Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPW52JT)

• DOT Name: Nucleotide sugar transporter SLC35B4 (SLC35B4)
• Synonyms: Solute carrier family 35 member B4; UDP-xylose and UDP-N-acetylglucosamine transporter; YEA4 homolog
• Gene Name: SLC35B4
• UniProt ID: S35B4_HUMAN
• Pfam ID: PF08449
• Sequence:
  MRPALAVGLVFAGCCSNVIFLELLARKHPGCGNIVTFAQFLFIAVEGFLFEADLGRKPPA
  IPIRYYAIMVTMFFTVSVVNNYALNLNIAMPLHMIFRSGSLIANMILGIIILKKRYSIFK
  YTSIALVSVGIFICTFMSAKQVTSQSSLSENDGFQAFVWWLLGIGALTFALLMSARMGIF
  QETLYKRFGKHSKEALFYNHALPLPGFVFLASDIYDHAVLFNKSELYEIPVIGVTLPIMW
  FYLLMNIITQYVCIRGVFILTTECASLTVTLVVTLRKFVSLIFSILYFQNPFTLWHWLGT
  LFVFIGTLMYTEVWNNLGTTKSEPQKDSKKN
• Function: Antiporter that transports nucleotide sugars across the endoplasmic reticulum (ER) membrane in exchange for another nucleotide sugar. May couple UDP-alpha-D-glucuronate (UDP-GlcA) or UDP-alpha-D-xylose (UDP-Xyl) efflux to UDP-alpha-D-glucuronate (UDP-GlcA) influx into the ER lumen, which in turn stimulates glucuronidation and excretion of endobiotics and xenobiotics; [Isoform 1]: Has UDP-GlcA:UDP-GlcNAc antiporter activity; [Isoform 2]: Has UDP-GlcA:UDP-GlcNAc antiporter activity.
• Reactome Pathway: Transport of nucleotide sugars (R-HSA-727802)

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 Nucleotide sugar transporter SLC35B4 (SLC35B4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[7]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[9]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Nucleotide sugar transporter SLC35B4 (SLC35B4).	[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] 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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 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.
• [8] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.