Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6Y3HD)

• DOT Name: Proton myo-inositol cotransporter (SLC2A13)
• Synonyms: H(+)-myo-inositol cotransporter; Hmit; H(+)-myo-inositol symporter; Solute carrier family 2 member 13
• Gene Name: SLC2A13
• UniProt ID: MYCT_HUMAN
• Pfam ID: PF00083
• Sequence:
  MSRKASENVEYTLRSLSSLMGERRRKQPEPDAASAAGECSLLAAAESSTSLQSAGAGGGG
  VGDLERAARRQFQQDETPAFVYVVAVFSALGGFLFGYDTGVVSGAMLLLKRQLSLDALWQ
  ELLVSSTVGAAAVSALAGGALNGVFGRRAAILLASALFTAGSAVLAAANNKETLLAGRLV
  VGLGIGIASMTVPVYIAEVSPPNLRGRLVTINTLFITGGQFFASVVDGAFSYLQKDGWRY
  MLGLAAVPAVIQFFGFLFLPESPRWLIQKGQTQKARRILSQMRGNQTIDEEYDSIKNNIE
  EEEKEVGSAGPVICRMLSYPPTRRALIVGCGLQMFQQLSGINTIMYYSATILQMSGVEDD
  RLAIWLASVTAFTNFIFTLVGVWLVEKVGRRKLTFGSLAGTTVALIILALGFVLSAQVSP
  RITFKPIAPSGQNATCTRYSYCNECMLDPDCGFCYKMNKSTVIDSSCVPVNKASTNEAAW
  GRCENETKFKTEDIFWAYNFCPTPYSWTALLGLILYLVFFAPGMGPMPWTVNSEIYPLWA
  RSTGNACSSGINWIFNVLVSLTFLHTAEYLTYYGAFFLYAGFAAVGLLFIYGCLPETKGK
  KLEEIESLFDNRLCTCGTSDSDEGRYIEYIRVKGSNYHLSDNDASDVE
• Function: H(+)-myo-inositol cotransporter. Can also transport related stereoisomers.
• Tissue Specificity: Predominantly expressed in the brain.
• Reactome Pathway: Inositol transporters (R-HSA-429593)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Proton myo-inositol cotransporter (SLC2A13).	[1]

11 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 Proton myo-inositol cotransporter (SLC2A13).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Proton myo-inositol cotransporter (SLC2A13).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Proton myo-inositol cotransporter (SLC2A13).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[6]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[9]
Manganese	DMKT129	Investigative	Manganese increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[10]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Proton myo-inositol cotransporter (SLC2A13).	[11]

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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] 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.
• [10] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [11] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.