Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU6C41M)

• DOT Name: RNA/RNP complex-1-interacting phosphatase (DUSP11)
• Synonyms: EC 3.1.3.-; Dual specificity protein phosphatase 11; Phosphatase that interacts with RNA/RNP complex 1
• Gene Name: DUSP11
• Related Disease:
  Advanced cancer
  Hepatitis C virus infection
  Neoplasm
• UniProt ID: DUS11_HUMAN
• PDB ID: 4JMJ; 4MBB; 4NYH
• EC Number: 3.1.3.-
• Pfam ID: PF00782
• Sequence:
  MSQWHHPRSGWGRRRDFSGRSSAKKKGGNHIPERWKDYLPVGQRMPGTRFIAFKVPLQKS
  FEKKLAPEECFSPLDLFNKIREQNEELGLIIDLTYTQRYYKPEDLPETVPYLKIFTVGHQ
  VPDDETIFKFKHAVNGFLKENKDNDKLIGVHCTHGLNRTGYLICRYLIDVEGVRPDDAIE
  LFNRCRGHCLERQNYIEDLQNGPIRKNWNSSVPRSSDFEDSAHLMQPVHNKPVKQGPRYN
  LHQIQGHSAPRHFHTQTQSLQQSVRKFSENPHVYQRHHLPPPGPPGEDYSHRRYSWNVKP
  NASRAAQDRRRWYPYNYSRLSYPACWEWTQ
• Function: Possesses RNA 5'-triphosphatase and diphosphatase activities, but displays a poor protein-tyrosine phosphatase activity. In addition, has phosphatase activity with ATP, ADP and O-methylfluorescein phosphate (in vitro). Binds to RNA. May participate in nuclear mRNA metabolism.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[5]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[12]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[13]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA/RNP complex-1-interacting phosphatase (DUSP11).	[10]

References

• [1] PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers.Oncol Rep. 2004 Mar;11(3):655-9.
• [2] RNA triphosphatase DUSP11 enables exonuclease XRN-mediated restriction of hepatitis C virus.Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):8197-8202. doi: 10.1073/pnas.1802326115. Epub 2018 Jul 23.
• [3] Identification of differentially expressed genes involved in the formation of multicellular tumor spheroids by HT-29 colon carcinoma cells.Mol Ther. 2007 Jan;15(1):94-102. doi: 10.1038/sj.mt.6300003.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [6] 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.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate. Hum Exp Toxicol. 2007 Sep;26(9):747-52. doi: 10.1177/0960327107083453.