Details of Drug Off-Target (DOT)

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

• DOT Name: Sulfate anion transporter 1 (SLC26A1)
• Synonyms: SAT-1; Solute carrier family 26 member 1
• Gene Name: SLC26A1
• Related Disease: Nephrolithiasis susceptibility caused by SLC26A1
• UniProt ID: S26A1_HUMAN
• Pfam ID: PF01740 ; PF00916
• Sequence:
  MDESPEPLQQGRGPVPVRRQRPAPRGLREMLKARLWCSCSCSVLCVRALVQDLLPATRWL
  RQYRPREYLAGDVMSGLVIGIILVPQAIAYSLLAGLQPIYSLYTSFFANLIYFLMGTSRH
  VSVGIFSLLCLMVGQVVDRELQLAGFDPSQDGLQPGANSSTLNGSAAMLDCGRDCYAIRV
  ATALTLMTGLYQVLMGVLRLGFVSAYLSQPLLDGFAMGASVTILTSQLKHLLGVRIPRHQ
  GPGMVVLTWLSLLRGAGQANVCDVVTSTVCLAVLLAAKELSDRYRHRLRVPLPTELLVIV
  VATLVSHFGQLHKRFGSSVAGDIPTGFMPPQVPEPRLMQRVALDAVALALVAAAFSISLA
  EMFARSHGYSVRANQELLAVGCCNVLPAFLHCFATSAALAKSLVKTATGCRTQLSSVVSA
  TVVLLVLLALAPLFHDLQRSVLACVIVVSLRGALRKVWDLPRLWRMSPADALVWAGTAAT
  CMLVSTEAGLLAGVILSLLSLAGRTQRPRTALLARIGDTAFYEDATEFEGLVPEPGVRVF
  RFGGPLYYANKDFFLQSLYSLTGLDAGCMAARRKEGGSETGVGEGGPAQGEDLGPVSTRA
  ALVPAAAGFHTVVIDCAPLLFLDAAGVSTLQDLRRDYGALGISLLLACCSPPVRDILSRG
  GFLGEGPGDTAEEEQLFLSVHDAVQTARARHRELEATDAHL
• Function: Sodium-independent sulfate anion transporter. Can transport other anions including bicarbonate, thiosulfate and oxalate by mediating sulfate-thiosulfate, sulfate-hydrogencarbonate and sulfate-oxalate anion exchange. Mediates oxalate-hydrogencarbonate anion exchange.
• Tissue Specificity: Expressed most abundantly in the kidney and liver, with lower levels in the pancreas, testis, brain, small intestine, colon, and lung.
• KEGG Pathway: Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  Multifunctional anion exchangers (R-HSA-427601)
  Transport and synthesis of PAPS (R-HSA-174362)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephrolithiasis susceptibility caused by SLC26A1	DISV6KRJ	Moderate	Autosomal recessive	[1]

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 Sulfate anion transporter 1 (SLC26A1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sulfate anion transporter 1 (SLC26A1).	[7]

4 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 Sulfate anion transporter 1 (SLC26A1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sulfate anion transporter 1 (SLC26A1).	[4]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Sulfate anion transporter 1 (SLC26A1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sulfate anion transporter 1 (SLC26A1).	[6]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.