Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP3N8N3)

• DOT Name: Solute carrier family 13 member 4 (SLC13A4)
• Synonyms: Na(+)/sulfate cotransporter SUT-1; NaS2
• Gene Name: SLC13A4
• UniProt ID: S13A4_HUMAN
• Pfam ID: PF00939
• Sequence:
  MGLLQGLLRVRKLLLVVCVPLLLLPLPVLHPSSEASCAYVLIVTAVYWVSEAVPLGAAAL
  VPAFLYPFFGVLRSNEVAAEYFKNTTLLLVGVICVAAAVEKWNLHKRIALRMVLMAGAKP
  GMLLLCFMCCTTLLSMWLSNTSTTAMVMPIVEAVLQELVSAEDEQLVAGNSNTEEAEPIS
  LDVKNSQPSLELIFVNEESNADLTTLMHNENLNGVPSITNPIKTANQHQGKKQHPSQEKP
  QVLTPSPRKQKLNRKYRSHHDQMICKCLSLSISYSATIGGLTTIIGTSTSLIFLEHFNNQ
  YPAAEVVNFGTWFLFSFPISLIMLVVSWFWMHWLFLGCNFKETCSLSKKKKTKREQLSEK
  RIQEEYEKLGDISYPEMVTGFFFILMTVLWFTREPGFVPGWDSFFEKKGYRTDATVSVFL
  GFLLFLIPAKKPCFGKKNDGENQEHSLGTEPIITWKDFQKTMPWEIVILVGGGYALASGS
  KSSGLSTWIGNQMLSLSSLPPWAVTLLACILVSIVTEFVSNPATITIFLPILCSLSETLH
  INPLYTLIPVTMCISFAVMLPVGNPPNAIVFSYGHCQIKDMVKAGLGVNVIGLVIVMVAI
  NTWGVSLFHLDTYPAWARVSNITDQA
• Function: Sodium:sulfate symporter that mediates sulfate reabsorption in the high endothelial venules (HEV).
• Tissue Specificity: Highly expressed in placenta and testis with intermediate levels in brain and lower levels in heart, thymus and liver.
• Reactome Pathway: Sodium-coupled sulphate, di- and tri-carboxylate transporters (R-HSA-433137)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Solute carrier family 13 member 4 (SLC13A4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Solute carrier family 13 member 4 (SLC13A4).	[2]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Solute carrier family 13 member 4 (SLC13A4).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 13 member 4 (SLC13A4).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Solute carrier family 13 member 4 (SLC13A4).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Solute carrier family 13 member 4 (SLC13A4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Solute carrier family 13 member 4 (SLC13A4).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.