Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPC6NXA)

• DOT Name: Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2)
• Synonyms: Porcine endogenous retrovirus A receptor 1; PERV-A receptor 1; Protein GPR172A; Riboflavin transporter 3; hRFT3
• Gene Name: SLC52A2
• Related Disease: Brown-Vialetto-van Laere syndrome 2
• UniProt ID: S52A2_HUMAN
• Pfam ID: PF06237
• Sequence:
  MAAPTPARPVLTHLLVALFGMGSWAAVNGIWVELPVVVKELPEGWSLPSYVSVLVALGNL
  GLLVVTLWRRLAPGKDEQVPIRVVQVLGMVGTALLASLWHHVAPVAGQLHSVAFLALAFV
  LALACCASNVTFLPFLSHLPPRFLRSFFLGQGLSALLPCVLALVQGVGRLECPPAPINGT
  PGPPLDFLERFPASTFFWALTALLVASAAAFQGLLLLLPPPPSVPTGELGSGLQVGAPGA
  EEEVEESSPLQEPPSQAAGTTPGPDPKAYQLLSARSACLLGLLAATNALTNGVLPAVQSF
  SCLPYGRLAYHLAVVLGSAANPLACFLAMGVLCRSLAGLGGLSLLGVFCGGYLMALAVLS
  PCPPLVGTSAGVVLVVLSWVLCLGVFSYVKVAASSLLHGGGRPALLAAGVAIQVGSLLGA
  VAMFPPTSIYHVFHSRKDCADPCDS
• Function: Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism. Humans are unable to synthesize vitamin B2/riboflavin and must obtain it via intestinal absorption. May also act as a receptor for 4-hydroxybutyrate (Probable); (Microbial infection) In case of infection by retroviruses, acts as a cell receptor to retroviral envelopes similar to the porcine endogenous retrovirus (PERV-A).
• Tissue Specificity: Highly expressed in brain, fetal brain and salivary gland. Weakly expressed in other tissues.
• Reactome Pathway: Vitamin B2 (riboflavin) metabolism (R-HSA-196843)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brown-Vialetto-van Laere syndrome 2	DIS91N83	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2) affects the response to substance of Methotrexate.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[8]

5 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 52, riboflavin transporter, member 2 (SLC52A2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 52, riboflavin transporter, member 2 (SLC52A2).	[7]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] 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.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] 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.
• [7] 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.
• [8] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.