Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6YZPWC)

• DOT Name: Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3)
• Synonyms: EC 3.4.19.12; Dermal papilla-derived protein 5; Deubiquitinating enzyme MINDY-3; Protein CARP
• Gene Name: MINDY3
• Related Disease:
  Astrocytoma
  Breast adenocarcinoma
  Cerebellar ataxia
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Hypertrophic cardiomyopathy
  Inflammatory bowel disease
  Intellectual disability
  Lung carcinoma
  Non-small-cell lung cancer
  Rhabdomyosarcoma
  Stomach cancer
  MALT lymphoma
  Neoplasm
  Stroke
• UniProt ID: MINY3_HUMAN
• EC Number: 3.4.19.12
• Pfam ID: PF13898
• Sequence:
  MSELTKELMELVWGTKSSPGLSDTIFCRWTQGFVFSESEGSALEQFEGGPCAVIAPVQAF
  LLKKLLFSSEKSSWRDCSEEEQKELLCHTLCDILESACCDHSGSYCLVSWLRGKTTEETA
  SISGSPAESSCQVEHSSALAVEELGFERFHALIQKRSFRSLPELKDAVLDQYSMWGNKFG
  VLLFLYSVLLTKGIENIKNEIEDASEPLIDPVYGHGSQSLINLLLTGHAVSNVWDGDREC
  SGMKLLGIHEQAAVGFLTLMEALRYCKVGSYLKSPKFPIWIVGSETHLTVFFAKDMALVA
  PEAPSEQARRVFQTYDPEDNGFIPDSLLEDVMKALDLVSDPEYINLMKNKLDPEGLGIIL
  LGPFLQEFFPDQGSSGPESFTVYHYNGLKQSNYNEKVMYVEGTAVVMGFEDPMLQTDDTP
  IKRCLQTKWPYIELLWTTDRSPSLN
• Function: Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
• Tissue Specificity: Widely expressed with high levels in heart, skeletal muscle, and kidney, and low levels in liver and brain . Also expressed in lung (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Strong	Biomarker	[1]
Breast adenocarcinoma	DISMPHJ0	Strong	Altered Expression	[2]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[3]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[5]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[6]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[7]
Intellectual disability	DISMBNXP	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[8]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[9]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[10]
MALT lymphoma	DIS1AVVE	moderate	Altered Expression	[11]
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]
Stroke	DISX6UHX	moderate	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[22]

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 Ubiquitin carboxyl-terminal hydrolase MINDY-3 (MINDY3).	[20]

References

• [1] Carbonic anhydrase related protein expression in astrocytomas and oligodendroglial tumors.BMC Cancer. 2018 May 23;18(1):584. doi: 10.1186/s12885-018-4493-4.
• [2] In vitro antiestrogenic effects of aryl methyl sulfone metabolites of polychlorinated biphenyls and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene on 17beta-estradiol-induced gene expression in several bioassay systems.Toxicol Sci. 2002 Oct;69(2):362-72. doi: 10.1093/toxsci/69.2.362.
• [3] Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.Hum Mol Genet. 2013 Feb 1;22(3):417-32. doi: 10.1093/hmg/dds438. Epub 2012 Oct 18.
• [4] MLP and CARP are linked to chronic PKC signalling in dilated cardiomyopathy.Nat Commun. 2016 Jun 29;7:12120. doi: 10.1038/ncomms12120.
• [5] Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. Eur Heart J. 2009 Sep;30(17):2128-36. doi: 10.1093/eurheartj/ehp225. Epub 2009 Jun 12.
• [6] Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy.J Am Coll Cardiol. 2009 Jul 21;54(4):334-42. doi: 10.1016/j.jacc.2008.12.082.
• [7] Association of CARD8 with inflammatory bowel disease in Koreans.J Hum Genet. 2011 Mar;56(3):217-23. doi: 10.1038/jhg.2010.170. Epub 2011 Jan 20.
• [8] C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer.Oncogene. 2011 Sep 29;30(39):4107-17. doi: 10.1038/onc.2011.116. Epub 2011 Apr 18.
• [9] Carp, a cardiac ankyrin-repeated protein, and its new homologue, Arpp, are differentially expressed in heart, skeletal muscle, and rhabdomyosarcomas.Am J Pathol. 2002 May;160(5):1767-78. doi: 10.1016/S0002-9440(10)61123-6.
• [10] CARP is a potential tumor suppressor in gastric carcinoma and a single-nucleotide polymorphism in CARP gene might increase the risk of gastric carcinoma.PLoS One. 2014 May 28;9(5):e97743. doi: 10.1371/journal.pone.0097743. eCollection 2014.
• [11] Bcl10 expression, rearrangement and mutation in MALT lymphoma: correlation with expression of nuclear factor-kappaB.Int J Oncol. 2001 Aug;19(2):283-9.
• [12] Assessment of R18, COG1410, and APP96-110 in Excitotoxicity and Traumatic Brain Injury.Transl Neurosci. 2017 Nov 15;8:147-157. doi: 10.1515/tnsci-2017-0021. eCollection 2017.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] 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.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [17] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [18] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.