Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM96T5U)

• DOT Name: Solute carrier family 22 member 13 (SLC22A13)
• Synonyms: Organic anion transporter 10; OAT10; Organic cation transporter-like 3; ORCTL-3; ORCTL3
• Gene Name: SLC22A13
• UniProt ID: S22AD_HUMAN
• Pfam ID: PF00083
• Sequence:
  MAQFVQVLAEIGDFGRFQIQLLILLCVLNFLSPFYFFAHVFMVLDEPHHCAVAWVKNHTF
  NLSAAEQLVLSVPLDTAGHPEPCLMFRPPPANASLQDILSHRFNETQPCDMGWEYPENRL
  PSLKNEFNLVCDRKHLKDTTQSVFMAGLLVGTLMFGPLCDRIGRKATILAQLLLFTLIGL
  ATAFVPSFELYMALRFAVATAVAGLSFSNVTLLTEWVGPSWRTQAVVLAQCNFSLGQMVL
  AGLAYGFRNWRLLQITGTAPGLLLFFYFWALPESARWLLTRGRMDEAIQLIQKAASVNRR
  KLSPELMNQLVPEKTGPSGNALDLFRHPQLRKVTLIIFCVWFVDSLGYYGLSLQVGDFGL
  DVYLTQLIFGAVEVPARCSSIFMMQRFGRKWSQLGTLVLGGLMCIIIIFIPADLPVVVTM
  LAVVGKMATAAAFTISYVYSAELFPTILRQTGMGLVGIFSRIGGILTPLVILLGEYHAAL
  PMLIYGSLPIVAGLLCTLLPETHGQGLKDTLQDLELGPHPRSPKSVPSEKETEAKGRTSS
  PGVAFVSSTYF
• Function: Anion antiporter that mediates the transport of urate, orotate and nicotinate in exchange for organic or inorganic anions. Translocates urate and orotate across the apical membrane of proximal tubule epithelial cells and involved in urate renal reabsorption. Possibly involved in orotate renal reabsorption and nicotinate intestinal reabsorption. Mediates urate uptake by an exchange with organic anions such as (S)-lactate, succinate, glutathione and nicotinate. Urate and orotate transports are Cl(-)-dependent. Shows similar transport characteristics as the urate/orotate renal antiporter SLC22A12/URAT1 and may act as a compensator of SLC22A12/URAT1 in certain conditions (Probable).
• Tissue Specificity: Ubiquitous . Highly expressed in kidneys and to a weaker extent in brain, heart, and intestine . In kidneys, expressed in proximal convoluted tubule . In kidneys, also expressed in cortical collecting duct, whereas glomerulus and thick ascending limb exhibit no expression .
• Reactome Pathway: Nicotinamide salvaging (R-HSA-197264)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 22 member 13 (SLC22A13).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Solute carrier family 22 member 13 (SLC22A13).	[3]

2 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 Solute carrier family 22 member 13 (SLC22A13).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Solute carrier family 22 member 13 (SLC22A13).	[4]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] 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.
• [3] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [4] 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.