Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0XBOVJ)

DOT Name 2-hydroxyacyl-CoA lyase 1 (HACL1)
Synonyms EC 4.1.2.63; 2-hydroxyphytanoyl-CoA lyase; 2-HPCL; Phytanoyl-CoA 2-hydroxylase 2
Gene Name HACL1
Related Disease
Cholestasis ( )
UniProt ID
HACL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
4.1.2.63
Pfam ID
PF02775 ; PF00205 ; PF02776
Sequence
MPDSNFAERSEEQVSGAKVIAQALKTQDVEYIFGIVGIPVTEIAIAAQQLGIKYIGMRNE
QAACYAASAIGYLTSRPGVCLVVSGPGLIHALGGMANANMNCWPLLVIGGSSERNQETMG
AFQEFPQVEACRLYTKFSARPSSIEAIPFVIEKAVRSSIYGRPGACYVDIPADFVNLQVN
VNSIKYMERCMSPPISMAETSAVCTAASVIRNAKQPLLIIGKGAAYAHAEESIKKLVEQY
KLPFLPTPMGKGVVPDNHPYCVGAARSRALQFADVIVLFGARLNWILHFGLPPRYQPDVK
FIQVDICAEELGNNVKPAVTLLGNIHAVTKQLLEELDKTPWQYPPESKWWKTLREKMKSN
EAASKELASKKSLPMNYYTVFYHVQEQLPRDCFVVSEGANTMDIGRTVLQNYLPRHRLDA
GTFGTMGVGLGFAIAAAVVAKDRSPGQWIICVEGDSAFGFSGMEVETICRYNLPIILLVV
NNNGIYQGFDTDTWKEMLKFQDATAVVPPMCLLPNSHYEQVMTAFGGKGYFVQTPEELQK
SLRQSLADTTKPSLINIMIEPQATRKAQDFHWLTRSNM
Function
Peroxisomal 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 degradation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids. Plays a significant role in the biosynthesis of heptadecanal in the liver.
Tissue Specificity Widely expressed.
KEGG Pathway
Peroxisome (hsa04146 )
Reactome Pathway
Peroxisomal protein import (R-HSA-9033241 )
Alpha-oxidation of phytanate (R-HSA-389599 )
BioCyc Pathway
MetaCyc:HS05516-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cholestasis DISDJJWE Strong Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of 2-hydroxyacyl-CoA lyase 1 (HACL1). [12]
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⏷ Show the Full List of 11 Drug(s)

References

1 Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.Chem Res Toxicol. 2016 Mar 21;29(3):342-51. doi: 10.1021/acs.chemrestox.5b00491. Epub 2016 Mar 9.
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 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 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.
8 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.
9 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.
10 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
11 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.
12 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.