Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP16ERR)

• DOT Name: Protein inscuteable homolog (INSC)
• Gene Name: INSC
• UniProt ID: INSC_HUMAN
• PDB ID: 3SF4
• Pfam ID: PF19427 ; PF16748
• Sequence:
  MRRPPGNGEAASEGPGGWGLWGVQESRRLCCAGHDRCKQALLQIGINMMALPGGRHLDSV
  TLPGQRLHLMQVDSVQRWMEDLKLMTECECMCVLQAKPISLEEDAQGDLILAGGPGPGDP
  LQLLLKRGWVISTELRRIGQKLAQDRWARVHSMSVRLTCHARSMVSEYSAVSRNSLKEMG
  EIEKLLMEKCSELSAVTERCLQVENEHVLKSMKACVSETLSMLGQHFGQLLELALTREVQ
  ALVRKIDASDNIYTTESTTGNLFSLTQEGAPLCRIIAKEGGVVALFKVCRQDSFRCLYPQ
  ALRTLASICCVEEGVHQLEKVDGVLCLADILTDNSHSEATRAEAAAVVAQVTSPHLPVTQ
  HLSSFLESMEEIVTALVKLCQEASSGEVFLLASAALANITFFDTMACEMLLQLNAIRVLL
  EACSDKQRVDTPYTRDQIVTILANMSVLEQCASDIIQENGVQLIMGMLSEKPRSGTPAEV
  AACERVQQKAAVTLARLSRDPDVAREAVRLSCMSRLIELCRSPSERNSSDAVLVACLAAL
  RRLAGVCPEGLQDSDFQQLVQPRLVDSFLLCSNMEESFV
• Function: May function as an adapter linking the Par3 complex to the GPSM1/GPSM2 complex. Involved in spindle orientation during mitosis. May regulate cell proliferation and differentiation in the developing nervous system. May play a role in the asymmetric division of fibroblasts and participate in the process of stratification of the squamous epithelium.
• Tissue Specificity: Isoform 1 is expressed in various tissues with stronger expression in liver, kidney and small intestine. Isoform 2 is abundantly expressed in small intestine and to a lower extent in lung and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein inscuteable homolog (INSC).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein inscuteable homolog (INSC).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein inscuteable homolog (INSC).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein inscuteable homolog (INSC).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein inscuteable homolog (INSC).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein inscuteable homolog (INSC).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein inscuteable homolog (INSC).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein inscuteable homolog (INSC).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein inscuteable homolog (INSC).	[7]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.