Details of Drug Off-Target (DOT)

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

• DOT Name: Neutral amino acid uniporter 4 (SLC36A4)
• Synonyms: Solute carrier family 36 member 4
• Gene Name: SLC36A4
• UniProt ID: S36A4_HUMAN
• Pfam ID: PF01490
• Sequence:
  MEAAATPAAAGAARREELDMDVMRPLINEQNFDGTSDEEHEQELLPVQKHYQLDDQEGIS
  FVQTLMHLLKGNIGTGLLGLPLAIKNAGIVLGPISLVFIGIISVHCMHILVRCSHFLCLR
  FKKSTLGYSDTVSFAMEVSPWSCLQKQAAWGRSVVDFFLVITQLGFCSVYIVFLAENVKQ
  VHEGFLESKVFISNSTNSSNPCERRSVDLRIYMLCFLPFIILLVFIRELKNLFVLSFLAN
  VSMAVSLVIIYQYVVRNMPDPHNLPIVAGWKKYPLFFGTAVFAFEGIGVVLPLENQMKES
  KRFPQALNIGMGIVTTLYVTLATLGYMCFHDEIKGSITLNLPQDVWLYQSVKILYSFGIF
  VTYSIQFYVPAEIIIPGITSKFHTKWKQICEFGIRSFLVSITCAGAILIPRLDIVISFVG
  AVSSSTLALILPPLVEILTFSKEHYNIWMVLKNISIAFTGVVGFLLGTYITVEEIIYPTP
  KVVAGTPQSPFLNLNSTCLTSGLK
• Function: Uniporter that mediates the transport of neutral amino acids like L-tryptophan, proline and alanine. The transport activity is sodium ions-independent, electroneutral and therefore functions via facilitated diffusion.
• Tissue Specificity: Expressed in retinal pigmented epithelial cells.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Tryptophan catabolism (R-HSA-71240)
  Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Neutral amino acid uniporter 4 (SLC36A4).	[8]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.