Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ1MRN2)

• DOT Name: Solute carrier family 35 member B1 (SLC35B1)
• Synonyms: ATP/ADP exchanger ER; AXER; Endoplasmic reticulum ATP/ADP translocase; UDP-galactose transporter-related protein 1; UGTrel1
• Gene Name: SLC35B1
• UniProt ID: S35B1_HUMAN
• Pfam ID: PF08449
• Sequence:
  MASSSSLVPDRLRLPLCFLGVFVCYFYYGILQEKITRGKYGEGAKQETFTFALTLVFIQC
  VINAVFAKILIQFFDTARVDRTRSWLYAACSISYLGAMVSSNSALQFVNYPTQVLGKSCK
  PIPVMLLGVTLLKKKYPLAKYLCVLLIVAGVALFMYKPKKVVGIEEHTVGYGELLLLLSL
  TLDGLTGVSQDHMRAHYQTGSNHMMLNINLWSTLLLGMGILFTGELWEFLSFAERYPAII
  YNILLFGLTSALGQSFIFMTVVYFGPLTCSIITTTRKFFTILASVILFANPISPMQWVGT
  VLVFLGLGLDAKFGKGAKKTSH
• Function: ATP:ADP antiporter that catalyzes the exchange of ATP and ADP across the endoplasmic reticulum (ER) membrane. Imports ATP from the cytosol to the ER lumen and exports ADP in the opposite direction. Regulates ER energy metabolism and protein biogenesis. Appears to be part of a calcium-dependent ER to cytosol low energy response axis, where calcium efflux from ER to the cytosol triggers ATP import into the ER lumen to maintain sufficient ATP supply. Provides ATP to ER chaperone HSPA5 that drives protein folding and trafficking in the ER. Can transport dATP, UTP or UDP in exchange for ATP, but the physiological relevance of this process remains to be established ; [Isoform 1]: ATP:ADP antiporter; [Isoform 2]: ATP:ADP antiporter.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Solute carrier family 35 member B1 (SLC35B1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Solute carrier family 35 member B1 (SLC35B1).	[7]

7 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 Solute carrier family 35 member B1 (SLC35B1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 35 member B1 (SLC35B1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Solute carrier family 35 member B1 (SLC35B1).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Solute carrier family 35 member B1 (SLC35B1).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Solute carrier family 35 member B1 (SLC35B1).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Solute carrier family 35 member B1 (SLC35B1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Solute carrier family 35 member B1 (SLC35B1).	[9]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [7] 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.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.