Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDAF6U3)

• DOT Name: Very long chain fatty acid elongase 2 (ELOVL2)
• Synonyms: EC 2.3.1.199; 3-keto acyl-CoA synthase ELOVL2; ELOVL fatty acid elongase 2; ELOVL FA elongase 2; Elongation of very long chain fatty acids protein 2; Very long chain 3-ketoacyl-CoA synthase 2; Very long chain 3-oxoacyl-CoA synthase 2
• Gene Name: ELOVL2
• Related Disease:
  Chronic kidney disease
  Chronic renal failure
  Thyroid gland papillary carcinoma
  Acute coronary syndrome
  Adult glioblastoma
  Autism spectrum disorder
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Male infertility
  Melanoma
  Non-alcoholic fatty liver disease
  Coronary heart disease
• UniProt ID: ELOV2_HUMAN
• EC Number: 2.3.1.199
• Pfam ID: PF01151
• Sequence:
  MEHLKAFDDEINAFLDNMFGPRDSRVRGWFMLDSYLPTFFLTVMYLLSIWLGNKYMKNRP
  ALSLRGILTLYNLGITLLSAYMLAELILSTWEGGYNLQCQDLTSAGEADIRVAKVLWWYY
  FSKSVEFLDTIFFVLRKKTSQITFLHVYHHASMFNIWWCVLNWIPCGQSFFGPTLNSFIH
  ILMYSYYGLSVFPSMHKYLWWKKYLTQAQLVQFVLTITHTMSAVVKPCGFPFGCLIFQSS
  YMLTLVILFLNFYVQTYRKKPMKKDMQEPPAGKEVKNGFSKAYFTAANGVMNKKAQ
• 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 catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA), acting specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. May participate in the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
• Tissue Specificity: Liver and 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:ENSG00000096256-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[2]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Male infertility	DISY3YZZ	Strong	Biomarker	[7]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[8]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	Very long chain fatty acid elongase 2 (ELOVL2) affects the response to substance of Cyclophosphamide.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Very long chain fatty acid elongase 2 (ELOVL2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Very long chain fatty acid elongase 2 (ELOVL2).	[24]

22 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 Very long chain fatty acid elongase 2 (ELOVL2).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[20]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[19]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[29]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Very long chain fatty acid elongase 2 (ELOVL2).	[30]

References

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• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] 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.
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• [25] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
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• [27] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [28] 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.
• [29] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [30] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
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