Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT0OC1Q)

• DTP Name: Organic anion transporter 2 (SLC22A7)
• Gene Name: SLC22A7
• UniProt ID: Q9Y694 (S22A7_HUMAN)
• VARIDT ID: DTD0005
• Synonyms: NLT; Novel liver transporter; OAT2; SLC22A7; Solute carrier family 22 member 7; hOAT11; hOAT2
• DTP Family:
  Major Facilitator Superfamily (MFS)
  Organic Cation Transporter (OCT) Family
• Tissue Specificity: Highly expressed in the liver and, to a lesser extent, in the kidney
• Sequence:
  MGFEELLEQVGGFGPFQLRNVALLALPRVLLPLHFLLPIFLAAVPAHRCALPGAPANFSH
  QDVWLEAHLPREPDGTLSSCLRFAYPQALPNTTLGEERQSRGELEDEPATVPCSQGWEYD
  HSEFSSTIATESQWDLVCEQKGLNRAASTFFFAGVLVGAVAFGYLSDRFGRRRLLLVAYV
  STLVLGLASAASVSYVMFAITRTLTGSALAGFTIIVMPLELEWLDVEHRTVAGVLSSTFW
  TGGVMLLALVGYLIRDWRWLLLAVTLPCAPGILSLWWVPESARWLLTQGHVKEAHRYLLH
  CARLNGRPVCEDSFSQEAVSKVAAGERVVRRPSYLDLFRTPRLRHISLCCVVVWFGVNFS
  YYGLSLDVSGLGLNVYQTQLLFGAVELPSKLLVYLSVRYAGRRLTQAGTLLGTALAFGTR
  LLVSSDMKSWSTVLAVMGKAFSEAAFTTAYLFTSELYPTVLRQTGMGLTALVGRLGGSLA
  PLAALLDGVWLSLPKLTYGGIALLAAGTALLLPETRQAQLPETIQDVERKSAPTSLQEEE
  MPMKQVQN
• Function: This sodium-independent transporter mediates the transport of multispecific organic anion. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
• Endogenous Substrate(s): Organic anions; 2'-Deoxyguanosine
• TCDB ID: 2.A.1.19.25
• Gene ID: 10864
• KEGG Pathway: Bile secretion (hsa04976)
• Reactome Pathway:
  Aspirin ADME (R-HSA-9749641)
  Organic anion transport (R-HSA-561048)

Molecular Interaction Atlas (MIA) of This DTP

15 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[1]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[2]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[3]
Bumetanide	DMRV7H0	Congestive heart failure	BD10	Approved	[4]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[5]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[6]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[7]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[4]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[8]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[4]
Penciclovir	DMOUMDV	Herpes simplex labialis	1F00.01	Approved	[9]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[10]
Tetracycline	DMZA017	Acne vulgaris	ED80	Approved	[11]
Theophylline	DMRJFN9	Bronchitis	CA20	Approved	[7]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[12]

1 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[13]

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	3.29E-03	6.66E-02	3.17E-01
Adrenocortical carcinoma	2D11.Z	Kidney	1.95E-01	-1.44E-01	-5.78E-01
Alopecia	ED70	Skin from scalp	6.05E-02	-8.72E-02	-2.61E-01
Alzheimer's disease	8A20	Entorhinal cortex	5.96E-02	-5.09E-02	-3.48E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	5.58E-01	-6.51E-02	-5.16E-01
Aortic stenosis	BB70	Calcified aortic valve	4.72E-01	1.43E-01	2.14E-01
Apnea	7A40	Hyperplastic tonsil	1.71E-01	9.56E-02	2.49E-01
Arthropathy	FA00-FA5Z	Peripheral blood	4.13E-01	7.94E-02	5.73E-01
Asthma	CA23	Nasal and bronchial airway	2.51E-03	-1.49E-01	-4.21E-01
Atopic dermatitis	EA80	Skin	1.44E-03	8.56E-02	8.64E-01
Autism	6A02	Whole blood	1.77E-01	-8.55E-02	-3.21E-01
Autoimmune uveitis	9A96	Peripheral monocyte	3.28E-02	-1.84E-01	-1.32E+00
Autosomal dominant monocytopenia	4B04	Whole blood	3.33E-01	-1.14E-01	-6.97E-01
Bacterial infection of gingival	1C1H	Gingival tissue	6.60E-01	-1.29E-02	-5.57E-02
Batten disease	5C56.1	Whole blood	2.69E-01	9.99E-02	9.73E-01
Behcet's disease	4A62	Peripheral blood	8.98E-01	0.00E+00	0.00E+00
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	2.41E-01	-5.79E-02	-3.69E-01
Bladder cancer	2C94	Bladder tissue	1.83E-03	5.51E-01	1.87E+00
Breast cancer	2C60-2C6Z	Breast tissue	7.89E-04	-6.26E-02	-3.18E-01
Cardioembolic stroke	8B11.20	Whole blood	2.26E-02	1.00E-01	4.59E-01
Cervical cancer	2C77	Cervical tissue	7.98E-01	1.03E-01	4.64E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.52E-01	7.13E-02	3.08E-01
Chronic hepatitis C	1E51.1	Whole blood	8.35E-01	-8.92E-02	-4.57E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	2.74E-01	1.12E-01	5.73E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	7.49E-01	-2.80E-02	-1.42E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	7.20E-01	-1.11E-01	-6.13E-01
Colon cancer	2B90	Colon tissue	3.75E-02	2.40E-02	1.05E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.38E-01	-1.68E-02	-2.97E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	8.31E-01	5.66E-03	3.53E-02
Endometriosis	GA10	Endometrium tissue	5.83E-03	1.30E-01	6.80E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.25E-01	5.55E-02	2.70E-01
Familial hypercholesterolemia	5C80.00	Whole blood	8.78E-06	-2.19E-01	-6.62E-01
Gastric cancer	2B72	Gastric tissue	7.52E-02	-3.56E-01	-2.26E+00
Glioblastopma	2A00.00	Nervous tissue	1.18E-19	1.57E-01	6.46E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.45E-02	-4.76E-01	-1.33E+00
Head and neck cancer	2D42	Head and neck tissue	2.87E-01	3.44E-02	1.70E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	9.22E-01	-6.99E-03	-7.04E-02
Huntington's disease	8A01.10	Whole blood	3.53E-01	8.72E-02	6.10E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	6.77E-01	4.38E-02	4.66E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.30E-01	6.54E-02	4.07E-01
Influenza	1.00E+30	Whole blood	1.40E-01	3.09E-01	1.43E+00
Interstitial cystitis	GC00.3	Bladder tissue	4.51E-01	7.59E-02	1.66E+00
Intracranial aneurysm	8B01.0	Intracranial artery	5.48E-01	-5.24E-02	-2.50E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	4.60E-01	5.04E-02	1.67E-01
Ischemic stroke	8B11	Peripheral blood	1.96E-01	-2.57E-02	-1.24E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	6.06E-02	6.04E-02	2.33E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	2.32E-01	1.22E-01	4.54E-01
Lateral sclerosis	8B60.4	Skin	3.51E-01	1.93E-01	8.46E-01
Liver cancer	2C12.0	Liver tissue	3.29E-25	-1.99E+00	-2.91E+00
Liver failure	DB99.7-DB99.8	Liver tissue	8.11E-05	-2.90E+00	-4.59E+00
Lung cancer	2C25	Lung tissue	1.05E-02	-1.12E-01	-3.78E-01
Lupus erythematosus	4A40	Whole blood	6.66E-03	-1.51E-01	-2.93E-01
Major depressive disorder	6A70-6A7Z	Whole blood	9.95E-02	5.75E-02	2.44E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	2.73E-01	-2.87E-02	-1.90E-01
Melanoma	2C30	Skin	8.74E-01	-1.81E-01	-4.45E-01
Multiple myeloma	2A83.1	Bone marrow	2.72E-01	-1.83E-01	-6.28E-01
Multiple myeloma	2A83.1	Peripheral blood	5.98E-01	-2.55E-02	-7.51E-02
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.52E-01	3.09E-02	1.04E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	8.06E-01	5.28E-02	2.83E-01
Myelofibrosis	2A20.2	Whole blood	1.11E-01	6.15E-02	4.17E-01
Myocardial infarction	BA41-BA50	Peripheral blood	8.12E-02	2.88E-01	5.83E-01
Myopathy	8C70.6	Muscle tissue	2.60E-05	-2.28E-01	-2.23E+00
Neonatal sepsis	KA60	Whole blood	1.50E-04	-2.07E-01	-6.49E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	4.00E-01	-4.03E-02	-1.53E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	7.70E-01	-1.62E-02	-4.89E-02
Obesity related type 2 diabetes	5A11	Omental adipose tissue	6.91E-01	5.96E-02	5.07E-01
Olive pollen allergy	CA08.00	Peripheral blood	3.15E-01	1.07E-01	5.40E-01
Oral cancer	2B6E	Oral tissue	4.48E-05	-3.75E-01	-1.28E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	5.88E-02	-3.01E-01	-8.81E-01
Osteoporosis	FB83.1	Bone marrow	2.68E-04	3.81E-01	5.49E+00
Ovarian cancer	2C73	Ovarian tissue	1.34E-02	-2.57E-01	-1.42E+00
Pancreatic cancer	2C10	Pancreas	2.79E-01	-1.45E-01	-4.54E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	5.46E-01	1.19E-02	6.02E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.06E-02	-7.11E-02	-4.61E-01
Pituitary cancer	2D12	Pituitary tissue	7.83E-01	-2.07E-02	-6.46E-02
Pituitary gonadotrope tumour	2D12	Pituitary tissue	6.58E-01	-3.49E-02	-1.56E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	8.52E-01	-4.75E-02	-1.32E-01
Polycythemia vera	2A20.4	Whole blood	3.07E-04	1.27E-01	9.07E-01
Pompe disease	5C51.3	Biceps muscle	6.69E-03	-1.77E-01	-2.57E+00
Preterm birth	KA21.4Z	Myometrium	2.27E-01	4.71E-03	4.42E-02
Prostate cancer	2C82	Prostate	7.54E-01	4.87E-02	1.11E-01
Psoriasis	EA90	Skin	4.44E-01	7.97E-02	2.41E-01
Rectal cancer	2B92	Rectal colon tissue	5.01E-01	-2.32E-02	-1.38E-01
Renal cancer	2C90-2C91	Kidney	3.23E-03	-1.85E+00	-1.73E+00
Retinoblastoma	2D02.2	Uvea	2.33E-01	-8.26E-02	-6.54E-01
Rheumatoid arthritis	FA20	Synovial tissue	5.94E-01	1.23E-02	9.63E-02
Rhinovirus infection	CA42.1	Nasal epithelium tissue	5.79E-01	9.16E-03	5.99E-02
Schizophrenia	6A20	Prefrontal cortex	4.52E-01	4.57E-02	2.18E-01
Schizophrenia	6A20	Superior temporal cortex	3.04E-01	-7.56E-02	-6.17E-01
Scleroderma	4A42.Z	Whole blood	1.60E-01	1.77E-01	7.12E-01
Seizure	8A60-8A6Z	Whole blood	5.20E-01	1.63E-01	7.19E-01
Sensitive skin	EK0Z	Skin	7.87E-01	-2.81E-03	-1.64E-02
Sepsis with septic shock	1G41	Whole blood	7.53E-07	-1.04E-01	-3.38E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.12E-01	4.24E-01	1.04E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	3.97E-02	1.99E-01	1.11E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	3.45E-01	1.21E-01	9.45E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	1.28E-01	-2.42E-01	-9.93E-01
Skin cancer	2C30-2C3Z	Skin	2.55E-01	4.54E-02	1.57E-01
Thrombocythemia	3B63	Whole blood	3.62E-01	3.05E-02	2.05E-01
Thrombocytopenia	3B64	Whole blood	2.08E-01	2.18E-01	1.21E+00
Thyroid cancer	2D10	Thyroid	2.75E-01	1.46E-02	5.44E-02
Tibial muscular dystrophy	8C75	Muscle tissue	5.32E-06	-3.09E-01	-1.96E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	6.40E-01	7.72E-02	7.23E-01
Type 2 diabetes	5A11	Liver tissue	2.96E-01	1.32E-02	4.61E-02
Ureter cancer	2C92	Urothelium	9.40E-01	-2.92E-02	-1.90E-01
Uterine cancer	2C78	Endometrium tissue	2.49E-06	-1.12E-01	-5.75E-01
Vitiligo	ED63.0	Skin	7.37E-01	5.63E-02	4.61E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Bumetanide	Approved	Oocytes-OAT2	Km = 7.52 microM	[4]
Dinoprostone	Approved	Proximal tubule (S2) cells-OAT2	Km = 0.713 microM	[5]
Erythromycin	Approved	Oocytes-OAT2	Km = 18.5 microM	[7]
Fluorouracil	Approved	Oocytes-OAT2	Km = 0.0538 microM	[4]
Tetracycline	Approved	Proximal tubule (S2) cells-OAT2	Km = 439.9 microM	[11]
Theophylline	Approved	Oocytes-OAT2	Km = 12.6 microM	[7]
Zidovudine	Approved	Proximal tubule (S2) cells-OAT2	Km = 26.8 microM	[12]

Clinical Trial Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
PGF2alpha	Clinical trial	Proximal tubule (S2) cells-OAT2	Km = 0.425 microM	[13]

References

• [1] Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
• [2] Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14.
• [3] Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82.
• [4] Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
• [5] Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
• [6] Human organic anion transporter 2 is an entecavir, but not tenofovir, transporter. Drug Metab Pharmacokinet. 2017 Feb;32(1):116-119.
• [7] Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22.
• [8] Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
• [9] In vitro studies with two human organic anion transporters: OAT2 and OAT7. Xenobiotica. 2018 Oct;48(10):1037-1049.
• [10] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [11] Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.
• [12] Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
• [13] Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802.