Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFM2W9G)

• DOT Name: DCN1-like protein 2 (DCUN1D2)
• Synonyms: DCNL2; DCUN1 domain-containing protein 2; Defective in cullin neddylation protein 1-like protein 2
• Gene Name: DCUN1D2
• UniProt ID: DCNL2_HUMAN
• PDB ID: 4GAO
• Pfam ID: PF03556 ; PF14555
• Sequence:
  MHKLKSSQKDKVRQFMACTQAGERTAIYCLTQNEWRLDEATDSFFQNPDSLHRESMRNAV
  DKKKLERLYGRYKDPQDENKIGVDGIQQFCDDLSLDPASISVLVIAWKFRAATQCEFSRK
  EFLDGMTELGCDSMEKLKALLPRLEQELKDTAKFKDFYQFTFTFAKNPGQKGLDLEMAVA
  YWKLVLSGRFKFLDLWNTFLMEHHKRSIPRDTWNLLLDFGNMIADDMSNYDEEGAWPVLI
  DDFVEYARPVVTGGKRSLF
• Function: Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and plays an essential role in the regulation of SCF (SKP1-CUL1-F-box protein)-type complexes activity.
• Tissue Specificity: Mostly expressed in liver, kidney and brain.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DCN1-like protein 2 (DCUN1D2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DCN1-like protein 2 (DCUN1D2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DCN1-like protein 2 (DCUN1D2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DCN1-like protein 2 (DCUN1D2).	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DCN1-like protein 2 (DCUN1D2).	[5]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.