Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS8JSRY)

• DOT Name: Glycine N-acyltransferase-like protein 1 (GLYATL1)
• Synonyms: EC 2.3.1.68; Acyl-CoA:glycine N-acyltransferase-like protein 1; Glutamine N-acyltransferase
• Gene Name: GLYATL1
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Metastatic prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: GLYL1_HUMAN
• EC Number: 2.3.1.68
• Pfam ID: PF08444 ; PF06021
• Sequence:
  MILLNNSHKLLALYKSLARSIPESLKVYGSVYHINHGNPFNMEVLVDSWPEYQMVIIRPQ
  KQEMTDDMDSYTNVYRMFSKEPQKSEEVLKNCEIVNWKQRLQIQGLQESLGEGIRVATFS
  KSVKVEHSRALLLVTEDILKLNASSKSKLGSWAETGHPDDEFESETPNFKYAQLDVSYSG
  LVNDNWKRGKNERSLHYIKRCIEDLPAACMLGPEGVPVSWVTMDPSCEVGMAYSMEKYRR
  TGNMARVMVRYMKYLRQKNIPFYISVLEENEDSRRFVGQFGFFEASCEWHQWTCYPQNLV
  PF
• Function: Acyltransferase which transfers an acyl group to the N-terminus of glutamine. Can use phenylacetyl-CoA as an acyl donor.
• Tissue Specificity: Expressed in liver and kidney and, at lower levels, in pancreas, testis, ovary and stomach.
• Reactome Pathway:
  Conjugation of benzoate with glycine (R-HSA-177135)
  Aspirin ADME (R-HSA-9749641)
  Conjugation of salicylate with glycine (R-HSA-177128)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[3]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glycine N-acyltransferase-like protein 1 (GLYATL1).	[12]

References

• [1] Characterization of glycine-N-acyltransferase like 1 (GLYATL1) in prostate cancer.Prostate. 2019 Oct;79(14):1629-1639. doi: 10.1002/pros.23887. Epub 2019 Aug 2.
• [2] Structure of Patt1 human proapoptotic histone acetyltransferase.J Mol Model. 2013 Dec;19(12):5533-8. doi: 10.1007/s00894-013-2043-1. Epub 2013 Nov 19.
• [3] 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.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] 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.
• [12] 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.