Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT01OALS)

• DOT Name: Chromaffin granule amine transporter (SLC18A1)
• Synonyms: Solute carrier family 18 member 1; Vesicular amine transporter 1; VAT1
• Gene Name: SLC18A1
• UniProt ID: VMAT1_HUMAN
• Pfam ID: PF07690
• Sequence:
  MLRTILDAPQRLLKEGRASRQLVLVVVFVALLLDNMLFTVVVPIVPTFLYDMEFKEVNSS
  LHLGHAGSSPHALASPAFSTIFSFFNNNTVAVEESVPSGIAWMNDTASTIPPPATEAISA
  HKNNCLQGTGFLEEEITRVGVLFASKAVMQLLVNPFVGPLTNRIGYHIPMFAGFVIMFLS
  TVMFAFSGTYTLLFVARTLQGIGSSFSSVAGLGMLASVYTDDHERGRAMGTALGGLALGL
  LVGAPFGSVMYEFVGKSAPFLILAFLALLDGALQLCILQPSKVSPESAKGTPLFMLLKDP
  YILVAAGSICFANMGVAILEPTLPIWMMQTMCSPKWQLGLAFLPASVSYLIGTNLFGVLA
  NKMGRWLCSLIGMLVVGTSLLCVPLAHNIFGLIGPNAGLGLAIGMVDSSMMPIMGHLVDL
  RHTSVYGSVYAIADVAFCMGFAIGPSTGGAIVKAIGFPWLMVITGVINIVYAPLCYYLRS
  PPAKEEKLAILSQDCPMETRMYATQKPTKEFPLGEDSDEEPDHEE
• Function: [Isoform 1]: Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports catecholamines and indolamines with higher affinity for serotonin. Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions related with emotion processing in response to environmental stimuli ; [Isoform 2]: Unable to uptake serotonin.
• Tissue Specificity: Expressed primarily in neuroendocrine tissues. Highly expressed in chromaffin cells of the adrenal medulla (at protein level). Detected in peripheral sympathetic ganglia (at protein level). Found in some paracrine cells in stomach and duodenum (at protein level) . Expressed in substantia nigra .; [Isoform 1]: Expressed in gastrointestinal tract.; [Isoform 2]: Expressed in gastrointestinal tract.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  Serotonergic sy.pse (hsa04726)
  Dopaminergic sy.pse (hsa04728)
  Parkinson disease (hsa05012)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
• Reactome Pathway: Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Reserpine	DM6VM38	Approved	Chromaffin granule amine transporter (SLC18A1) increases the Cytology abnormal ADR of Reserpine.	[5]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Serotonin	DMOFCRY	Investigative	Chromaffin granule amine transporter (SLC18A1) increases the uptake of Serotonin.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Chromaffin granule amine transporter (SLC18A1).	[1]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Chromaffin granule amine transporter (SLC18A1).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chromaffin granule amine transporter (SLC18A1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chromaffin granule amine transporter (SLC18A1).	[3]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [5] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [6] Functional identification and molecular cloning of a human brain vesicle monoamine transporter. J Neurochem. 1993 Dec;61(6):2314-7. doi: 10.1111/j.1471-4159.1993.tb07476.x.