Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT2EG60)

DTP Name Organic cation/carnitine transporter 1 (SLC22A4)
Gene Name SLC22A4
UniProt ID
Q9H015 (S22A4_HUMAN)
VARIDT ID
DTD0151
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Synonyms DFNB60; ET transporter; ETT; Ergothioneine transporter; OCTN1; SLC22A4; Solute carrier family 22 member 4; UT2H
DTP Family Major Facilitator Superfamily (MFS)
Organic Cation Transporter (OCT) Family
Tissue Specificity Widely expressed. Highly expressed in wholeblood, bone marrow, trachea and fetal liver. Weakly expressed inkidney, skeletal muscle, prostate, lung, pancreas, placenta,heart, uterus, spleen and spinal cord. Highly expressed inintestinal cell types affected by Crohn disease, includingepithelial cells. Expressed in CD68 macrophage and CD43 T-cellsbut not in CD20 B-cells. Predominantly expressed in CD14 cells inperipheral blood mononuclear cells.
Sequence
MRDYDEVIAFLGEWGPFQRLIFFLLSASIIPNGFNGMSVVFLAGTPEHRCRVPDAANLSS
AWRNNSVPLRLRDGREVPHSCSRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFS
QDVYLSTVVTEWNLVCEDNWKVPLTTSLFFVGVLLGSFVSGQLSDRFGRKNVLFATMAVQ
TGFSFLQIFSISWEMFTVLFVIVGMGQISNYVVAFILGTEILGKSVRIIFSTLGVCTFFA
VGYMLLPLFAYFIRDWRMLLLALTVPGVLCVPLWWFIPESPRWLISQRRFREAEDIIQKA
AKMNNIAVPAVIFDSVEELNPLKQQKAFILDLFRTRNIAIMTIMSLLLWMLTSVGYFALS
LDAPNLHGDAYLNCFLSALIEIPAYITAWLLLRTLPRRYIIAAVLFWGGGVLLFIQLVPV
DYYFLSIGLVMLGKFGITSAFSMLYVFTAELYPTLVRNMAVGVTSTASRVGSIIAPYFVY
LGAYNRMLPYIVMGSLTVLIGILTLFFPESLGMTLPETLEQMQKVKWFRSGKKTRDSMET
EENPKVLITAF
Function
This sodium-ion dependent transporter mediates the tranport of carnitine and sodium-ion. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. A key substrate of this transporter seems to be ergothioneine (ET).
Endogenous Substrate(s) Ergothioneine
TCDB ID
2.A.1.19.2
Gene ID
6583
KEGG Pathway
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
Organic cation transport (R-HSA-549127 )

Molecular Interaction Atlas (MIA) of This DTP

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTP
6 Approved Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cytarabine DMZD5QR Acute lymphoblastic leukaemia 2A85 Approved [1]
Gabapentin DM6T924 Complex partial seizure 8A68.0 Approved [2]
Ipratropium DMFQ320 Obstructive lung disease CA22.Z Approved [3]
Levacecarnine hci DMJBOCR Cognitive impairment 6D71 Approved [4]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [5]
Verapamil DMA7PEW Angina pectoris BA40 Approved [5]
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⏷ Show the Full List of 6 Approved Drug(s)
1 Investigative Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
[14C]TEA DM6SFYH Discovery agent N.A. Investigative [6]
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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 1.75E-47 -1.48E+00 -1.98E+00
Adrenocortical carcinoma 2D11.Z Kidney 1.78E-01 -1.92E-01 -2.93E-01
Alopecia ED70 Skin from scalp 1.25E-04 4.44E-01 7.66E-01
Alzheimer's disease 8A20 Entorhinal cortex 2.26E-01 5.94E-02 1.21E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 1.66E-01 -3.52E-02 -7.64E-02
Aortic stenosis BB70 Calcified aortic valve 8.74E-01 7.78E-02 1.22E-01
Apnea 7A40 Hyperplastic tonsil 9.55E-02 -1.66E-01 -6.09E-01
Arthropathy FA00-FA5Z Peripheral blood 4.48E-03 5.13E-01 1.36E+00
Asthma CA23 Nasal and bronchial airway 1.07E-02 -7.67E-02 -8.08E-02
Atopic dermatitis EA80 Skin 5.08E-02 -1.31E-01 -2.38E-01
Autism 6A02 Whole blood 9.33E-01 -1.97E-02 -2.70E-02
Autoimmune uveitis 9A96 Peripheral monocyte 5.66E-01 -4.64E-01 -3.02E-01
Autosomal dominant monocytopenia 4B04 Whole blood 1.60E-01 -3.15E-01 -9.09E-01
Bacterial infection of gingival 1C1H Gingival tissue 2.47E-05 1.60E-01 5.53E-01
Batten disease 5C56.1 Whole blood 2.75E-01 4.92E-01 8.42E-01
Behcet's disease 4A62 Peripheral blood 4.57E-01 3.26E-01 6.66E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 3.96E-01 -1.36E-02 -3.66E-02
Bladder cancer 2C94 Bladder tissue 3.15E-02 3.82E-01 8.60E-01
Breast cancer 2C60-2C6Z Breast tissue 1.27E-03 5.92E-02 9.10E-02
Cardioembolic stroke 8B11.20 Whole blood 8.55E-11 9.77E-01 2.54E+00
Cervical cancer 2C77 Cervical tissue 1.01E-01 3.29E-01 7.34E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 8.26E-01 4.98E-01 2.34E-01
Chronic hepatitis C 1E51.1 Whole blood 6.05E-01 -5.14E-01 -2.51E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 6.64E-01 -7.95E-02 -9.98E-02
Chronic obstructive pulmonary disease CA22 Small airway epithelium 8.72E-01 -1.72E-02 -3.45E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 5.74E-03 -1.56E+00 -1.70E+00
Colon cancer 2B90 Colon tissue 7.24E-27 -1.05E+00 -1.17E+00
Coronary artery disease BA80-BA8Z Peripheral blood 8.05E-01 2.90E-01 2.26E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 4.00E-01 -4.55E-02 -1.57E-01
Endometriosis GA10 Endometrium tissue 4.78E-01 8.67E-01 5.49E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 6.93E-02 -1.35E-01 -6.99E-01
Familial hypercholesterolemia 5C80.00 Whole blood 8.52E-05 -7.93E-01 -1.09E+00
Gastric cancer 2B72 Gastric tissue 1.44E-03 6.97E-01 6.38E+00
Glioblastopma 2A00.00 Nervous tissue 1.46E-111 1.00E+00 2.02E+00
Glioma 2A00.0Y-2A00.0Z White matter tissue 5.50E-03 1.34E+00 1.13E+00
Head and neck cancer 2D42 Head and neck tissue 2.76E-09 -1.20E-01 -3.47E-02
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 5.24E-01 -7.21E-02 -2.42E-01
Huntington's disease 8A01.10 Whole blood 3.17E-01 -6.20E-02 -1.85E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 6.83E-01 3.34E-01 3.53E-01
Immunodeficiency 4A00-4A20 Peripheral blood 2.47E-02 6.41E-02 4.47E-01
Influenza 1.00E+30 Whole blood 6.61E-01 -3.56E-01 -4.88E-01
Interstitial cystitis GC00.3 Bladder tissue 1.74E-02 9.22E-01 2.53E+00
Intracranial aneurysm 8B01.0 Intracranial artery 1.88E-01 7.34E-01 6.95E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 8.04E-01 2.33E-02 5.65E-02
Ischemic stroke 8B11 Peripheral blood 6.11E-02 3.97E-01 7.56E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 1.42E-01 3.95E-01 2.67E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 1.08E-01 -2.20E-01 -4.82E-01
Lateral sclerosis 8B60.4 Skin 7.22E-01 1.90E-01 1.93E-01
Liver cancer 2C12.0 Liver tissue 1.11E-11 2.22E-01 5.45E-01
Liver failure DB99.7-DB99.8 Liver tissue 5.43E-01 4.51E-01 6.98E-01
Lung cancer 2C25 Lung tissue 1.48E-19 -1.06E+00 -8.94E-01
Lupus erythematosus 4A40 Whole blood 6.24E-04 5.40E-01 3.30E-01
Major depressive disorder 6A70-6A7Z Whole blood 2.33E-02 1.91E-01 4.89E-01
Major depressive disorder 6A70-6A7Z Hippocampus 7.33E-01 -8.58E-02 -2.23E-01
Melanoma 2C30 Skin 1.40E-01 -8.19E-01 -6.47E-01
Multiple myeloma 2A83.1 Bone marrow 4.31E-04 8.88E-02 5.56E-01
Multiple myeloma 2A83.1 Peripheral blood 4.59E-01 8.30E-02 3.35E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 3.41E-01 -7.96E-02 -1.50E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 6.15E-06 -4.10E-01 -6.25E-01
Myelofibrosis 2A20.2 Whole blood 9.89E-02 2.70E-01 6.07E-01
Myocardial infarction BA41-BA50 Peripheral blood 3.49E-04 2.26E+00 1.05E+00
Myopathy 8C70.6 Muscle tissue 3.18E-01 5.32E-01 7.72E-01
Neonatal sepsis KA60 Whole blood 3.27E-17 1.90E+00 1.60E+00
Neuroectodermal tumour 2A00.11 Brain stem tissue 5.39E-04 -9.04E-01 -1.71E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 2.75E-01 4.68E-01 7.07E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 3.66E-01 -3.76E-02 -4.13E-02
Olive pollen allergy CA08.00 Peripheral blood 1.59E-01 -9.95E-01 -9.50E-01
Oral cancer 2B6E Oral tissue 1.71E-07 7.42E-01 1.58E+00
Osteoarthritis FA00-FA0Z Synovial tissue 2.63E-02 1.09E+00 2.20E+00
Osteoporosis FB83.1 Bone marrow 5.98E-02 -1.60E+00 -2.10E+00
Ovarian cancer 2C73 Ovarian tissue 8.81E-01 3.44E-01 2.55E-01
Pancreatic cancer 2C10 Pancreas 8.02E-02 2.44E-01 4.59E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.72E-02 -7.57E-01 -1.75E+00
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 6.62E-07 2.50E+00 2.86E+00
Pituitary cancer 2D12 Pituitary tissue 2.03E-04 8.41E-01 1.65E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 2.11E-06 1.99E+00 5.66E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 5.03E-01 -3.26E-02 -1.34E-01
Polycythemia vera 2A20.4 Whole blood 7.64E-19 8.55E-01 1.87E+00
Pompe disease 5C51.3 Biceps muscle 4.69E-01 6.27E-02 1.51E-01
Preterm birth KA21.4Z Myometrium 2.51E-01 -5.74E-01 -5.22E-01
Prostate cancer 2C82 Prostate 3.83E-02 -3.39E-01 -3.57E-01
Psoriasis EA90 Skin 4.95E-01 1.01E-02 1.82E-02
Rectal cancer 2B92 Rectal colon tissue 1.67E-03 -1.27E+00 -2.62E+00
Renal cancer 2C90-2C91 Kidney 5.12E-01 4.81E-01 4.42E-01
Retinoblastoma 2D02.2 Uvea 4.32E-01 3.36E-01 7.13E-01
Rheumatoid arthritis FA20 Synovial tissue 2.68E-03 3.88E-01 1.18E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 4.04E-01 -2.89E-01 -3.35E-01
Schizophrenia 6A20 Prefrontal cortex 7.97E-02 -6.02E-02 -1.03E-01
Schizophrenia 6A20 Superior temporal cortex 4.84E-01 -4.72E-02 -4.51E-01
Scleroderma 4A42.Z Whole blood 4.43E-01 2.79E-01 5.26E-01
Seizure 8A60-8A6Z Whole blood 8.59E-01 -1.06E-01 -8.38E-02
Sensitive skin EK0Z Skin 1.80E-02 -2.84E-01 -8.88E-01
Sepsis with septic shock 1G41 Whole blood 3.04E-72 2.08E+00 2.58E+00
Shwachman-Diamond syndrome 3A70.0 Bone marrow 4.09E-01 3.89E-01 1.20E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 6.09E-02 1.99E-01 7.23E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 9.73E-01 2.63E-02 3.07E-02
Sjogren's syndrome 4A43.2 Salivary gland tissue 7.32E-01 3.11E-01 4.51E-01
Skin cancer 2C30-2C3Z Skin 7.80E-02 -2.10E-01 -2.94E-01
Thrombocythemia 3B63 Whole blood 3.30E-02 3.27E-01 7.20E-01
Thrombocytopenia 3B64 Whole blood 3.85E-01 1.78E-02 1.20E-01
Thyroid cancer 2D10 Thyroid 4.81E-48 8.29E-01 2.89E+00
Tibial muscular dystrophy 8C75 Muscle tissue 1.87E-09 1.52E+00 3.41E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 1.97E-02 7.60E-01 2.97E+00
Type 2 diabetes 5A11 Liver tissue 6.93E-01 -4.89E-02 -1.64E-01
Ureter cancer 2C92 Urothelium 2.81E-02 -7.52E-02 -1.86E-01
Uterine cancer 2C78 Endometrium tissue 5.97E-05 -3.33E-01 -3.90E-01
Vitiligo ED63.0 Skin 9.19E-01 -3.39E-02 -3.77E-02
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⏷ Show the Full List of Expression Under 107 Diseases

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)
Drug Name Highest Status Cell Line Affinity REF
Ipratropium Approved Human embryonic kidney cells (HEK293)-OCTN1 Km = 444.0 microM [3]
Investigative Drug(s)
Drug Name Highest Status Cell Line Affinity REF
[14C]TEA Investigative Human embryonic kidney cells (HEK293)-OCTN1 Km = 436.0 microM [5]
[14C]TEA Investigative Human embryonic kidney cells (HEK293)-OCTN1 Km = 1800.0 microM [6]
[14C]TEA Investigative Oocytes-OCTN1 Km = 195.0 microM [5]

References

1 OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues. Cancer Res. 2017 Apr 15;77(8):2102-2111.
2 Effects of genetic variation in the novel organic cation transporter, OCTN1, on the renal clearance of gabapentin. Clin Pharmacol Ther. 2008 Mar;83(3):416-21.
3 Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95.
4 Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Mol Genet Metab. 2007 Dec;92(4):315-24.
5 Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73.
6 Functional effects of protein sequence polymorphisms in the organic cation/ergothioneine transporter OCTN1 (SLC22A4). Pharmacogenet Genomics. 2007 Sep;17(9):773-82.