Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF7WRM)

• DTT Name: Alanine/serine/cysteine transporter 2 (SLC1A5)
• Synonyms: Solute carrier family 1 member 5; Sodium-dependent neutral amino acid transporter type 2; RDRC; RDR; RD114/simian type D retrovirus receptor; Neutral amino acid transporter B(0); M7V1; Baboon M7 virus receptor; ATB(0); ASCT2
• Gene Name: SLC1A5
• DTT Type: Literature-reported target; [1]
• UniProt ID: AAAT_HUMAN
• TTD ID: T59493
• Sequence:
  MVADPPRDSKGLAAAEPTANGGLALASIEDQGAAAGGYCGSRDQVRRCLRANLLVLLTVV
  AVVAGVALGLGVSGAGGALALGPERLSAFVFPGELLLRLLRMIILPLVVCSLIGGAASLD
  PGALGRLGAWALLFFLVTTLLASALGVGLALALQPGAASAAINASVGAAGSAENAPSKEV
  LDSFLDLARNIFPSNLVSAAFRSYSTTYEERNITGTRVKVPVGQEVEGMNILGLVVFAIV
  FGVALRKLGPEGELLIRFFNSFNEATMVLVSWIMWYAPVGIMFLVAGKIVEMEDVGLLFA
  RLGKYILCCLLGHAIHGLLVLPLIYFLFTRKNPYRFLWGIVTPLATAFGTSSSSATLPLM
  MKCVEENNGVAKHISRFILPIGATVNMDGAALFQCVAAVFIAQLSQQSLDFVKIITILVT
  ATASSVGAAGIPAGGVLTLAIILEAVNLPVDHISLILAVDWLVDRSCTVLNVEGDALGAG
  LLQNYVDRTESRSTEPELIQVKSELPLDPLPVPTEEGNPLLKHYRGPAGDATVASEKESV
  M
• Function: Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids. Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development.
• KEGG Pathway:
  Protein digestion and absorption (hsa04974)
  Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DTT

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
benzylserine	DMHIGDM	Discovery agent	N.A.	Investigative	[2]
p-nitrophenyl glutamyl anilide	DM29RO1	Discovery agent	N.A.	Investigative	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Alanine/serine/cysteine/threonine transporter 2 (SLC1A5) DTP Info
• Gene Name: SLC1A5

9 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[3]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[3]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[4]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[5]
Levacecarnine hci	DMJBOCR	Cognitive impairment	6D71	Approved	[6]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[7]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[8]
Valganciclovir	DMS2IUH	Virus infection	1A24-1D9Z	Approved	[9]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[10]

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-threonine	DMFHTBX	Discovery agent	N.A.	Investigative	[10]

References

• [1] Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorg Med Chem. 2005 Feb 15;13(4):1111-8.
• [2] New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J Physiol. 2004 Jun 15;557(Pt 3):747-59.
• [3] Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):357-64.
• [4] Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1046-53.
• [5] High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes. Neurochem Int. 2006 May-Jun;48(6-7):611-5.
• [6] A polarized localization of amino acid/carnitine transporter B(0,+) (ATB(0,+)) in the blood-brain barrier. Biochem Biophys Res Commun. 2008 Nov 14;376(2):267-70.
• [7] Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells. FEBS Lett. 2005 Apr 25;579(11):2499-506.
• [8] Transport of amino acid-based prodrugs by the Na+- and Cl(-) -coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery. J Pharmacol Exp Ther. 2004 Mar;308(3):1138-47.
• [9] Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10.
• [10] D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. PLoS One. 2016 Jun 7;11(6):e0156551.