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 28-JAN-2026, entry version 196. 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=4; IntAct=EBI-1176214, EBI-3905068; CC Q8NHY2; P41161: ETV5; NbExp=4; IntAct=EBI-1176214, EBI-3905093; CC Q8NHY2; P05412: JUN; NbExp=5; IntAct=EBI-1176214, EBI-852823; CC Q8NHY2; P31947: SFN; NbExp=6; IntAct=EBI-1176214, EBI-476295; CC Q8NHY2; P04637: TP53; NbExp=5; IntAct=EBI-1176214, EBI-366083; 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}. 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; 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_001001740.4. [Q8NHY2-2] DR RefSeq; NP_001273573.1; NM_001286644.1. DR RefSeq; NP_071902.2; NM_022457.6. [Q8NHY2-1] DR RefSeq; XP_005245505.1; XM_005245448.4. [Q8NHY2-4] DR RefSeq; XP_054194172.1; XM_054338197.1. [Q8NHY2-4] 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; 337. DR CORUM; Q8NHY2; -. DR DIP; DIP-36661N; -. DR ELM; Q8NHY2; -. DR FunCoup; Q8NHY2; 2585. DR IntAct; Q8NHY2; 88. DR MINT; Q8NHY2; -. DR STRING; 9606.ENSP00000356641; -. DR ChEMBL; CHEMBL5465335; -. DR GlyGen; Q8NHY2; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q8NHY2; -. DR PhosphoSitePlus; Q8NHY2; -. DR BioMuta; RFWD2; -. DR DMDM; 55976539; -. DR jPOST; Q8NHY2; -. DR MassIVE; Q8NHY2; -. DR PaxDb; 9606-ENSP00000356641; -. DR PeptideAtlas; Q8NHY2; -. DR ProteomicsDB; 21473; -. DR ProteomicsDB; 73785; -. [Q8NHY2-1] DR ProteomicsDB; 73786; -. [Q8NHY2-2] DR ProteomicsDB; 73787; -. [Q8NHY2-3] DR Pumba; Q8NHY2; -. DR Antibodypedia; 34406; 248 antibodies from 30 providers. DR DNASU; 64326; -. DR Ensembl; ENST00000308769.12; ENSP00000310943.8; ENSG00000143207.22. [Q8NHY2-2] DR Ensembl; ENST00000367669.8; ENSP00000356641.3; ENSG00000143207.22. [Q8NHY2-1] DR Ensembl; ENST00000474194.1; ENSP00000433517.1; ENSG00000143207.22. [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 AGR; HGNC:17440; -. DR ClinPGx; PA134952161; -. DR CTD; 64326; -. DR DisGeNET; 64326; -. DR GeneCards; COP1; -. DR HGNC; HGNC:17440; COP1. DR HPA; ENSG00000143207; Low tissue specificity. DR MalaCards; COP1; -. DR MIM; 608067; gene. DR OpenTargets; ENSG00000143207; -. DR VEuPathDB; HostDB:ENSG00000143207; -. DR eggNOG; ENOG502QQ8V; Eukaryota. DR GeneTree; ENSGT00920000149161; -. DR HOGENOM; CLU_1677257_0_0_1; -. DR InParanoid; Q8NHY2; -. DR OMA; CWRQMSN; -. DR OrthoDB; 273771at2759; -. DR PAN-GO; Q8NHY2; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q8NHY2; -. 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 Agora; ENSG00000143207; -. DR BioGRID-ORCS; 64326; 183 hits in 1217 CRISPR screens. DR ChiTaRS; RFWD2; human. DR EvolutionaryTrace; Q8NHY2; -. 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 183 other cell types or tissues. DR ExpressionAtlas; Q8NHY2; baseline and differential. DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IC:UniProt. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. 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:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProt. 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:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProt. DR CDD; cd16504; RING-HC_COP1; 1. DR CDD; cd00200; WD40; 1. DR FunFam; 3.30.40.10:FF:000222; E3 ubiquitin-protein ligase COP1 isoform X2; 1. DR FunFam; 2.130.10.10:FF:000090; E3 ubiquitin-protein ligase RFWD2 isoform X1; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR042755; COP1. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR44080; E3 UBIQUITIN-PROTEIN LIGASE COP1; 1. DR PANTHER; PTHR44080:SF1; E3 UBIQUITIN-PROTEIN LIGASE COP1; 1. DR Pfam; PF00400; WD40; 5. DR Pfam; PF13923; zf-C3HC4_2; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00320; WD40; 6. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 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; Proteomics identification; Reference proteome; Repeat; KW Transferase; Ubl conjugation; Ubl conjugation pathway; WD repeat; Zinc; KW 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 //