Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTV2AOB)

DTP Name Excitatory amino acid transporter 4 (SLC1A6)
Gene Name SLC1A6
UniProt ID
P48664 (EAA4_HUMAN)
VARIDT ID
DTD0134
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Synonyms EAAT4; SLC1A6; Sodium-dependent glutamate/aspartate transporter; Solute carrier family 1 member 6
DTP Family Dicarboxylate/Amino Acid:Cation (Na(+) Or H(+)) Symporter (DAACS) Family ;
Tissue Specificity Brain. Expressed densely and selectively incell bodies of Purkinje cells.
Sequence
MSSHGNSLFLRESGQRLGRVGWLQRLQESLQQRALRTRLRLQTMTLEHVLRFLRRNAFIL
LTVSAVVIGVSLAFALRPYQLTYRQIKYFSFPGELLMRMLQMLVLPLIVSSLVTGMASLD
NKATGRMGMRAAVYYMVTTIIAVFIGILMVTIIHPGKGSKEGLHREGRIETIPTADAFMD
LIRNMFPPNLVEACFKQFKTQYSTRVVTRTMVRTENGSEPGASMPPPFSVENGTSFLENV
TRALGTLQEMLSFEETVPVPGSANGINALGLVVFSVAFGLVIGGMKHKGRVLRDFFDSLN
EAIMRLVGIIIWYAPVGILFLIAGKILEMEDMAVLGGQLGMYTLTVIVGLFLHAGIVLPL
IYFLVTHRNPFPFIGGMLQALITAMGTSSSSATLPITFRCLEEGLGVDRRITRFVLPVGA
TVNMDGTALYEALAAIFIAQVNNYELNLGQITTISITATAASVGAAGIPQAGLVTMVIVL
TSVGLPTEDITLIIAVDWFLDRLRTMTNVLGDSIGAAVIEHLSQRELELQEAELTLPSLG
KPYKSLMAQEKGASRGRGGNESAM
Function
This sodium-dependent, high-affinity amino acid transporter functions as a symporter and mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport. Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate.
Endogenous Substrate(s) Na+; Aspartate
TCDB ID
2.A.23.2.8
Gene ID
6511
KEGG Pathway
Synaptic vesicle cycle (hsa04721 )
Glutamatergic synapse (hsa04724 )
Spinocerebellar ataxia (hsa05017 )
Reactome Pathway
Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393 )
Glutamate Neurotransmitter Release Cycle (R-HSA-210500 )

Molecular Interaction Atlas (MIA) of This DTP

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTP
1 Approved Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-glutamic acid DM4PUDW Schizophrenia 6A20 Approved [5]
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Molecular Expression Atlas (MEA) of This DTP

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTP
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 1.57E-01 -3.59E-03 -3.29E-02
Adrenocortical carcinoma 2D11.Z Kidney 1.05E-01 7.13E-03 5.77E-02
Alopecia ED70 Skin from scalp 3.49E-15 -1.32E+00 -2.61E+00
Alzheimer's disease 8A20 Entorhinal cortex 4.80E-11 -1.12E+00 -1.15E+00
Ankylosing spondylitis FA92.0 Pheripheral blood 6.53E-01 1.36E-02 1.20E-01
Aortic stenosis BB70 Calcified aortic valve 7.72E-01 2.79E-01 3.59E-01
Apnea 7A40 Hyperplastic tonsil 2.17E-01 -1.43E-01 -4.43E+00
Arthropathy FA00-FA5Z Peripheral blood 3.82E-01 1.57E-02 9.77E-02
Asthma CA23 Nasal and bronchial airway 8.10E-01 4.83E-04 1.08E-03
Atopic dermatitis EA80 Skin 9.20E-14 -1.24E+00 -3.03E+00
Autism 6A02 Whole blood 4.66E-01 1.75E-02 1.40E-01
Autoimmune uveitis 9A96 Peripheral monocyte 2.34E-01 -7.10E-02 -2.73E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.41E-01 -6.40E-02 -2.72E-01
Bacterial infection of gingival 1C1H Gingival tissue 1.88E-01 -1.99E-02 -1.31E-01
Batten disease 5C56.1 Whole blood 3.70E-01 7.58E-02 5.94E-01
Behcet's disease 4A62 Peripheral blood 1.59E-01 6.55E-02 5.27E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 6.15E-01 -8.18E-02 -1.69E-01
Bladder cancer 2C94 Bladder tissue 1.04E-06 4.82E-01 1.37E+00
Breast cancer 2C60-2C6Z Breast tissue 2.56E-05 -3.82E-02 -1.35E-01
Cardioembolic stroke 8B11.20 Whole blood 1.46E-02 1.02E-01 7.42E-01
Cervical cancer 2C77 Cervical tissue 3.17E-01 -1.07E-01 -5.31E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 9.75E-01 1.65E-02 1.18E-01
Chronic hepatitis C 1E51.1 Whole blood 5.16E-01 4.29E-02 2.66E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 5.91E-01 2.44E-02 2.04E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 5.44E-01 7.13E-03 5.62E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 9.86E-01 3.58E-02 3.11E-01
Colon cancer 2B90 Colon tissue 4.60E-01 -6.67E-03 -3.70E-02
Coronary artery disease BA80-BA8Z Peripheral blood 1.55E-01 5.80E-02 2.25E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 3.21E-01 -5.19E-03 -2.95E-02
Endometriosis GA10 Endometrium tissue 8.40E-01 -1.61E-02 -7.78E-02
Familial hypercholesterolemia 5C80.00 Peripheral blood 2.65E-01 -6.04E-02 -4.02E-01
Familial hypercholesterolemia 5C80.00 Whole blood 7.86E-01 2.13E-02 1.51E-01
Gastric cancer 2B72 Gastric tissue 9.08E-01 -7.98E-02 -6.65E-01
Glioblastopma 2A00.00 Nervous tissue 2.53E-73 -2.41E+00 -1.91E+00
Glioma 2A00.0Y-2A00.0Z White matter tissue 2.59E-02 3.10E-01 1.30E+00
Head and neck cancer 2D42 Head and neck tissue 1.87E-01 -1.48E-02 -9.06E-02
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 1.77E-01 -5.35E-01 -5.63E-01
Huntington's disease 8A01.10 Whole blood 6.63E-01 3.85E-02 2.15E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 5.29E-01 -1.28E-01 -8.18E-01
Immunodeficiency 4A00-4A20 Peripheral blood 9.90E-01 -5.65E-03 -5.19E-02
Influenza 1.00E+30 Whole blood 3.98E-01 6.64E-03 2.83E-02
Interstitial cystitis GC00.3 Bladder tissue 9.52E-01 -3.94E-02 -8.93E-01
Intracranial aneurysm 8B01.0 Intracranial artery 6.04E-01 -1.10E-03 -8.79E-03
Irritable bowel syndrome DD91.0 Rectal colon tissue 1.57E-01 5.32E-01 7.70E-01
Ischemic stroke 8B11 Peripheral blood 8.38E-01 -3.68E-02 -2.12E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 9.80E-01 4.16E-02 7.92E-02
Lateral sclerosis 8B60.4 Cervical spinal cord 1.23E-01 3.17E-01 7.99E-01
Lateral sclerosis 8B60.4 Skin 2.96E-01 5.26E-02 4.73E-01
Liver cancer 2C12.0 Liver tissue 4.24E-06 -2.71E-01 -7.27E-01
Liver failure DB99.7-DB99.8 Liver tissue 2.32E-02 -1.82E-01 -1.60E+00
Lung cancer 2C25 Lung tissue 1.52E-32 1.07E-01 9.43E-01
Lupus erythematosus 4A40 Whole blood 5.58E-01 -4.43E-02 -1.74E-01
Major depressive disorder 6A70-6A7Z Whole blood 3.85E-01 -1.76E-02 -5.37E-02
Major depressive disorder 6A70-6A7Z Hippocampus 8.06E-01 9.91E-02 1.97E-01
Melanoma 2C30 Skin 2.32E-02 -1.46E+00 -1.12E+00
Multiple myeloma 2A83.1 Bone marrow 1.28E-01 -2.40E-01 -9.43E-01
Multiple myeloma 2A83.1 Peripheral blood 5.78E-02 5.52E-02 5.97E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 1.44E-01 -2.22E-01 -8.80E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 6.04E-02 -9.22E-01 -9.23E-01
Myelofibrosis 2A20.2 Whole blood 4.27E-01 -1.20E-01 -9.25E-01
Myocardial infarction BA41-BA50 Peripheral blood 1.59E-01 7.75E-02 2.11E-01
Myopathy 8C70.6 Muscle tissue 7.84E-01 -6.31E-02 -2.88E-01
Neonatal sepsis KA60 Whole blood 4.75E-07 8.55E-02 6.59E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 5.56E-01 -8.48E-01 -1.58E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 8.55E-01 -3.63E-02 -3.16E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 2.57E-01 3.13E-02 2.54E-01
Olive pollen allergy CA08.00 Peripheral blood 7.80E-01 -1.01E-02 -3.65E-02
Oral cancer 2B6E Oral tissue 3.24E-01 -4.29E-02 -2.00E-01
Osteoarthritis FA00-FA0Z Synovial tissue 6.63E-01 4.96E-02 2.48E-01
Osteoporosis FB83.1 Bone marrow 5.30E-02 2.16E-01 3.89E+00
Ovarian cancer 2C73 Ovarian tissue 3.70E-02 -3.48E-02 -1.83E-01
Pancreatic cancer 2C10 Pancreas 5.93E-02 -2.23E-01 -3.22E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.72E-01 -4.36E-01 -8.12E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 9.03E-01 -1.47E-02 -1.57E-01
Pituitary cancer 2D12 Pituitary tissue 4.05E-01 -1.96E-02 -6.92E-02
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.44E-01 -1.33E-01 -4.34E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 3.61E-01 -4.70E-03 -2.02E-02
Polycythemia vera 2A20.4 Whole blood 8.90E-01 9.22E-03 5.73E-02
Pompe disease 5C51.3 Biceps muscle 5.86E-02 -7.21E-02 -6.44E-01
Preterm birth KA21.4Z Myometrium 3.86E-01 4.76E-02 5.34E-01
Prostate cancer 2C82 Prostate 1.35E-02 -3.50E-01 -6.33E-01
Psoriasis EA90 Skin 6.36E-12 -5.88E-01 -7.98E-01
Rectal cancer 2B92 Rectal colon tissue 8.88E-01 5.06E-02 1.81E-01
Renal cancer 2C90-2C91 Kidney 1.71E-02 -2.32E-01 -9.31E-01
Retinoblastoma 2D02.2 Uvea 2.40E-06 -1.35E+00 -2.59E+00
Rheumatoid arthritis FA20 Synovial tissue 1.93E-01 9.10E-02 4.29E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 2.64E-01 1.30E-02 1.23E-01
Schizophrenia 6A20 Prefrontal cortex 6.89E-03 -6.66E-01 -4.18E-01
Schizophrenia 6A20 Superior temporal cortex 3.30E-01 -4.18E-01 -6.02E-01
Scleroderma 4A42.Z Whole blood 4.30E-01 -1.46E-03 -1.88E-02
Seizure 8A60-8A6Z Whole blood 6.28E-01 -1.12E-01 -6.91E-01
Sensitive skin EK0Z Skin 4.54E-01 1.41E-01 3.54E-01
Sepsis with septic shock 1G41 Whole blood 2.44E-02 5.78E-04 4.23E-03
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.28E-01 4.82E-02 2.77E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 1.56E-01 5.53E-02 5.69E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 2.38E-01 1.07E-01 1.41E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 8.93E-01 -2.70E-02 -1.92E-01
Skin cancer 2C30-2C3Z Skin 1.67E-85 -2.67E+00 -2.88E+00
Thrombocythemia 3B63 Whole blood 4.78E-02 6.63E-02 4.24E-01
Thrombocytopenia 3B64 Whole blood 9.62E-01 -4.79E-02 -3.81E-01
Thyroid cancer 2D10 Thyroid 2.65E-02 3.38E-02 2.23E-01
Tibial muscular dystrophy 8C75 Muscle tissue 2.10E-03 -1.25E-01 -9.41E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 2.82E-01 -3.07E-01 -2.01E+00
Type 2 diabetes 5A11 Liver tissue 4.53E-01 -1.15E-01 -2.33E-01
Ureter cancer 2C92 Urothelium 6.84E-01 8.80E-03 6.14E-02
Uterine cancer 2C78 Endometrium tissue 4.29E-01 -2.84E-01 -5.62E-01
Vitiligo ED63.0 Skin 7.06E-01 -2.32E-01 -4.02E-01
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⏷ Show the Full List of Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DTP

DTP DTT Name Excitatory amino acid transporter 4 (SLC1A6) DTT Info
DTP DTT Type Literature-reported
4 Investigative Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
D-aspartic acid DM7Z892 Discovery agent N.A. Investigative [1]
DL-TBOA DM2HGNU Discovery agent N.A. Investigative [2]
Threo-3-methylglutamate DMOE3IJ Discovery agent N.A. Investigative [3]
[3H]ETB-TBOA DMWGY61 Discovery agent N.A. Investigative [4]
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References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 871).
2 Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5). J Neurochem. 2001 Oct;79(2):297-302.
3 Pharmacological characterization of threo-3-methylglutamic acid with excitatory amino acid transporters in native and recombinant systems. J Neurochem. 2001 Apr;77(2):550-7.
4 Characterization of the tritium-labeled analog of L-threo-beta-benzyloxyaspartate binding to glutamate transporters. Mol Pharmacol. 2007 Jan;71(1):294-302.
5 The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol Aspects Med. 2013 Apr-Jun;34(2-3):108-20.