Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTZGT0P)

• DTP Name: Multidrug and toxin extrusion protein 1 (SLC47A1)
• Gene Name: SLC47A1
• UniProt ID: Q96FL8 (S47A1_HUMAN)
• VARIDT ID: DTD0007
• Synonyms: MATE-1; MATE1; SLC47A1; Solute carrier family 47 member 1; hMATE-1
• DTP Family:
  Multidrug/Oligosaccharidyl-Lipid/Polysaccharide (MOP) Flippase Superfamily
  Multi Antimicrobial Extrusion (MATE) Family
• Tissue Specificity: Highly expressed in the liver , the kidney, and skeletal muscle, lower expression in the adrenal gland, testes, and heart
• Sequence:
  MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISS
  VFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSA
  LVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLN
  QGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKL
  HQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYE
  LAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDH
  VGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVG
  LPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNV
  PRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRK
  QLVLRRGLLLLGVFLILLVGILVRFYVRIQ
• Function: This transporter is responsible for secretion of cationic drugs across the brush border membranes. This transporter is for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin. Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid.
• Endogenous Substrate(s): N,N-dimethyl-4-4'-bipiridinium; N-methylnicotinamide; Cephalosporins; Creatinine; Guanidine
• TCDB ID: 2.A.66.1.14
• Gene ID: 55244
• Reactome Pathway: Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)

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	[2]
Auranofin	DMWE2N4	Inflammatory arthritis	FA2Z	Approved	[3]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[4]
Chloroquine	DMSI5CB	Malaria	1F40-1F45	Approved	[5]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[2]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[6]
Emtricitabine	DMBMUWZ	Hepatitis virus infection	1E50-1E51	Approved	[7]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[8]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[2]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[2]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[9]
Metformin	DM89QE1	Colorectal carcinoma		Approved	[10]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[2]
Pyrimethamine	DM5X7VY	Malaria	1F40-1F45	Approved	[11]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[2]

2 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mephenoxalone	DMX4IS3	N. A.	N. A.	Preclinical	[12]
N-methylpyridinium	DMVUKEW	N. A.	N. A.	Preclinical	[2]

2 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
paraquat	DMR8O3X	Discovery agent	N.A.	Investigative	[13]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[14]

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	1.82E-30	-8.87E-01	-1.82E+00
Adrenocortical carcinoma	2D11.Z	Kidney	6.70E-09	-4.90E-01	-2.31E+00
Alopecia	ED70	Skin from scalp	1.22E-04	4.68E-01	9.49E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.20E-01	3.45E-01	3.37E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.02E-01	3.93E-01	8.95E-01
Aortic stenosis	BB70	Calcified aortic valve	4.41E-01	2.10E-02	1.34E-02
Apnea	7A40	Hyperplastic tonsil	9.48E-02	-5.00E-01	-2.42E+00
Arthropathy	FA00-FA5Z	Peripheral blood	9.24E-01	-2.80E-02	-1.05E-01
Asthma	CA23	Nasal and bronchial airway	4.76E-02	8.26E-02	8.04E-02
Atopic dermatitis	EA80	Skin	2.97E-04	-4.11E-01	-1.63E+00
Autism	6A02	Whole blood	9.23E-01	-2.37E-02	-1.03E-01
Autoimmune uveitis	9A96	Peripheral monocyte	2.69E-01	1.41E-01	8.16E-01
Autosomal dominant monocytopenia	4B04	Whole blood	4.69E-01	4.50E-03	8.15E-03
Bacterial infection of gingival	1C1H	Gingival tissue	1.71E-04	2.84E-01	7.97E-01
Batten disease	5C56.1	Whole blood	9.93E-01	8.78E-03	2.76E-02
Behcet's disease	4A62	Peripheral blood	4.96E-02	-1.80E-01	-6.46E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	8.17E-01	1.11E+00	6.63E-01
Bladder cancer	2C94	Bladder tissue	5.12E-02	-4.58E-01	-1.18E+00
Breast cancer	2C60-2C6Z	Breast tissue	4.58E-22	-5.44E-01	-9.06E-01
Cardioembolic stroke	8B11.20	Whole blood	3.10E-01	-3.07E-01	-4.85E-01
Cervical cancer	2C77	Cervical tissue	3.57E-01	-1.63E-01	-2.91E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.70E-01	8.72E-02	1.69E-01
Chronic hepatitis C	1E51.1	Whole blood	9.67E-01	3.16E-01	4.34E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	6.47E-01	-2.82E-02	-5.49E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	7.53E-01	-5.62E-02	-9.77E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.00E-01	-8.38E-02	-4.82E-01
Colon cancer	2B90	Colon tissue	4.92E-10	-3.20E-01	-6.91E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	4.31E-01	-3.42E-02	-1.65E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	1.25E-01	-1.29E-01	-4.76E-01
Endometriosis	GA10	Endometrium tissue	9.37E-02	-7.78E-01	-3.83E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.05E-01	-7.61E-02	-5.56E-01
Familial hypercholesterolemia	5C80.00	Whole blood	6.32E-02	1.16E-01	4.77E-01
Gastric cancer	2B72	Gastric tissue	1.65E-01	4.06E-01	9.54E-01
Glioblastopma	2A00.00	Nervous tissue	4.24E-03	-6.54E-02	-5.91E-02
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.87E-01	-2.98E-01	-2.48E-01
Head and neck cancer	2D42	Head and neck tissue	2.40E-01	-2.50E-01	-3.64E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	4.71E-01	-1.30E-01	-4.07E-01
Huntington's disease	8A01.10	Whole blood	1.35E-01	5.59E-03	4.24E-02
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	3.22E-04	1.15E+00	3.26E+00
Immunodeficiency	4A00-4A20	Peripheral blood	5.41E-01	1.93E-03	2.61E-02
Influenza	1.00E+30	Whole blood	1.22E-01	1.46E-01	7.23E-01
Interstitial cystitis	GC00.3	Bladder tissue	5.54E-02	6.34E-01	1.42E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.83E-02	1.17E+00	2.25E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.48E-01	1.64E-01	2.14E-01
Ischemic stroke	8B11	Peripheral blood	2.77E-01	5.06E-03	1.62E-02
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.81E-01	-1.57E-01	-2.39E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	6.31E-01	-7.55E-02	-6.60E-02
Lateral sclerosis	8B60.4	Skin	2.77E-03	3.66E-01	4.05E+00
Liver cancer	2C12.0	Liver tissue	4.21E-13	-8.15E-01	-1.25E+00
Liver failure	DB99.7-DB99.8	Liver tissue	5.89E-05	-2.44E+00	-9.35E+00
Lung cancer	2C25	Lung tissue	1.37E-11	-4.84E-01	-6.68E-01
Lupus erythematosus	4A40	Whole blood	7.81E-01	-2.11E-02	-3.77E-02
Major depressive disorder	6A70-6A7Z	Whole blood	4.20E-02	1.05E-01	1.82E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	8.27E-01	3.17E-02	1.95E-02
Melanoma	2C30	Skin	1.15E-03	-1.49E+00	-9.62E-01
Multiple myeloma	2A83.1	Bone marrow	3.76E-03	1.24E+00	2.11E+00
Multiple myeloma	2A83.1	Peripheral blood	1.60E-01	1.34E-02	4.27E-02
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.26E-02	-7.73E-01	-1.16E+00
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	4.37E-05	-3.92E-02	-1.46E-01
Myelofibrosis	2A20.2	Whole blood	8.23E-01	2.40E-03	1.32E-02
Myocardial infarction	BA41-BA50	Peripheral blood	4.74E-02	3.36E-01	6.00E-01
Myopathy	8C70.6	Muscle tissue	1.77E-04	-1.11E+00	-2.63E+00
Neonatal sepsis	KA60	Whole blood	1.94E-01	-5.67E-02	-2.40E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	9.77E-02	-9.75E-01	-7.25E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	1.14E-01	3.41E-01	7.06E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	1.45E-01	-2.90E-01	-7.08E-01
Olive pollen allergy	CA08.00	Peripheral blood	2.48E-01	7.45E-02	3.51E-01
Oral cancer	2B6E	Oral tissue	9.80E-02	-3.40E-01	-3.51E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	4.28E-01	-1.50E-01	-2.33E-01
Osteoporosis	FB83.1	Bone marrow	7.62E-01	1.78E-01	2.87E-01
Ovarian cancer	2C73	Ovarian tissue	4.56E-02	-1.45E+00	-1.03E+00
Pancreatic cancer	2C10	Pancreas	3.06E-03	5.01E-01	7.90E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	2.12E-03	2.15E-01	1.36E+00
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.23E-02	1.02E-01	5.78E-01
Pituitary cancer	2D12	Pituitary tissue	1.12E-06	-3.16E+00	-2.95E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	5.85E-07	-3.40E+00	-4.02E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.30E-01	-1.47E-01	-8.03E-01
Polycythemia vera	2A20.4	Whole blood	2.39E-02	3.75E-02	1.90E-01
Pompe disease	5C51.3	Biceps muscle	1.20E-01	-4.54E-01	-9.65E-01
Preterm birth	KA21.4Z	Myometrium	3.81E-03	-1.32E+00	-1.67E+00
Prostate cancer	2C82	Prostate	9.65E-01	7.94E-01	6.15E-01
Psoriasis	EA90	Skin	2.87E-02	3.64E-03	7.22E-03
Rectal cancer	2B92	Rectal colon tissue	4.85E-03	-7.05E-01	-2.06E+00
Renal cancer	2C90-2C91	Kidney	4.05E-01	-5.76E-01	-3.45E-01
Retinoblastoma	2D02.2	Uvea	3.58E-03	1.17E+00	5.58E+00
Rheumatoid arthritis	FA20	Synovial tissue	1.80E-01	-2.58E-01	-3.86E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	8.66E-01	3.00E-02	1.72E-01
Schizophrenia	6A20	Prefrontal cortex	4.13E-01	-5.60E-02	-4.48E-02
Schizophrenia	6A20	Superior temporal cortex	1.47E-01	-1.49E-01	-7.09E-01
Scleroderma	4A42.Z	Whole blood	3.07E-01	-7.72E-02	-3.07E-01
Seizure	8A60-8A6Z	Whole blood	9.84E-01	7.99E-02	1.51E-01
Sensitive skin	EK0Z	Skin	3.88E-01	-2.31E-02	-8.57E-02
Sepsis with septic shock	1G41	Whole blood	1.95E-01	7.10E-02	2.49E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.35E-01	-2.90E-01	-7.97E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	9.33E-01	-2.04E-02	-8.40E-02
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.07E-01	1.37E-02	9.49E-03
Sjogren's syndrome	4A43.2	Salivary gland tissue	8.48E-02	5.90E-01	1.73E+00
Skin cancer	2C30-2C3Z	Skin	8.26E-66	-1.55E+00	-2.26E+00
Thrombocythemia	3B63	Whole blood	1.65E-02	1.27E-01	6.82E-01
Thrombocytopenia	3B64	Whole blood	1.88E-01	-5.66E-01	-6.55E-01
Thyroid cancer	2D10	Thyroid	5.55E-07	8.81E-01	1.62E+00
Tibial muscular dystrophy	8C75	Muscle tissue	4.99E-10	-2.34E+00	-5.44E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	3.25E-01	-9.49E-01	-7.95E-01
Type 2 diabetes	5A11	Liver tissue	8.87E-02	-3.07E-01	-1.09E+00
Ureter cancer	2C92	Urothelium	1.92E-01	3.61E-02	1.53E-01
Uterine cancer	2C78	Endometrium tissue	3.72E-05	-9.71E-01	-4.82E-01
Vitiligo	ED63.0	Skin	5.26E-01	-2.05E-01	-2.61E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Aciclovir	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 2640.0 microM	[2]
Cimetidine	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 170.0 microM	[2]
Ganciclovir	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 5120.0 microM	[2]
Metformin	Approved	Human cervical cancer cell line (Hela)-MATE1	Km = 202.0 microM	[10]
Metformin	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 227.0 microM	[13]
Metformin	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 780.0 microM	[2]
Procainamide	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 1230.0 microM	[2]
Topotecan	Approved	Human embryonic kidney cells (HEK293)-MATE1	Km = 70.0 microM	[2]

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
paraquat	Investigative	Human embryonic kidney cells (HEK293)-MATE1	Km = 169.0 microM	[13]
[14C]TEA	Investigative	Human embryonic kidney cells (HEK293)-MATE1	Km = 220.0 microM	[14]
[14C]TEA	Investigative	Human embryonic kidney cells (HEK293)-MATE1	Km = 380.0 microM	[15]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Solute carrier family 47 member 1 (SLC47A1) DTT Info
• DTP DTT Type: Successful

1 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metformin	DM89QE1	Colorectal carcinoma		Approved	[1]

1 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[1]

References

• [1] Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res. 2006 Aug;23(8):1696-701.
• [2] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
• [3] Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017 Oct 9;8(56):96062-96078.
• [4] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [5] Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
• [6] FDA Drug Development and Drug Interactions
• [7] Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters. Xenobiotica. 2017 Jan;47(1):77-85.
• [8] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones. J Pharmacol Exp Ther. 2009 Feb;328(2):628-34.
• [9] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [10] Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
• [11] Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity. Drug Metab Dispos. 2018 May;46(5):592-599.
• [12] Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). J Pharmacol Exp Ther. 2010 Sep 1;334(3):936-44.
• [13] Genetic variants in multidrug and toxic compound extrusion-1, hMATE1, alter transport function. Pharmacogenomics J. 2009 Apr;9(2):127-36.
• [14] A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17923-8.
• [15] The role of microRNA in the delayed negative feedback regulation of gene expression. Biochem Biophys Res Commun. 2007 Jul 6;358(3):722-6.