Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT48T0N)

• DTP Name: L-type amino acid transporter 1 (SLC7A5)
• Gene Name: SLC7A5
• UniProt ID: Q01650 (LAT1_HUMAN)
• VARIDT ID: DTD0471
• Synonyms: 4F2 LC; 4F2 light chain; 4F2LC; CD98; CD98 light chain; CD98LC; D16S469E; E16; Integral membrane protein E16; LAT1; Large neutral amino acids transporter small subunit 1; MPE16; SLC7A5; Solute carrier family 7 member 5; hLAT1; y+ system cationic amino acid transporter
• DTP Family:
  Amino Acid-Polyamine-Organocation (APC) Family
  L-type Amino Acid Transporter (LAT) Family
• Tissue Specificity: Expressed abundantly in adult lung, liver,brain, skeletal muscle, placenta, bone marrow, testis, restinglymphocytes and monocytes, and in fetal liver. Weaker expressionin thymus, cornea, retina, peripheral leukocytes, spleen, kidney,colon and lymph node. During gestation, expression in the placentawas significantly stronger at full-term than at the mid-trimesterstage. Also expressed in all human tumor cell lines tested and inthe astrocytic process of primary astrocytic gliomas. Expressed inretinal endothelial cells and in the intestinal epithelial cellline Caco-2.
• Sequence:
  MAGAGPKRRALAAPAAEEKEEAREKMLAAKSADGSAPAGEGEGVTLQRNITLLNGVAIIV
  GTIIGSGIFVTPTGVLKEAGSPGLALVVWAACGVFSIVGALCYAELGTTISKSGGDYAYM
  LEVYGSLPAFLKLWIELLIIRPSSQYIVALVFATYLLKPLFPTCPVPEEAAKLVACLCVL
  LLTAVNCYSVKAATRVQDAFAAAKLLALALIILLGFVQIGKGDVSNLDPNFSFEGTKLDV
  GNIVLALYSGLFAYGGWNYLNFVTEEMINPYRNLPLAIIISLPIVTLVYVLTNLAYFTTL
  STEQMLSSEAVAVDFGNYHLGVMSWIIPVFVGLSCFGSVNGSLFTSSRLFFVGSREGHLP
  SILSMIHPQLLTPVPSLVFTCVMTLLYAFSKDIFSVINFFSFFNWLCVALAIIGMIWLRH
  RKPELERPIKVNLALPVFFILACLFLIAVSFWKTPVECGIGFTIILSGLPVYFFGVWWKN
  KPKWLLQGIFSTTVLCQKLMQVVPQET
• Function: This sodium-independent, high-affinity transporter involved in cellular amino acid uptake and mediates the transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L-leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation.
• Endogenous Substrate(s): S-nitroso-L-cysteine
• TCDB ID: 2.A.3.8.25
• Gene ID: 8140
• Reactome Pathway:
  Amino acid transport across the plasma membrane (R-HSA-352230)
  Tryptophan catabolism (R-HSA-71240)
  Basigin interactions (R-HSA-210991)
• BioCyc Pathway: MetaCyc:ENSG00000103257-MON

Molecular Interaction Atlas (MIA) of This DTP

4 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[3]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[4]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[5]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[6]

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-leucine	DMQHN7I	Discovery agent	N.A.	Investigative	[4]

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	2.72E-04	3.49E-01	4.69E-01
Adrenocortical carcinoma	2D11.Z	Kidney	1.59E-02	3.59E-01	4.38E-01
Alopecia	ED70	Skin from scalp	4.22E-03	-1.25E-01	-3.70E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.99E-01	1.73E-01	3.72E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	8.94E-01	-1.01E-01	-2.47E-01
Aortic stenosis	BB70	Calcified aortic valve	7.49E-01	1.27E-01	3.81E-01
Apnea	7A40	Hyperplastic tonsil	7.66E-01	2.51E-01	5.15E-01
Arthropathy	FA00-FA5Z	Peripheral blood	5.32E-01	1.75E-01	3.96E-01
Asthma	CA23	Nasal and bronchial airway	9.56E-09	4.27E-01	5.81E-01
Atopic dermatitis	EA80	Skin	1.22E-06	1.01E+00	2.07E+00
Autism	6A02	Whole blood	1.38E-01	1.34E-03	2.97E-03
Autoimmune uveitis	9A96	Peripheral monocyte	1.58E-01	-2.03E+00	-1.61E+00
Autosomal dominant monocytopenia	4B04	Whole blood	1.42E-01	1.58E+00	9.58E-01
Bacterial infection of gingival	1C1H	Gingival tissue	6.32E-09	4.03E-01	8.86E-01
Batten disease	5C56.1	Whole blood	7.57E-01	-6.34E-02	-2.36E-01
Behcet's disease	4A62	Peripheral blood	5.14E-01	-5.07E-02	-1.42E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	2.00E-02	2.15E-01	8.70E-01
Bladder cancer	2C94	Bladder tissue	1.88E-06	1.39E+00	3.59E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.17E-127	1.66E+00	2.39E+00
Cardioembolic stroke	8B11.20	Whole blood	1.04E-01	2.32E-01	3.00E-01
Cervical cancer	2C77	Cervical tissue	1.07E-02	-9.05E-01	-1.11E+00
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	3.13E-01	5.73E-02	1.73E-01
Chronic hepatitis C	1E51.1	Whole blood	4.87E-01	5.07E-01	4.27E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	8.50E-01	1.70E-01	1.79E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	2.96E-04	3.30E-01	8.32E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	3.18E-02	3.37E-01	2.13E+00
Colon cancer	2B90	Colon tissue	2.89E-127	3.10E+00	4.82E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.07E-01	1.10E-01	2.40E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	1.52E-01	-1.71E-01	-5.60E-01
Endometriosis	GA10	Endometrium tissue	1.05E-01	3.34E-01	4.44E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	5.34E-01	1.14E-01	3.03E-01
Familial hypercholesterolemia	5C80.00	Whole blood	4.19E-02	-1.69E-01	-3.64E-01
Gastric cancer	2B72	Gastric tissue	3.61E-01	2.81E-01	5.66E-01
Glioblastopma	2A00.00	Nervous tissue	1.38E-06	-8.57E-02	-1.56E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	6.34E-05	8.55E-01	1.76E+00
Head and neck cancer	2D42	Head and neck tissue	5.60E-17	1.72E+00	7.50E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.04E-01	5.89E-01	8.03E-01
Huntington's disease	8A01.10	Whole blood	2.12E-01	1.64E-01	9.68E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	3.28E-01	-2.08E-02	-2.11E-02
Immunodeficiency	4A00-4A20	Peripheral blood	9.78E-02	2.24E-01	6.73E-01
Influenza	1.00E+30	Whole blood	7.44E-01	2.34E-01	5.04E-01
Interstitial cystitis	GC00.3	Bladder tissue	1.01E-01	4.51E-01	1.14E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.34E-01	1.54E+00	9.38E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.60E-03	2.71E-01	6.06E-01
Ischemic stroke	8B11	Peripheral blood	2.53E-01	6.97E-01	6.66E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	6.64E-12	5.04E-01	1.04E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	7.99E-01	-2.98E-01	-5.45E-01
Lateral sclerosis	8B60.4	Skin	9.36E-01	-9.02E-02	-8.07E-02
Liver cancer	2C12.0	Liver tissue	6.72E-01	-2.74E-01	-5.61E-01
Liver failure	DB99.7-DB99.8	Liver tissue	1.60E-04	1.49E+00	2.73E+00
Lung cancer	2C25	Lung tissue	7.20E-70	1.66E+00	2.05E+00
Lupus erythematosus	4A40	Whole blood	9.89E-04	-2.09E-01	-2.31E-01
Major depressive disorder	6A70-6A7Z	Whole blood	5.96E-02	6.58E-02	1.67E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	3.88E-01	1.23E-01	5.43E-01
Melanoma	2C30	Skin	3.45E-02	5.95E-01	6.05E-01
Multiple myeloma	2A83.1	Bone marrow	1.68E-06	1.15E+00	3.73E+00
Multiple myeloma	2A83.1	Peripheral blood	7.13E-01	7.20E-02	1.40E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	2.86E-01	-2.39E-01	-7.84E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	6.79E-03	-4.45E-01	-6.29E-01
Myelofibrosis	2A20.2	Whole blood	1.61E-02	1.21E+00	3.80E+00
Myocardial infarction	BA41-BA50	Peripheral blood	1.13E-03	4.34E-01	4.54E-01
Myopathy	8C70.6	Muscle tissue	1.42E-01	-1.62E-01	-3.44E-01
Neonatal sepsis	KA60	Whole blood	1.70E-08	4.37E-01	7.14E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	3.46E-03	-4.51E-01	-1.22E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	2.04E-01	-1.96E-01	-5.33E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.52E-01	-6.18E-01	-3.87E-01
Olive pollen allergy	CA08.00	Peripheral blood	9.56E-01	-6.68E-02	-6.30E-02
Oral cancer	2B6E	Oral tissue	2.89E-04	8.46E-01	8.63E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	6.44E-01	3.35E-01	1.35E-01
Osteoporosis	FB83.1	Bone marrow	4.69E-01	5.58E-01	2.16E+00
Ovarian cancer	2C73	Ovarian tissue	2.05E-02	6.97E-01	9.93E-01
Pancreatic cancer	2C10	Pancreas	9.65E-01	1.25E-02	1.41E-02
Parkinson's disease	8A00.0	Substantia nigra tissue	3.35E-01	2.44E-01	6.10E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.95E-05	6.34E-01	1.46E+00
Pituitary cancer	2D12	Pituitary tissue	6.40E-02	-4.90E-01	-5.55E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	2.62E-02	-5.31E-01	-5.51E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	4.51E-01	-5.42E-03	-4.58E-02
Polycythemia vera	2A20.4	Whole blood	2.39E-05	4.73E-01	1.39E+00
Pompe disease	5C51.3	Biceps muscle	1.43E-05	8.79E-01	2.77E+00
Preterm birth	KA21.4Z	Myometrium	2.64E-01	-2.50E-01	-3.20E-01
Prostate cancer	2C82	Prostate	2.11E-02	-5.83E-01	-6.52E-01
Psoriasis	EA90	Skin	3.83E-26	1.62E+00	2.00E+00
Rectal cancer	2B92	Rectal colon tissue	2.33E-05	2.32E+00	4.63E+00
Renal cancer	2C90-2C91	Kidney	7.07E-01	7.17E-02	9.91E-02
Retinoblastoma	2D02.2	Uvea	3.80E-08	1.68E+00	3.47E+00
Rheumatoid arthritis	FA20	Synovial tissue	8.17E-04	1.43E+00	2.02E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	4.94E-02	-2.48E-02	-6.49E-02
Schizophrenia	6A20	Prefrontal cortex	7.15E-01	7.04E-02	9.06E-02
Schizophrenia	6A20	Superior temporal cortex	6.53E-01	7.44E-02	2.27E-01
Scleroderma	4A42.Z	Whole blood	6.33E-02	-1.04E-01	-3.37E-01
Seizure	8A60-8A6Z	Whole blood	3.34E-02	-1.97E-01	-3.01E-01
Sensitive skin	EK0Z	Skin	3.30E-02	4.43E-01	1.78E+00
Sepsis with septic shock	1G41	Whole blood	3.39E-30	4.55E-01	1.17E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.10E-02	5.57E-01	1.31E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	4.12E-02	2.17E-01	4.21E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	2.02E-02	4.21E-01	1.55E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	1.97E-01	2.87E-01	1.23E+00
Skin cancer	2C30-2C3Z	Skin	4.40E-70	1.78E+00	1.83E+00
Thrombocythemia	3B63	Whole blood	2.52E-01	2.52E-01	7.98E-01
Thrombocytopenia	3B64	Whole blood	2.32E-01	5.96E-01	1.09E+00
Thyroid cancer	2D10	Thyroid	4.67E-07	5.32E-01	5.93E-01
Tibial muscular dystrophy	8C75	Muscle tissue	1.34E-01	-2.57E-01	-5.21E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	6.69E-01	-1.14E-01	-6.38E-01
Type 2 diabetes	5A11	Liver tissue	6.42E-01	-6.85E-02	-2.31E-01
Ureter cancer	2C92	Urothelium	6.24E-01	1.88E-01	9.09E-01
Uterine cancer	2C78	Endometrium tissue	8.36E-09	1.18E+00	9.42E-01
Vitiligo	ED63.0	Skin	8.18E-01	-2.98E-01	-4.55E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Gabapentin	Approved	hCMEC/D3 cells-LAT1	Km = 530 microM	[3]
Levodopa	Approved	Human embryonic kidney cells (HEK293)-LAT1	Km = 200 microM	[5]
Pregabalin	Approved	hCMEC/D3 cells-LAT1	Km = 288 microM	[6]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Large neutral amino acids transporter 1 (SLC7A5) DTT Info
• DTP DTT Type: Literature-reported

3 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-2-Amino-1,2,3,4-tetrahydro-2-naphthoic acid	DMX768L	Discovery agent	N.A.	Investigative	[1]
(+/-)-2-Aminoindane-2-carboxylic acid	DML5URN	Discovery agent	N.A.	Investigative	[1]
BCH	DM9IN0U	Discovery agent	N.A.	Investigative	[2]

References

• [1] Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 and their affinities for the large neutral amino acid transporter... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3688-91.
• [2] Amino acid transporter molecule as a drug target. Nippon Yakurigaku Zasshi. 1999 Oct;114 Suppl 1:11P-16P.
• [3] Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol. 2013 Jun 1;85(11):1672-83.
• [4] Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
• [5] Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Sci Rep. 2017 Mar 8;7:43580.
• [6] Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharm Res. 2018 Oct 29;35(12):246.