General Information of Drug Therapeutic Target (DTT) (ID: TTTR957)

DTT Name Solute carrier family 29 member 4 (SLC29A4)
Synonyms hENT4; Plasma membrane monoamine transporter; PSEC0113; PMAT; Equilibrative nucleoside transporter 4; ENT4
Gene Name SLC29A4
DTT Type
Literature-reported target
[1]
UniProt ID
S29A4_HUMAN
TTD ID
T25728
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGSVGSQRLEEPSVAGTPDPGVVMSFTFDSHQLEEAAEAAQGQGLRARGVPAFTDTTLDE
PVPDDRYHAIYFAMLLAGVGFLLPYNSFITDVDYLHHKYPGTSIVFDMSLTYILVALAAV
LLNNVLVERLTLHTRITAGYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGC
TVQQSSFYGYTGMLPKRYTQGVMTGESTAGVMISLSRILTKLLLPDERASTLIFFLVSVA
LELLCFLLHLLVRRSRFVLFYTTRPRDSHRGRPGLGRGYGYRVHHDVVAGDVHFEHPAPA
LAPNESPKDSPAHEVTGSGGAYMRFDVPRPRVQRSWPTFRALLLHRYVVARVIWADMLSI
AVTYFITLCLFPGLESEIRHCILGEWLPILIMAVFNLSDFVGKILAALPVDWRGTHLLAC
SCLRVVFIPLFILCVYPSGMPALRHPAWPCIFSLLMGISNGYFGSVPMILAAGKVSPKQR
ELAGNTMTVSYMSGLTLGSAVAYCTYSLTRDAHGSCLHASTANGSILAGL
Function
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 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.
Reactome Pathway
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
decynium 22 DMWCTZ7 Discovery agent N.A. Investigative [1]
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The Drug Transporter (DTP) Role of This DTT

DTT DTP Name Equilibrative nucleoside transporter 4 (SLC29A4) DTP Info
Gene Name SLC29A4
2 Approved Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ergotidine DM78IME Osteoarthritis FA00-FA05 Approved [2]
Metformin DM89QE1 Colorectal carcinoma Approved [3]
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1 Investigative Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
SEROTONIN DMOFCRY Discovery agent N.A. Investigative [4]
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References

1 Interaction of organic cations with a newly identified plasma membrane monoamine transporter. Mol Pharmacol. 2005 Nov;68(5):1397-407.
2 Histamine uptake mediated by plasma membrane monoamine transporter and organic cation transporters in rat mast cell lines. Eur J Pharmacol. 2019 Apr 15;849:75-83.
3 Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
4 Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene. Mol Autism. 2014 Aug 13;5:43.