Target General Infomation
Target ID
T12819
Former ID
TTDI01954
Target Name
E3 ubiquitin protein ligase COP1
Gene Name
RFWD2
Synonyms
Constitutive photomorphogenesis protein 1 homolog; E3 ubiquitinprotein ligase RFWD2; RING finger and WD repeat domain protein 2; RING finger protein 200; hCOP1; RFWD2
Target Type
Successful
Disease Heart arrhythmia [ICD10: I47-I49]
Malaria [ICD10: B54]
Tachyarrhythmias [ICD9: 427, 785.0; ICD10: I47-I49, R00.0]
Ventricular arrhythmias [ICD9: 427.1; ICD10: I47.2]
Function
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 proteinsigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation.
BioChemical Class
Carbon-nitrogen ligase
UniProt ID
EC Number
EC 6.3.2.-
Sequence
MSGSRQAGSGSAGTSPGSSAASSVTSASSSLSSSPSPPSVAVSAAALVSGGVAQAAGSGG
LGGPVRPVLVAPAVSGSGGGAVSTGLSRHSCAARPSAGVGGSSSSLGSGSRKRPLLAPLC
NGLINSYEDKSNDFVCPICFDMIEEAYMTKCGHSFCYKCIHQSLEDNNRCPKCNYVVDNI
DHLYPNFLVNELILKQKQRFEEKRFKLDHSVSSTNGHRWQIFQDWLGTDQDNLDLANVNL
MLELLVQKKKQLEAESHAAQLQILMEFLKVARRNKREQLEQIQKELSVLEEDIKRVEEMS
GLYSPVSEDSTVPQFEAPSPSHSSIIDSTEYSQPPGFSGSSQTKKQPWYNSTLASRRKRL
TAHFEDLEQCYFSTRMSRISDDSRTASQLDEFQECLSKFTRYNSVRPLATLSYASDLYNG
SSIVSSIEFDRDCDYFAIAGVTKKIKVYEYDTVIQDAVDIHYPENEMTCNSKISCISWSS
YHKNLLASSDYEGTVILWDGFTGQRSKVYQEHEKRCWSVDFNLMDPKLLASGSDDAKVKL
WSTNLDNSVASIEAKANVCCVKFSPSSRYHLAFGCADHCVHYYDLRNTKQPIMVFKGHRK
AVSYAKFVSGEEIVSASTDSQLKLWNVGKPYCLRSFKGHINEKNFVGLASNGDYIACGSE
NNSLYLYYKGLSKTLLTFKFDTVKSVLDKDRKEDDTNEFVSAVCWRALPDGESNVLIAAN
SQGTIKVLELV
Drugs and Mode of Action
Drug(s) Flecainide Drug Info Approved Tachyarrhythmias [538298], [539654]
Procainamide Drug Info Approved Ventricular arrhythmias [468043], [538376]
Propafenone Drug Info Approved Tachyarrhythmias [536095], [539655]
Quinine Drug Info Approved Malaria [538576], [539633]
Tocainide Drug Info Approved Ventricular arrhythmias [538501], [542331]
Barucainide Drug Info Terminated Heart arrhythmia [544576]
Modulator Barucainide Drug Info [532190]
Flecainide Drug Info [556264]
Procainamide Drug Info [556264]
Propafenone Drug Info [556264]
Quinine Drug Info [556264]
Tocainide Drug Info [556264]
Pathways
KEGG Pathway p53 signaling pathway
Ubiquitin mediated proteolysis
PANTHER Pathway P53 pathway feedback loops 1
Pathway Interaction Database ATM pathway
Direct p53 effectors
p53 pathway
References
Ref 468043(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4811).
Ref 536095New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22.
Ref 538298FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075442.
Ref 538376FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 089257.
Ref 538501FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018257.
Ref 538576FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021799.
Ref 539633(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2510).
Ref 539654(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2560).
Ref 539655(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2561).
Ref 542331(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7309).
Ref 544576Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000197)
Ref 532190Barucainide, a novel class Ib antiarrhythmic agent with a slow kinetic property: electrophysiologic observations in isolated canine and rabbit cardiac muscle. Am Heart J. 1990 May;119(5):1050-60.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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