Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWB58F5)

DOT Name Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)
Synonyms EC 6.2.1.1; Acetate--CoA ligase 3; Acyl-CoA synthetase short-chain family member 3; Propionate--CoA ligase; EC 6.2.1.17
Gene Name ACSS3
Related Disease
Advanced cancer ( )
Gastric cancer ( )
Neoplasm ( )
Stomach cancer ( )
UniProt ID
ACSS3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
6.2.1.1; 6.2.1.17
Pfam ID
PF16177 ; PF00501 ; PF13193
Sequence
MKPSWLQCRKVTSAGGLGGPLPGSSPARGAGAALRALVVPGPRGGLGGRGCRALSSGSGS
EYKTHFAASVTDPERFWGKAAEQISWYKPWTKTLENKHSPSTRWFVEGMLNICYNAVDRH
IENGKGDKIAIIYDSPVTNTKATFTYKEVLEQVSKLAGVLVKHGIKKGDTVVIYMPMIPQ
AMYTMLACARIGAIHSLIFGGFASKELSSRIDHVKPKVVVTASFGIEPGRRVEYVPLVEE
ALKIGQHKPDKILIYNRPNMEAVPLAPGRDLDWDEEMAKAQSHDCVPVLSEHPLYILYTS
GTTGLPKGVIRPTGGYAVMLHWSMSSIYGLQPGEVWWAASDLGWVVGHSYICYGPLLHGN
TTVLYEGKPVGTPDAGAYFRVLAEHGVAALFTAPTAIRAIRQQDPGAALGKQYSLTRFKT
LFVAGERCDVETLEWSKNVFRVPVLDHWWQTETGSPITASCVGLGNSKTPPPGQAGKSVP
GYNVMILDDNMQKLKARCLGNIVVKLPLPPGAFSGLWKNQEAFKHLYFEKFPGYYDTMDA
GYMDEEGYLYVMSRVDDVINVAGHRISAGAIEESILSHGTVADCAVVGKEDPLKGHVPLA
LCVLRKDINATEEQVLEEIVKHVRQNIGPVAAFRNAVFVKQLPKTRSGKIPRSALSAIVN
GKPYKITSTIEDPSIFGHVEEMLKQA
Function Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids. Propionate is the preferred substrate. Can utilize acetate and butyrate with a much lower affinity.
KEGG Pathway
Propanoate metabolism (hsa00640 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Synthesis of Ketone Bodies (R-HSA-77111 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Gastric cancer DISXGOUK Strong Altered Expression [1]
Neoplasm DISZKGEW Strong Altered Expression [1]
Stomach cancer DISKIJSX Strong Altered Expression [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [11]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [14]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [15]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3). [13]
------------------------------------------------------------------------------------

References

1 Mitochondrial Acetyl-CoA Synthetase 3 is Biosignature of Gastric Cancer Progression.Cancer Med. 2018 Apr;7(4):1240-1252. doi: 10.1002/cam4.1295. Epub 2018 Mar 1.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
5 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
10 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
13 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.
14 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
15 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.