Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW26XXB)

• DOT Name: Adenylosuccinate synthetase isozyme 2 (ADSS2)
• Synonyms: AMPSase 2; AdSS 2; EC 6.3.4.4; Adenylosuccinate synthetase, acidic isozyme; Adenylosuccinate synthetase, liver isozyme; L-type adenylosuccinate synthetase; IMP--aspartate ligase 2
• Gene Name: ADSS2
• Related Disease:
  Atopic dermatitis
  Herpes simplex infection
  Insulinoma
  Schizophrenia
  Skin and skin-structure infection
• UniProt ID: PURA2_HUMAN
• PDB ID: 2V40
• EC Number: 6.3.4.4
• Pfam ID: PF00709
• Sequence:
  MAFAETYPAASSLPNGDCGRPRARPGGNRVTVVLGAQWGDEGKGKVVDLLAQDADIVCRC
  QGGNNAGHTVVVDSVEYDFHLLPSGIINPNVTAFIGNGVVIHLPGLFEEAEKNVQKGKGL
  EGWEKRLIISDRAHIVFDFHQAADGIQEQQRQEQAGKNLGTTKKGIGPVYSSKAARSGLR
  MCDLVSDFDGFSERFKVLANQYKSIYPTLEIDIEGELQKLKGYMEKIKPMVRDGVYFLYE
  ALHGPPKKILVEGANAALLDIDFGTYPFVTSSNCTVGGVCTGLGMPPQNVGEVYGVVKAY
  TTRVGIGAFPTEQDNEIGELLQTRGREFGVTTGRKRRCGWLDLVLLKYAHMINGFTALAL
  TKLDILDMFTEIKVGVAYKLDGEIIPHIPANQEVLNKVEVQYKTLPGWNTDISNARAFKE
  LPVNAQNYVRFIEDELQIPVKWIGVGKSRESMIQLF
• Function: Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Biomarker	[1]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[1]
Insulinoma	DISIU1JS	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Skin and skin-structure infection	DIS3F9EY	Strong	Biomarker	[1]

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 Adenylosuccinate synthetase isozyme 2 (ADSS2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[10]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[13]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adenylosuccinate synthetase isozyme 2 (ADSS2).	[17]

References

• [1] Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon--producing CD8+ T cells.Br J Dermatol. 2013 Sep;169(3):700-3. doi: 10.1111/bjd.12382.
• [2] Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism.Cell Rep. 2015 Oct 6;13(1):157-167. doi: 10.1016/j.celrep.2015.08.072. Epub 2015 Sep 24.
• [3] Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population.BMC Med Genet. 2008 Dec 30;9:119. doi: 10.1186/1471-2350-9-119.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [8] 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.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [11] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [12] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [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] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [17] 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.