ID CSN3_HUMAN Reviewed; 423 AA. AC Q9UNS2; O43191; Q7LDR6; DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JUL-2009, entry version 72. DE RecName: Full=COP9 signalosome complex subunit 3; DE Short=Signalosome subunit 3; DE Short=SGN3; DE AltName: Full=JAB1-containing signalosome subunit 3; GN Name=COPS3; Synonyms=CSN3; 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 TISSUE SPECIFICITY. RC TISSUE=Brain; RX MEDLINE=99208679; PubMed=10191102; DOI=10.1006/geno.1998.5748; RA Potocki L., Chen K.-S., Lupski J.R.; RT "Subunit 3 of the COP9 signal transduction complex is conserved from RT plants to humans and maps within the smith-magenis syndrome critical RT region in 17p11.2."; RL Genomics 57:180-182(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [3] RP PROTEIN SEQUENCE OF 2-13. RC TISSUE=Platelet; RX MEDLINE=22608298; PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., RA Thomas G.R., Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass RT spectrometric identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [4] RP PROTEIN SEQUENCE OF 2-13; 31-37; 244-251 AND 313-336, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma, and Platelet; RA Bienvenut W.V., Quadroni M.; RL Submitted (OCT-2005) to UniProtKB. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-423, PARTIAL PROTEIN SEQUENCE, RP FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Cervix carcinoma; RX MEDLINE=98194867; 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 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 [7] RP INTERACTION WITH IKBKG. RX PubMed=11418127; DOI=10.1016/S0014-5793(01)02535-2; RA Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B.; RT "CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced RT NF-kappaB activation."; RL FEBS Lett. 499:133-136(2001). RN [8] 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 [9] 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 [10] 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 [11] RP FUNCTION, AND INTERACTION WITH CK2 AND PKD. 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 [12] RP OVEREXPRESSION IN OSTEOSARCOMA. RX PubMed=12917637; DOI=10.1038/sj.onc.1206671; RA Henriksen J., Aagesen T.H., Maelandsmo G.M., Lothe R.A., Myklebost O., RA Forus A.; RT "Amplification and overexpression of COPS3 in osteosarcomas RT potentially target TP53 for proteasome-mediated degradation."; RL Oncogene 22:5358-5361(2003). RN [13] RP OVEREXPRESSION IN OSTEOSARCOMA. RX PubMed=15325100; DOI=10.1016/j.cancergencyto.2004.03.007; RA Van Dartel M., Hulsebos T.J.M.; RT "Amplification and overexpression of genes in 17p11.2 approximately RT p12 in osteosarcoma."; RL Cancer Genet. Cytogenet. 153:77-80(2004). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410, AND MASS RP SPECTROMETRY. RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [15] RP INITIATOR METHIONINE REMOVAL, ACETYLATION AT ALA-2, AND RP PHOSPHORYLATION AT SER-423. RX PubMed=18850735; DOI=10.1021/pr800574c; RA Fang L., Wang X., Yamoah K., Chen P.L., Pan Z.Q., Huang L.; RT "Characterization of the human COP9 signalosome complex using affinity RT purification and mass spectrometry."; RL J. Proteome Res. 7:4914-4925(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410, AND MASS RP SPECTROMETRY. 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 [17] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. 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/ICSBP, possibly via CC its association with CK2 and PKD kinases. CSN-dependent CC phosphorylation of TP53 and JUN promotes and protects degradation CC by the Ubl system, respectively. 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 COPS4 and COPS8. Interacts with CK2 and PKD. Interacts with the CC translation initiation factor EIF3S6 and IKBKG. CC -!- INTERACTION: CC P10398:ARAF; NbExp=3; IntAct=EBI-350590, EBI-365961; CC Q9Y6K9:IKBKG; NbExp=1; IntAct=EBI-350590, EBI-81279; CC O14832:PHYH; NbExp=1; IntAct=EBI-350590, EBI-721853; CC P04049:RAF1; NbExp=2; IntAct=EBI-350590, EBI-365996; CC Q9P2S5:WDR8; NbExp=1; IntAct=EBI-350590, EBI-1054904; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high level in CC heart and skeletal muscle. CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- MISCELLANEOUS: Amplified and overexpressed in some osteosarcomas CC (OS), suggesting that it may participate in TP53 degradation in CC OS. CC -!- SIMILARITY: Belongs to the CSN3 family. CC -!- SIMILARITY: Contains 1 PCI domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF098109; AAD41247.1; -; mRNA. DR EMBL; BC001891; AAH01891.1; -; mRNA. DR EMBL; AF031647; AAC14197.1; ALT_INIT; mRNA. DR IPI; IPI00025721; -. DR RefSeq; NP_003644.2; -. DR UniGene; Hs.6076; -. DR IntAct; Q9UNS2; 7. DR PhosphoSite; Q9UNS2; -. DR PeptideAtlas; Q9UNS2; -. DR PRIDE; Q9UNS2; -. DR Ensembl; ENST00000268717; ENSP00000268717; ENSG00000141030; Homo sapiens. DR GeneID; 8533; -. DR KEGG; hsa:8533; -. DR UCSC; uc002grd.1; human. DR GeneCards; GC17M017090; -. DR H-InvDB; HIX0013583; -. DR HGNC; HGNC:2239; COPS3. DR MIM; 604665; gene. DR PharmGKB; PA26755; -. DR HOGENOM; Q9UNS2; -. DR HOVERGEN; Q9UNS2; -. DR OMA; Q9UNS2; ALYFFEV. DR NextBio; 31960; -. DR ArrayExpress; Q9UNS2; -. DR Bgee; Q9UNS2; -. DR CleanEx; HS_COPS3; -. DR CleanEx; HS_CSN3; -. DR GermOnline; ENSG00000141030; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0008180; C:signalosome; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0009416; P:response to light stimulus; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR000717; PCI. DR InterPro; IPR011991; Wing_hlx_DNA_bd. DR Gene3D; G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1. DR Pfam; PF01399; PCI; 1. DR SMART; SM00088; PINT; 1. PE 1: Evidence at protein level; KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; KW Nucleus; Phosphoprotein; Signalosome. FT INIT_MET 1 1 Removed. FT CHAIN 2 423 COP9 signalosome complex subunit 3. FT /FTId=PRO_0000120978. FT DOMAIN 195 362 PCI. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 410 410 Phosphoserine. FT MOD_RES 423 423 Phosphoserine. SQ SEQUENCE 423 AA; 47873 MW; 1D371050C7D7BF8D CRC64; MASALEQFVN SVRQLSAQGQ MTQLCELINK SGELLAKNLS HLDTVLGALD VQEHSLGVLA VLFVKFSMPS VPDFETLFSQ VQLFISTCNG EHIRYATDTF AGLCHQLTNA LVERKQPLRG IGILKQAIDK MQMNTNQLTS IHADLCQLCL LAKCFKPALP YLDVDMMDIC KENGAYDAKH FLCYYYYGGM IYTGLKNFER ALYFYEQAIT TPAMAVSHIM LESYKKYILV SLILLGKVQQ LPKYTSQIVG RFIKPLSNAY HELAQVYSTN NPSELRNLVN KHSETFTRDN NMGLVKQCLS SLYKKNIQRL TKTFLTLSLQ DMASRVQLSG PQEAEKYVLH MIEDGEIFAS INQKDGMVSF HDNPEKYNNP AMLHNIDQEM LKCIELDERL KAMDQEITVN PQFVQKSMGS QEDDSGNKPS SYS //