Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT3EAQP)

• DTP Name: Equilibrative nucleoside transporter 4 (SLC29A4)
• Gene Name: SLC29A4
• UniProt ID: Q7RTT9 (S29A4_HUMAN)
• VARIDT ID: DTD0250
• Synonyms: ENT4; PMAT; Plasma membrane monoamine transporter; SLC29A4; Solute carrier family 29 member 4; hENT4
• DTP Family: Equilibrative Nucleoside Transporter (ENT) Family
• Tissue Specificity: Expressed abundantly in the heart, in bothcardiomyocytes and vascular endothelial cells (at protein level).Highly expressed in brain, kidney and skeletal muscle. In thebrain expressed in cerebellum, cerebral cortex, medulla, occipitalpole, frontal and temporal lobes putamen and in the spinal cord.Lower expression in liver, pancreas, and liver. Expressed inendometrial tissue, exclusively in the stroma. Expression is highin the proliferative phase, decreases during the secretory phase,and is no longer detectable in the menstrual phase.
• Sequence:
  MGSVGSQRLEEPSVAGTPDPGVVMSFTFDSHQLEEAAEAAQGQGLRARGVPAFTDTTLDE
  PVPDDRYHAIYFAMLLAGVGFLLPYNSFITDVDYLHHKYPGTSIVFDMSLTYILVALAAV
  LLNNVLVERLTLHTRITAGYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGC
  TVQQSSFYGYTGMLPKRYTQGVMTGESTAGVMISLSRILTKLLLPDERASTLIFFLVSVA
  LELLCFLLHLLVRRSRFVLFYTTRPRDSHRGRPGLGRGYGYRVHHDVVAGDVHFEHPAPA
  LAPNESPKDSPAHEVTGSGGAYMRFDVPRPRVQRSWPTFRALLLHRYVVARVIWADMLSI
  AVTYFITLCLFPGLESEIRHCILGEWLPILIMAVFNLSDFVGKILAALPVDWRGTHLLAC
  SCLRVVFIPLFILCVYPSGMPALRHPAWPCIFSLLMGISNGYFGSVPMILAAGKVSPKQR
  ELAGNTMTVSYMSGLTLGSAVAYCTYSLTRDAHGSCLHASTANGSILAGL
• Function: This transporter functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine. Adenosine is efficiently transported but in a fashion highly sensitive to extracellular pH, with maximal activity in the pH range 5. 5 to 6. 5. Glu-206 is essential for the cation selectivity and may function as the charge sensor for cationic substrates. Transport is chloride and sodium-independent but appears to be sensitive to changes in membrane potential. Weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. May play a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia.
• Endogenous Substrate(s): 1-methyl-4-phenylpyridinium
• TCDB ID: 2.A.57.1.5
• Gene ID: 222962
• Reactome Pathway: Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936)

Molecular Interaction Atlas (MIA) of This DTP

2 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[2]
Metformin	DM89QE1	Colorectal carcinoma		Approved	[3]

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SEROTONIN	DMOFCRY	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	6.64E-04	5.02E-02	2.46E-01
Adrenocortical carcinoma	2D11.Z	Kidney	8.98E-01	-3.47E-02	-1.47E-01
Alopecia	ED70	Skin from scalp	9.95E-02	9.55E-02	2.78E-01
Alzheimer's disease	8A20	Entorhinal cortex	8.75E-03	-8.78E-02	-2.77E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	8.14E-01	6.67E-03	1.06E-01
Aortic stenosis	BB70	Calcified aortic valve	9.91E-01	6.54E-02	8.18E-02
Apnea	7A40	Hyperplastic tonsil	1.72E-01	-7.15E-02	-4.91E-01
Arthropathy	FA00-FA5Z	Peripheral blood	2.71E-01	3.86E-02	2.24E-01
Asthma	CA23	Nasal and bronchial airway	8.97E-03	9.51E-02	2.59E-01
Atopic dermatitis	EA80	Skin	6.58E-02	1.70E-01	6.74E-01
Autism	6A02	Whole blood	8.85E-01	7.66E-02	3.49E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.14E-01	-1.72E-01	-9.55E-01
Autosomal dominant monocytopenia	4B04	Whole blood	1.81E-01	-7.96E-02	-6.95E-01
Bacterial infection of gingival	1C1H	Gingival tissue	8.99E-06	1.34E-01	5.67E-01
Batten disease	5C56.1	Whole blood	7.83E-01	-5.97E-03	-7.83E-02
Behcet's disease	4A62	Peripheral blood	7.76E-01	1.65E-02	1.09E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	7.65E-01	3.80E-02	1.23E-01
Bladder cancer	2C94	Bladder tissue	1.67E-03	2.92E-01	1.53E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.13E-44	-6.19E-01	-1.01E+00
Cardioembolic stroke	8B11.20	Whole blood	3.96E-05	2.66E-01	1.11E+00
Cervical cancer	2C77	Cervical tissue	3.17E-02	-8.29E-02	-3.89E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	9.96E-01	-2.14E-02	-1.02E-01
Chronic hepatitis C	1E51.1	Whole blood	1.53E-01	6.60E-02	5.92E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	2.37E-01	5.92E-02	2.90E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.81E-02	6.08E-02	3.15E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	6.71E-01	-4.45E-02	-3.14E-01
Colon cancer	2B90	Colon tissue	1.60E-31	-2.85E-01	-1.32E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	4.82E-01	-7.18E-02	-1.59E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	2.62E-01	-5.10E-02	-1.83E-01
Endometriosis	GA10	Endometrium tissue	1.59E-01	-1.18E-01	-5.16E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.90E-01	-2.76E-02	-2.16E-01
Familial hypercholesterolemia	5C80.00	Whole blood	2.87E-02	-1.38E-01	-8.31E-01
Gastric cancer	2B72	Gastric tissue	8.47E-02	-3.74E-01	-2.35E+00
Glioblastopma	2A00.00	Nervous tissue	6.12E-05	-2.22E-01	-5.32E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.13E-05	1.05E+00	2.29E+00
Head and neck cancer	2D42	Head and neck tissue	3.01E-01	3.20E-02	1.61E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	9.61E-02	-1.37E-01	-5.53E-01
Huntington's disease	8A01.10	Whole blood	3.03E-01	3.40E-02	2.04E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	9.97E-01	4.26E-02	2.65E-01
Immunodeficiency	4A00-4A20	Peripheral blood	1.78E-01	1.03E-01	1.04E+00
Influenza	1.00E+30	Whole blood	1.09E-01	1.69E-01	8.24E-01
Interstitial cystitis	GC00.3	Bladder tissue	5.62E-01	3.23E-02	2.14E-01
Intracranial aneurysm	8B01.0	Intracranial artery	2.01E-01	-5.03E-02	-2.15E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	8.79E-01	-4.81E-03	-2.38E-02
Ischemic stroke	8B11	Peripheral blood	9.95E-01	-8.97E-03	-6.82E-02
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.34E-01	3.29E-02	9.85E-02
Lateral sclerosis	8B60.4	Cervical spinal cord	7.76E-01	-5.85E-03	-1.75E-02
Lateral sclerosis	8B60.4	Skin	8.49E-01	7.29E-03	6.20E-02
Liver cancer	2C12.0	Liver tissue	9.03E-04	-8.61E-03	-3.07E-02
Liver failure	DB99.7-DB99.8	Liver tissue	5.55E-01	2.13E-02	1.22E-01
Lung cancer	2C25	Lung tissue	1.41E-61	2.91E-01	1.67E+00
Lupus erythematosus	4A40	Whole blood	3.41E-01	6.60E-02	1.82E-01
Major depressive disorder	6A70-6A7Z	Whole blood	1.90E-01	5.89E-02	2.24E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.05E-01	-2.11E-02	-7.32E-02
Melanoma	2C30	Skin	3.56E-02	-3.11E-01	-5.53E-01
Multiple myeloma	2A83.1	Bone marrow	1.07E-02	-1.59E-01	-1.25E+00
Multiple myeloma	2A83.1	Peripheral blood	4.37E-01	1.38E-01	7.94E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	9.03E-01	1.44E-01	4.54E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	9.44E-01	4.54E-04	2.89E-03
Myelofibrosis	2A20.2	Whole blood	6.36E-04	1.99E-01	1.46E+00
Myocardial infarction	BA41-BA50	Peripheral blood	8.27E-01	-2.91E-02	-4.24E-02
Myopathy	8C70.6	Muscle tissue	1.38E-02	-2.37E-01	-1.37E+00
Neonatal sepsis	KA60	Whole blood	3.11E-01	4.44E-02	1.90E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	9.70E-02	-6.63E-02	-3.06E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	8.78E-01	6.39E-02	4.83E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	1.39E-02	3.81E-01	2.13E+00
Olive pollen allergy	CA08.00	Peripheral blood	1.19E-03	3.06E-01	2.91E+00
Oral cancer	2B6E	Oral tissue	6.51E-05	-1.78E-01	-8.43E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	3.10E-01	-1.08E-01	-3.80E-01
Osteoporosis	FB83.1	Bone marrow	1.81E-03	4.47E-01	2.84E+00
Ovarian cancer	2C73	Ovarian tissue	1.41E-02	-2.64E-01	-1.07E+00
Pancreatic cancer	2C10	Pancreas	6.27E-03	-3.51E-01	-7.17E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	6.77E-01	7.67E-02	2.27E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	7.77E-03	-1.27E-01	-9.97E-01
Pituitary cancer	2D12	Pituitary tissue	6.11E-03	4.72E-01	1.13E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	6.99E-02	2.59E-01	1.06E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	4.66E-01	-2.04E-02	-3.08E-01
Polycythemia vera	2A20.4	Whole blood	5.26E-04	1.17E-01	7.54E-01
Pompe disease	5C51.3	Biceps muscle	3.39E-01	-9.84E-02	-3.15E-01
Preterm birth	KA21.4Z	Myometrium	9.49E-01	2.87E-02	2.08E-01
Prostate cancer	2C82	Prostate	1.29E-06	4.70E-01	1.46E+00
Psoriasis	EA90	Skin	1.47E-08	2.46E-01	7.31E-01
Rectal cancer	2B92	Rectal colon tissue	3.91E-01	-6.03E-02	-3.24E-01
Renal cancer	2C90-2C91	Kidney	6.88E-01	5.34E-02	2.04E-01
Retinoblastoma	2D02.2	Uvea	8.88E-08	-1.04E+00	-6.65E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.39E-02	-3.11E-01	-7.57E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	2.70E-01	-3.23E-02	-2.87E-01
Schizophrenia	6A20	Prefrontal cortex	1.43E-01	-1.29E-01	-2.91E-01
Schizophrenia	6A20	Superior temporal cortex	4.93E-01	1.01E-01	6.19E-01
Scleroderma	4A42.Z	Whole blood	1.41E-02	-1.91E-01	-1.33E+00
Seizure	8A60-8A6Z	Whole blood	2.13E-01	-7.80E-02	-5.27E-01
Sensitive skin	EK0Z	Skin	9.12E-01	4.85E-02	4.87E-01
Sepsis with septic shock	1G41	Whole blood	8.00E-04	1.15E-02	5.15E-02
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.95E-01	1.26E-01	4.55E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.87E-02	1.33E-01	8.10E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	3.57E-02	9.37E-01	3.09E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	8.27E-01	6.32E-03	6.44E-02
Skin cancer	2C30-2C3Z	Skin	2.32E-01	3.13E-02	6.41E-02
Thrombocythemia	3B63	Whole blood	3.89E-02	1.31E-01	8.97E-01
Thrombocytopenia	3B64	Whole blood	3.08E-01	7.19E-01	9.30E-01
Thyroid cancer	2D10	Thyroid	2.42E-18	-4.30E-01	-1.40E+00
Tibial muscular dystrophy	8C75	Muscle tissue	5.58E-02	-2.28E-01	-8.96E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	6.30E-01	3.85E-01	2.24E+00
Type 2 diabetes	5A11	Liver tissue	3.65E-02	-1.72E-01	-1.01E+00
Ureter cancer	2C92	Urothelium	6.47E-01	-1.03E-01	-3.76E-01
Uterine cancer	2C78	Endometrium tissue	9.62E-14	-3.03E-01	-7.72E-01
Vitiligo	ED63.0	Skin	6.36E-02	-1.79E-01	-4.04E-01

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Solute carrier family 29 member 4 (SLC29A4) DTT Info
• DTP DTT Type: Literature-reported

1 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
decynium 22	DMWCTZ7	Discovery agent	N.A.	Investigative	[1]

References

• [1] Interaction of organic cations with a newly identified plasma membrane monoamine transporter. Mol Pharmacol. 2005 Nov;68(5):1397-407.
• [2] Histamine uptake mediated by plasma membrane monoamine transporter and organic cation transporters in rat mast cell lines. Eur J Pharmacol. 2019 Apr 15;849:75-83.
• [3] Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
• [4] Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene. Mol Autism. 2014 Aug 13;5:43.