Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7QOPX)

DOT Name	2-Hydroxyacid oxidase 1 (HAO1)
Synonyms	HAOX1; EC 1.1.3.15; Glycolate oxidase; GO; GOX; Glyoxylate oxidase; EC 1.2.3.5
Gene Name	HAO1
UniProt ID	HAOX1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2NZL; 2RDT; 2RDU; 2RDW; 2W0U; 5QIB; 5QIC; 5QID; 5QIE; 5QIF; 5QIG; 5QIH; 6GMB; 6GMC; 6W44; 6W45; 6W4C; 7M2O; 7R4N; 7R4O; 7R4P
EC Number	1.1.3.15; 1.2.3.5
Pfam ID	PF01070
Sequence	MLPRLICINDYEQHAKSVLPKSIYDYYRSGANDEETLADNIAAFSRWKLYPRMLRNVAET DLSTSVLGQRVSMPICVGATAMQRMAHVDGELATVRACQSLGTGMMLSSWATSSIEEVAE AGPEALRWLQLYIYKDREVTKKLVRQAEKMGYKAIFVTVDTPYLGNRLDDVRNRFKLPPQ LRMKNFETSTLSFSPEENFGDDSGLAAYVAKAIDPSISWEDIKWLRRLTSLPIVAKGILR GDDAREAVKHGLNGILVSNHGARQLDGVPATIDVLPEIVEAVEGKVEVFLDGGVRKGTDV LKALALGAKAVFVGRPIVWGLAFQGEKGVQDVLEILKEEFRLAMALSGCQNVKVIDKTLV RKNPLAVSKI
Function	Broad substrate specificity (S)-2-hydroxy-acid oxidase that preferentially oxidizes glycolate. The glyoxylate produced by the oxidation of glycolate can then be utilized by alanine-glyoxylate aminotransferase for the peroxisomal synthesis of glycine; this pathway appears to be an important step for the detoxification of glyoxylate which, if allowed to accumulate, may be metabolized to oxalate with formation of kidney stones. Can also catalyze the oxidation of glyoxylate, and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, albeit with much lower catalytic efficiency. Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2. Is not active on L-lactate and 2-hydroxybutanoate.
Tissue Specificity	Highly expressed in liver.
KEGG Pathway	Glyoxylate and dicarboxylate metabolism (hsa00630 ) Metabolic pathways (hsa01100 ) Carbon metabolism (hsa01200 ) Peroxisome (hsa04146 )
Reactome Pathway	Peroxisomal protein import (R-HSA-9033241 ) Glyoxylate metabolism and glycine degradation (R-HSA-389661 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

6 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-Hydroxyacid oxidase 1 (HAO1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2-Hydroxyacid oxidase 1 (HAO1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2-Hydroxyacid oxidase 1 (HAO1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 2-Hydroxyacid oxidase 1 (HAO1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of 2-Hydroxyacid oxidase 1 (HAO1).	[4]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of 2-Hydroxyacid oxidase 1 (HAO1).	[5]
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References

1	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2	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.
3	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
4	Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
5	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.