Details of the Drug Therapeutic Target (DTT)

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
• 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

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]

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	Respiratory allergy	4A80	Approved	[2]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[3]

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]

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.