COP1_HUMAN
ID COP1_HUMAN Reviewed; 731 AA.
AC Q8NHY2; E9PKI0; Q504W6; Q6H103; Q9H6L7; X5D9B4;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=E3 ubiquitin-protein ligase COP1 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:12615916};
DE AltName: Full=Constitutive photomorphogenesis protein 1 homolog {ECO:0000303|PubMed:12466024};
DE Short=hCOP1 {ECO:0000303|PubMed:12466024};
DE AltName: Full=RING finger and WD repeat domain protein 2 {ECO:0000305};
DE AltName: Full=RING finger protein 200;
DE AltName: Full=RING-type E3 ubiquitin transferase RFWD2 {ECO:0000305};
GN Name=COP1 {ECO:0000312|HGNC:HGNC:17440};
GN Synonyms=RFWD2 {ECO:0000312|HGNC:HGNC:17440}, RNF200;
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 [GENOMIC DNA] (ISOFORM 1), FUNCTION, HOMODIMERIZATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=12466024; DOI=10.1186/1471-2121-3-30;
RA Yi C., Wang H., Wei N., Deng X.-W.;
RT "An initial biochemical and cell biological characterization of the
RT mammalian homologue of a central plant developmental switch, COP1.";
RL BMC Cell Biol. 3:30-30(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INTERACTION WITH JUN; JUNB AND JUND, MUTAGENESIS OF
RP 111-ARG--ARG-113; CYS-136 AND CYS-139, AND CATALYTIC ACTIVITY.
RX PubMed=12615916; DOI=10.1074/jbc.m212681200;
RA Bianchi E., Denti S., Catena R., Rossetti G., Polo S., Gasparian S.,
RA Putignano S., Rogge L., Pardi R.;
RT "Characterization of human constitutive photomorphogenesis protein 1, a
RT RING finger ubiquitin ligase that interacts with Jun transcription factors
RT and modulates their transcriptional activity.";
RL J. Biol. Chem. 278:19682-19690(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, ALTERNATIVE SPLICING, COMPONENT OF THE DCX
RP DET1-COP1 COMPLEX WITH RBX1; CUL4A; DET1 AND DDB1, AND MUTAGENESIS OF
RP CYS-136 AND CYS-139.
RX PubMed=14739464; DOI=10.1126/science.1093549;
RA Wertz I.E., O'Rourke K.M., Zhang Z., Dornan D., Arnott D., Deshaies R.J.,
RA Dixit V.M.;
RT "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin
RT ligase.";
RL Science 303:1371-1374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Brain;
RX PubMed=24722188; DOI=10.1038/ncomms4650;
RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M.,
RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I.,
RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A.,
RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D.,
RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.;
RT "Protein interaction network of alternatively spliced isoforms from brain
RT links genetic risk factors for autism.";
RL Nat. Commun. 5:3650-3650(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Hepatoma, and Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [9]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND INTERACTION WITH TP53.
RX PubMed=15103385; DOI=10.1038/nature02514;
RA Dornan D., Wertz I., Shimizu H., Arnott D., Frantz G.D., Dowd P.,
RA O'Rourke K., Koeppen H., Dixit V.M.;
RT "The ubiquitin ligase COP1 is a critical negative regulator of p53.";
RL Nature 429:86-92(2004).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 4), AND SUBUNIT.
RX PubMed=17968316; DOI=10.1038/sj.onc.1210892;
RA Savio M.G., Rotondo G., Maglie S., Rossetti G., Bender J.R., Pardi R.;
RT "COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1)
RT product, stabilizes UV stress-induced c-Jun through inhibition of full-
RT length COP1.";
RL Oncogene 27:2401-2411(2008).
RN [11]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=19837670; DOI=10.1074/jbc.m109.056499;
RA Li D.Q., Divijendra Natha Reddy S., Pakala S.B., Wu X., Zhang Y.,
RA Rayala S.K., Kumar R.;
RT "MTA1 coregulator regulates p53 stability and function.";
RL J. Biol. Chem. 284:34545-34552(2009).
RN [12]
RP FUNCTION, INTERACTION WITH MTA1, MUTAGENESIS OF CYS-136; CYS-139; CYS-156
RP AND CYS-159, AND AUTOUBIQUITINATION.
RX PubMed=19805145; DOI=10.1073/pnas.0908027106;
RA Li D.Q., Ohshiro K., Reddy S.D., Pakala S.B., Lee M.H., Zhang Y.,
RA Rayala S.K., Kumar R.;
RT "E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17493-17498(2009).
RN [13]
RP INTERACTION WITH TRIB1.
RX PubMed=20410507; DOI=10.1182/blood-2009-07-229450;
RA Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O.,
RA Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.;
RT "Differential ability of Tribbles family members to promote degradation of
RT C/EBPalpha and induce acute myelogenous leukemia.";
RL Blood 116:1321-1328(2010).
RN [14]
RP FUNCTION, INTERACTION WITH COPS6 AND SFN, AND MUTAGENESIS OF CYS-136 AND
RP CYS-139.
RX PubMed=21625211; DOI=10.1038/onc.2011.192;
RA Choi H.H., Gully C., Su C.H., Velazquez-Torres G., Chou P.C., Tseng C.,
RA Zhao R., Phan L., Shaiken T., Chen J., Yeung S.C., Lee M.H.;
RT "COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3
RT ubiquitin ligase for 14-3-3sigma.";
RL Oncogene 30:4791-4801(2011).
RN [15] {ECO:0007744|PDB:5HQG, ECO:0007744|PDB:5IGQ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 376-731 ALONE OR IN COMPLEX WITH
RP A TRIB1 PEPTIDE, FUNCTION, DOMAIN, INTERACTION WITH TRIB1 AND TRIB2, AND
RP ACTIVITY REGULATION.
RX PubMed=27041596; DOI=10.1016/j.str.2016.03.002;
RA Uljon S., Xu X., Durzynska I., Stein S., Adelmant G., Marto J.A.,
RA Pear W.S., Blacklow S.C.;
RT "Structural basis for substrate selectivity of the E3 ligase COP1.";
RL Structure 24:687-696(2016).
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 (Probable). {ECO:0000269|PubMed:12466024, ECO:0000269|PubMed:12615916,
CC ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15103385,
CC ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670,
CC ECO:0000269|PubMed:21625211, ECO:0000303|PubMed:27041596}.
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:0000269|PubMed:12615916};
CC -!- ACTIVITY REGULATION: TRIB1 competes with substrates for RFWD2 binding.
CC {ECO:0000269|PubMed:27041596}.
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. Isoform 4 forms heterodimers
CC with isoform 1, preventing its association with DET1. Interacts with
CC p53/TP53 and MTA1. Interacts with TRIB1 (via C-terminus) and TRIB2
CC (PubMed:20410507, PubMed:27041596). {ECO:0000269|PubMed:12615916,
CC ECO:0000269|PubMed:15103385, ECO:0000269|PubMed:17968316,
CC ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670,
CC ECO:0000269|PubMed:20410507, ECO:0000269|PubMed:21625211,
CC ECO:0000269|PubMed:27041596}.
CC -!- INTERACTION:
CC Q8NHY2; Q7L5N1: COPS6; NbExp=3; IntAct=EBI-1176214, EBI-486838;
CC Q8NHY2; P14921-1: ETS1; NbExp=3; IntAct=EBI-1176214, EBI-913224;
CC Q8NHY2; P15036: ETS2; NbExp=2; IntAct=EBI-1176214, EBI-1646991;
CC Q8NHY2; P50549: ETV1; NbExp=2; IntAct=EBI-1176214, EBI-3905068;
CC Q8NHY2; P31947: SFN; NbExp=6; IntAct=EBI-1176214, EBI-476295;
CC Q8NHY2-1; P50549-1: ETV1; NbExp=2; IntAct=EBI-9698228, EBI-15926557;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm. Note=In the nucleus,
CC it forms nuclear speckles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8NHY2-1; Sequence=Displayed;
CC Name=2; Synonyms=delta24;
CC IsoId=Q8NHY2-2; Sequence=VSP_012024, VSP_012025;
CC Name=3;
CC IsoId=Q8NHY2-3; Sequence=VSP_012026, VSP_012027;
CC Name=4; Synonyms=COP1D;
CC IsoId=Q8NHY2-4; Sequence=VSP_012025;
CC Name=5; Synonyms=E;
CC IsoId=Q8NHY2-5; Sequence=VSP_055894, VSP_055895;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at low level. Expressed at
CC higher level in testis, placenta, skeletal muscle and heart.
CC {ECO:0000269|PubMed:12615916, ECO:0000269|PubMed:15103385}.
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:15103385}.
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) (By similarity).
CC {ECO:0000250|UniProtKB:Q9R1A8}.
CC -!- DOMAIN: The WD40 domain (386-731) is necessary and sufficient for TRIB1
CC binding (PubMed:27041596). {ECO:0000269|PubMed:27041596}.
CC -!- PTM: Autoubiquitinated. MTA1 destabilizes it by promoting its
CC autoubiquitination. {ECO:0000269|PubMed:19805145}.
CC -!- MISCELLANEOUS: [Isoform 4]: Unable to associate with other components
CC of the CRL complex. Acts as a dominant-negative. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the COP1 family. {ECO:0000305}.
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DR EMBL; AF508940; AAM34692.1; -; mRNA.
DR EMBL; BK000438; DAA01050.1; -; Genomic_DNA.
DR EMBL; AF527539; AAQ08989.1; -; mRNA.
DR EMBL; AY509921; AAS82851.1; -; mRNA.
DR EMBL; KJ534928; AHW56568.1; -; mRNA.
DR EMBL; KJ535076; AHW56715.1; -; mRNA.
DR EMBL; AK025789; BAB15239.1; -; mRNA.
DR EMBL; AK314750; BAG37289.1; -; mRNA.
DR EMBL; AL162736; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL513329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91000.1; -; Genomic_DNA.
DR EMBL; BC094728; AAH94728.1; -; mRNA.
DR CCDS; CCDS30944.1; -. [Q8NHY2-1]
DR CCDS; CCDS44279.1; -. [Q8NHY2-2]
DR RefSeq; NP_001001740.1; NM_001001740.3. [Q8NHY2-2]
DR RefSeq; NP_001273573.1; NM_001286644.1.
DR RefSeq; NP_071902.2; NM_022457.6. [Q8NHY2-1]
DR PDB; 5HQG; X-ray; 2.00 A; A=376-731.
DR PDB; 5IGQ; X-ray; 3.90 A; A/B/C/D/E/F=386-731.
DR PDBsum; 5HQG; -.
DR PDBsum; 5IGQ; -.
DR AlphaFoldDB; Q8NHY2; -.
DR SMR; Q8NHY2; -.
DR BioGRID; 122136; 138.
DR CORUM; Q8NHY2; -.
DR DIP; DIP-36661N; -.
DR ELM; Q8NHY2; -.
DR IntAct; Q8NHY2; 54.
DR MINT; Q8NHY2; -.
DR STRING; 9606.ENSP00000356641; -.
DR GlyGen; Q8NHY2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NHY2; -.
DR PhosphoSitePlus; Q8NHY2; -.
DR BioMuta; RFWD2; -.
DR DMDM; 55976539; -.
DR EPD; Q8NHY2; -.
DR jPOST; Q8NHY2; -.
DR MassIVE; Q8NHY2; -.
DR MaxQB; Q8NHY2; -.
DR PaxDb; Q8NHY2; -.
DR PeptideAtlas; Q8NHY2; -.
DR PRIDE; Q8NHY2; -.
DR ProteomicsDB; 21473; -.
DR ProteomicsDB; 73785; -. [Q8NHY2-1]
DR ProteomicsDB; 73786; -. [Q8NHY2-2]
DR ProteomicsDB; 73787; -. [Q8NHY2-3]
DR Antibodypedia; 34406; 256 antibodies from 30 providers.
DR DNASU; 64326; -.
DR Ensembl; ENST00000308769.12; ENSP00000310943.8; ENSG00000143207.21. [Q8NHY2-2]
DR Ensembl; ENST00000367669.8; ENSP00000356641.3; ENSG00000143207.21. [Q8NHY2-1]
DR Ensembl; ENST00000474194.1; ENSP00000433517.1; ENSG00000143207.21. [Q8NHY2-5]
DR GeneID; 64326; -.
DR KEGG; hsa:64326; -.
DR MANE-Select; ENST00000367669.8; ENSP00000356641.3; NM_022457.7; NP_071902.2.
DR UCSC; uc001gku.3; human. [Q8NHY2-1]
DR CTD; 64326; -.
DR DisGeNET; 64326; -.
DR GeneCards; COP1; -.
DR HGNC; HGNC:17440; COP1.
DR HPA; ENSG00000143207; Low tissue specificity.
DR MIM; 608067; gene.
DR neXtProt; NX_Q8NHY2; -.
DR OpenTargets; ENSG00000143207; -.
DR PharmGKB; PA134952161; -.
DR VEuPathDB; HostDB:ENSG00000143207; -.
DR eggNOG; ENOG502QQ8V; Eukaryota.
DR GeneTree; ENSGT00920000149161; -.
DR HOGENOM; CLU_1677257_0_0_1; -.
DR InParanoid; Q8NHY2; -.
DR OMA; RMHAHFD; -.
DR OrthoDB; 857220at2759; -.
DR PhylomeDB; Q8NHY2; -.
DR TreeFam; TF328912; -.
DR PathwayCommons; Q8NHY2; -.
DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q8NHY2; -.
DR SIGNOR; Q8NHY2; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 64326; 173 hits in 1133 CRISPR screens.
DR ChiTaRS; RFWD2; human.
DR GeneWiki; RFWD2; -.
DR GenomeRNAi; 64326; -.
DR Pharos; Q8NHY2; Tbio.
DR PRO; PR:Q8NHY2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8NHY2; protein.
DR Bgee; ENSG00000143207; Expressed in ileal mucosa and 181 other tissues.
DR ExpressionAtlas; Q8NHY2; baseline and differential.
DR Genevisible; Q8NHY2; HS.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
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 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..731
FT /note="E3 ubiquitin-protein ligase COP1"
FT /id="PRO_0000055879"
FT REPEAT 419..458
FT /note="WD 1"
FT REPEAT 468..508
FT /note="WD 2"
FT REPEAT 511..551
FT /note="WD 3"
FT REPEAT 553..593
FT /note="WD 4"
FT REPEAT 597..635
FT /note="WD 5"
FT REPEAT 638..677
FT /note="WD 6"
FT REPEAT 691..729
FT /note="WD 7"
FT ZN_FING 136..174
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..645
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000269|PubMed:27041596"
FT COILED 233..301
FT /evidence="ECO:0000255"
FT MOTIF 109..113
FT /note="Nuclear localization signal 1"
FT MOTIF 195..206
FT /note="Nuclear localization signal 2"
FT MOTIF 235..245
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT SITE 472
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000269|PubMed:27041596"
FT SITE 491
FT /note="Interaction with TRIB1"
FT /evidence="ECO:0000269|PubMed:27041596"
FT VAR_SEQ 1..264
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012026"
FT VAR_SEQ 157
FT /note="Y -> E (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:24722188"
FT /id="VSP_055894"
FT VAR_SEQ 158..731
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:24722188"
FT /id="VSP_055895"
FT VAR_SEQ 211..214
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14739464"
FT /id="VSP_012024"
FT VAR_SEQ 277..296
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14739464"
FT /id="VSP_012025"
FT VAR_SEQ 342
FT /note="Q -> QAGVQWRYLGSLQPPPPRYKRFSCLTLPSSWDYRRLPPHL (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012027"
FT MUTAGEN 111..113
FT /note="RKR->AKA: Abolishes localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:12615916"
FT MUTAGEN 136
FT /note="C->A: Abolishes p53 ubiquitination and degradation
FT but not that of JUN; when associated with A-139."
FT /evidence="ECO:0000269|PubMed:12615916,
FT ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:19805145,
FT ECO:0000269|PubMed:21625211"
FT MUTAGEN 136
FT /note="C->S: Loss of SFN and MTA1 ubiquitination and
FT degradation; when associated with S-139. Loss of
FT stabilization by COPS6; when associated with S-139."
FT /evidence="ECO:0000269|PubMed:12615916,
FT ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:19805145,
FT ECO:0000269|PubMed:21625211"
FT MUTAGEN 139
FT /note="C->A: Abolishes p53 ubiquitination and degradation
FT but not that of JUN; when associated with A-136."
FT /evidence="ECO:0000269|PubMed:12615916,
FT ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:19805145,
FT ECO:0000269|PubMed:21625211"
FT MUTAGEN 139
FT /note="C->S: Loss of SFN and MTA1 ubiquitination and
FT degradation; when associated with S-136. Loss of
FT stabilization by COPS6; when associated with S-136."
FT /evidence="ECO:0000269|PubMed:12615916,
FT ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:19805145,
FT ECO:0000269|PubMed:21625211"
FT MUTAGEN 156
FT /note="C->S: Loss of MTA1 ubiquitination and degradation;
FT when associated with S-159."
FT /evidence="ECO:0000269|PubMed:19805145"
FT MUTAGEN 159
FT /note="C->S: Loss of MTA1 ubiquitination and degradation;
FT when associated with S-156."
FT /evidence="ECO:0000269|PubMed:19805145"
FT HELIX 392..399
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 404..412
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 424..429
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 433..440
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 443..449
FT /evidence="ECO:0007829|PDB:5HQG"
FT HELIX 450..453
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 464..468
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 473..478
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 485..490
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 495..499
FT /evidence="ECO:0007829|PDB:5HQG"
FT TURN 500..502
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 505..509
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 528..533
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 536..542
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 549..553
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 558..563
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 570..575
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 580..584
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 592..595
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 602..617
FT /evidence="ECO:0007829|PDB:5HQG"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 621..626
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 633..636
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 648..651
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 654..658
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 662..668
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 676..679
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 700..705
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 709..711
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 715..720
FT /evidence="ECO:0007829|PDB:5HQG"
FT STRAND 723..731
FT /evidence="ECO:0007829|PDB:5HQG"
SQ SEQUENCE 731 AA; 80474 MW; C4B262268D01FA00 CRC64;
MSGSRQAGSG SAGTSPGSSA ASSVTSASSS LSSSPSPPSV AVSAAALVSG GVAQAAGSGG
LGGPVRPVLV APAVSGSGGG AVSTGLSRHS CAARPSAGVG GSSSSLGSGS RKRPLLAPLC
NGLINSYEDK SNDFVCPICF DMIEEAYMTK CGHSFCYKCI HQSLEDNNRC PKCNYVVDNI
DHLYPNFLVN ELILKQKQRF EEKRFKLDHS VSSTNGHRWQ IFQDWLGTDQ DNLDLANVNL
MLELLVQKKK QLEAESHAAQ LQILMEFLKV ARRNKREQLE QIQKELSVLE EDIKRVEEMS
GLYSPVSEDS TVPQFEAPSP SHSSIIDSTE YSQPPGFSGS SQTKKQPWYN STLASRRKRL
TAHFEDLEQC YFSTRMSRIS DDSRTASQLD EFQECLSKFT RYNSVRPLAT LSYASDLYNG
SSIVSSIEFD RDCDYFAIAG VTKKIKVYEY DTVIQDAVDI HYPENEMTCN SKISCISWSS
YHKNLLASSD YEGTVILWDG FTGQRSKVYQ EHEKRCWSVD FNLMDPKLLA SGSDDAKVKL
WSTNLDNSVA SIEAKANVCC VKFSPSSRYH LAFGCADHCV HYYDLRNTKQ PIMVFKGHRK
AVSYAKFVSG EEIVSASTDS QLKLWNVGKP YCLRSFKGHI NEKNFVGLAS NGDYIACGSE
NNSLYLYYKG LSKTLLTFKF DTVKSVLDKD RKEDDTNEFV SAVCWRALPD GESNVLIAAN
SQGTIKVLEL V
