Drug Transporter (DT) Information

General Information of DT
DT ID DTD0009
Gene Name SLC22A3
Protein Name Organic cation transporter 3
Gene ID
6581
UniProt ID
O75751
TCDB ID
2.A.1.19.24
3D Structure

Modelled DT Structure

Method: multi-sequence alignment based machine learning

Detail: Structure Info

Synonyms OCT3; EMT; EMTH; Extraneuronal monoamine transporter; SLC22A3; Solute carrier family 22 member 3
DT Family Major Facilitator Superfamily (MFS)
Organic Cation Transporter (OCT) Family
Tissue Specificity Highly expressed in the kidney, liver, placenta, heart, and skeletal muscle,to a lesser extent, in other organs including the lung and brain, as well as in cancer-derived cell lines
Function This transporter may play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain and mediate potential-dependent transport of a variety of organic cations.
Disease(s) Cataract [ICD-11:9B10]
Neurogenic shock [ICD-11:MG40.Y]
Respiratory allergies [ICD-11:4A80]
Type 2 diabetes [ICD-11:5A11]
Severe mood disorders [ICD-11:6A8Z]
Endogenous Substrate(s) Monoamines
Variability Data of This Drug Transporter (DT)

Regulatory Variability Data of This DT (VARIDT 4.0)

(α) Tissue Distribution Level of Organic cation transporter 3
Tissue Distribution Level (TD)

(β) Cell Distribution Level of Organic cation transporter 3
Cell Distribution Level (CD)

(γ) Organelle Distribution Level of Organic cation transporter 3
Organelle Distribution Level (Subc)

Regulatory Variability Data of This DT

(α) Microbiota Influence of Organic cation transporter 3
Microbiota Influence (MBI)

(β) Post-translational Modification of Organic cation transporter 3
Post-translational Modification (PTM)

(γ) Transcriptional Regulation of Organic cation transporter 3
Transcriptional Regulation (TSR)

(δ) Epigenetic Regulation of Organic cation transporter 3
Epigenetic Regulation (EGR)

(ε) Exogenous Modulation of Organic cation transporter 3
Exogenous Modulation (EGM)

Structural Variability Data of This DT

(β) Inter-species Structural Differences
Inter-species Structural Differences (ISD)

General Variability Data of This DT

(α) Genetic Polymorphisms of Organic cation transporter 3
Genetic Polymorphisms of This DT (GPD)

(β) Disease-specific Protein Abundances of Organic cation transporter 3
Disease-specific Protein Abundances of This DT (DPAD)

(γ) Species- and Tissue-specific DT Abundances
Species/Tissue-specific Protein Abundances of This DT (S/TPAD)
Molecular Transporting Profile of This DT

Full List of Drug(s) Transported by This DT

 Approved Drug

 Click to Show/Hide the Full List of Drug:         10 Drugs in Total
Drug Name Highest Status Detail Indication ICD 11 Ref
Acetylcholine
 Approved Drug Info Cataract 9B10 [1]
Amphetamine
 Approved Drug Info Attention deficit hyperactivity disorder 6A05 [2]
Clonidine
 Approved Drug Info High blood pressure BA00 [3]
Entecavir
 Approved Drug Info Chronic hepatitis B infection 1E51.0 [4]
Epinephrine
 Approved Drug Info Asthma CA23 [5]
Ergotidine
 Approved Drug Info Migraine 8A80 [5]
Metformin
 Approved Drug Info Type 2 diabetes 5A11 [6]
Norepinephrine
 Approved Drug Info Septic shock 1G41 [5]
Propranolol
 Approved Drug Info Migraine 8A80 [3]
Sodium chloride
 Approved Drug Info Severe mood disorders 6A8Z [7]

 Withdrawn, Discontinued or Preclinical Drug

 Click to Show/Hide the Full List of Drug:           2 Drugs in Total
Drug Name Highest Status Detail Indication ICD 11 Ref
Etilefrine
 Withdrawn Drug Info Hypotension BA2Z [8]
N-methylpyridinium
 Preclinical Drug Info Colon cancer 2B90.Z [9]

Endogenous Metabolites (EMs) Handled by This DT

 Endogenous Metabolites (EMs)

 Click to Show/Hide the Full List of EMs:           3 EMs in Total
EM Name PubChem CID Detail Experimental Material Ref
Epinephrine
5816
EM Info Identified using HEK293 cells-OCT3 [5]
Histamine
774
EM Info Identified using HEK293 cells-OCT3 [5]
Norepinephrine
439260
EM Info Identified using HEK293 cells-OCT3 [5]

Drug-DT Affinity Assessed by Cell Line

 Approved Drug

 Click to Show/Hide the Full List of Drug:         35 Drugs in Total
Drug Name Highest Status Detail Cell Line Affinity Ref
Epinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =240 microM [5]
Epinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =240 microM [5]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =180 microM [10]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =220 microM [5]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =180 microM [10]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =220 microM [5]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =180 microM [10]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =220 microM [5]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =180 microM [10]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =220 microM [5]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =180 microM [10]
Ergotidine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =220 microM [5]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Metformin Approved Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2260 microM [6]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =510 microM [11]
Norepinephrine Approved Drug Info Human embryonic kidney cells (HEK293)-OCT3 Km =2630 microM [5]

 Withdrawn, Discontinued or Preclinical Drug

 Click to Show/Hide the Full List of Drug:           6 Drugs in Total
Drug Name Highest Status Detail Cell Line Affinity Ref
Etilefrine Withdrawn Drug Info Chinese hamster ovary (CHO) cells-OCT3 Km =2800 microM [8]
N-methylpyridinium Preclinical Drug Info Human retinal pigment epithelial (HRPE) cells-OCT3 Km =47 microM [9]
N-methylpyridinium Preclinical Drug Info Human retinal pigment epithelial (HRPE) cells-OCT3 Km =47 microM [9]
N-methylpyridinium Preclinical Drug Info Human retinal pigment epithelial (HRPE) cells-OCT3 Km =47 microM [9]
N-methylpyridinium Preclinical Drug Info Human retinal pigment epithelial (HRPE) cells-OCT3 Km =47 microM [9]
N-methylpyridinium Preclinical Drug Info Human retinal pigment epithelial (HRPE) cells-OCT3 Km =47 microM [9]
References
1 Organic cation transporters: physiology, toxicology and special focus on ethidium as a novel substrate. Curr Drug Metab. 2009 Jul;10(6):617-31.
2 Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9.
3 Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
4 Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
5 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
6 Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
7 Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004 Mar 17;24(11):2846-51.
8 Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol. 2005 Dec 5;70(12):1851-60.
9 Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58.
10 Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10.
11 Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51.

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