COP1_MOUSE
ID COP1_MOUSE Reviewed; 733 AA.
AC Q9R1A8;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=E3 ubiquitin-protein ligase COP1 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8NHY2};
DE AltName: Full=Constitutive photomorphogenesis protein 1 homolog {ECO:0000305};
DE Short=mCOP1 {ECO:0000305};
DE AltName: Full=RING finger and WD repeat domain protein 2 {ECO:0000305};
DE AltName: Full=RING-type E3 ubiquitin transferase RFWD2 {ECO:0000305};
GN Name=Cop1 {ECO:0000312|MGI:MGI:1347046};
GN Synonyms=Rfwd2 {ECO:0000312|MGI:MGI:1347046}, RNF200;
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 [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DOMAIN, AND MUTAGENESIS OF 113-ARG-LYS-114; 197-LYS--ARG-201;
RP 205-LYS--LYS-208; 244-LEU--LEU-246 AND 358-ARG--LYS-360.
RC STRAIN=C57BL/6J;
RX PubMed=10395541; DOI=10.1016/s0960-9822(99)80314-5;
RA Wang H., Kang D., Deng X.-W., Wei N.;
RT "Evidence for functional conservation of a mammalian homologue of the
RT light-responsive plant protein COP1.";
RL Curr. Biol. 9:711-714(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins. E3 ubiquitin
CC ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
CC form of a thioester and then directly transfers the ubiquitin to
CC targeted substrates. Involved in JUN ubiquitination and degradation.
CC Directly involved in p53 (TP53) ubiquitination and degradation, thereby
CC abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53
CC independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase
CC activity by functioning as the essential RING domain subunit of larger
CC E3 complexes. In contrast, it does not constitute the catalytic RING
CC subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the
CC ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3
CC protein sigma/SFN ubiquitination and proteasomal degradation, leading
CC to AKT activation and promotion of cell survival. Ubiquitinates MTA1
CC leading to its proteasomal degradation. Upon binding to TRIB1,
CC ubiquitinates CEBPA, which lacks a canonical COP1-binding motif.
CC {ECO:0000250|UniProtKB:Q8NHY2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q8NHY2};
CC -!- ACTIVITY REGULATION: TRIB1 competes with substrates for RFWD2 binding.
CC {ECO:0000250|UniProtKB:Q8NHY2}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Homodimerization is mediated by the coiled coil
CC domain. Component of the DCX DET1-COP1 ubiquitin ligase complex at
CC least composed of RBX1, DET1, DDB1, CUL4A and COP1. Isoform 2 does not
CC interact with CUL4A but still binds to RBX1, suggesting that the
CC interaction may be mediated by another cullin protein. Isoform 1 and
CC isoform 2 interact with CUL5 but not with CUL1, CUL2 not CUL3.
CC Interacts with bZIP transcription factors JUN, JUNB and JUND but not
CC with FOS, ATF2 nor XBP1. Interacts with p53 (TP53). Interacts with
CC COPS6; this interaction stabilizes RFWD2 through reducing its auto-
CC ubiquitination and decelerating its turnover rate. Interacts with SFN;
CC this interaction leads to SFN degradation. Interacts with p53/TP53 and
CC MTA1. Interacts with TRIB1 (via C-terminus) and TRIB2.
CC {ECO:0000250|UniProtKB:Q8NHY2}.
CC -!- INTERACTION:
CC Q9R1A8; Q3U182: Crtc2; NbExp=3; IntAct=EBI-15656898, EBI-8018890;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:10395541}.
CC Cytoplasm {ECO:0000269|PubMed:10395541}. Note=In the nucleus, it forms
CC nuclear speckles.
CC -!- DOMAIN: The RING finger domain, in addition to its role in
CC ubiquitination, functions as a structural scaffold to bring two
CC clusters of positive-charged residues within spatial proximity to mimic
CC a bipartite nuclear localization signal (NLS).
CC {ECO:0000269|PubMed:10395541}.
CC -!- DOMAIN: The WD40 domain (386-731) is necessary and sufficient for TRIB1
CC binding. {ECO:0000250|UniProtKB:Q8NHY2}.
CC -!- SIMILARITY: Belongs to the COP1 family. {ECO:0000305}.
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DR EMBL; AF151110; AAD51094.2; -; mRNA.
DR EMBL; BC082804; AAH82804.1; -; mRNA.
DR CCDS; CCDS35745.1; -.
DR RefSeq; NP_036061.1; NM_011931.3.
DR AlphaFoldDB; Q9R1A8; -.
DR SMR; Q9R1A8; -.
DR BioGRID; 204934; 15.
DR DIP; DIP-60522N; -.
DR IntAct; Q9R1A8; 1.
DR STRING; 10090.ENSMUSP00000076160; -.
DR iPTMnet; Q9R1A8; -.
DR PhosphoSitePlus; Q9R1A8; -.
DR MaxQB; Q9R1A8; -.
DR PaxDb; Q9R1A8; -.
DR PRIDE; Q9R1A8; -.
DR ProteomicsDB; 255186; -.
DR Antibodypedia; 34406; 256 antibodies from 30 providers.
DR DNASU; 26374; -.
DR Ensembl; ENSMUST00000076894; ENSMUSP00000076160; ENSMUSG00000040782.
DR GeneID; 26374; -.
DR KEGG; mmu:26374; -.
DR UCSC; uc007ddz.1; mouse.
DR CTD; 64326; -.
DR MGI; MGI:1347046; Cop1.
DR VEuPathDB; HostDB:ENSMUSG00000040782; -.
DR eggNOG; ENOG502QQ8V; Eukaryota.
DR GeneTree; ENSGT00920000149161; -.
DR HOGENOM; CLU_006994_2_1_1; -.
DR InParanoid; Q9R1A8; -.
DR OMA; RMHAHFD; -.
DR OrthoDB; 857220at2759; -.
DR PhylomeDB; Q9R1A8; -.
DR TreeFam; TF328912; -.
DR Reactome; R-MMU-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-MMU-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 26374; 16 hits in 80 CRISPR screens.
DR ChiTaRS; Rfwd2; mouse.
DR PRO; PR:Q9R1A8; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9R1A8; protein.
DR Bgee; ENSMUSG00000040782; Expressed in animal zygote and 220 other tissues.
DR ExpressionAtlas; Q9R1A8; baseline and differential.
DR Genevisible; Q9R1A8; MM.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0010212; P:response to ionizing radiation; ISO:MGI.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR042755; COP1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR44080; PTHR44080; 1.
DR Pfam; PF00400; WD40; 5.
DR SMART; SM00184; RING; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Metal-binding; Nucleus; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..733
FT /note="E3 ubiquitin-protein ligase COP1"
FT /id="PRO_0000055880"
FT REPEAT 421..460
FT /note="WD 1"
FT REPEAT 470..510
FT /note="WD 2"
FT REPEAT 513..553
FT /note="WD 3"
FT REPEAT 555..595
FT /note="WD 4"
FT REPEAT 599..637
FT /note="WD 5"
FT REPEAT 640..679
FT /note="WD 6"
FT REPEAT 695..731
FT /note="WD 7"
FT ZN_FING 138..176
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 645..647
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000250|UniProtKB:Q8NHY2"
FT COILED 231..306
FT /evidence="ECO:0000255"
FT MOTIF 111..115
FT /note="Nuclear localization signal 1"
FT MOTIF 197..208
FT /note="Nuclear localization signal 2"
FT MOTIF 237..247
FT /note="Nuclear export signal"
FT SITE 474
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000250|UniProtKB:Q8NHY2"
FT SITE 493
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000250|UniProtKB:Q8NHY2"
FT MUTAGEN 113..114
FT /note="RK->SN: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:10395541"
FT MUTAGEN 197..201
FT /note="KQKQR->NQNQS: Does not affect the subcellular
FT localization."
FT /evidence="ECO:0000269|PubMed:10395541"
FT MUTAGEN 205..208
FT /note="KRFK->TSFT: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:10395541"
FT MUTAGEN 244..246
FT /note="LEL->AEA: Abolishes nuclear export."
FT /evidence="ECO:0000269|PubMed:10395541"
FT MUTAGEN 358..360
FT /note="RRK->SRT: Abolishes the nuclear speckle localization
FT but not the nuclear localization."
FT /evidence="ECO:0000269|PubMed:10395541"
SQ SEQUENCE 733 AA; 80441 MW; 894AEA412BACC737 CRC64;
MSGSRQAGSG SAGTSPGSSA ASSVTSASSS LSSSPSPPSV AASAATLVSG GVAPAAGSGG
LGGPGRPVLV AAAVSGSASA GGAVSAGQSR LSCAARPSAG VGGSSSSLGS SSRKRPLLVP
LCNGLLNSYE DKSNDFVCPI CFDMIEEAYM TKCGHSFCYK CIHQSLEDNN RCPKCNYVVD
NIDHLYPNFL VNELILKQKQ RFEEKRFKLD HSVSSTNGHR WQIFQDLLGT DQDNLDLANV
NLMLELLVQK KKQLEAESHA AQLQILMEFL KVARRNKREQ LEQIQKELSV LEEDIKRVEE
MSGLYSPVSE DSTVPQFEAP SPSHSSIIDS TEYSQPPGFS GTSQTKKQPW YNSTLASRRK
RLTAHFEDLE QCYFSTRMSR ISDDSRTASQ LDEFQECLSK FTRYNSVRPL ATLSYASDLY
NGSSIVSSIE FDRDCDYFAI AGVTKKIKVY EYGTVIQDAV DIHYPENEMT CNSKISCISW
SSYHKNLLAS SDYEGTVILW DGFTGQRSKV YQEHEKRCWS VDFNLMDPKL LASGSDDAKV
KLWSTNLDNS VASIEAKANV CCVKFSPSSR YHLAFGCADH CVHYYDLRNT KQPIMVFKGH
RKAVSYAKFV SGEEIVSAST DSQLKLWNVG KPYCLRSFKG HINEKNFVGL ASNGDYIACG
SENNSLYLYY KGLSKTLLTF KFDTVKSVLD KDRKEDDTNE FVSAVCWRAL SDGESNVLIA
ANSQGTIKVL ELV
