Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL3RA91)

• DOT Name: Smad nuclear-interacting protein 1 (SNIP1)
• Synonyms: FHA domain-containing protein SNIP1
• Gene Name: SNIP1
• Related Disease:
  Advanced cancer
  Childhood epilepsy with centrotemporal spikes
  Inflammatory bowel disease
  Leiomyoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Schizophrenia
  Uterine fibroids
  Neuroblastoma
  Progressive multifocal leukoencephalopathy
  Psychomotor retardation, epilepsy, and craniofacial dysmorphism
• UniProt ID: SNIP1_HUMAN
• PDB ID: 5Z56; 5Z57; 5Z58; 6FF7; 7ABG; 7ABH; 7ABI; 7DVQ
• Pfam ID: PF00498
• Sequence:
  MKAVKSERERGSRRRHRDGDVVLPAGVVVKQERLSPEVAPPAHRRPDHSGGSPSPPTSEP
  ARSGHRGNRARGVSRSPPKKKNKASGRRSKSPRSKRNRSPHHSTVKVKQEREDHPRRGRE
  DRQHREPSEQEHRRARNSDRDRHRGHSHQRRTSNERPGSGQGQGRDRDTQNLQAQEEERE
  FYNARRREHRQRNDVGGGGSESQELVPRPGGNNKEKEVPAKEKPSFELSGALLEDTNTFR
  GVVIKYSEPPEARIPKKRWRLYPFKNDEVLPVMYIHRQSAYLLGRHRRIADIPIDHPSCS
  KQHAVFQYRLVEYTRADGTVGRRVKPYIIDLGSGNGTFLNNKRIEPQRYYELKEKDVLKF
  GFSSREYVLLHESSDTSEIDRKDDEDEEEEEEVSDS
• Function: Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA.
• Tissue Specificity: Ubiquitous, with highest expression in heart and skeletal muscle.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[2]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[3]
Leiomyoma	DISLDDFN	Strong	Genetic Variation	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[8]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[9]
Progressive multifocal leukoencephalopathy	DISX02WS	Limited	Biomarker	[10]
Psychomotor retardation, epilepsy, and craniofacial dysmorphism	DISP341L	Limited	Autosomal recessive	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Smad nuclear-interacting protein 1 (SNIP1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Smad nuclear-interacting protein 1 (SNIP1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Smad nuclear-interacting protein 1 (SNIP1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Smad nuclear-interacting protein 1 (SNIP1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Smad nuclear-interacting protein 1 (SNIP1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Smad nuclear-interacting protein 1 (SNIP1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Smad nuclear-interacting protein 1 (SNIP1).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Smad nuclear-interacting protein 1 (SNIP1).	[18]

References

• [1] Regulation of cyclin D1 RNA stability by SNIP1.Cancer Res. 2008 Sep 15;68(18):7621-8. doi: 10.1158/0008-5472.CAN-08-1217.
• [2] Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.Eur J Hum Genet. 2018 Feb;26(2):258-264. doi: 10.1038/s41431-017-0034-x. Epub 2018 Jan 22.
• [3] Smad nuclear interacting protein 1 (SNIP1) inhibits intestinal inflammation through regulation of epithelial barrier function.Mucosal Immunol. 2018 May;11(3):835-845. doi: 10.1038/mi.2017.95. Epub 2017 Nov 8.
• [4] Insulin-like growth factors II exon 9 and E-cadherin-Pml I but not myeloperoxidase promoter-463, urokinase-ApaL I nor xeroderma pigmentosum polymorphisms are associated with higher susceptibility to leiomyoma.Anticancer Res. 2010 Jun;30(6):2203-8.
• [5] High expression of SNIP1 correlates with poor prognosis in non-small cell lung cancer and SNIP1 interferes with the recruitment of HDAC1 to RB in vitro.Lung Cancer. 2013 Oct;82(1):24-30. doi: 10.1016/j.lungcan.2013.07.015. Epub 2013 Aug 9.
• [6] Impact of NAD(P)H:quinone oxidoreductase-1 on pigmentation.J Invest Dermatol. 2010 Mar;130(3):784-92. doi: 10.1038/jid.2009.280. Epub 2009 Sep 17.
• [7] Clinical implication of programmed cell death-1 ligand-1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition.Hum Pathol. 2018 Oct;80:28-39. doi: 10.1016/j.humpath.2018.03.025. Epub 2018 Apr 7.
• [8] Linkage disequilibrium on the COMT gene in French schizophrenics and controls.Am J Med Genet. 1999 Oct 15;88(5):452-7. doi: 10.1002/(sici)1096-8628(19991015)88:5<452::aid-ajmg2>3.3.co;2-s.
• [9] A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma.Clin Cancer Res. 2016 Jul 1;22(13):3398-409. doi: 10.1158/1078-0432.CCR-15-2081. Epub 2016 Apr 13.
• [10] Selective activation of NFAT by promyelocytic leukemia protein.Oncogene. 2008 Jun 19;27(27):3821-30. doi: 10.1038/onc.2008.2. Epub 2008 Feb 4.
• [11] Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. doi: 10.1371/journal.pone.0028936. Epub 2012 Jan 17.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.