Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFYZK8R)

• DOT Name: Sodium/nucleoside cotransporter 2 (SLC28A2)
• Synonyms: Concentrative nucleoside transporter 2; CNT 2; hCNT2; Na(+)/nucleoside cotransporter 2; Sodium-coupled nucleoside transporter 2; Sodium/purine nucleoside co-transporter; SPNT; Solute carrier family 28 member 2
• Gene Name: SLC28A2
• UniProt ID: S28A2_HUMAN
• Pfam ID: PF07670 ; PF07662 ; PF01773
• Sequence:
  MEKASGRQSIALSTVETGTVNPGLELMEKEVEPEGSKRTDAQGHSLGDGLGPSTYQRRSR
  WPFSKARSFCKTHASLFKKILLGLLCLAYAAYLLAACILNFQRALALFVITCLVIFVLVH
  SFLKKLLGKKLTRCLKPFENSRLRLWTKWVFAGVSLVGLILWLALDTAQRPEQLIPFAGI
  CMFILILFACSKHHSAVSWRTVFSGLGLQFVFGILVIRTDLGYTVFQWLGEQVQIFLNYT
  VAGSSFVFGDTLVKDVFAFQALPIIIFFGCVVSILYYLGLVQWVVQKVAWFLQITMGTTA
  TETLAVAGNIFVGMTEAPLLIRPYLGDMTLSEIHAVMTGGFATISGTVLGAFIAFGVDAS
  SLISASVMAAPCALASSKLAYPEVEESKFKSEEGVKLPRGKERNVLEAASNGAVDAIGLA
  TNVAANLIAFLAVLAFINAALSWLGELVDIQGLTFQVICSYLLRPMVFMMGVEWTDCPMV
  AEMVGIKFFINEFVAYQQLSQYKNKRLSGMEEWIEGEKQWISVRAEIITTFSLCGFANLS
  SIGITLGGLTSIVPHRKSDLSKVVVRALFTGACVSLISACMAGILYVPRGAEADCVSFPN
  TSFTNRTYETYMCCRGLFQSTSLNGTNPPSFSGPWEDKEFSAMALTNCCGFYNNTVCA
• Function: Sodium-dependent and purine-selective transporter. Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine). Plays a critical role in specific uptake and salvage of purine nucleosides in kidney and other tissues. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).
• Tissue Specificity: Expressed in heart and skeletal muscle followed by liver, kidney, intestine, pancreas, placenta and brain . Weak expression in lung . In testis, primarily localized to the apicolateral membranes of Sertoli cells and vascular endothelial cells, and weakly expressed in Leydig cells, peritubular myoid cells and germ cells .
• Reactome Pathway:
  Azathioprine ADME (R-HSA-9748787)
  Ribavirin ADME (R-HSA-9755088)
  Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine	DMM2NSK	Approved	Sodium/nucleoside cotransporter 2 (SLC28A2) increases the transport of Adenosine.	[7]
Uridine	DMQTREB	Approved	Sodium/nucleoside cotransporter 2 (SLC28A2) increases the transport of Uridine.	[7]
AMG 386	DMQJXL4	Phase 3	Sodium/nucleoside cotransporter 2 (SLC28A2) increases the transport of AMG 386.	[7]
Purine Riboside	DMHNS0V	Investigative	Sodium/nucleoside cotransporter 2 (SLC28A2) increases the transport of Purine Riboside.	[7]

5 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 Sodium/nucleoside cotransporter 2 (SLC28A2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sodium/nucleoside cotransporter 2 (SLC28A2).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sodium/nucleoside cotransporter 2 (SLC28A2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sodium/nucleoside cotransporter 2 (SLC28A2).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sodium/nucleoside cotransporter 2 (SLC28A2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium/nucleoside cotransporter 2 (SLC28A2).	[3]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] 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.
• [5] 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.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol Membr Biol. 1998 Oct-Dec;15(4):203-11. doi: 10.3109/09687689709044322.