Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO68C3Y)

DOT Name	Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT)
Synonyms	KAT/AadAT; 2-aminoadipate aminotransferase; 2-aminoadipate transaminase; EC 2.6.1.39; Alpha-aminoadipate aminotransferase; AadAT; Glycine transaminase AADAT; EC 2.6.1.4; Kynurenine aminotransferase II; Kynurenine--glyoxylate transaminase AADAT; EC 2.6.1.63; Kynurenine--oxoglutarate aminotransferase II; Kynurenine--oxoglutarate transaminase 2; EC 2.6.1.7; Kynurenine--oxoglutarate transaminase II; Methionine--glyoxylate transaminase AADAT; EC 2.6.1.73
Gene Name	AADAT
UniProt ID	AADAT_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2QLR; 2R2N; 2VGZ; 2XH1; 3DC1; 3UE8; 4GDY; 4GE4; 4GE7; 4GE9; 4GEB; 5EFS; 5EUN; 5TF5; 6D0A; 6T8P; 6T8Q
EC Number	2.6.1.39; 2.6.1.4; 2.6.1.63; 2.6.1.7; 2.6.1.73
Pfam ID	PF00155
Sequence	MNYARFITAASAARNPSPIRTMTDILSRGPKSMISLAGGLPNPNMFPFKTAVITVENGKT IQFGEEMMKRALQYSPSAGIPELLSWLKQLQIKLHNPPTIHYPPSQGQMDLCVTSGSQQG LCKVFEMIINPGDNVLLDEPAYSGTLQSLHPLGCNIINVASDESGIVPDSLRDILSRWKP EDAKNPQKNTPKFLYTVPNGNNPTGNSLTSERKKEIYELARKYDFLIIEDDPYYFLQFNK FRVPTFLSMDVDGRVIRADSFSKIISSGLRIGFLTGPKPLIERVILHIQVSTLHPSTFNQ LMISQLLHEWGEEGFMAHVDRVIDFYSNQKDAILAAADKWLTGLAEWHVPAAGMFLWIKV KGINDVKELIEEKAVKMGVLMLPGNAFYVDSSAPSPYLRASFSSASPEQMDVAFQVLAQL IKESL
Function	Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).
Tissue Specificity	Higher expression in the liver. Also found in heart, brain, kidney, pancreas, prostate, testis and ovary.
KEGG Pathway	Lysine degradation (hsa00310 ) Tryptophan metabolism (hsa00380 ) Metabolic pathways (hsa01100 ) 2-Oxocarboxylic acid metabolism (hsa01210 )
Reactome Pathway	Tryptophan catabolism (R-HSA-71240 ) Lysine catabolism (R-HSA-71064 )
BioCyc Pathway	MetaCyc:HS03239-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

10 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 Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[5]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT).	[8]
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References

1	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.
2	Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
3	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.
4	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.
5	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
6	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.
7	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.
8	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.