Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQYW1J3)

• DOT Name: Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2)
• Synonyms: EC 3.4.19.12; Deubiquitinating enzyme MINDY-2; Protein FAM63B
• Gene Name: MINDY2
• Related Disease:
  Schizophrenia
  Bipolar disorder
• UniProt ID: MINY2_HUMAN
• PDB ID: 6Z49; 6Z7V; 7NPI
• EC Number: 3.4.19.12
• Pfam ID: PF04424
• Sequence:
  MESSPESLQPLEHGVAAGPASGTGSSQEGLQETRLAAGDGPGVWAAETSGGNGLGAAAAR
  RSLPDSASPAGSPEVPGPCSSSAGLDLKDSGLESPAAAEAPLRGQYKVTASPETAVAGVG
  HELGTAGDAGARPDLAGTCQAELTAAGSEEPSSAGGLSSSCSDPSPPGESPSLDSLESFS
  NLHSFPSSCEFNSEEGAENRVPEEEEGAAVLPGAVPLCKEEEGEETAQVLAASKERFPGQ
  SVYHIKWIQWKEENTPIITQNENGPCPLLAILNVLLLAWKVKLPPMMEIITAEQLMEYLG
  DYMLDAKPKEISEIQRLNYEQNMSDAMAILHKLQTGLDVNVRFTGVRVFEYTPECIVFDL
  LDIPLYHGWLVDPQIDDIVKAVGNCSYNQLVEKIISCKQSDNSELVSEGFVAEQFLNNTA
  TQLTYHGLCELTSTVQEGELCVFFRNNHFSTMTKYKGQLYLLVTDQGFLTEEKVVWESLH
  NVDGDGNFCDSEFHLRPPSDPETVYKGQQDQIDQDYLMALSLQQEQQSQEINWEQIPEGI
  SDLELAKKLQEEEDRRASQYYQEQEQAAAAAAAASTQAQQGQPAQASPSSGRQSGNSERK
  RKEPREKDKEKEKEKNSCVIL
• Function: Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins. Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63'. May play a regulatory role at the level of protein turnover.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ubiquitin carboxyl-terminal hydrolase MINDY-2 (MINDY2).	[5]

References

• [1] DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder.Psychiatry Clin Neurosci. 2018 Apr;72(4):245-254. doi: 10.1111/pcn.12645. Epub 2018 Mar 11.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.