Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHHFU00)

• DOT Name: U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35)
• Synonyms: U11/U12 snRNP 35 kDa protein; U11/U12-35K; Protein HM-1; U1 snRNP-binding protein homolog
• Gene Name: SNRNP35
• Related Disease: Vibrio cholerae infection
• UniProt ID: U1SBP_HUMAN
• Pfam ID: PF00076
• Sequence:
  MNDWMPIAKEYDPLKAGSIDGTDEDPHDRAVWRAMLARYVPNKGVIGDPLLTLFVARLNL
  QTKEDKLKEVFSRYGDIRRLRLVRDLVTGFSKGYAFIEYKEERAVIKAYRDADGLVIDQH
  EIFVDYELERTLKGWIPRRLGGGLGGKKESGQLRFGGRDRPFRKPINLPVVKNDLYREGK
  RERRERSRSRERHWDSRTRDRDHDRGREKRWQEREPTRVWPDNDWERERDFRDDRIKGRE
  KKERGK
• Tissue Specificity: Expressed in heart, liver, skeletal muscle and pancreas.
• Reactome Pathway: mRNA Splicing - Minor Pathway (R-HSA-72165)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[1]

14 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 U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[7]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[16]

2 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 affects the methylation of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of U11/U12 small nuclear ribonucleoprotein 35 kDa protein (SNRNP35).	[14]

References

• [1] Function of a heterologous muscarinic receptor in T cell antigen receptor signal transduction mutants.J Biol Chem. 1989 Oct 15;264(29):17190-7.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] 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.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] 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.
• [16] 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.