Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB1FZJU)

• DOT Name: Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2)
• Synonyms: EC 6.2.1.1; Acetate--CoA ligase; Acetyl-CoA synthetase; ACS; AceCS; Acetyl-CoA synthetase 1; AceCS1; Acyl-CoA synthetase short-chain family member 2; Acyl-activating enzyme; Propionate--CoA ligase; EC 6.2.1.17
• Gene Name: ACSS2
• UniProt ID: ACSA_HUMAN
• EC Number: 6.2.1.1; 6.2.1.17
• Pfam ID: PF16177 ; PF00501 ; PF13193
• Sequence:
  MGLPEERVRSGSGSRGQEEAGAGGRARSWSPPPEVSRSAHVPSLQRYRELHRRSVEEPRE
  FWGDIAKEFYWKTPCPGPFLRYNFDVTKGKIFIEWMKGATTNICYNVLDRNVHEKKLGDK
  VAFYWEGNEPGETTQITYHQLLVQVCQFSNVLRKQGIQKGDRVAIYMPMIPELVVAMLAC
  ARIGALHSIVFAGFSSESLCERILDSSCSLLITTDAFYRGEKLVNLKELADEALQKCQEK
  GFPVRCCIVVKHLGRAELGMGDSTSQSPPIKRSCPDVQISWNQGIDLWWHELMQEAGDEC
  EPEWCDAEDPLFILYTSGSTGKPKGVVHTVGGYMLYVATTFKYVFDFHAEDVFWCTADIG
  WITGHSYVTYGPLANGATSVLFEGIPTYPDVNRLWSIVDKYKVTKFYTAPTAIRLLMKFG
  DEPVTKHSRASLQVLGTVGEPINPEAWLWYHRVVGAQRCPIVDTFWQTETGGHMLTPLPG
  ATPMKPGSATFPFFGVAPAILNESGEELEGEAEGYLVFKQPWPGIMRTVYGNHERFETTY
  FKKFPGYYVTGDGCQRDQDGYYWITGRIDDMLNVSGHLLSTAEVESALVEHEAVAEAAVV
  GHPHPVKGECLYCFVTLCDGHTFSPKLTEELKKQIREKIGPIATPDYIQNAPGLPKTRSG
  KIMRRVLRKIAQNDHDLGDMSTVADPSVISHLFSHRCLTIQ
• Function: Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids. Acetate is the preferred substrate. Can also utilize propionate with a much lower affinity. Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis. Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription. The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival. Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes. Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pyruvate metabolism (hsa00620)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Propanoate metabolism (hsa00640)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway:
  Ethanol oxidation (R-HSA-71384)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
• BioCyc Pathway: MetaCyc:HS05484-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[14]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[14]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[15]
Sodium acetate anhydrous	DMH21E0	Approved	Sodium acetate anhydrous increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[17]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[18]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[21]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[24]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[16]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2).	[25]

References

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