Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT48WEM)

• DTP Name: Proton-coupled amino acid transporter 1 (SLC36A1)
• Gene Name: SLC36A1
• UniProt ID: Q7Z2H8 (S36A1_HUMAN)
• VARIDT ID: DTD0318
• Synonyms: LYAAT1; PAT1; Proton/amino acid transporter 1; SLC36A1; Solute carrier family 36 member 1; TRAMD3; hPAT1
• DTP Family: Amino Acid/Auxin Permease (AAAP) Family
• Sequence:
  MSTQRLRNEDYHDYSSTDVSPEESPSEGLNNLSSPGSYQRFGQSNSTTWFQTLIHLLKGN
  IGTGLLGLPLAVKNAGIVMGPISLLIIGIVAVHCMGILVKCAHHFCRRLNKSFVDYGDTV
  MYGLESSPCSWLRNHAHWGRRVVDFFLIVTQLGFCCVYFVFLADNFKQVIEAANGTTNNC
  HNNETVILTPTMDSRLYMLSFLPFLVLLVFIRNLRALSIFSLLANITMLVSLVMIYQFIV
  QRIPDPSHLPLVAPWKTYPLFFGTAIFSFEGIGMVLPLENKMKDPRKFPLILYLGMVIVT
  ILYISLGCLGYLQFGANIQGSITLNLPNCWLYQSVKLLYSIGIFFTYALQFYVPAEIIIP
  FFVSRAPEHCELVVDLFVRTVLVCLTCILAILIPRLDLVISLVGSVSSSALALIIPPLLE
  VTTFYSEGMSPLTIFKDALISILGFVGFVVGTYEALYELIQPSNAPIFINSTCAFI
• Function: This tranporter has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognizes their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid.
• Endogenous Substrate(s): H+
• TCDB ID: 2.A.18.8.7
• Gene ID: 206358
• 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 DTP

6 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[2]
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[3]
Gaboxadol	DMI53FU	Insomnia	7A00-7A0Z	Approved	[4]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[5]
L-Proline	DMKSTWR	Malnutrition	5B50-5B71	Approved	[6]
Vigabatrin	DMYT0OG	Alcohol dependence	6C40.2	Approved	[7]

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	3.18E-34	-4.78E-01	-1.68E+00
Adrenocortical carcinoma	2D11.Z	Kidney	1.19E-03	1.63E-01	8.19E-01
Alopecia	ED70	Skin from scalp	1.62E-02	-7.89E-02	-3.30E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.87E-04	-1.37E-01	-5.38E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	1.93E-02	4.53E-01	1.93E+00
Aortic stenosis	BB70	Calcified aortic valve	6.60E-02	1.22E-01	6.07E-01
Apnea	7A40	Hyperplastic tonsil	8.78E-01	-2.03E-02	-1.40E-01
Arthropathy	FA00-FA5Z	Peripheral blood	1.38E-02	2.16E-01	8.22E-01
Asthma	CA23	Nasal and bronchial airway	9.10E-01	1.49E-03	4.89E-03
Atopic dermatitis	EA80	Skin	1.59E-04	1.32E-01	1.34E+00
Autism	6A02	Whole blood	8.40E-01	2.53E-02	1.23E-01
Autoimmune uveitis	9A96	Peripheral monocyte	8.01E-02	1.62E-01	1.03E+00
Autosomal dominant monocytopenia	4B04	Whole blood	4.48E-01	1.15E-02	3.32E-02
Bacterial infection of gingival	1C1H	Gingival tissue	3.44E-02	-6.90E-02	-3.02E-01
Batten disease	5C56.1	Whole blood	9.00E-01	-2.35E-02	-1.52E-01
Behcet's disease	4A62	Peripheral blood	9.88E-01	4.52E-02	2.65E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.21E-01	-4.22E-02	-1.98E-01
Bladder cancer	2C94	Bladder tissue	1.65E-03	2.44E-01	1.58E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.16E-35	1.87E-01	8.34E-01
Cardioembolic stroke	8B11.20	Whole blood	1.22E-07	4.35E-01	2.07E+00
Cervical cancer	2C77	Cervical tissue	6.13E-04	-1.07E-01	-7.16E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	6.83E-01	1.14E-01	1.95E-01
Chronic hepatitis C	1E51.1	Whole blood	7.33E-01	4.62E-02	2.95E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	1.30E-01	8.60E-02	4.14E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	7.46E-03	6.45E-02	3.49E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.84E-01	-4.28E-02	-2.38E-01
Colon cancer	2B90	Colon tissue	1.50E-67	-9.64E-01	-2.43E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	6.54E-01	-8.51E-02	-1.68E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	6.33E-01	-1.53E-01	-4.98E-01
Endometriosis	GA10	Endometrium tissue	1.32E-01	8.47E-02	3.72E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.28E-01	-4.51E-02	-4.33E-01
Familial hypercholesterolemia	5C80.00	Whole blood	3.96E-01	2.41E-02	1.29E-01
Gastric cancer	2B72	Gastric tissue	8.23E-02	3.18E-01	2.00E+00
Glioblastopma	2A00.00	Nervous tissue	4.34E-34	-2.06E-01	-6.86E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	2.36E-01	1.11E-01	3.33E-01
Head and neck cancer	2D42	Head and neck tissue	1.76E-24	3.88E-01	1.58E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	6.99E-01	6.31E-02	2.35E-01
Huntington's disease	8A01.10	Whole blood	7.00E-01	-4.20E-02	-2.61E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.58E-01	-1.11E-01	-6.25E-01
Immunodeficiency	4A00-4A20	Peripheral blood	3.88E-02	8.12E-02	8.67E-01
Influenza	1.00E+30	Whole blood	4.83E-05	-6.38E-01	-1.01E+01
Interstitial cystitis	GC00.3	Bladder tissue	7.92E-01	3.87E-02	5.29E-01
Intracranial aneurysm	8B01.0	Intracranial artery	5.77E-05	6.54E-01	2.97E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	7.76E-02	-7.28E-02	-3.04E-01
Ischemic stroke	8B11	Peripheral blood	5.77E-01	1.88E-02	8.64E-02
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.97E-01	-6.15E-02	-1.74E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	5.52E-02	1.96E-01	9.74E-01
Lateral sclerosis	8B60.4	Skin	5.33E-04	1.82E-01	3.88E+00
Liver cancer	2C12.0	Liver tissue	2.28E-01	1.73E-02	7.52E-02
Liver failure	DB99.7-DB99.8	Liver tissue	9.61E-03	3.27E-01	1.72E+00
Lung cancer	2C25	Lung tissue	2.65E-33	3.22E-01	1.39E+00
Lupus erythematosus	4A40	Whole blood	3.93E-03	1.88E-01	4.53E-01
Major depressive disorder	6A70-6A7Z	Whole blood	4.22E-03	1.20E-01	5.37E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	2.51E-01	-2.25E-02	-1.02E-01
Melanoma	2C30	Skin	8.40E-02	3.71E-01	6.12E-01
Multiple myeloma	2A83.1	Bone marrow	2.27E-01	-5.74E-02	-2.49E-01
Multiple myeloma	2A83.1	Peripheral blood	1.70E-01	-9.55E-02	-8.54E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	3.58E-01	7.00E-02	2.27E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.48E-03	6.75E-02	4.29E-01
Myelofibrosis	2A20.2	Whole blood	6.34E-02	3.23E-01	2.04E+00
Myocardial infarction	BA41-BA50	Peripheral blood	3.96E-02	2.60E-01	3.43E-01
Myopathy	8C70.6	Muscle tissue	1.30E-01	3.81E-01	8.86E-01
Neonatal sepsis	KA60	Whole blood	3.18E-34	6.63E-01	2.21E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	4.60E-01	1.21E-01	3.97E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	5.05E-01	3.97E-02	2.69E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	3.61E-01	1.03E-01	6.40E-01
Olive pollen allergy	CA08.00	Peripheral blood	2.06E-01	3.74E-01	7.54E-01
Oral cancer	2B6E	Oral tissue	2.40E-05	1.83E-01	8.88E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	9.48E-01	1.43E-01	3.93E-01
Osteoporosis	FB83.1	Bone marrow	9.64E-01	2.96E-02	1.94E-01
Ovarian cancer	2C73	Ovarian tissue	2.28E-01	6.51E-03	1.99E-02
Pancreatic cancer	2C10	Pancreas	2.57E-01	1.46E-02	5.75E-02
Parkinson's disease	8A00.0	Substantia nigra tissue	2.41E-01	1.14E-01	7.69E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	8.92E-05	2.35E-01	1.60E+00
Pituitary cancer	2D12	Pituitary tissue	2.37E-01	3.18E-01	9.09E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	9.28E-01	7.56E-02	4.90E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	2.34E-01	4.54E-02	4.48E-01
Polycythemia vera	2A20.4	Whole blood	9.25E-08	2.37E-01	1.20E+00
Pompe disease	5C51.3	Biceps muscle	1.29E-07	6.93E-01	4.32E+00
Preterm birth	KA21.4Z	Myometrium	6.74E-01	-1.77E-02	-8.43E-02
Prostate cancer	2C82	Prostate	7.64E-01	-3.41E-01	-4.00E-01
Psoriasis	EA90	Skin	8.43E-02	-6.99E-02	-2.32E-01
Rectal cancer	2B92	Rectal colon tissue	1.08E-04	-5.87E-01	-3.68E+00
Renal cancer	2C90-2C91	Kidney	6.13E-05	3.33E-01	2.03E+00
Retinoblastoma	2D02.2	Uvea	5.07E-08	7.29E-01	5.32E+00
Rheumatoid arthritis	FA20	Synovial tissue	6.85E-01	-2.61E-01	-6.43E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	9.83E-01	-2.58E-02	-1.84E-01
Schizophrenia	6A20	Prefrontal cortex	6.95E-01	-3.69E-02	-1.86E-01
Schizophrenia	6A20	Superior temporal cortex	6.46E-01	-4.78E-02	-5.17E-01
Scleroderma	4A42.Z	Whole blood	1.26E-01	1.00E-01	3.10E-01
Seizure	8A60-8A6Z	Whole blood	7.89E-01	-9.72E-02	-3.31E-01
Sensitive skin	EK0Z	Skin	1.12E-01	1.61E-01	1.29E+00
Sepsis with septic shock	1G41	Whole blood	4.99E-99	8.01E-01	3.21E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.70E-02	1.28E-01	3.92E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	9.67E-01	-4.51E-02	-2.94E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	1.83E-01	-1.68E-01	-1.10E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	9.67E-01	4.06E-02	3.17E-01
Skin cancer	2C30-2C3Z	Skin	1.89E-14	2.95E-01	9.15E-01
Thrombocythemia	3B63	Whole blood	3.38E-04	1.70E-01	1.10E+00
Thrombocytopenia	3B64	Whole blood	2.68E-01	1.94E-01	8.72E-01
Thyroid cancer	2D10	Thyroid	2.47E-19	2.84E-01	1.09E+00
Tibial muscular dystrophy	8C75	Muscle tissue	2.73E-02	2.15E-01	8.95E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.42E-01	-1.02E-02	-1.12E-01
Type 2 diabetes	5A11	Liver tissue	2.51E-01	1.40E-02	8.88E-02
Ureter cancer	2C92	Urothelium	6.66E-01	-3.74E-02	-2.24E-01
Uterine cancer	2C78	Endometrium tissue	1.45E-01	8.12E-02	2.48E-01
Vitiligo	ED63.0	Skin	1.36E-01	5.59E-02	3.56E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Aminolevulinic acid hci	Approved	Monkey kidney fibroblast-like cell (COS)7-hPAT1	Km = 6800.0 microM	[2]
Vigabatrin	Approved	X.Laevis oocytes-hPAT1	Km = 5200.0 microM	[7]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Solute carrier family 36 member 1 (SLC36A1) DTT Info
• DTP DTT Type: Literature-reported

2 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5-hydroxy-L-tryptophan	DMDWZGJ	Discovery agent	N.A.	Investigative	[1]
indole-3-propionic acid	DMF0VAG	Discovery agent	N.A.	Investigative	[1]

References

• [1] Serotonin, L-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J. 2005 Sep;19(11):1468-73.
• [2] Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1). Br J Pharmacol. 2010 Mar;159(6):1339-53.
• [3] Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol. 2005 Aug;204(2):604-13.
• [4] Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan. Br J Pharmacol. 2009 Aug;157(8):1380-9.
• [5] Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1: characterization of conditions for affinity and transport experiments in Caco-2 cells. Eur J Pharm Sci. 2008 Sep 2;35(1-2):86-95.
• [6] PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. Am J Physiol Endocrinol Metab. 2014 Jan 1;306(1):E65-74.
• [7] Rectal absorption of vigabatrin, a substrate of the proton coupled amino acid transporter (PAT1, Slc36a1), in rats. Pharm Res. 2012 Apr;29(4):1134-42.