General Information of Drug Therapeutic Target (DTT) (ID: TT05DLS)

DTT Name E3 ubiquitin-protein ligase COP1 (RFWD2)
Synonyms
hCOP1; RNF200; RING-type E3 ubiquitin transferase RFWD2; RING finger protein 200; RING finger and WD repeat domain protein 2; E3 ubiquitinprotein ligase RFWD2; Constitutive photomorphogenesis protein 1 homolog; COP1
Gene Name RFWD2
DTT Type
Successful target
[1]
BioChemical Class
Acyltransferase
UniProt ID
COP1_HUMAN
TTD ID
T12819
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.3.2.27
Sequence
MSGSRQAGSGSAGTSPGSSAASSVTSASSSLSSSPSPPSVAVSAAALVSGGVAQAAGSGG
LGGPVRPVLVAPAVSGSGGGAVSTGLSRHSCAARPSAGVGGSSSSLGSGSRKRPLLAPLC
NGLINSYEDKSNDFVCPICFDMIEEAYMTKCGHSFCYKCIHQSLEDNNRCPKCNYVVDNI
DHLYPNFLVNELILKQKQRFEEKRFKLDHSVSSTNGHRWQIFQDWLGTDQDNLDLANVNL
MLELLVQKKKQLEAESHAAQLQILMEFLKVARRNKREQLEQIQKELSVLEEDIKRVEEMS
GLYSPVSEDSTVPQFEAPSPSHSSIIDSTEYSQPPGFSGSSQTKKQPWYNSTLASRRKRL
TAHFEDLEQCYFSTRMSRISDDSRTASQLDEFQECLSKFTRYNSVRPLATLSYASDLYNG
SSIVSSIEFDRDCDYFAIAGVTKKIKVYEYDTVIQDAVDIHYPENEMTCNSKISCISWSS
YHKNLLASSDYEGTVILWDGFTGQRSKVYQEHEKRCWSVDFNLMDPKLLASGSDDAKVKL
WSTNLDNSVASIEAKANVCCVKFSPSSRYHLAFGCADHCVHYYDLRNTKQPIMVFKGHRK
AVSYAKFVSGEEIVSASTDSQLKLWNVGKPYCLRSFKGHINEKNFVGLASNGDYIACGSE
NNSLYLYYKGLSKTLLTFKFDTVKSVLDKDRKEDDTNEFVSAVCWRALPDGESNVLIAAN
SQGTIKVLELV
Function
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 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif. E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins.
KEGG Pathway
p53 signaling pathway (hsa04115 )
Ubiquitin mediated proteolysis (hsa04120 )
Reactome Pathway
Neddylation (R-HSA-8951664 )
Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
5 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Flecainide DMSQDLE Tachyarrhythmias BC71 Approved [1]
Procainamide DMNMXR8 Ventricular arrhythmias BC71 Approved [1]
Propafenone DMPIBJK Tachyarrhythmias BC71 Approved [1]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [1]
Tocainide DMYNMDP Ventricular arrhythmias BC71 Approved [1]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Barucainide DMTMS3L Heart arrhythmia BC65 Terminated [2]
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References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
2 Barucainide, 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.