SLC29A4
Domain
Glu-206 is essential for cation selectivity and may function as the charge sensor for cationic substrates.
Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs (PubMed:15448143, PubMed:16099839, PubMed:16873718, PubMed:17018840, PubMed:17121826, PubMed:20592246, PubMed:20858707, PubMed:22396231, PubMed:31537831). Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations (PubMed:15448143, PubMed:20592246, PubMed:22396231). Functions as a Na(+)- and Cl(-)-independent bidirectional transporter (PubMed:15448143, PubMed:16099839, PubMed:22396231, PubMed:31537831). Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure (PubMed:16873718, PubMed:17018840, PubMed:20592246, PubMed:22396231, PubMed:31537831). Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system (PubMed:15448143, PubMed:16099839, PubMed:17018840, PubMed:17121826, PubMed:20858707, PubMed:22396231). Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain (By similarity). Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia (PubMed:16873718, PubMed:20592246, PubMed:31537831). May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney (PubMed:17018840). Also transports guanidine (PubMed:16099839).
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Tissue Specificity
Mainly expressed in brain and skeletal muscle (PubMed:15448143, PubMed:16873718, PubMed:20592246, PubMed:20858707). In brain, expressed in cerebellum, cerebral cortex, medulla oblongata, occipital pole, frontal and temporal lobes putamen, spinal cord, substancia nigra, hippocampus, caudate nucleus, nucleus accumbens, pons and choroid plexus (PubMed:15448143, PubMed:16873718, PubMed:20858707, PubMed:23255610). Expressed in heart, in both cardiomyocytes and vascular endothelial cells (PubMed:15448143, PubMed:16873718, PubMed:20858707). Also expressed in adrenal gland, small intestine, pancreas, kidney, liver, bone marrow, lymph node (PubMed:15448143, PubMed:16873718, PubMed:17018840, PubMed:20858707). Located in endometrial stroma, where the expression is high in the proliferative phase, decreases during the secretory phase, and is no longer detectable in the menstrual phase (PubMed:17393420).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Apical cell membrane
- Multi-pass membrane protein
- Located to the plasma membranes of ventricular myocytes and vascular endothelial cells (PubMed:16873718). Targeted to the apical membranes of differentiated kidney epithelial cells (PubMed:17018840). Localized to the apical blood-cerebrospinal fluid (CSF)-facing membrane of the choroid plexus epithelium (PubMed:23255610).
Alternative names
ENT4, PMAT, PSEC0113, SLC29A4, Equilibrative nucleoside transporter 4, hENT4, Plasma membrane monoamine transporter, Solute carrier family 29 member 4