Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ4D276)

• DOT Name: Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1)
• Synonyms: Porcine endogenous retrovirus A receptor 2; PERV-A receptor 2; huPAR-2; Protein GPR172B; Riboflavin transporter 1; hRFT1
• Gene Name: SLC52A1
• Related Disease:
  Maternal riboflavin deficiency
  Ariboflavinosis
• UniProt ID: S52A1_HUMAN
• Pfam ID: PF06237
• Sequence:
  MAAPTLGRLVLTHLLVALFGMGSWAAVNGIWVELPVVVKDLPEGWSLPSYLSVVVALGNL
  GLLVVTLWRQLAPGKGEQVPIQVVQVLSVVGTALLAPLWHHVAPVAGQLHSVAFLTLALV
  LAMACCTSNVTFLPFLSHLPPPFLRSFFLGQGLSALLPCVLALVQGVGRLECPPAPTNGT
  SGPPLDFPERFPASTFFWALTALLVTSAAAFRGLLLLLPSLPSVTTGGSGPELQLGSPGA
  EEEEKEEEEALPLQEPPSQAAGTIPGPDPEAHQLFSAHGAFLLGLMAFTSAVTNGVLPSV
  QSFSCLPYGRLAYHLAVVLGSAANPLACFLAMGVLCRSLAGLVGLSLLGMLFGAYLMALA
  ILSPCPPLVGTTAGVVLVVLSWVLCLCVFSYVKVAASSLLHGGGRPALLAAGVAIQVGSL
  LGAGAMFPPTSIYHVFQSRKDCVDPCGP
• 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 ; (Microbial infection) May function as a cell receptor to retroviral envelopes similar to the porcine endogenous retrovirus (PERV-A).
• Tissue Specificity: Widely expressed. Highly expressed in the testis, placenta and small intestine. Expressed at lower level in other tissues.
• Reactome Pathway: Vitamin B2 (riboflavin) metabolism (R-HSA-196843)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Maternal riboflavin deficiency	DISUPNKI	Supportive	Autosomal dominant	[1]
Ariboflavinosis	DISGKSZF	Limited	Unknown	[1]

3 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 1 (SLC52A1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Solute carrier family 52, riboflavin transporter, member 1 (SLC52A1).	[7]

References

• [1] Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Mol Genet Metab. 2007 Sep-Oct;92(1-2):109-14. doi: 10.1016/j.ymgme.2007.06.017. Epub 2007 Aug 8.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [7] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.