Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT39XG28)

• DOT Name: Sodium-dependent dopamine transporter (SLC6A3)
• Synonyms: DA transporter; DAT; Solute carrier family 6 member 3
• Gene Name: SLC6A3
• Related Disease:
  Classic dopamine transporter deficiency syndrome
  SLC6A3-related dopamine transporter deficiency syndrome
  Parkinsonism-dystonia, infantile
• UniProt ID: SC6A3_HUMAN
• Pfam ID: PF00209
• Sequence:
  MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR
  ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL
  GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC
  NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL
  TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV
  DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS
  GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGI
  DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA
  GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI
  VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKD
  RELVDRGEVRQFTLRHWLKV
• Function: Mediates sodium- and chloride-dependent transport of dopamine. Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling.
• Tissue Specificity: Highly expressed in substantia nigra . Expressed in axonal varicosities in dopaminergic nerve terminals (at protein level) . Expressed in the striatum (at protein level) .
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  Dopaminergic sy.pse (hsa04728)
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
• Reactome Pathway:
  Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660)
  Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) (R-HSA-5619081)
  Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) (R-HSA-5660724)
  Dopamine clearance from the synaptic cleft (R-HSA-379401)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic dopamine transporter deficiency syndrome	DIS8JB37	Definitive	Autosomal recessive	[1]
SLC6A3-related dopamine transporter deficiency syndrome	DISI6ZWZ	Definitive	Autosomal recessive	[2]
Parkinsonism-dystonia, infantile	DISUX01X	Supportive	Autosomal recessive	[3]

This DOT Affected the Drug Response of 10 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Clozapine	DMFC71L	Approved	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of Clozapine.	[20]
Cocaine	DMSOX7I	Approved	Sodium-dependent dopamine transporter (SLC6A3) increases the response to substance of Cocaine.	[21]
Methamphetamine	DMPM4SK	Approved	Sodium-dependent dopamine transporter (SLC6A3) increases the response to substance of Methamphetamine.	[22]
Citalopram	DM2G9AE	Approved	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of Citalopram.	[24]
Amphetamine	DMSZQAK	Approved	Sodium-dependent dopamine transporter (SLC6A3) decreases the response to substance of Amphetamine.	[25]
Naltrexone	DMUL45H	Approved	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of Naltrexone.	[26]
Modafinil	DMYILBE	Approved	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of Modafinil.	[27]
PMID28870136-Compound-52	DMFDERP	Patented	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of PMID28870136-Compound-52.	[27]
Paraquat	DMR8O3X	Investigative	Sodium-dependent dopamine transporter (SLC6A3) affects the response to substance of Paraquat.	[28]
Manganese	DMKT129	Investigative	Sodium-dependent dopamine transporter (SLC6A3) increases the response to substance of Manganese.	[29]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Norepinephrine	DMOUC09	Approved	Sodium-dependent dopamine transporter (SLC6A3) increases the uptake of Norepinephrine.	[23]
Serotonin	DMOFCRY	Investigative	Sodium-dependent dopamine transporter (SLC6A3) increases the uptake of Serotonin.	[23]
Phenethylamine	DMX0G4F	Investigative	Sodium-dependent dopamine transporter (SLC6A3) increases the transport of Phenethylamine.	[30]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sodium-dependent dopamine transporter (SLC6A3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium-dependent dopamine transporter (SLC6A3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sodium-dependent dopamine transporter (SLC6A3).	[15]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sodium-dependent dopamine transporter (SLC6A3).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin affects the activity of Sodium-dependent dopamine transporter (SLC6A3).	[9]
Dopamine	DMPGUCF	Approved	Dopamine increases the activity of Sodium-dependent dopamine transporter (SLC6A3).	[10]
Bupropion	DM5PCS7	Approved	Bupropion increases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[11]
Dextroamphetamine	DMMIHVP	Approved	Dextroamphetamine decreases the activity of Sodium-dependent dopamine transporter (SLC6A3).	[12]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[16]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the activity of Sodium-dependent dopamine transporter (SLC6A3).	[17]
Ibogaine	DM3HJX7	Investigative	Ibogaine increases the expression of Sodium-dependent dopamine transporter (SLC6A3).	[11]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol affects the binding of Sodium-dependent dopamine transporter (SLC6A3).	[8]
Vanoxerine	DMBQPA5	Discontinued in Phase 1	Vanoxerine affects the binding of Sodium-dependent dopamine transporter (SLC6A3).	[14]
QUINPIROLE	DMDNHEP	Investigative	QUINPIROLE affects the localization of Sodium-dependent dopamine transporter (SLC6A3).	[18]
[3H]WIN35428	DMI8RU0	Investigative	[3H]WIN35428 affects the binding of Sodium-dependent dopamine transporter (SLC6A3).	[19]

References

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