SLC22A3 Membrane Protein Introduction

Introduction of SLC22A3

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. SLC22A3 is broadly distributed in many tissues, including the placenta, salivary glands, heart, brain, and intestine and inhibited by recreational and pharmaceutical drugs. Specifically, human SLC22A3 is located to the basolateral membrane of placental epithelium, the sinusoidal membrane of hepatocytes, and the luminal membrane of bronchial epithelial cells. It is also a bidirectional transporter, and there is evidence that SLC22A3 may play an important role in neurotransmitter efflux.

Basic Information of SLC22A3
Protein Name	Solute carrier family 22 member 3
Gene Name	SLC22A3
Aliases	Extraneuronal monoamine transporter, EMT, Organic cation transporter 3
Organism	Homo sapiens (Human)
UniProt ID	O75751
Transmembrane Times	7
Length (aa)	556
Sequence	MPSFDEALQRVGEFGRFQRRVFLLLCLTGVTFAFLFVGVVFLGTQPDHYWCRGPSAAALAERCGWSPEEEWNRTAPASRGPEPPERRGRCQRYLLEAANDSASATSALSCADPLAAFPNRSAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDKALQILRRIAKCNGKYLSSNYSEITVTDEEVSNPSFLDLVRTPQMRKCTLILMFAWFTSAVVYQGLVMRLGIIGGNLYIDFFISGVVELPGALLILLTIERLGRRLPFAASNIVAGVACLVTAFLPEGIAWLRTTVATLGRLGITMAFEIVYLVNSELYPTTLRNFGVSLCSGLCDFGGIIAPFLLFRLAAVWLELPLIIFGILASICGGLVMLLPETKGIALPETVDDVEKLGSPHSCKCGRNKKTPVSRSHL

Function of SLC22A3 Membrane Protein

SLC22A3 is an important membrane transporter, which plays a role in cellular metabolic homeostasis by transporting endogenous and exogenous cation compounds across the membrane. SLC22A3 is a low-affinity transporter with a high capacity to non-selectively transport monoamines. It is also a bidirectional transporter, and there is evidence that SLC22A3 may play an important role in neurotransmitter efflux. Human SLC22A3 has differential expression between normal and cancerous tissues. An upregulated SLC22A3 expression is observed in the cancerous tissues of colon rectum and stomach compared to the normal tissues, however, significantly decreased expression is found in several other cancerous tissues, including uterus, breast, ovary and lung cancers.

Fig.1 Schematic model of the transporters in major organs responsible for drug disposition. (Li, 2014)

Application of SLC22A3 Membrane Protein in Literature

Lee N., et al. Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs. Mol Pharmacol. 2018, 94(4):1125-1131. PubMed ID: 30012584

This article showed that modulation of placental OCT3 expression or activity by gestational age, genetic polymorphism, or pharmacological inhibitors might alter fetal exposure to metformin or other drugs transported by OCT3.
Huang H.C., et al. Differential expression of organic cation transporter 3 in oral submucous fibrosis-associated buccal squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018. PubMed ID: 29523428

The authors revealed that the expression of OCT3 was associated with oral submucous fibrosis (OSF) progression and the differentiation of buccal squamous cell carcinoma (BSCC). OCT3 might serve as a molecular marker for the prevention and early diagnosis of OSF and BSCC.
Wagner D.J., et al. Disposition of Methamphetamine and Major Metabolites in Mice: Role of Organic Cation Transporter 3 (Oct3) in Tissue Selective Accumulation of para-hydroxymethamphetamine. Drug Metab Dispos. 2018, 46(9):1277-1284. PubMed ID: 29915156

This article identified that OCT3 was an important determinant of tissue uptake and exposure to p-OHMA in salivary glands and skeletal muscle, suggesting that local tissue accumulation of methamphetamine and/or its metabolites may play a role in several of the reported peripheral toxicities of methamphetamine.
Mayer F.P., et al. An unsuspected role for organic cation transporter 3 in the actions of amphetamine. Neuroscience. 2018, 43(12):2408-2417. PubMed ID: 29773909

This article supported that OCT3 acted as a new player in the actions of amphetamine, indicating that OCT3 may be a potential new target for the treatment of psychostimulant abuse.
Adefurin A., et al. Organic cation transporter 3: A cellular mechanism underlying rapid, non-genomic glucocorticoid regulation of monoaminergic neurotransmission, physiology, and behavior. Horm Behav. 2018. PubMed ID: 29738736

This article demonstrated that corticosterone could exert rapid, GR-independent actions on neuronal physiology and behavior by inhibiting OCT3-mediated monoamine clearance.

SLC22A3 Preparation Options

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Reference

Li Q, et al. (2014). Role of solute carriers in response to anticancer drugs. Molecular and Cellular Therapies. 2: 15.

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