Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3GCY98)

• DOT Name: OTU domain-containing protein 7A (OTUD7A)
• Synonyms: EC 3.4.19.12; Zinc finger protein Cezanne 2
• Gene Name: OTUD7A
• Related Disease:
  Advanced cancer
  Bipolar disorder
  Cardiac failure
  Depression
  Hepatocellular carcinoma
  Major depressive disorder
  Schizophrenia
  Complex neurodevelopmental disorder
• UniProt ID: OTU7A_HUMAN
• PDB ID: 2L2D
• EC Number: 3.4.19.12
• Pfam ID: PF02338 ; PF01754
• Sequence:
  MVSSVLPNPTSAECWAALLHDPMTLDMDAVLSDFVRSTGAEPGLARDLLEGKNWDLTAAL
  SDYEQLRQVHTANLPHVFNEGRGPKQPEREPQPGHKVERPCLQRQDDIAQEKRLSRGISH
  ASSAIVSLARSHVASECNNEQFPLEMPIYTFQLPDLSVYSEDFRSFIERDLIEQATMVAL
  EQAGRLNWWSTVCTSCKRLLPLATTGDGNCLLHAASLGMWGFHDRDLVLRKALYTMMRTG
  AEREALKRRWRWQQTQQNKEEEWEREWTELLKLASSEPRTHFSKNGGTGGGVDNSEDPVY
  ESLEEFHVFVLAHILRRPIVVVADTMLRDSGGEAFAPIPFGGIYLPLEVPPNRCHCSPLV
  LAYDQAHFSALVSMEQRDQQREQAVIPLTDSEHKLLPLHFAVDPGKDWEWGKDDNDNARL
  AHLILSLEAKLNLLHSYMNVTWIRIPSETRAPLAQPESPTASAGEDVQSLADSLDSDRDS
  VCSNSNSNNGKNGKDKEKEKQRKEKDKTRADSVANKLGSFSKTLGIKLKKNMGGLGGLVH
  GKMGRANSANGKNGDSAERGKEKKAKSRKGSKEESGASASTSPSEKTTPSPTDKAAGASP
  AEKGGGPRGDAWKYSTDVKLSLNILRAAMQGERKFIFAGLLLTSHRHQFHEEMIGYYLTS
  AQERFSAEQEQRRRDAATAAAAAAAAAAATAKRPPRRPETEGVPVPERASPGPPTQLVLK
  LKERPSPGPAAGRAARAAAGGTASPGGGARRASASGPVPGRSPPAPARQSVIHVQASGAR
  DEACAPAVGALRPCATYPQQNRSLSSQSYSPARAAALRTVNTVESLARAVPGALPGAAGT
  AGAAEHKSQTYTNGFGALRDGLEFADADAPTARSNGECGRGGPGPVQRRCQRENCAFYGR
  AETEHYCSYCYREELRRRREARGARP
• Function: Has deubiquitinating activity towards 'Lys-11'-linked polyubiquitin chains.
• Reactome Pathway: Ovarian tumor domain proteases (R-HSA-5689896)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of OTU domain-containing protein 7A (OTUD7A).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of OTU domain-containing protein 7A (OTUD7A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of OTU domain-containing protein 7A (OTUD7A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of OTU domain-containing protein 7A (OTUD7A).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of OTU domain-containing protein 7A (OTUD7A).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of OTU domain-containing protein 7A (OTUD7A).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of OTU domain-containing protein 7A (OTUD7A).	[12]

References

• [1] Snail1-dependent transcriptional repression of Cezanne2 in hepatocellular carcinoma.Oncogene. 2014 May 29;33(22):2836-45. doi: 10.1038/onc.2013.243. Epub 2013 Jun 24.
• [2] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [3] Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.Circ Cardiovasc Genet. 2010 Jun;3(3):248-55. doi: 10.1161/CIRCGENETICS.109.895995. Epub 2010 Apr 17.
• [4] Elevated TNIP3 mRNA Expression in TNF--Secreting Cells from Patients with Major Depressive Disorder.Neuroimmunomodulation. 2019;26(3):153-158. doi: 10.1159/000501083. Epub 2019 Jul 15.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [11] 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.
• [12] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.