Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT89NYVC)

• DOT Name: Very long chain fatty acid elongase 7 (ELOVL7)
• Synonyms: EC 2.3.1.199; 3-keto acyl-CoA synthase ELOVL7; ELOVL fatty acid elongase 7; ELOVL FA elongase 7; Elongation of very long chain fatty acids protein 7; Very long chain 3-ketoacyl-CoA synthase 7; Very long chain 3-oxoacyl-CoA synthase 7
• Gene Name: ELOVL7
• Related Disease:
  Parkinson disease
  Cytomegalovirus infection
  Hidradenitis suppurativa
  Inflammatory bowel disease
  Multiple system atrophy
  Prostate cancer
  Prostate carcinoma
  Castration-resistant prostate carcinoma
  Neoplasm
• UniProt ID: ELOV7_HUMAN
• PDB ID: 6Y7F
• EC Number: 2.3.1.199
• Pfam ID: PF01151
• Sequence:
  MAFSDLTSRTVHLYDNWIKDADPRVEDWLLMSSPLPQTILLGFYVYFVTSLGPKLMENRK
  PFELKKAMITYNFFIVLFSVYMCYEFVMSGWGIGYSFRCDIVDYSRSPTALRMARTCWLY
  YFSKFIELLDTIFFVLRKKNSQVTFLHVFHHTIMPWTWWFGVKFAAGGLGTFHALLNTAV
  HVVMYSYYGLSALGPAYQKYLWWKKYLTSLQLVQFVIVAIHISQFFFMEDCKYQFPVFAC
  IIMSYSFMFLLLFLHFWYRAYTKGQRLPKTVKNGTCKNKDN
• 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 with higher activity toward C18 acyl-CoAs, especially C18:3(n-3) acyl-CoAs and C18:3(n-6)-CoAs. Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs, and weakly toward C20:0-CoA. Little or no activity toward C22:0-, C24:0-, or C26:0-CoAs. May participate in the production of saturated and polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
• Tissue Specificity: Expressed in most tissues except heart and skeletal muscle.
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
• Reactome Pathway: Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)
• BioCyc Pathway: MetaCyc:ENSG00000164181-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Genetic Variation	[1]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[2]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Genetic Variation	[3]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[3]
Multiple system atrophy	DISASEYE	Strong	Genetic Variation	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

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 Very long chain fatty acid elongase 7 (ELOVL7).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[11]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[12]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Very long chain fatty acid elongase 7 (ELOVL7).	[19]

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 Very long chain fatty acid elongase 7 (ELOVL7).	[15]

References

• [1] Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance.Front Genet. 2019 Jan 25;9:701. doi: 10.3389/fgene.2018.00701. eCollection 2018.
• [2] Human Cytomegalovirus pUL37x1 Is Important for Remodeling of Host Lipid Metabolism.J Virol. 2019 Oct 15;93(21):e00843-19. doi: 10.1128/JVI.00843-19. Print 2019 Nov 1.
• [3] Identification of Clinical and Genetic Parameters Associated with Hidradenitis Suppurativa in Inflammatory Bowel Disease.Inflamm Bowel Dis. 2016 Jan;22(1):106-13. doi: 10.1097/MIB.0000000000000579.
• [4] A genome-wide association study in multiple system atrophy.Neurology. 2016 Oct 11;87(15):1591-1598. doi: 10.1212/WNL.0000000000003221. Epub 2016 Sep 14.
• [5] Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism.Cancer Res. 2009 Oct 15;69(20):8133-40. doi: 10.1158/0008-5472.CAN-09-0775. Epub 2009 Oct 13.
• [6] Reactivation of androgen receptor-regulated lipid biosynthesis drives the progression of castration-resistant prostate cancer.Oncogene. 2018 Feb 8;37(6):710-721. doi: 10.1038/onc.2017.385. Epub 2017 Oct 23.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.