Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT044C50)

• DOT Name: Dual specificity protein phosphatase 13A (DUSP13B)
• Synonyms: DUSP13A; EC 3.1.3.16; EC 3.1.3.48; Branching-enzyme interacting DSP; Muscle-restricted DSP; MDSP
• Gene Name: DUSP13B
• UniProt ID: DS13A_HUMAN
• PDB ID: 5XJV
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MAETSLPELGGEDKATPCPSILELEELLRAGKSSCSRVDEVWPNLFIGDAATANNRFELW
  KLGITHVLNAAHKGLYCQGGPDFYGSSVSYLGVPAHDLPDFDISAYFSSAADFIHRALNT
  PGAKVLVHCVVGVSRSATLVLAYLMLHQRLSLRQAVITVRQHRWVFPNRGFLHQLCRLDQ
  QLRGAGQS
• Function: Probable protein tyrosine phosphatase. Has phosphatase activity with synthetic substrates. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.
• Tissue Specificity: Skeletal muscle specific.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Dual specificity protein phosphatase 13A (DUSP13B).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Dual specificity protein phosphatase 13A (DUSP13B).	[9]

9 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 Dual specificity protein phosphatase 13A (DUSP13B).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[5]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dual specificity protein phosphatase 13A (DUSP13B).	[10]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis. Environ Mol Mutagen. 2009 Jan;50(1):46-59.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.