Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3 gene. Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. OCT3 is widely distributed in brain tissue. It is not yet completely clear whether its location is primarily neuronal or glial. Organic cation transporter 3 is a polyspecific transporter whose transport is independent of sodium. Known substrates for transport include: histamine, serotonin, norepinephrine, dopamine and MPP+. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however. ransport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine. Transport is also inhibited by the chemical decynium-22 and physiological concentrations of corticosterone and cortisol. Ki values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100 times lower than Ki values of OCT1 and OCT2.
Background References
1. Fu L. et. al. RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer. Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4631-E4640.
2. Hsu CM. et. al. Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget. 2017 Sep 4;8(43):74348-74358.
Sequence Similarity
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Tissue Specificity
Expressed in placenta, skeletal muscle, prostate, aorta, liver, fetal lung, salivary gland, adrenal gland, kidney and brain cortex. No expression detected in spleen.
Western blot analysis of SLC22A3 on human placenta tissue lysates with Rabbit anti-SLC22A3 antibody (ET7110-35) at 1/2,000 dilution.
Lysates/proteins at 20 µg/Lane.
Predicted band size: 61 kDa Observed band size: 80 kDa
Exposure time: 2 minutes;
10% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (ET7110-35) at 1/2,000 dilution was used in 5% NFDM/TBST at room temperature for 2 hours. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1/200,000 dilution was used for 1 hour at room temperature.
Immunohistochemical analysis of paraffin-embedded human colon carcinoma tissue using anti-SLC22A3 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET7110-35, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Flow cytometric analysis of SLC22A3 was done on A549 cells. The cells were fixed, permeabilized and stained with the primary antibody (ET7110-35, 1/50) (red). After incubation of the primary antibody at room temperature for an hour, the cells were stained with a Alexa Fluor 488-conjugated Goat anti-Rabbit IgG Secondary antibody at 1/1000 dilution for 30 minutes.Unlabelled sample was used as a control (cells without incubation with primary antibody; black).
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