Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT64VOCE)

• DOT Name: Protein shisa-5 (SHISA5)
• Synonyms: Putative NF-kappa-B-activating protein 120; Scotin
• Gene Name: SHISA5
• UniProt ID: SHSA5_HUMAN
• Pfam ID: PF13908
• Sequence:
  MTAPVPAPRILLPLLLLLLLTPPPGARGEVCMASRGLSLFPESCPDFCCGTCDDQYCCSD
  VLKKFVWSEERCAVPEASVPASVEPVEQLGSALRFRPGYNDPMSGFGATLAVGLTIFVLS
  VVTIIICFTCSCCCLYKTCRRPRPVVTTTTSTTVVHAPYPQPPSVPPSYPGPSYQGYHTM
  PPQPGMPAAPYPMQYPPPYPAQPMGPPAYHETLAGGAAAPYPASQPPYNPAYMDAPKAAL
• Function: Can induce apoptosis in a caspase-dependent manner and plays a role in p53/TP53-dependent apoptosis.
• KEGG Pathway: p53 sig.ling pathway (hsa04115)
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Protein shisa-5 (SHISA5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein shisa-5 (SHISA5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein shisa-5 (SHISA5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein shisa-5 (SHISA5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein shisa-5 (SHISA5).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein shisa-5 (SHISA5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein shisa-5 (SHISA5).	[7]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Protein shisa-5 (SHISA5).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein shisa-5 (SHISA5).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein shisa-5 (SHISA5).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein shisa-5 (SHISA5).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein shisa-5 (SHISA5).	[12]

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] 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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [9] 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.
• [10] 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.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.