Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIEL5QZ)

• DOT Name: Proton-coupled amino acid transporter 1 (SLC36A1)
• Synonyms: Proton/amino acid transporter 1; hPAT1; Solute carrier family 36 member 1
• Gene Name: SLC36A1
• UniProt ID: S36A1_HUMAN
• Pfam ID: PF01490
• Sequence:
  MSTQRLRNEDYHDYSSTDVSPEESPSEGLNNLSSPGSYQRFGQSNSTTWFQTLIHLLKGN
  IGTGLLGLPLAVKNAGIVMGPISLLIIGIVAVHCMGILVKCAHHFCRRLNKSFVDYGDTV
  MYGLESSPCSWLRNHAHWGRRVVDFFLIVTQLGFCCVYFVFLADNFKQVIEAANGTTNNC
  HNNETVILTPTMDSRLYMLSFLPFLVLLVFIRNLRALSIFSLLANITMLVSLVMIYQFIV
  QRIPDPSHLPLVAPWKTYPLFFGTAIFSFEGIGMVLPLENKMKDPRKFPLILYLGMVIVT
  ILYISLGCLGYLQFGANIQGSITLNLPNCWLYQSVKLLYSIGIFFTYALQFYVPAEIIIP
  FFVSRAPEHCELVVDLFVRTVLVCLTCILAILIPRLDLVISLVGSVSSSALALIIPPLLE
  VTTFYSEGMSPLTIFKDALISILGFVGFVVGTYEALYELIQPSNAPIFINSTCAFI
• Function: Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA. May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis. May play a role in specifying sites for exocytosis in neurons.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Proton-coupled neutral amino acid transporters (R-HSA-428559)
  Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Proton-coupled amino acid transporter 1 (SLC36A1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[4]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Proton-coupled amino acid transporter 1 (SLC36A1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Proton-coupled amino acid transporter 1 (SLC36A1).	[2]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] 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.
• [6] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.