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