Aliases for SLC29A4 Gene
External Ids for SLC29A4 Gene
Previous GeneCards Identifiers for SLC29A4 Gene
This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
GeneCards Summary for SLC29A4 Gene
SLC29A4 (Solute Carrier Family 29 (Equilibrative Nucleoside Transporter), Member 4) is a Protein Coding gene. Diseases associated with SLC29A4 include desmoplastic small round cell tumor. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. GO annotations related to this gene include nucleoside transmembrane transporter activity. An important paralog of this gene is SLC29A3.
UniProtKB/Swiss-Prot for SLC29A4 Gene
Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine. In (PubMed:16873718) adenosine is efficiently transported but in a fashion highly sensitive to extracellular pH, with maximal activity in the pH range 5.5 to 6.5. Glu-206 is essential for the cation selectivity and may function as the charge sensor for cationic substrates. Transport is chloride and sodium-independent but appears to be sensitive to changes in membrane potential. Weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. May play a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia.
Nucleoside transporters are divided into two families; the Na+-dependent solute carrier family 28 (SLC28) and the equilibrative solute carrier family 29 (SLC29). SLC28 family transporters (CNT1-3) display subtype-selective expression patterns; CNT1 is localized primarily to epithelial tissue whereas CNT2 and CNT3 have more widespread distributions. SLC29 family transporters (ENT1-4) are glycosylated proteins, localized to the plasma and mitochondrial membranes. They are expressed in the heart, brain, mammary gland, erythrocytes and placenta, and also in fetal liver and spleen. They mediate nucleoside influx and efflux and exhibit highest affinity for adenosine. CNT and ENT transporters play critical roles in nucleoside salvage pathways where they mediate the first step of nucleotide biosynthesis. In addition, these transporters work in concert to terminate adenosine signaling and are vital determinants in the response to a variety of anticancer and antiviral treatments, as they modulate the entry of these nucleoside analogs into target tissues.