Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWHCL4U)

• DOT Name: Nucleotide sugar transporter SLC35D2 (SLC35D2)
• Synonyms: Homolog of Fringe connection protein 1; HFRC1; SQV7-like protein; SQV7L; Solute carrier family 35 member D2; UDP-galactose transporter-related protein 8; UGTrel8
• Gene Name: SLC35D2
• UniProt ID: S35D2_HUMAN
• Pfam ID: PF03151
• Sequence:
  MTAGGQAEAEGAGGEPGAARLPSRVARLLSALFYGTCSFLIVLVNKALLTTYGFPSPIFL
  GIGQMAATIMILYVSKLNKIIHFPDFDKKIPVKLFPLPLLYVGNHISGLSSTSKLSLPMF
  TVLRKFTIPLTLLLETIILGKQYSLNIILSVFAIILGAFIAAGSDLAFNLEGYIFVFLND
  IFTAANGVYTKQKMDPKELGKYGVLFYNACFMIIPTLIISVSTGDLQQATEFNQWKNVVF
  ILQFLLSCFLGFLLMYSTVLCSYYNSALTTAVVGAIKNVSVAYIGILIGGDYIFSLLNFV
  GLNICMAGGLRYSFLTLSSQLKPKPVGEENICLDLKS
• Function: Nucleotide sugar antiporter transporting UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-glucose (UDP-Glc) from the cytosol into the lumen of the Golgi in exchange of UMP. By supplying UDP-N-acetylglucosamine, a donor substrate to heparan sulfate synthases, probably takes part in the synthesis of these glycoconjugates.
• Tissue Specificity: Highly expressed in heart, kidney, small intestine, placenta, lung and peripheral blood leukocyte. Weakly expressed in skeletal muscle and spleen. Not expressed in brain, colon and thymus.
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  Transport of nucleotide sugars (R-HSA-727802)
  Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Nucleotide sugar transporter SLC35D2 (SLC35D2) affects the uptake of 3-iodothyronamine.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[10]
T83193	DMHO29Y	Patented	T83193 decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[12]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of Nucleotide sugar transporter SLC35D2 (SLC35D2).	[11]

References

• [1] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [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] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutat Res. 2007 Mar 1;616(1-2):60-9. doi: 10.1016/j.mrfmmm.2006.11.022. Epub 2006 Dec 18.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.