Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT3HUVD)

• DTP Name: Organic cation/carnitine transporter 2 (SLC22A5)
• Gene Name: SLC22A5
• UniProt ID: O76082 (S22A5_HUMAN)
• VARIDT ID: DTD0023
• Synonyms: CDSP; High-affinity sodium-dependent carnitine cotransporter; OCTN2; SLC22A5; Solute carrier family 22 member 5
• DTP Family:
  Major Facilitator Superfamily (MFS)
  Organic Cation Transporter (OCT) Family
• Tissue Specificity: Strongly expressed in kidney, skeletal muscle,heart and placenta. Highly expressed in intestinal cell typesaffected by Crohn disease, including epithelial cells. Expressedin CD68 macrophage and CD43 T-cells but not in CD20 B-cells.
• Sequence:
  MRDYDEVTAFLGEWGPFQRLIFFLLSASIIPNGFTGLSSVFLIATPEHRCRVPDAANLSS
  AWRNHTVPLRLRDGREVPHSCRRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFS
  QDVYLSTIVTEWNLVCEDDWKAPLTISLFFVGVLLGSFISGQLSDRFGRKNVLFVTMGMQ
  TGFSFLQIFSKNFEMFVVLFVLVGMGQISNYVAAFVLGTEILGKSVRIIFSTLGVCIFYA
  FGYMVLPLFAYFIRDWRMLLVALTMPGVLCVALWWFIPESPRWLISQGRFEEAEVIIRKA
  AKANGIVVPSTIFDPSELQDLSSKKQQSHNILDLLRTWNIRMVTIMSIMLWMTISVGYFG
  LSLDTPNLHGDIFVNCFLSAMVEVPAYVLAWLLLQYLPRRYSMATALFLGGSVLLFMQLV
  PPDLYYLATVLVMVGKFGVTAAFSMVYVYTAELYPTVVRNMGVGVSSTASRLGSILSPYF
  VYLGAYDRFLPYILMGSLTILTAILTLFLPESFGTPLPDTIDQMLRVKGMKHRKTPSHTR
  MLKDGQERPTILKSTAF
• Function: This sodium-ion dependent transporter involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11. 3.
• Endogenous Substrate(s): Acetyl carnitine; Butyryl-L-carnitine; Gamma-butryo-betaine; Glycine betaine; Na+
• TCDB ID: 2.A.1.19.3
• Gene ID: 6584
• KEGG Pathway: Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Organic cation transport (R-HSA-549127)
  Defective SLC22A5 causes systemic primary carnitine deficiency (CDSP) (R-HSA-5619053)
  Carnitine metabolism (R-HSA-200425)

Molecular Interaction Atlas (MIA) of This DTP

10 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[2]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[3]
Levacecarnine hci	DMJBOCR	Cognitive impairment	6D71	Approved	[4]
Mepyramine	DMB4SFH	Allergic rhinitis	CA08.0	Approved	[5]
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[6]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[7]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[3]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[8]
Acetylcarnitine	DM4UE3K	Chronic fatigue syndrome	8E49	Phase 4	[9]

2 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
acetyl-L-carnitine	DM74HGJ	Discovery agent	N.A.	Investigative	[7]
D-carnitine	DMHNAJ7	N. A.	N. A.	Investigative	[10]

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	1.81E-06	1.17E-01	4.40E-01
Adrenocortical carcinoma	2D11.Z	Kidney	7.94E-02	9.74E-02	5.06E-01
Alopecia	ED70	Skin from scalp	2.98E-01	5.46E-02	3.68E-01
Alzheimer's disease	8A20	Entorhinal cortex	3.49E-09	1.50E-01	6.50E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	4.16E-01	9.29E-02	4.34E-01
Aortic stenosis	BB70	Calcified aortic valve	3.47E-02	-2.55E-01	-1.10E+00
Apnea	7A40	Hyperplastic tonsil	8.12E-01	-6.68E-02	-6.34E-01
Arthropathy	FA00-FA5Z	Peripheral blood	8.66E-01	-1.18E-02	-7.55E-02
Asthma	CA23	Nasal and bronchial airway	2.90E-03	1.58E-01	3.11E-01
Atopic dermatitis	EA80	Skin	1.87E-02	1.28E-01	8.58E-01
Autism	6A02	Whole blood	9.97E-01	2.67E-02	1.20E-01
Autoimmune uveitis	9A96	Peripheral monocyte	2.46E-01	4.78E-01	9.83E-01
Autosomal dominant monocytopenia	4B04	Whole blood	7.23E-01	-2.40E-02	-1.36E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.06E-03	-7.16E-02	-4.39E-01
Batten disease	5C56.1	Whole blood	4.29E-01	1.18E-01	5.66E-01
Behcet's disease	4A62	Peripheral blood	2.44E-01	6.64E-02	2.72E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	9.67E-02	2.74E-02	1.83E-01
Bladder cancer	2C94	Bladder tissue	5.43E-02	-3.78E-01	-1.49E+00
Breast cancer	2C60-2C6Z	Breast tissue	4.98E-05	1.36E-01	4.34E-01
Cardioembolic stroke	8B11.20	Whole blood	1.23E-01	7.37E-02	4.08E-01
Cervical cancer	2C77	Cervical tissue	6.36E-06	-3.95E-01	-1.34E+00
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	2.74E-01	-5.61E-02	-3.67E-01
Chronic hepatitis C	1E51.1	Whole blood	9.43E-01	-4.75E-02	-4.16E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	4.23E-01	7.41E-03	4.50E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	2.93E-01	3.10E-02	1.80E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.88E-03	-2.93E-01	-1.16E+00
Colon cancer	2B90	Colon tissue	3.05E-73	-1.00E+00	-2.60E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.46E-01	-1.19E-01	-1.68E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.26E-01	-2.92E-02	-2.11E-01
Endometriosis	GA10	Endometrium tissue	2.01E-01	-1.03E-01	-2.70E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.76E-02	8.97E-02	4.78E-01
Familial hypercholesterolemia	5C80.00	Whole blood	8.88E-04	2.80E-01	1.44E+00
Gastric cancer	2B72	Gastric tissue	1.77E-01	-4.21E-01	-1.55E+00
Glioblastopma	2A00.00	Nervous tissue	1.49E-04	1.13E-01	3.47E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	5.70E-02	-3.23E-01	-6.60E-01
Head and neck cancer	2D42	Head and neck tissue	2.25E-13	-4.27E-01	-9.40E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.06E-01	3.94E-02	2.70E-01
Huntington's disease	8A01.10	Whole blood	5.19E-01	-8.06E-02	-5.45E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.53E-02	2.89E-01	2.12E+00
Immunodeficiency	4A00-4A20	Peripheral blood	7.39E-01	-2.95E-02	-3.28E-01
Influenza	1.00E+30	Whole blood	1.06E-01	2.03E-01	1.33E+00
Interstitial cystitis	GC00.3	Bladder tissue	2.83E-06	-8.45E-01	-5.82E+00
Intracranial aneurysm	8B01.0	Intracranial artery	6.33E-02	2.07E-01	8.24E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.56E-01	2.89E-03	1.51E-02
Ischemic stroke	8B11	Peripheral blood	2.07E-02	5.99E-02	3.78E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	3.15E-02	6.11E-02	2.66E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	2.66E-01	2.85E-02	1.30E-01
Lateral sclerosis	8B60.4	Skin	5.23E-01	1.45E-01	7.28E-01
Liver cancer	2C12.0	Liver tissue	7.04E-12	2.58E-01	1.20E+00
Liver failure	DB99.7-DB99.8	Liver tissue	5.40E-02	-1.91E-01	-1.57E+00
Lung cancer	2C25	Lung tissue	9.11E-05	4.75E-02	2.24E-01
Lupus erythematosus	4A40	Whole blood	1.37E-01	8.70E-02	2.98E-01
Major depressive disorder	6A70-6A7Z	Whole blood	7.02E-01	2.51E-02	1.23E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	1.13E-01	-5.69E-03	-4.16E-02
Melanoma	2C30	Skin	1.13E-02	-4.16E-01	-8.00E-01
Multiple myeloma	2A83.1	Bone marrow	4.88E-05	3.23E-01	2.52E+00
Multiple myeloma	2A83.1	Peripheral blood	1.59E-01	-1.16E-01	-4.43E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.02E-01	-1.34E-02	-2.51E-02
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	6.68E-04	8.15E-02	3.54E-01
Myelofibrosis	2A20.2	Whole blood	4.90E-01	-3.06E-02	-2.46E-01
Myocardial infarction	BA41-BA50	Peripheral blood	3.15E-02	-3.81E-01	-6.88E-01
Myopathy	8C70.6	Muscle tissue	3.73E-01	-1.60E-01	-2.94E-01
Neonatal sepsis	KA60	Whole blood	4.29E-01	-2.24E-02	-1.06E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	9.94E-02	-1.79E-01	-5.81E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	8.68E-01	-1.94E-02	-1.15E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.79E-01	-2.52E-01	-8.33E-01
Olive pollen allergy	CA08.00	Peripheral blood	1.55E-03	-4.77E-01	-3.35E+00
Oral cancer	2B6E	Oral tissue	5.45E-02	-1.12E-01	-2.42E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	5.20E-01	-2.31E-02	-1.18E-01
Osteoporosis	FB83.1	Bone marrow	9.78E-01	-7.47E-02	-3.55E-01
Ovarian cancer	2C73	Ovarian tissue	6.46E-01	1.51E-01	7.17E-01
Pancreatic cancer	2C10	Pancreas	1.96E-03	-4.96E-01	-1.35E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	9.94E-01	1.54E-02	6.61E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	8.76E-01	-4.79E-02	-2.65E-01
Pituitary cancer	2D12	Pituitary tissue	7.26E-02	-1.53E-01	-5.64E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	4.73E-01	-1.80E-01	-5.69E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	8.03E-02	-9.61E-02	-4.81E-01
Polycythemia vera	2A20.4	Whole blood	4.82E-03	-9.87E-02	-7.40E-01
Pompe disease	5C51.3	Biceps muscle	8.66E-02	3.01E-01	8.96E-01
Preterm birth	KA21.4Z	Myometrium	1.46E-01	1.47E-01	6.29E-01
Prostate cancer	2C82	Prostate	7.18E-01	-1.67E-02	-3.70E-02
Psoriasis	EA90	Skin	8.18E-03	-6.96E-02	-2.86E-01
Rectal cancer	2B92	Rectal colon tissue	1.08E-13	-9.75E-01	-1.19E+01
Renal cancer	2C90-2C91	Kidney	1.36E-01	-2.68E-01	-4.17E-01
Retinoblastoma	2D02.2	Uvea	6.25E-03	3.29E-01	1.62E+00
Rheumatoid arthritis	FA20	Synovial tissue	8.42E-01	-2.12E-01	-4.31E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	3.78E-02	-5.67E-02	-6.16E-01
Schizophrenia	6A20	Prefrontal cortex	1.15E-01	3.66E-02	1.68E-01
Schizophrenia	6A20	Superior temporal cortex	4.31E-01	4.52E-02	3.51E-01
Scleroderma	4A42.Z	Whole blood	3.53E-01	-1.19E-01	-7.93E-01
Seizure	8A60-8A6Z	Whole blood	8.29E-01	1.32E-02	1.05E-01
Sensitive skin	EK0Z	Skin	6.93E-01	-2.30E-02	-2.11E-01
Sepsis with septic shock	1G41	Whole blood	1.05E-06	-1.02E-01	-4.61E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	2.37E-01	-1.47E-01	-7.97E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	8.73E-01	-3.28E-02	-2.38E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	2.20E-01	-1.77E-01	-1.89E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	1.11E-02	-3.93E-01	-2.94E+00
Skin cancer	2C30-2C3Z	Skin	3.76E-01	4.05E-03	1.27E-02
Thrombocythemia	3B63	Whole blood	1.30E-01	-8.33E-03	-7.34E-02
Thrombocytopenia	3B64	Whole blood	7.56E-01	-1.06E-01	-8.07E-01
Thyroid cancer	2D10	Thyroid	1.95E-01	3.38E-02	1.51E-01
Tibial muscular dystrophy	8C75	Muscle tissue	2.16E-05	-6.39E-01	-1.69E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	5.08E-02	3.22E-01	1.59E+00
Type 2 diabetes	5A11	Liver tissue	2.24E-01	-1.14E-01	-8.52E-01
Ureter cancer	2C92	Urothelium	7.54E-01	-4.80E-02	-3.42E-01
Uterine cancer	2C78	Endometrium tissue	2.09E-21	-6.37E-01	-1.21E+00
Vitiligo	ED63.0	Skin	9.42E-01	3.61E-02	3.82E-01

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)-OCTN2	Km = 53.0 microM	[3]
Levacecarnine hci	Approved	Human cervical cancer cell line (Hela)-OCTN2	Km = 3.5 microM	[11]
Levacecarnine hci	Approved	Human embryonic kidney cells (HEK293)-OCTN2	Km = 2.66 microM	[12]
Levacecarnine hci	Approved	Human embryonic kidney cells (HEK293)-OCTN2	Km = 4.3 microM	[7]
Levacecarnine hci	Approved	Human embryonic kidney cells (HEK293)-OCTN2	Km = 10.9 microM	[7]
Levacecarnine hci	Approved	Human enterocyte-like 2 cells (Caco-2)-OCTN2	Km = 14.07 microM	[13]
Levacecarnine hci	Approved	Oocytes-OCTN2	Km = 4.8 microM	[10]
Levacecarnine hci	Approved	Rat brain endothelial cells-OCTN2	Km = 54.0 microM	[14]

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
acetyl-L-carnitine	Investigative	Human embryonic kidney cells (HEK293)-OCTN2	Km = 8.5 microM	[7]

References

• [1] Novel organic cation transporter 2-mediated carnitine uptake in placental choriocarcinoma (BeWo) cells. J Pharmacol Exp Ther. 2005 Jan;312(1):192-8.
• [2] Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
• [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] Colistin is substrate of the carnitine/organic cation transporter 2 (OCTN2, SLC22A5). Drug Metab Dispos. 2017 Dec;45(12):1240-1244.
• [5] Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine in mice. Biopharm Drug Dispos. 2009 Dec;30(9):495-507.
• [6] Mutations affecting GABAergic signaling in seizures and epilepsy. Pflugers Arch. 2010 Jul;460(2):505-23.
• [7] Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84.
• [8] Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore. Drug Metab Pharmacokinet. 2010;25(1):112-9.
• [9] Cloning and functional characterization of a novel up-regulator, cartregulin, of carnitine transporter, OCTN2. Arch Biochem Biophys. 2006 Aug 1;452(1):29-37.
• [10] Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol. 2000 Sep;279(3):F584-91.
• [11] beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707.
• [12] Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney. Biochim Biophys Acta. 2001 Jun 6;1512(2):273-84.
• [13] Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2003 May;284(5):G863-71.
• [14] Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the blood-brain barrier. Brain Res. 2003 Apr 4;968(1):69-79.