Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTW7AE3)

• DTP Name: Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)
• Gene Name: SLC1A5
• UniProt ID: Q15758 (AAAT_HUMAN)
• VARIDT ID: DTD0133
• Synonyms: AAAT; ASCT2; ATB(0); ATBO; Baboon M7 virus receptor; M7V1; M7VS1; Neutral amino acid transporter B(0); R16; RD114/simian type D retrovirus receptor; RDR; RDRC; SLC1A5; Sodium-dependent neutral amino acid transporter type 2; Solute carrier family 1 member 5
• DTP Family: Dicarboxylate/Amino Acid:Cation (Na(+) Or H(+)) Symporter (DAACS) Family
• Tissue Specificity: Placenta, lung, skeletal muscle, kidney,pancreas, and intestine.
• Sequence:
  MVADPPRDSKGLAAAEPTANGGLALASIEDQGAAAGGYCGSRDQVRRCLRANLLVLLTVV
  AVVAGVALGLGVSGAGGALALGPERLSAFVFPGELLLRLLRMIILPLVVCSLIGGAASLD
  PGALGRLGAWALLFFLVTTLLASALGVGLALALQPGAASAAINASVGAAGSAENAPSKEV
  LDSFLDLARNIFPSNLVSAAFRSYSTTYEERNITGTRVKVPVGQEVEGMNILGLVVFAIV
  FGVALRKLGPEGELLIRFFNSFNEATMVLVSWIMWYAPVGIMFLVAGKIVEMEDVGLLFA
  RLGKYILCCLLGHAIHGLLVLPLIYFLFTRKNPYRFLWGIVTPLATAFGTSSSSATLPLM
  MKCVEENNGVAKHISRFILPIGATVNMDGAALFQCVAAVFIAQLSQQSLDFVKIITILVT
  ATASSVGAAGIPAGGVLTLAIILEAVNLPVDHISLILAVDWLVDRSCTVLNVEGDALGAG
  LLQNYVDRTESRSTEPELIQVKSELPLDPLPVPTEEGNPLLKHYRGPAGDATVASEKESV
  M
• Function: This 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.
• Endogenous Substrate(s): Thyroid hormones; Thyroid hormone derivatives
• TCDB ID: 2.A.23.3.3
• Gene ID: 6510
• 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 DTP

9 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Virus infection	1A24-1D9Z	Approved	[3]
Ganciclovir	DM1MBYQ	Virus infection	1A24-1D9Z	Approved	[3]
Glycine	DMIOZ29	Malnutrition	5B50-5B71	Approved	[4]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[5]
Levacecarnine HCL	DMJBOCR	Cognitive impairment	6D71	Approved	[6]
Nitric Oxide	DM1RBYG	Respiratory failure	CB41	Approved	[7]
Valaciclovir	DMHKS94	Virus infection	1A24-1D9Z	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 DTP

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

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	8.54E-01	-4.54E-02	-7.57E-02
Adrenocortical carcinoma	2D11.Z	Kidney	6.61E-05	-4.31E-01	-1.51E+00
Alopecia	ED70	Skin from scalp	1.36E-01	-1.08E-01	-2.77E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.49E-06	2.11E-01	8.76E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	9.00E-01	2.08E-02	8.09E-02
Aortic stenosis	BB70	Calcified aortic valve	5.45E-01	1.13E-01	3.03E-01
Apnea	7A40	Hyperplastic tonsil	9.68E-02	2.63E-01	4.73E-01
Arthropathy	FA00-FA5Z	Peripheral blood	3.32E-01	1.05E-01	3.59E-01
Asthma	CA23	Nasal and bronchial airway	1.29E-01	9.09E-02	1.25E-01
Atopic dermatitis	EA80	Skin	1.00E-08	4.32E-01	1.85E+00
Autism	6A02	Whole blood	1.32E-01	-1.36E-01	-3.62E-01
Autoimmune uveitis	9A96	Peripheral monocyte	4.49E-01	-1.17E-02	-5.81E-02
Autosomal dominant monocytopenia	4B04	Whole blood	4.63E-02	3.23E-01	1.39E+00
Bacterial infection of gingival	1C1H	Gingival tissue	5.47E-16	6.74E-01	1.49E+00
Batten disease	5C56.1	Whole blood	8.41E-01	6.04E-02	2.35E-01
Behcet's disease	4A62	Peripheral blood	4.74E-01	4.24E-02	9.29E-02
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	2.93E-01	-9.68E-02	-4.97E-01
Bladder cancer	2C94	Bladder tissue	3.29E-03	-5.17E-01	-1.37E+00
Breast cancer	2C60-2C6Z	Breast tissue	6.03E-01	4.37E-03	7.86E-03
Cardioembolic stroke	8B11.20	Whole blood	1.43E-01	-3.14E-01	-7.16E-01
Cervical cancer	2C77	Cervical tissue	4.04E-03	2.40E-01	4.43E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	2.06E-02	2.03E-01	4.81E-01
Chronic hepatitis C	1E51.1	Whole blood	4.31E-01	1.25E-01	4.53E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	6.83E-01	3.90E-02	1.03E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	2.91E-01	-2.22E-01	-4.04E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	7.37E-01	9.89E-02	1.83E-01
Colon cancer	2B90	Colon tissue	3.78E-13	3.23E-01	8.25E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.68E-03	1.63E-01	2.09E+00
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.87E-01	1.67E-01	4.24E-01
Endometriosis	GA10	Endometrium tissue	1.00E+00	2.27E-01	3.21E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	8.10E-01	3.86E-02	1.66E-01
Familial hypercholesterolemia	5C80.00	Whole blood	4.65E-03	3.79E-01	1.15E+00
Gastric cancer	2B72	Gastric tissue	2.90E-01	5.23E-01	1.27E+00
Glioblastopma	2A00.00	Nervous tissue	1.65E-14	2.15E-01	5.03E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.43E-01	5.57E-01	9.15E-01
Head and neck cancer	2D42	Head and neck tissue	4.51E-03	1.36E-01	3.09E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	4.83E-01	-3.03E-02	-1.56E-01
Huntington's disease	8A01.10	Whole blood	2.56E-01	-1.00E-01	-6.84E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	3.52E-02	-4.68E-01	-1.98E+00
Immunodeficiency	4A00-4A20	Peripheral blood	4.59E-02	1.41E-01	1.42E+00
Influenza	1.00E+30	Whole blood	1.49E-01	-3.47E-01	-7.62E-01
Interstitial cystitis	GC00.3	Bladder tissue	7.13E-03	-1.30E+00	-2.23E+00
Intracranial aneurysm	8B01.0	Intracranial artery	3.98E-01	-6.11E-01	-1.14E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	6.04E-02	-5.53E-01	-8.78E-01
Ischemic stroke	8B11	Peripheral blood	4.83E-01	-1.03E-01	-4.54E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	6.96E-03	-4.36E-01	-7.72E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	6.84E-01	-2.09E-03	-8.56E-03
Lateral sclerosis	8B60.4	Skin	9.59E-01	4.31E-02	9.75E-02
Liver cancer	2C12.0	Liver tissue	3.00E-05	1.96E-01	5.11E-01
Liver failure	DB99.7-DB99.8	Liver tissue	4.09E-06	7.20E-01	4.06E+00
Lung cancer	2C25	Lung tissue	7.79E-03	-1.21E-01	-3.80E-01
Lupus erythematosus	4A40	Whole blood	5.14E-05	-2.46E-01	-5.81E-01
Major depressive disorder	6A70-6A7Z	Whole blood	8.43E-02	5.61E-02	1.73E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	1.95E-01	-3.50E-02	-1.80E-01
Melanoma	2C30	Skin	8.44E-01	1.22E-02	1.10E-02
Multiple myeloma	2A83.1	Bone marrow	5.68E-05	1.05E+00	2.79E+00
Multiple myeloma	2A83.1	Peripheral blood	5.51E-01	-3.64E-01	-3.48E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	9.03E-01	2.99E-01	6.85E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.48E-01	1.21E-01	2.76E-01
Myelofibrosis	2A20.2	Whole blood	2.79E-02	6.27E-01	1.70E+00
Myocardial infarction	BA41-BA50	Peripheral blood	9.68E-01	2.30E-02	4.51E-02
Myopathy	8C70.6	Muscle tissue	7.43E-01	2.60E-02	1.65E-01
Neonatal sepsis	KA60	Whole blood	5.69E-05	2.32E-01	4.15E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.39E-02	-3.70E-01	-1.09E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	7.10E-01	2.70E-02	1.77E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.87E-01	9.04E-02	3.34E-01
Olive pollen allergy	CA08.00	Peripheral blood	1.92E-03	5.60E-01	3.40E+00
Oral cancer	2B6E	Oral tissue	2.75E-01	3.06E-01	4.90E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	6.04E-01	3.26E-01	2.74E-01
Osteoporosis	FB83.1	Bone marrow	1.43E-03	1.42E+00	3.58E+00
Ovarian cancer	2C73	Ovarian tissue	5.93E-01	8.93E-02	1.59E-01
Pancreatic cancer	2C10	Pancreas	6.42E-01	1.72E-01	3.89E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	3.77E-01	1.05E-01	3.13E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.24E-04	3.08E-01	1.15E+00
Pituitary cancer	2D12	Pituitary tissue	2.51E-01	-1.76E-01	-4.80E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	5.23E-03	-4.10E-01	-1.25E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	8.68E-01	5.00E-03	2.38E-02
Polycythemia vera	2A20.4	Whole blood	3.92E-04	2.55E-01	6.97E-01
Pompe disease	5C51.3	Biceps muscle	9.31E-01	-7.97E-02	-2.84E-01
Preterm birth	KA21.4Z	Myometrium	2.93E-01	7.05E-02	1.49E-01
Prostate cancer	2C82	Prostate	2.97E-04	-1.19E+00	-1.26E+00
Psoriasis	EA90	Skin	5.38E-10	-3.22E-01	-5.61E-01
Rectal cancer	2B92	Rectal colon tissue	1.47E-01	1.02E-01	4.40E-01
Renal cancer	2C90-2C91	Kidney	1.22E-03	-4.18E-01	-1.25E+00
Retinoblastoma	2D02.2	Uvea	5.70E-05	9.24E-01	4.31E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.23E-04	5.84E-01	2.22E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	6.55E-01	2.70E-02	1.59E-01
Schizophrenia	6A20	Prefrontal cortex	3.94E-02	1.60E-01	3.03E-01
Schizophrenia	6A20	Superior temporal cortex	7.08E-01	3.00E-02	1.89E-01
Scleroderma	4A42.Z	Whole blood	5.20E-03	-3.85E-01	-1.51E+00
Seizure	8A60-8A6Z	Whole blood	1.30E-01	-2.10E-01	-5.50E-01
Sensitive skin	EK0Z	Skin	9.58E-01	-3.76E-02	-4.14E-01
Sepsis with septic shock	1G41	Whole blood	1.15E-01	-8.68E-02	-1.79E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.23E-02	4.69E-01	2.54E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	4.62E-01	2.97E-01	6.48E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	8.05E-01	9.16E-02	2.73E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.72E-01	7.15E-02	2.80E-01
Skin cancer	2C30-2C3Z	Skin	1.82E-01	6.66E-02	1.12E-01
Thrombocythemia	3B63	Whole blood	5.35E-01	9.59E-02	2.56E-01
Thrombocytopenia	3B64	Whole blood	5.46E-01	6.79E-01	6.64E-01
Thyroid cancer	2D10	Thyroid	7.30E-25	8.69E-01	1.69E+00
Tibial muscular dystrophy	8C75	Muscle tissue	8.33E-01	-2.12E-03	-1.05E-02
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	2.89E-02	3.88E-01	2.74E+00
Type 2 diabetes	5A11	Liver tissue	7.35E-01	1.51E-01	8.14E-01
Ureter cancer	2C92	Urothelium	6.57E-01	2.78E-02	1.58E-01
Uterine cancer	2C78	Endometrium tissue	2.44E-02	1.10E-01	2.10E-01
Vitiligo	ED63.0	Skin	3.83E-01	-1.45E-01	-3.92E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Glycine	Approved	HRPE cells-ASCT2	Km = 320 microM	[4]
D-Serine	Phase 4	Oocytes-ASCT2	Km = 167 microM	[10]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Alanine/serine/cysteine transporter 2 (SLC1A5) DTT Info
• DTP DTT Type: Literature-reported

2 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzylserine	DMHIGDM	Discovery agent	N.A.	Investigative	[1]
P-Nitrophenyl Glutamyl Anilide	DM29RO1	Discovery agent	N.A.	Investigative	[2]

References

• [1] 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.
• [2] 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.
• [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.