Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WWYXD)

DOT Name Glycine N-acyltransferase (GLYAT)
Synonyms
EC 2.3.1.13; Acyl-CoA:glycine N-acyltransferase; AAc; Aralkyl acyl-CoA N-acyltransferase; Aralkyl acyl-CoA:amino acid N-acyltransferase; Benzoyl-coenzyme A:glycine N-acyltransferase; Glycine N-benzoyltransferase; EC 2.3.1.71; HRP-1(CLP)
Gene Name GLYAT
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Bipolar disorder ( )
Carcinoma ( )
Cardiovascular disease ( )
Gestational trophoblastic neoplasia ( )
Hepatocellular carcinoma ( )
Ankylosing spondylitis ( )
Aplasia cutis congenita ( )
Ataxia-telangiectasia ( )
Corpus callosum, agenesis of ( )
Inflammatory bowel disease ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
Amyotrophic lateral sclerosis ( )
Crohn disease ( )
Neoplasm ( )
Psoriasis ( )
Sclerosing cholangitis ( )
Ulcerative colitis ( )
UniProt ID
GLYAT_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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EC Number
2.3.1.13; 2.3.1.71
Pfam ID
PF08444 ; PF06021
Sequence
MMLPLQGAQMLQMLEKSLRKSLPASLKVYGTVFHINHGNPFNLKAVVDKWPDFNTVVVCP
QEQDMTDDLDHYTNTYQIYSKDPQNCQEFLGSPELINWKQHLQIQSSQPSLNEAIQNLAA
IKSFKVKQTQRILYMAAETAKELTPFLLKSKILSPNGGKPKAINQEMFKLSSMDVTHAHL
VNKFWHFGGNERSQRFIERCIQTFPTCCLLGPEGTPVCWDLMDQTGEMRMAGTLPEYRLH
GLVTYVIYSHAQKLGKLGFPVYSHVDYSNEAMQKMSYTLQHVPIPRSWNQWNCVPL
Function
Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate numerous substrates to form a variety of N-acylglycines, with a preference for benzoyl-CoA over phenylacetyl-CoA as acyl donors. Thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid.
Tissue Specificity Predominantly expressed in liver (at protein level) and kidney. Down-regulated in hepatocellular carcinoma and other liver cancers.
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

19 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Alzheimer disease DISF8S70 Strong Altered Expression [2]
Bipolar disorder DISAM7J2 Strong Biomarker [3]
Carcinoma DISH9F1N Strong Biomarker [4]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [5]
Gestational trophoblastic neoplasia DIS4EJNA Strong Genetic Variation [4]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [6]
Ankylosing spondylitis DISRC6IR moderate Genetic Variation [7]
Aplasia cutis congenita DISMDAYM moderate Genetic Variation [8]
Ataxia-telangiectasia DISP3EVR moderate Genetic Variation [8]
Corpus callosum, agenesis of DISO9P40 moderate Genetic Variation [8]
Inflammatory bowel disease DISGN23E moderate Genetic Variation [9]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W moderate Genetic Variation [8]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [10]
Crohn disease DIS2C5Q8 Limited Genetic Variation [7]
Neoplasm DISZKGEW Limited Genetic Variation [8]
Psoriasis DIS59VMN Limited Genetic Variation [7]
Sclerosing cholangitis DIS7GZNB Limited Genetic Variation [7]
Ulcerative colitis DIS8K27O Limited Genetic Variation [7]
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⏷ Show the Full List of 19 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 (GLYAT). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Glycine N-acyltransferase (GLYAT). [12]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Glycine N-acyltransferase (GLYAT). [11]
Testosterone DM7HUNW Approved Testosterone increases the expression of Glycine N-acyltransferase (GLYAT). [13]
Progesterone DMUY35B Approved Progesterone increases the expression of Glycine N-acyltransferase (GLYAT). [14]
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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 Glycine N-acyltransferase (GLYAT). [15]
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References

1 Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation.Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1139-53. doi: 10.1517/17425255.2013.796929. Epub 2013 May 8.
2 Impaired expression of GABA transporters in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus.Neuroscience. 2017 May 20;351:108-118. doi: 10.1016/j.neuroscience.2017.03.041. Epub 2017 Apr 4.
3 Polymorphisms and haplotypes in the YWHAE gene increase susceptibility to bipolar disorder in Chinese Han population.J Clin Psychiatry. 2012 Oct;73(10):e1276-82. doi: 10.4088/JCP.12m07824.
4 Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union.Cancer. 1998 Jul 15;83(2):267-75.
5 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
6 Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma.Biochem Biophys Res Commun. 2012 Apr 20;420(4):901-6. doi: 10.1016/j.bbrc.2012.03.099. Epub 2012 Mar 27.
7 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
8 Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma.Cancer Res. 1997 Sep 1;57(17):3772-8.
9 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
10 Communication Matters-Pitfalls and Promise of Hightech Communication Devices in Palliative Care of Severely Physically Disabled Patients With Amyotrophic Lateral Sclerosis.Front Neurol. 2018 Jul 27;9:603. doi: 10.3389/fneur.2018.00603. eCollection 2018.
11 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.
12 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
13 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
14 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
15 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.