Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34J8RK)

• DOT Name: Proton-coupled amino acid transporter 2 (SLC36A2)
• Synonyms: Proton/amino acid transporter 2; Solute carrier family 36 member 2; Transmembrane domain rich protein 1; Tramdorin-1
• Gene Name: SLC36A2
• Related Disease:
  Iminoglycinuria
  Hyperglycinuria
• UniProt ID: S36A2_HUMAN
• Pfam ID: PF01490
• Sequence:
  MSVTKSTEGPQGAVAIKLDLMSPPESAKKLENKDSTFLDESPSESAGLKKTKGITVFQAL
  IHLVKGNMGTGILGLPLAVKNAGILMGPLSLLVMGFIACHCMHILVKCAQRFCKRLNKPF
  MDYGDTVMHGLEANPNAWLQNHAHWGRHIVSFFLIITQLGFCCVYIVFLADNLKQVVEAV
  NSTTNNCYSNETVILTPTMDSRLYMLSFLPFLVLLVLIRNLRILTIFSMLANISMLVSLV
  IIIQYITQEIPDPSRLPLVASWKTYPLFFGTAIFSFESIGVVLPLENKMKNARHFPAILS
  LGMSIVTSLYIGMAALGYLRFGDDIKASISLNLPNCWLYQSVKLLYIAGILCTYALQFYV
  PAEIIIPFAISRVSTRWALPLDLSIRLVMVCLTCLLAILIPRLDLVISLVGSVSGTALAL
  IIPPLLEVTTFYSEGMSPLTIFKDALISILGFVGFVVGTYQALDELLKSEDSHPFSNSTT
  FVR
• Function: Electrogenic proton/amino acid symporter with a high selectivity for the small side chains amino acids glycine, alanine and proline, where both L- and D-enantiomers are transported. Extension of the backbone length, as in beta-alanine and 4-aminobutanoate or methylation of the amino group, as in sarcosine and N,N-dimethylglycine, are also tolerated but decrease transport efficiency. A free carboxyl group is preferred.
• Tissue Specificity: Abundantly expressed in kidney and muscle. Expressed in the S1 segment of the proximal tubule close to the glomerulus.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Proton-coupled neutral amino acid transporters (R-HSA-428559)
  Defective SLC36A2 causes iminoglycinuria (IG) and hyperglycinuria (HG) (R-HSA-5619041)
  Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Iminoglycinuria	DISB20Y5	Supportive	Autosomal recessive	[1]
Hyperglycinuria	DISL7D0R	Limited	Semidominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Proton-coupled amino acid transporter 2 (SLC36A2).	[3]

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 Proton-coupled amino acid transporter 2 (SLC36A2).	[4]

References

• [1] Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. J Clin Invest. 2008 Dec;118(12):3881-92. doi: 10.1172/JCI36625. Epub 2008 Nov 6.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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.