Details of Drug Off-Target (DOT)

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

• DOT Name: 2-hydroxyacyl-CoA lyase 2 (ILVBL)
• Synonyms: EC 4.1.2.-; Acetolactate synthase-like protein; IlvB-like protein
• Gene Name: ILVBL
• Related Disease:
  Asthma
  Tuberculosis
• UniProt ID: HACL2_HUMAN
• EC Number: 4.1.2.-
• Pfam ID: PF02775 ; PF00205 ; PF02776
• Sequence:
  METPAAAAPAGSLFPSFLLLACGTLVAALLGAAHRLGLFYQLLHKVDKASVRHGGENVAA
  VLRAHGVRFIFTLVGGHISPLLVACEKLGIRVVDTRHEVTAVFAADAMARLSGTVGVAAV
  TAGPGLTNTVTAVKNAQMAQSPILLLGGAASTLLQNRGALQAVDQLSLFRPLCKFCVSVR
  RVRDIVPTLRAAMAAAQSGTPGPVFVELPVDVLYPYFMVQKEMVPAKPPKGLVGRVVSWY
  LENYLANLFAGAWEPQPEGPLPLDIPQASPQQVQRCVEILSRAKRPLMVLGSQALLTPTS
  ADKLRAAVETLGVPCFLGGMARGLLGRNHPLHIRENRSAALKKADVIVLAGTVCDFRLSY
  GRVLSHSSKIIIVNRNREEMLLNSDIFWKPQEAVQGDVGSFVLKLVEGLQGQTWAPDWVE
  ELREADRQKEQTFREKAAMPVAQHLNPVQVLQLVEETLPDNSILVVDGGDFVGTAAHLVQ
  PRGPLRWLDPGAFGTLGVGAGFALGAKLCRPDAEVWCLFGDGAFGYSLIEFDTFVRHKIP
  VMALVGNDAGWTQISREQVPSLGSNVACGLAYTDYHKAAMGLGARGLLLSRENEDQVVKV
  LHDAQQQCRDGHPVVVNILIGRTDFRDGSIAV
• Function: Endoplasmic reticulum 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner. Involved in the phytosphingosine degradation pathway.
• Tissue Specificity: Expressed in all tissues tested, with highest expression in heart, pancreas and placenta.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Limited	Genetic Variation	[1]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[5]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of 2-hydroxyacyl-CoA lyase 2 (ILVBL).	[10]

References

• [1] Association analysis of ILVBL gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.BMC Pulm Med. 2017 Dec 16;17(1):210. doi: 10.1186/s12890-017-0556-6.
• [2] Biochemical and transcription analysis of acetohydroxyacid synthase isoforms in Mycobacterium tuberculosis identifies these enzymes as potential targets for drug development.Microbiology (Reading). 2011 Jan;157(Pt 1):29-37. doi: 10.1099/mic.0.041343-0. Epub 2010 Sep 30.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-60.