Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH70U4Z)

• DOT Name: Very long chain fatty acid elongase 3 (ELOVL3)
• Synonyms: EC 2.3.1.199; 3-keto acyl-CoA synthase ELOVL3; Cold-inducible glycoprotein of 30 kDa; ELOVL fatty acid elongase 3; ELOVL FA elongase 3; Elongation of very long chain fatty acids protein 3; Very long chain 3-ketoacyl-CoA synthase 3; Very long chain 3-oxoacyl-CoA synthase 3
• Gene Name: ELOVL3
• Related Disease:
  Type-1/2 diabetes
  Prostate cancer
  Prostate carcinoma
  Atopic dermatitis
• UniProt ID: ELOV3_HUMAN
• EC Number: 2.3.1.199
• Pfam ID: PF01151
• Sequence:
  MVTAMNVSHEVNQLFQPYNFELSKDMRPFFEEYWATSFPIALIYLVLIAVGQNYMKERKG
  FNLQGPLILWSFCLAIFSILGAVRMWGIMGTVLLTGGLKQTVCFINFIDNSTVKFWSWVF
  LLSKVIELGDTAFIILRKRPLIFIHWYHHSTVLVYTSFGYKNKVPAGGWFVTMNFGVHAI
  MYTYYTLKAANVKPPKMLPMLITSLQILQMFVGAIVSILTYIWRQDQGCHTTMEHLFWSF
  ILYMTYFILFAHFFCQTYIRPKVKAKTKSQ
• Function: Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated and unsaturated acyl-CoA substrates with higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
• Tissue Specificity: Testis.
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway:
  alpha-linolenic acid (ALA) metabolism (R-HSA-2046106)
  Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)
  Linoleic acid (LA) metabolism (R-HSA-2046105)
• BioCyc Pathway: MetaCyc:ENSG00000119915-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[3]

8 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 Very long chain fatty acid elongase 3 (ELOVL3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[12]
Linalool	DMGZQ5P	Investigative	Linalool decreases the expression of Very long chain fatty acid elongase 3 (ELOVL3).	[13]

2 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 Very long chain fatty acid elongase 3 (ELOVL3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Very long chain fatty acid elongase 3 (ELOVL3).	[10]

References

• [1] Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.FASEB J. 2019 Apr;33(4):5425-5439. doi: 10.1096/fj.201801818R. Epub 2019 Feb 13.
• [2] The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis.Biochim Biophys Acta Gene Regul Mech. 2019 Aug;1862(8):834-845. doi: 10.1016/j.bbagrm.2019.05.005. Epub 2019 May 30.
• [3] Lipid abnormalities in atopic skin are driven by type 2 cytokines.JCI Insight. 2018 Feb 22;3(4):e98006. doi: 10.1172/jci.insight.98006. eCollection 2018 Feb 22.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [13] Linalool is a PPARalpha ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014 Jun;55(6):1098-110.