Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYCN07T)

DOT Name Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS)
Synonyms LKR/SDH
Gene Name AASS
Related Disease
Hepatocellular carcinoma ( )
Hyperlysinemia ( )
Neoplasm ( )
Intellectual disability ( )
UniProt ID
AASS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5L76; 5L78; 5O1N; 5O1O; 5O1P; 8DDA; 8E8T; 8E8U; 8E8V
EC Number
1.5.1.8; 1.5.1.9
Pfam ID
PF05222 ; PF16653 ; PF03435
Sequence
MLQVHRTGLGRLGVSLSKGLHHKAVLAVRREDVNAWERRAPLAPKHIKGITNLGYKVLIQ
PSNRRAIHDKDYVKAGGILQEDISEACLILGVKRPPEEKLMSRKTYAFFSHTIKAQEANM
GLLDEILKQEIRLIDYEKMVDHRGVRVVAFGQWAGVAGMINILHGMGLRLLALGHHTPFM
HIGMAHNYRNSSQAVQAVRDAGYEISLGLMPKSIGPLTFVFTGTGNVSKGAQAIFNELPC
EYVEPHELKEVSQTGDLRKVYGTVLSRHHHLVRKTDAVYDPAEYDKHPERYISRFNTDIA
PYTTCLINGIYWEQNTPRLLTRQDAQSLLAPGKFSPAGVEGCPALPHKLVAICDISADTG
GSIEFMTECTTIEHPFCMYDADQHIIHDSVEGSGILMCSIDNLPAQLPIEATECFGDMLY
PYVEEMILSDATQPLESQNFSPVVRDAVITSNGTLPDKYKYIQTLRESRERAQSLSMGTR
RKVLVLGSGYISEPVLEYLSRDGNIEITVGSDMKNQIEQLGKKYNINPVSMDICKQEEKL
GFLVAKQDLVISLLPYVLHPLVAKACITNKVNMVTASYITPALKELEKSVEDAGITIIGE
LGLDPGLDHMLAMETIDKAKEVGATIESYISYCGGLPAPEHSNNPLRYKFSWSPVGVLMN
VMQSATYLLDGKVVNVAGGISFLDAVTSMDFFPGLNLEGYPNRDSTKYAEIYGISSAHTL
LRGTLRYKGYMKALNGFVKLGLINREALPAFRPEANPLTWKQLLCDLVGISPSSEHDVLK
EAVLKKLGGDNTQLEAAEWLGLLGDEQVPQAESILDALSKHLVMKLSYGPEEKDMIVMRD
SFGIRHPSGHLEHKTIDLVAYGDINGFSAMAKTVGLPTAMAAKMLLDGEIGAKGLMGPFS
KEIYGPILERIKAEGIIYTTQSTIKP
Function Bifunctional enzyme that catalyzes the first two steps in lysine degradation.
Tissue Specificity Expressed in all 16 tissues examined with highest expression in the liver.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Lysine catabolism (R-HSA-71064 )
BioCyc Pathway
MetaCyc:HS00244-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Definitive Biomarker [1]
Hyperlysinemia DISL2MKS Definitive Autosomal recessive [2]
Neoplasm DISZKGEW Definitive Genetic Variation [1]
Intellectual disability DISMBNXP Strong Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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 Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [9]
Selenium DM25CGV Approved Selenium decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [10]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [11]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [12]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [16]
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⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS). [13]
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References

1 WITHDRAWN: Prognostic biomarker AASS suppresses proliferation, migration and predicts a good survival of hepatocellular carcinoma in vivo and in vitro.Life Sci. 2019 May 31:S0024-3205(19)30436-9. doi: 10.1016/j.lfs.2019.05.080. Online ahead of print.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
4 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.
5 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.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
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 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
10 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
11 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
12 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.
13 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
14 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
15 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.
16 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.