CSN2_MOUSE
ID CSN2_MOUSE Reviewed; 443 AA.
AC P61202; O88950; Q15647; Q3V1W6; Q8R5B0; Q9CWU1; Q9R249; Q9UNQ5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=COP9 signalosome complex subunit 2;
DE Short=SGN2;
DE Short=Signalosome subunit 2;
DE AltName: Full=Alien homolog;
DE AltName: Full=JAB1-containing signalosome subunit 2;
DE AltName: Full=Thyroid receptor-interacting protein 15;
DE Short=TR-interacting protein 15;
DE Short=TRIP-15;
GN Name=Cops2; Synonyms=Csn2, Trip15;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=10087198; DOI=10.1006/geno.1998.5728;
RA Schaefer L., Beermann M.L., Miller J.B.;
RT "Coding sequence, genomic organization, chromosomal localization, and
RT expression pattern of the signalosome component Cops2: the mouse homologue
RT of Drosophila alien.";
RL Genomics 56:310-316(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-443 (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-443 (ISOFORM 1), AND IDENTIFICATION IN THE
RP CSN COMPLEX.
RC STRAIN=C57BL/6J;
RX PubMed=9707402; DOI=10.1016/s0960-9822(07)00372-7;
RA Wei N., Tsuge T., Serino G., Dohmae N., Takio K., Matsui M., Deng X.-W.;
RT "The COP9 complex is conserved between plants and mammals and is related to
RT the 26S proteasome regulatory complex.";
RL Curr. Biol. 8:919-922(1998).
RN [5]
RP FUNCTION, AND INTERACTION WITH CUL1 AND CUL2.
RX PubMed=11967155; DOI=10.1016/s0960-9822(02)00791-1;
RA Yang X., Menon S., Lykke-Andersen K., Tsuge T., Xiao D., Wang X.,
RA Rodriguez-Suarez R.J., Zhang H., Wei N.;
RT "The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase
RT progression via deneddylation of SCF Cul1.";
RL Curr. Biol. 12:667-672(2002).
RN [6]
RP FUNCTION, AND INTERACTION WITH NIF3L1.
RX PubMed=12522100; DOI=10.1074/jbc.m209856200;
RA Akiyama H., Fujisawa N., Tashiro Y., Takanabe N., Sugiyama A., Tashiro F.;
RT "The role of transcriptional corepressor Nif3l1 in early stage of neural
RT differentiation via cooperation with Trip15/CSN2.";
RL J. Biol. Chem. 278:10752-10762(2003).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12972599; DOI=10.1128/mcb.23.19.6790-6797.2003;
RA Lykke-Andersen K., Schaefer L., Menon S., Deng X.-W., Miller J.B., Wei N.;
RT "Disruption of the COP9 signalosome Csn2 subunit in mice causes deficient
RT cell proliferation, accumulation of p53 and cyclin E, and early embryonic
RT death.";
RL Mol. Cell. Biol. 23:6790-6797(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Essential component of the COP9 signalosome complex (CSN), a
CC complex involved in various cellular and developmental processes. The
CC 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 Ubl
CC 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/ICSBP, possibly via its association
CC with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN
CC promotes and protects degradation by the Ubl system, respectively.
CC Involved in early stage of neuronal differentiation via its interaction
CC with NIF3L1. {ECO:0000269|PubMed:11967155, ECO:0000269|PubMed:12522100,
CC ECO:0000269|PubMed:12972599}.
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 (PubMed:9707402). In the complex, it probably interacts directly with
CC COPS1, COPS4, COPS5, COPS6 and COPS7 (COPS7A or COPS7B)
CC (PubMed:9707402). Specifically interacts with the ligand binding domain
CC of the thyroid receptor (TR). Does not require the presence of thyroid
CC hormone for its interaction. Interacts with CUL1 and CUL2
CC (PubMed:11967155). Interacts with IRF8/ICSBP1 and with nuclear
CC receptors NR2F1 and NR0B1 (By similarity). Interacts with NIF3L1
CC (PubMed:12522100). {ECO:0000250|UniProtKB:P61201,
CC ECO:0000269|PubMed:11967155, ECO:0000269|PubMed:12522100,
CC ECO:0000269|PubMed:9707402}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10087198}. Nucleus
CC {ECO:0000269|PubMed:10087198}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61202-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61202-2; Sequence=VSP_011885;
CC -!- TISSUE SPECIFICITY: Widely expressed in embryonic, fetal and adult
CC tissues, except cartilage and smooth muscle.
CC {ECO:0000269|PubMed:10087198}.
CC -!- PTM: Phosphorylated by CK2 and PKD kinases. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Its absence causes arrest of embryo development
CC at the peri-implantation stage. Blastocysts without Cops2 fail to
CC outgrow in culture and exhibit a cell proliferation defect in inner
CC cell mass, accompanied by a slight decrease in Oct4. In addition, lack
CC of Cops2 disrupts the CSN complex and results in a drastic increase in
CC cyclin E. It also induces elevated levels of p53 and p21, which may
CC contribute to premature cell cycle arrest of the mutant.
CC {ECO:0000269|PubMed:12972599}.
CC -!- SIMILARITY: Belongs to the CSN2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH23096.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF087688; AAC36309.1; -; mRNA.
DR EMBL; AF114247; AAD26162.1; -; Genomic_DNA.
DR EMBL; AF114236; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114237; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114238; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114239; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114240; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114241; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114242; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114244; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114245; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AF114246; AAD26162.1; JOINED; Genomic_DNA.
DR EMBL; AK010383; BAB26900.1; -; mRNA.
DR EMBL; AK084421; BAC39179.1; -; mRNA.
DR EMBL; AK132207; BAE21033.1; -; mRNA.
DR EMBL; BC023096; AAH23096.1; ALT_INIT; mRNA.
DR EMBL; AF071312; AAC33899.1; -; mRNA.
DR CCDS; CCDS16679.1; -. [P61202-1]
DR CCDS; CCDS71133.1; -. [P61202-2]
DR RefSeq; NP_001272441.1; NM_001285512.1.
DR RefSeq; NP_034069.2; NM_009939.3. [P61202-1]
DR AlphaFoldDB; P61202; -.
DR SMR; P61202; -.
DR BioGRID; 198836; 42.
DR CORUM; P61202; -.
DR IntAct; P61202; 1.
DR STRING; 10090.ENSMUSP00000106090; -.
DR iPTMnet; P61202; -.
DR PhosphoSitePlus; P61202; -.
DR EPD; P61202; -.
DR jPOST; P61202; -.
DR MaxQB; P61202; -.
DR PaxDb; P61202; -.
DR PeptideAtlas; P61202; -.
DR PRIDE; P61202; -.
DR ProteomicsDB; 285375; -. [P61202-1]
DR ProteomicsDB; 285376; -. [P61202-2]
DR Antibodypedia; 12106; 424 antibodies from 39 providers.
DR DNASU; 12848; -.
DR Ensembl; ENSMUST00000028635; ENSMUSP00000028635; ENSMUSG00000027206. [P61202-1]
DR Ensembl; ENSMUST00000110463; ENSMUSP00000106090; ENSMUSG00000027206. [P61202-2]
DR GeneID; 12848; -.
DR KEGG; mmu:12848; -.
DR UCSC; uc008mdb.2; mouse. [P61202-1]
DR CTD; 9318; -.
DR MGI; MGI:1330276; Cops2.
DR VEuPathDB; HostDB:ENSMUSG00000027206; -.
DR eggNOG; KOG1464; Eukaryota.
DR GeneTree; ENSGT00530000063301; -.
DR HOGENOM; CLU_028981_0_1_1; -.
DR InParanoid; P61202; -.
DR OMA; RNYQEAG; -.
DR TreeFam; TF105738; -.
DR Reactome; R-MMU-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-MMU-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9013422; RHOBTB1 GTPase cycle.
DR BioGRID-ORCS; 12848; 17 hits in 75 CRISPR screens.
DR ChiTaRS; Cops2; mouse.
DR PRO; PR:P61202; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P61202; protein.
DR Bgee; ENSMUSG00000027206; Expressed in otic placode and 267 other tissues.
DR ExpressionAtlas; P61202; baseline and differential.
DR Genevisible; P61202; MM.
DR GO; GO:0008180; C:COP9 signalosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI.
DR GO; GO:1903507; P:negative regulation of nucleic acid-templated transcription; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0030182; P:neuron differentiation; ISO:MGI.
DR GO; GO:0000338; P:protein deneddylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
DR GO; GO:0001834; P:trophectodermal cell proliferation; IMP:MGI.
DR InterPro; IPR037750; COPS2.
DR InterPro; IPR000717; PCI_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR10678:SF3; PTHR10678:SF3; 1.
DR Pfam; PF01399; PCI; 1.
DR SMART; SM00088; PINT; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50250; PCI; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Signalosome.
FT CHAIN 1..443
FT /note="COP9 signalosome complex subunit 2"
FT /id="PRO_0000120969"
FT DOMAIN 254..416
FT /note="PCI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01185"
FT REGION 1..275
FT /note="Mediates interaction with NIF3L1"
FT /evidence="ECO:0000250|UniProtKB:P61203"
FT VAR_SEQ 124
FT /note="Q -> QNSDFLCQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011885"
FT CONFLICT 40
FT /note="K -> Y (in Ref. 2; BAB26900)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="S -> T (in Ref. 2; BAB26900)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="R -> K (in Ref. 3; AAH23096)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 443 AA; 51597 MW; 1DB6FA774C13BC59 CRC64;
MSDMEDDFMC DDEEDYDLEY SEDSNSEPNV DLENQYYNSK ALKEDDPKAA LSSFQKVLEL
EGEKGEWGFK ALKQMIKINF KLTNFPEMMN RYKQLLTYIR SAVTRNYSEK SINSILDYIS
TSKQMDLLQE FYETTLEALK DAKNDRLWFK TNTKLGKLYL EREEYGKLQK ILRQLHQSCQ
TDDGEDDLKK GTQLLEIYAL EIQMYTAQKN NKKLKALYEQ SLHIKSAIPH PLIMGVIREC
GGKMHLREGE FEKAHTDFFE AFKNYDESGS PRRTTCLKYL VLANMLMKSG INPFDSQEAK
PYKNDPEILA MTNLVSAYQN NDITEFEKIL KTNHSNIMDD PFIREHIEEL LRNIRTQVLI
KLIKPYTRIH IPFISKELNI DVADVESLLV QCILDNTIHG RIDQVNQLLE LDHQKRGGAR
YTALDKWTNQ LNSLNQAVVS KLA
