -.
DR SMR; Q92905; 2-257.
DR DIP; DIP-34546N; -.
DR IntAct; Q92905; 124.
DR MINT; MINT-1188008; -.
DR STRING; 9606.ENSP00000350512; -.
DR MEROPS; M67.002; -.
DR PhosphoSite; Q92905; -.
DR DMDM; 55976562; -.
DR REPRODUCTION-2DPAGE; IPI00009958; -.
DR PaxDb; Q92905; -.
DR PRIDE; Q92905; -.
DR DNASU; 10987; -.
DR Ensembl; ENST00000357849; ENSP00000350512; ENSG00000121022.
DR GeneID; 10987; -.
DR KEGG; hsa:10987; -.
DR UCSC; uc003xxd.3; human.
DR CTD; 10987; -.
DR GeneCards; GC08M068005; -.
DR HGNC; HGNC:2240; COPS5.
DR HPA; CAB004242; -.
DR HPA; HPA004845; -.
DR MIM; 604850; gene.
DR neXtProt; NX_Q92905; -.
DR PharmGKB; PA26757; -.
DR eggNOG; COG1310; -.
DR HOGENOM; HOG000116528; -.
DR HOVERGEN; HBG051137; -.
DR InParanoid; Q92905; -.
DR KO; K09613; -.
DR OMA; MQEVQSI; -.
DR OrthoDB; EOG72NRQC; -.
DR ChiTaRS; COPS5; human.
DR GenomeRNAi; 10987; -.
DR NextBio; 41743; -.
DR PRO; PR:Q92905; -.
DR ArrayExpress; Q92905; -.
DR Bgee; Q92905; -.
DR CleanEx; HS_COPS5; -.
DR Genevestigator; Q92905; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005852; C:eukaryotic translation initiation factor 3 complex; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR InterPro; IPR000555; JAB_MPN_dom.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Nucleus; Protease; Reference proteome; Signalosome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 COP9 signalosome complex subunit 5.
FT /FTId=PRO_0000194835.
FT DOMAIN 53 164 MPN.
FT MOTIF 138 151 JAMM motif.
FT METAL 138 138 Zinc; catalytic (Probable).
FT METAL 140 140 Zinc; catalytic (By similarity).
FT METAL 151 151 Zinc; catalytic (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MUTAGEN 138 138 H->Q: Abolishes ability to deneddylate
FT cullins, without affecting the 'Lys-63'-
FT specific deubiquitination associated with
FT the COP9 signalosome complex.
FT CONFLICT 43 45 KPW -> NLG (in Ref. 2; AAD03468).
FT CONFLICT 129 129 R -> H (in Ref. 1; AAB16847).
FT HELIX 6 16
FT HELIX 33 42
FT TURN 45 47
FT STRAND 54 58
FT HELIX 59 71
FT TURN 72 74
FT STRAND 78 86
FT STRAND 89 97
FT HELIX 104 107
FT HELIX 112 124
FT STRAND 125 127
FT STRAND 133 139
FT TURN 141 143
FT HELIX 149 161
FT STRAND 167 170
FT STRAND 183 188
FT STRAND 221 223
FT STRAND 225 231
FT HELIX 235 250
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
//
ID CSN5_HUMAN Reviewed; 334 AA.
AC Q92905; O15386; Q6AW95; Q86WQ4; Q9BQ17;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 126.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT of AP-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
RT subunits. 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.,
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 [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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND 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
RT ARH-77.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
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 BCL3.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S.,
RA Wulczyn F.G., Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel
RT and 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.,
RA 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.,
RA Grell M., Finkelmeier D., Brunner H., Bernhagen J.;
RT "Intracellular action of the cytokine MIF to modulate AP-1 activity
RT and the 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.,
RA Rogge L., Pardi R.;
RT "Integrin LFA-1 interacts with the transcriptional co-activator JAB1
RT to 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.,
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 [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.,
RA Yang X., 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.,
RA Engles J., 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.,
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 [19]
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 [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
RT cell migration and is negatively regulated by the Met adaptor Ran-
RT binding 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
RT transforming growth factor beta signaling by binding to Smad7 and
RT promoting its degradation.";
RL Mol. Cell. Biol. 24:2251-2262(2004).
RN [23]
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
RT interferon-related pathways through enhancing p21 and p27 proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006).
RN [24]
RP IDENTIFICATION IN THE CSN COMPLEX, CLEAVAGE OF INITIATOR METHIONINE,
RP AND 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 [25]
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 [26]
RP FUNCTION, IDENTIFICATION IN THE SIGNALOSOME COMPLEX, INTERACTION WITH
RP THE 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-
RT associated Brcc36 and proteasomal Poh1.";
RL EMBO J. 28:621-631(2009).
RN [27]
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 [28]
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).
CC -!- FUNCTION: Probable protease subunit of the COP9 signalosome
CC complex (CSN), a complex involved in various cellular and
CC developmental processes. The CSN complex is an essential regulator
CC of the ubiquitin (Ubl) conjugation pathway by mediating the
CC deneddylation of the cullin subunits of the SCF-type E3 ligase
CC complexes, leading to decrease the Ubl ligase activity of SCF-type
CC complexes such as SCF, CSA or DDB2. The complex is also involved
CC in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA,
CC ITPK1 and IRF8, possibly via its association with CK2 and PKD
CC kinases. CSN-dependent phosphorylation of TP53 and JUN promotes
CC and protects degradation by the Ubl system, respectively. In the
CC complex, it probably acts as the catalytic center that mediates
CC the cleavage of Nedd8 from cullins. It however has no
CC metalloprotease activity by itself and requires the other subunits
CC of the CSN complex. Interacts directly with a large number of
CC proteins that are regulated by the CSN complex, confirming a key
CC role in the complex. Promotes the proteasomal degradation of
CC BRSK2.
CC -!- COFACTOR: Divalent metal ions (By similarity).
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 COPS1,
CC COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B). The CSN complex
CC interacts with the BRISC complex. Also exists as monomeric form.
CC Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3,
CC GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of
CC a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts
CC with IFIT3. Interacts with BRSK2.
CC -!- INTERACTION:
CC O95273:CCNDBP1; NbExp=5; IntAct=EBI-594661, EBI-748961;
CC P46527:CDKN1B; NbExp=3; IntAct=EBI-594661, EBI-519280;
CC P55085:F2RL1; NbExp=8; IntAct=EBI-594661, EBI-4303189;
CC Q9H8M7:FAM188A; NbExp=3; IntAct=EBI-594661, EBI-724928;
CC Q13098:GPS1; NbExp=3; IntAct=EBI-594661, EBI-725197;
CC P35372:OPRM1; NbExp=5; IntAct=EBI-594661, EBI-2624570;
CC Q5VTR2:RNF20; NbExp=2; IntAct=EBI-594661, EBI-2372238;
CC O15105:SMAD7; NbExp=10; IntAct=EBI-594661, EBI-3861591;
CC P10599:TXN; NbExp=8; IntAct=EBI-594661, EBI-594644;
CC P09936:UCHL1; NbExp=3; IntAct=EBI-594661, EBI-714860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, perinuclear
CC region. Note=Nuclear localization is diminished in the presence of
CC IFIT3.
CC -!- DOMAIN: The JAMM motif is essential for the protease activity of
CC the CSN complex resulting in deneddylation of cullins. It
CC constitutes the catalytic center of the complex (By similarity).
CC -!- MISCELLANEOUS: The CSN complex is associated with some 'Lys-63'-
CC specific deubiquitination. Such activity is however not mediated
CC by the core CSN complex but by the BRCC3/BRCC36 component of the
CC BRISC complex.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. CSN5 subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL82571.1; Type=Erroneous initiation;
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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 PIR; S71820; S71820.
DR RefSeq; NP_006828.2; NM_006837.2.
DR RefSeq; XP_005251195.1; XM_005251138.1.
DR UniGene; Hs.491912; -.
DR PDB; 4F7O; X-ray; 2.60 A; A/B=1-257.
DR PDBsum; 4F7O; -.
DR ProteinModelPortal; Q92905; -.
DR SMR; Q92905; 2-257.
DR DIP; DIP-34546N; -.
DR IntAct; Q92905; 124.
DR MINT; MINT-1188008; -.
DR STRING; 9606.ENSP00000350512; -.
DR MEROPS; M67.002; -.
DR PhosphoSite; Q92905; -.
DR DMDM; 55976562; -.
DR REPRODUCTION-2DPAGE; IPI00009958; -.
DR PaxDb; Q92905; -.
DR PRIDE; Q92905; -.
DR DNASU; 10987; -.
DR Ensembl; ENST00000357849; ENSP00000350512; ENSG00000121022.
DR GeneID; 10987; -.
DR KEGG; hsa:10987; -.
DR UCSC; uc003xxd.3; human.
DR CTD; 10987; -.
DR GeneCards; GC08M068005; -.
DR HGNC; HGNC:2240; COPS5.
DR HPA; CAB004242; -.
DR HPA; HPA004845; -.
DR MIM; 604850; gene.
DR neXtProt; NX_Q92905; -.
DR PharmGKB; PA26757; -.
DR eggNOG; COG1310; -.
DR HOGENOM; HOG000116528; -.
DR HOVERGEN; HBG051137; -.
DR InParanoid; Q92905; -.
DR KO; K09613; -.
DR OMA; MQEVQSI; -.
DR OrthoDB; EOG72NRQC; -.
DR ChiTaRS; COPS5; human.
DR GenomeRNAi; 10987; -.
DR NextBio; 41743; -.
DR PRO; PR:Q92905; -.
DR ArrayExpress; Q92905; -.
DR Bgee; Q92905; -.
DR CleanEx; HS_COPS5; -.
DR Genevestigator; Q92905; -.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005852; C:eukaryotic translation initiation factor 3 complex; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0010388; P:cullin deneddylation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR InterPro; IPR000555; JAB_MPN_dom.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Nucleus; Protease; Reference proteome; Signalosome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 COP9 signalosome complex subunit 5.
FT /FTId=PRO_0000194835.
FT DOMAIN 53 164 MPN.
FT MOTIF 138 151 JAMM motif.
FT METAL 138 138 Zinc; catalytic (Probable).
FT METAL 140 140 Zinc; catalytic (By similarity).
FT METAL 151 151 Zinc; catalytic (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MUTAGEN 138 138 H->Q: Abolishes ability to deneddylate
FT cullins, without affecting the 'Lys-63'-
FT specific deubiquitination associated with
FT the COP9 signalosome complex.
FT CONFLICT 43 45 KPW -> NLG (in Ref. 2; AAD03468).
FT CONFLICT 129 129 R -> H (in Ref. 1; AAB16847).
FT HELIX 6 16
FT HELIX 33 42
FT TURN 45 47
FT STRAND 54 58
FT HELIX 59 71
FT TURN 72 74
FT STRAND 78 86
FT STRAND 89 97
FT HELIX 104 107
FT HELIX 112 124
FT STRAND 125 127
FT STRAND 133 139
FT TURN 141 143
FT HELIX 149 161
FT STRAND 167 170
FT STRAND 183 188
FT STRAND 221 223
FT STRAND 225 231
FT HELIX 235 250
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
//
MIM
604850
*RECORD*
*FIELD* NO
604850
*FIELD* TI
*604850 COP9, SUBUNIT 5; COPS5
;;JUN ACTIVATION DOMAIN-BINDING PROTEIN; JAB1;;
SGN5;;
read moreMOV34 FAMILY, 38-KD MEMBER
*FIELD* TX
CLONING
Using the more variable activation domain of JUN (165160) as bait in a
yeast 2-hybrid system, Claret et al. (1996) identified a protein, which
they called JAB1 for 'Jun activation domain-binding protein,' that
interacts with JUN and JUND (165162) but not with JUNB (165161) or
v-jun. As a result, JAB1 selectively potentiates transactivation by only
JUN or JUND. The JAB1 gene encodes a protein of 334 amino acids with a
relative molecular mass of 37.5 kD. The N-terminal region of JAB1 shows
57% identity to the products of the open reading frame F37A4.5 of C.
elegans and the S. pombe pad1+ gene, which was identified genetically as
a coactivator of a subset of AP1 target genes. The JAB1 and pad1+
proteins are functionally interchangeable. They define a new group of
coactivators that increase the specificity of target gene activation by
AP1 proteins. In vitro, JAB1 specifically stabilizes complexes of JUN or
JUND with AP1 sites and does not affect binding of either JUNB or v-jun.
Amino acids 31 to 57 of JUN, which are absent in v-jun, contain the
JAB1-interaction surface. JAB1 interacts with JUN and stimulates its
activity in mammalian cells. The 1.5-kb JAB1 transcript is widely
expressed. Immunofluorescence analysis indicated that JAB1 is a nuclear
protein. Although JAB1 does not form a heterodimer with JUN or JUND, its
effect on their DNA binding and transactivation abilities is analogous
to the effect of the Extradenticle coactivator on homeodomain proteins
of the Bithorax complex in Drosophila.
GENE FAMILY
Asano et al. (1997) identified JAB1 as a member of the MOV34 (PSMD7;
157970) family. They referred to JAB1 as the 38-kD MOV34 homolog.
GENE FUNCTION
Bianchi et al. (2000) found that JAB1 interacts with the cytoplasmic
domain of the beta-2 subunit of the alpha-L/beta-2 integrin LFA1
(155370/600065). Bianchi et al. (2000) found that JAB1 is present both
in the nucleus and in the cytoplasm of cells and that a fraction of JAB1
colocalizes with LFA1 at the cell membrane. LFA1 engagement is followed
by an increase of the nuclear pool of JAB1, paralleled by enhanced
binding of c-Jun-containing AP1 complexes to their DNA consensus site
and increased transactivation of an AP1-dependent promoter. Bianchi et
al. (2000) suggested that signaling through the LFA1 integrin may affect
JUN-driven transcription by regulating JAB1 nuclear localization. This
represented a new pathway for integrin-dependent modulation of gene
expression.
Using full-length macrophage migration inhibitory factor (MIF; 153620)
as bait in a yeast 2-hybrid screen of a brain cDNA library, Kleemann et
al. (2000) captured JAB1 as an interacting partner of MIF. By
coimmunoprecipitation and pull-down experiments, Kleemann et al. (2000)
confirmed the specific MIF-JAB1 association. Confocal microscopic
analysis demonstrated that the MIF-JAB1 complex is localized in the
cytosol near the peripheral plasma membrane, suggesting a potential
connection between MIF and the integrin signaling pathways. Luciferase
reporter and gel shift analyses showed that endogenous and exogenous MIF
inhibited JAB1-induced AP1 transcriptional activity but did not
interfere with nuclear factor kappa-B (NFKB; 164011) activity. Likewise,
recombinant MIF inhibited JAB1-stimulated and tumor necrosis factor
(TNF; 191160)-induced JNK (601158) activity. MIF also induced p27
(CDKN1B; 600778) expression and mirrored CDKN1B-mediated growth arrest
through inhibition of JAB1-dependent degradation of CDKN1B. Mutational
analysis indicated that a 16-residue MIF peptide spanning amino acids 50
through 65, including cys60, strongly competed with wildtype MIF for
JAB1 binding. Kleemann et al. (2000) suggested that signaling through
MIF-JAB1 is independent of a potential MIF receptor and noted that JAB1
is the only protein demonstrated to interact with MIF.
Gemmill et al. (2002) isolated the Drosophila homolog of TRC8 (603046)
and studied its function by genetic manipulations and a yeast 2-hybrid
screen. Human and Drosophila TRC8 proteins localize to the endoplasmic
reticulum. Loss of either Drosophila Trc8 or Vhl (608537) resulted in an
identical ventral midline defect. Direct interaction between Trc8 and
Vhl in drosophila was confirmed by GST-pull-down and
coimmunoprecipitation experiments. Gemmill et al. (2002) found that in
Drosophila, overexpression of Trc8 inhibited growth consistent with its
presumed role as a tumor suppressor gene. Human JAB1 localization was
dependent on VHL mutant status. Thus, the VHL, TRC8, and JAB1 proteins
appear to be linked both physically and functionally, and all 3 may
participate in the development of kidney cancer.
COP9 signalosome cleaves the ubiquitin-like protein NEDD8 (603171) from
the CUL1 (603134) subunit of SCF ubiquitin ligases. Cope et al. (2002)
found that the JAB1/MPN domain metalloenzyme (JAMM) motif in the
JAB1/COPS5 subunit underlies the COP9 signalosome's NEDD8 isopeptidase
activity. The JAMM motif consists of a his-X-his-X(10)-asp motif (where
X indicates any residue) accompanied by an upstream glutamate. The JAMM
motif is found in proteins from archaea, bacteria, and eukaryotes,
including the RPN11 subunit of the 26S proteasome. Metal chelators and
point mutations within the JAMM motif abolished COP9
signalosome-dependent cleavage of NEDD8 from CUL1, yet had little effect
on COP9 signalosome complex assembly. Cope et al. (2002) proposed that
JAMM isopeptidases play important roles in a variety of physiologic
pathways.
The marked box domain and adjacent region of the E2F1 gene (189971) are
critical for the specificity of E2F1 apoptosis induction. Using the
marked box domain of E2F1 in a yeast 2-hybrid screen of a human thymus
cDNA library, Hallstrom and Nevins (2006) identified JAB1 as an E2F1
binding partner. JAB1 and E2F1 coexpression in rat embryonic fibroblasts
synergistically induced apoptosis, coincident with the induction of p53
(191170) protein accumulation. In contrast, JAB1 did not synergize with
E2F1 to promote cell cycle entry. Cells depleted of JAB1 were deficient
for both E2F1-induced apoptosis and induction of p53 accumulation.
Hallstrom and Nevins (2006) concluded that JAB1 is an essential cofactor
for the apoptotic function of E2F1.
MAPPING
Hartz (2004) mapped the COPS5 gene to chromosome 8q13.2 based on an
alignment of the COPS5 sequence (GenBank GENBANK U65928) with the
genomic sequence.
ANIMAL MODEL
Tomoda et al. (2004) found that Jab1 null mouse embryos died soon after
implantation. Mutant embryonic cells, which lacked other Cop9
signalosome components, expressed higher levels of p27, p53 (191170),
and cyclin E (123837), resulting in impaired proliferation and
accelerated apoptosis. Jab1 heterozygous mice were healthy and fertile
but smaller than their wildtype littermates. Heterozygous mouse
embryonic fibroblasts proliferated poorly, showed an inefficient
downregulation of p27 during G1, and were delayed in the progression
from G0 to S phase compared with wildtype cells. The levels of cyclin E
and deneddylated Cul1 were unchanged and p53 was not induced in
heterozygous mutant cells. Tomoda et al. (2004) concluded that JAB1
controls cell cycle progression and cell survival by regulating multiple
signaling pathways.
*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 RNA
binding and macromolecular assembly. J. Biol. Chem. 272: 27042-27052,
1997.
2. Bianchi, E.; Denti, S.; Granata, A.; Bossi, G.; Geginat, J.; Villa,
A.; Rogge, L.; Pardi, R.: Integrin LFA-1 interacts with the transcriptional
co-activator JAB1 to modulate AP-1 activity. Nature 404: 617-621,
2000.
3. Claret, F.-X.; Hibi, M.; Dhut, S.; Toda, T.; Karin, M.: A new
group of conserved coactivators that increase the specificity of AP-1
transcription factors. Nature 383: 453-457, 1996.
4. Cope, G. A.; Suh, G. S. B.; Aravind, L.; Schwarz, S. E.; Zipursky,
S. L.; Koonin, E. V.; Deshaies, R. J.: Role of predicted metalloprotease
motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 298:
608-611, 2002.
5. Gemmill, R. M.; Bemis, L. T.; Lee, J. P.; Sozen, M. A.; Baron,
A.; Zeng, C.; Erickson, P. F.; Hooper, J. E.; Drabkin, H. A.: The
TRC8 hereditary kidney cancer gene suppresses growth and functions
with VHL in a common pathway. Oncogene 21: 3507-3516, 2002.
6. Hallstrom, T. C.; Nevins, J. R.: Jab1 is a specificity factor
for E2F1-induced apoptosis. Genes Dev. 20: 613-623, 2006.
7. Hartz, P. A.: Personal Communication. Baltimore, Md 12/29/2004.
8. Kleemann, R.; Hausser, A.; Geiger, G.; Mischke, R.; Burger-Kentischer,
A.; Flieger, O.; Johannes, F.-J.; Roger, T.; Calandra, T.; Kapurniotu,
A.; Grell, M.; Finkelmeier, D.; Brunner, H.; Bernhagen, J.: Intracellular
action of the cytokine MIF to modulate AP-1 activity and the cell
cycle through Jab1. Nature 408: 211-216, 2000.
9. Tomoda, K.; Yoneda-Kato, N.; Fukumoto, A.; Yamanaka, S.; Kato,
J.: Multiple functions of Jab1 are required for early embryonic development
and growth potential in mice. J. Biol. Chem. 279: 43013-43018, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 3/28/2006
Patricia A. Hartz - updated: 1/6/2005
Ada Hamosh - updated: 11/19/2002
Victor A. McKusick - updated: 9/9/2002
Paul J. Converse - updated: 11/7/2000
Ada Hamosh - updated: 5/2/2000
*FIELD* CD
Ada Hamosh: 4/18/2000
*FIELD* ED
mgross: 07/18/2012
carol: 5/16/2007
wwang: 4/3/2006
terry: 3/28/2006
terry: 2/3/2006
mgross: 1/10/2005
terry: 1/6/2005
ckniffin: 3/23/2004
alopez: 11/19/2002
terry: 11/18/2002
tkritzer: 9/9/2002
mgross: 11/7/2000
alopez: 6/19/2000
carol: 5/2/2000
alopez: 4/19/2000
alopez: 4/18/2000
*RECORD*
*FIELD* NO
604850
*FIELD* TI
*604850 COP9, SUBUNIT 5; COPS5
;;JUN ACTIVATION DOMAIN-BINDING PROTEIN; JAB1;;
SGN5;;
read moreMOV34 FAMILY, 38-KD MEMBER
*FIELD* TX
CLONING
Using the more variable activation domain of JUN (165160) as bait in a
yeast 2-hybrid system, Claret et al. (1996) identified a protein, which
they called JAB1 for 'Jun activation domain-binding protein,' that
interacts with JUN and JUND (165162) but not with JUNB (165161) or
v-jun. As a result, JAB1 selectively potentiates transactivation by only
JUN or JUND. The JAB1 gene encodes a protein of 334 amino acids with a
relative molecular mass of 37.5 kD. The N-terminal region of JAB1 shows
57% identity to the products of the open reading frame F37A4.5 of C.
elegans and the S. pombe pad1+ gene, which was identified genetically as
a coactivator of a subset of AP1 target genes. The JAB1 and pad1+
proteins are functionally interchangeable. They define a new group of
coactivators that increase the specificity of target gene activation by
AP1 proteins. In vitro, JAB1 specifically stabilizes complexes of JUN or
JUND with AP1 sites and does not affect binding of either JUNB or v-jun.
Amino acids 31 to 57 of JUN, which are absent in v-jun, contain the
JAB1-interaction surface. JAB1 interacts with JUN and stimulates its
activity in mammalian cells. The 1.5-kb JAB1 transcript is widely
expressed. Immunofluorescence analysis indicated that JAB1 is a nuclear
protein. Although JAB1 does not form a heterodimer with JUN or JUND, its
effect on their DNA binding and transactivation abilities is analogous
to the effect of the Extradenticle coactivator on homeodomain proteins
of the Bithorax complex in Drosophila.
GENE FAMILY
Asano et al. (1997) identified JAB1 as a member of the MOV34 (PSMD7;
157970) family. They referred to JAB1 as the 38-kD MOV34 homolog.
GENE FUNCTION
Bianchi et al. (2000) found that JAB1 interacts with the cytoplasmic
domain of the beta-2 subunit of the alpha-L/beta-2 integrin LFA1
(155370/600065). Bianchi et al. (2000) found that JAB1 is present both
in the nucleus and in the cytoplasm of cells and that a fraction of JAB1
colocalizes with LFA1 at the cell membrane. LFA1 engagement is followed
by an increase of the nuclear pool of JAB1, paralleled by enhanced
binding of c-Jun-containing AP1 complexes to their DNA consensus site
and increased transactivation of an AP1-dependent promoter. Bianchi et
al. (2000) suggested that signaling through the LFA1 integrin may affect
JUN-driven transcription by regulating JAB1 nuclear localization. This
represented a new pathway for integrin-dependent modulation of gene
expression.
Using full-length macrophage migration inhibitory factor (MIF; 153620)
as bait in a yeast 2-hybrid screen of a brain cDNA library, Kleemann et
al. (2000) captured JAB1 as an interacting partner of MIF. By
coimmunoprecipitation and pull-down experiments, Kleemann et al. (2000)
confirmed the specific MIF-JAB1 association. Confocal microscopic
analysis demonstrated that the MIF-JAB1 complex is localized in the
cytosol near the peripheral plasma membrane, suggesting a potential
connection between MIF and the integrin signaling pathways. Luciferase
reporter and gel shift analyses showed that endogenous and exogenous MIF
inhibited JAB1-induced AP1 transcriptional activity but did not
interfere with nuclear factor kappa-B (NFKB; 164011) activity. Likewise,
recombinant MIF inhibited JAB1-stimulated and tumor necrosis factor
(TNF; 191160)-induced JNK (601158) activity. MIF also induced p27
(CDKN1B; 600778) expression and mirrored CDKN1B-mediated growth arrest
through inhibition of JAB1-dependent degradation of CDKN1B. Mutational
analysis indicated that a 16-residue MIF peptide spanning amino acids 50
through 65, including cys60, strongly competed with wildtype MIF for
JAB1 binding. Kleemann et al. (2000) suggested that signaling through
MIF-JAB1 is independent of a potential MIF receptor and noted that JAB1
is the only protein demonstrated to interact with MIF.
Gemmill et al. (2002) isolated the Drosophila homolog of TRC8 (603046)
and studied its function by genetic manipulations and a yeast 2-hybrid
screen. Human and Drosophila TRC8 proteins localize to the endoplasmic
reticulum. Loss of either Drosophila Trc8 or Vhl (608537) resulted in an
identical ventral midline defect. Direct interaction between Trc8 and
Vhl in drosophila was confirmed by GST-pull-down and
coimmunoprecipitation experiments. Gemmill et al. (2002) found that in
Drosophila, overexpression of Trc8 inhibited growth consistent with its
presumed role as a tumor suppressor gene. Human JAB1 localization was
dependent on VHL mutant status. Thus, the VHL, TRC8, and JAB1 proteins
appear to be linked both physically and functionally, and all 3 may
participate in the development of kidney cancer.
COP9 signalosome cleaves the ubiquitin-like protein NEDD8 (603171) from
the CUL1 (603134) subunit of SCF ubiquitin ligases. Cope et al. (2002)
found that the JAB1/MPN domain metalloenzyme (JAMM) motif in the
JAB1/COPS5 subunit underlies the COP9 signalosome's NEDD8 isopeptidase
activity. The JAMM motif consists of a his-X-his-X(10)-asp motif (where
X indicates any residue) accompanied by an upstream glutamate. The JAMM
motif is found in proteins from archaea, bacteria, and eukaryotes,
including the RPN11 subunit of the 26S proteasome. Metal chelators and
point mutations within the JAMM motif abolished COP9
signalosome-dependent cleavage of NEDD8 from CUL1, yet had little effect
on COP9 signalosome complex assembly. Cope et al. (2002) proposed that
JAMM isopeptidases play important roles in a variety of physiologic
pathways.
The marked box domain and adjacent region of the E2F1 gene (189971) are
critical for the specificity of E2F1 apoptosis induction. Using the
marked box domain of E2F1 in a yeast 2-hybrid screen of a human thymus
cDNA library, Hallstrom and Nevins (2006) identified JAB1 as an E2F1
binding partner. JAB1 and E2F1 coexpression in rat embryonic fibroblasts
synergistically induced apoptosis, coincident with the induction of p53
(191170) protein accumulation. In contrast, JAB1 did not synergize with
E2F1 to promote cell cycle entry. Cells depleted of JAB1 were deficient
for both E2F1-induced apoptosis and induction of p53 accumulation.
Hallstrom and Nevins (2006) concluded that JAB1 is an essential cofactor
for the apoptotic function of E2F1.
MAPPING
Hartz (2004) mapped the COPS5 gene to chromosome 8q13.2 based on an
alignment of the COPS5 sequence (GenBank GENBANK U65928) with the
genomic sequence.
ANIMAL MODEL
Tomoda et al. (2004) found that Jab1 null mouse embryos died soon after
implantation. Mutant embryonic cells, which lacked other Cop9
signalosome components, expressed higher levels of p27, p53 (191170),
and cyclin E (123837), resulting in impaired proliferation and
accelerated apoptosis. Jab1 heterozygous mice were healthy and fertile
but smaller than their wildtype littermates. Heterozygous mouse
embryonic fibroblasts proliferated poorly, showed an inefficient
downregulation of p27 during G1, and were delayed in the progression
from G0 to S phase compared with wildtype cells. The levels of cyclin E
and deneddylated Cul1 were unchanged and p53 was not induced in
heterozygous mutant cells. Tomoda et al. (2004) concluded that JAB1
controls cell cycle progression and cell survival by regulating multiple
signaling pathways.
*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 RNA
binding and macromolecular assembly. J. Biol. Chem. 272: 27042-27052,
1997.
2. Bianchi, E.; Denti, S.; Granata, A.; Bossi, G.; Geginat, J.; Villa,
A.; Rogge, L.; Pardi, R.: Integrin LFA-1 interacts with the transcriptional
co-activator JAB1 to modulate AP-1 activity. Nature 404: 617-621,
2000.
3. Claret, F.-X.; Hibi, M.; Dhut, S.; Toda, T.; Karin, M.: A new
group of conserved coactivators that increase the specificity of AP-1
transcription factors. Nature 383: 453-457, 1996.
4. Cope, G. A.; Suh, G. S. B.; Aravind, L.; Schwarz, S. E.; Zipursky,
S. L.; Koonin, E. V.; Deshaies, R. J.: Role of predicted metalloprotease
motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 298:
608-611, 2002.
5. Gemmill, R. M.; Bemis, L. T.; Lee, J. P.; Sozen, M. A.; Baron,
A.; Zeng, C.; Erickson, P. F.; Hooper, J. E.; Drabkin, H. A.: The
TRC8 hereditary kidney cancer gene suppresses growth and functions
with VHL in a common pathway. Oncogene 21: 3507-3516, 2002.
6. Hallstrom, T. C.; Nevins, J. R.: Jab1 is a specificity factor
for E2F1-induced apoptosis. Genes Dev. 20: 613-623, 2006.
7. Hartz, P. A.: Personal Communication. Baltimore, Md 12/29/2004.
8. Kleemann, R.; Hausser, A.; Geiger, G.; Mischke, R.; Burger-Kentischer,
A.; Flieger, O.; Johannes, F.-J.; Roger, T.; Calandra, T.; Kapurniotu,
A.; Grell, M.; Finkelmeier, D.; Brunner, H.; Bernhagen, J.: Intracellular
action of the cytokine MIF to modulate AP-1 activity and the cell
cycle through Jab1. Nature 408: 211-216, 2000.
9. Tomoda, K.; Yoneda-Kato, N.; Fukumoto, A.; Yamanaka, S.; Kato,
J.: Multiple functions of Jab1 are required for early embryonic development
and growth potential in mice. J. Biol. Chem. 279: 43013-43018, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 3/28/2006
Patricia A. Hartz - updated: 1/6/2005
Ada Hamosh - updated: 11/19/2002
Victor A. McKusick - updated: 9/9/2002
Paul J. Converse - updated: 11/7/2000
Ada Hamosh - updated: 5/2/2000
*FIELD* CD
Ada Hamosh: 4/18/2000
*FIELD* ED
mgross: 07/18/2012
carol: 5/16/2007
wwang: 4/3/2006
terry: 3/28/2006
terry: 2/3/2006
mgross: 1/10/2005
terry: 1/6/2005
ckniffin: 3/23/2004
alopez: 11/19/2002
terry: 11/18/2002
tkritzer: 9/9/2002
mgross: 11/7/2000
alopez: 6/19/2000
carol: 5/2/2000
alopez: 4/19/2000
alopez: 4/18/2000