Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZNC1C)

• DOT Name: Cysteine/serine-rich nuclear protein 2 (CSRNP2)
• Synonyms: CSRNP-2; Protein FAM130A1; TGF-beta-induced apoptosis protein 12; TAIP-12
• Gene Name: CSRNP2
• UniProt ID: CSRN2_HUMAN
• Pfam ID: PF16019
• Sequence:
  MDAFTGSGLKRKFDDVDVGSSVSNSDDEISSSDSADSCDSLNPPTTASFTPTSILKRQKQ
  LRRKNVRFDQVTVYYFARRQGFTSVPSQGGSSLGMAQRHNSVRSYTLCEFAQEQEVNHRE
  ILREHLKEEKLHAKKMKLTKNGTVESVEADGLTLDDVSDEDIDVENVEVDDYFFLQPLPT
  KRRRALLRASGVHRIDAEEKQELRAIRLSREECGCDCRLYCDPEACACSQAGIKCQVDRM
  SFPCGCSRDGCGNMAGRIEFNPIRVRTHYLHTIMKLELESKRQVSRPAAPDEEPSPTASC
  SLTGAQGSETQDFQEFIAENETAVMHLQSAEELERLKAEEDSSGSSASLDSSIESLGVCI
  LEEPLAVPEELCPGLTAPILIQAQLPPGSSVLCFTENSDHPTASTVNSPSYLNSGPLVYY
  QVEQRPVLGVKGEPGTEEGSASFPKEKDLNVFSLPVTSLVACSSTDPAALCKSEVGKTPT
  LEALLPEDCNPEEPENEDFHPSWSPSSLPFRTDNEEGCGMVKTSQQNEDRPPEDSSLELP
  LAV
• Function: Binds to the consensus sequence 5'-AGAGTG-3' and has transcriptional activator activity. May play a role in apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Cysteine/serine-rich nuclear protein 2 (CSRNP2) affects the response to substance of Mitoxantrone.	[15]

13 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 Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cysteine/serine-rich nuclear protein 2 (CSRNP2).	[9]

References

• [1] 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.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] 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.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [11] 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.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Prediction of doxorubicin sensitivity in breast tumors based on gene expression profiles of drug-resistant cell lines correlates with patient survival. Oncogene. 2005 Nov 17;24(51):7542-51. doi: 10.1038/sj.onc.1208908.