Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4A2A8P)

• DOT Name: EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT)
• Synonyms: EC 2.4.1.255; Extracellular O-linked N-acetylglucosamine transferase
• Gene Name: EOGT
• Related Disease:
  Adams-Oliver syndrome 1
  Adams-Oliver syndrome 4
  Corpus callosum, agenesis of
  Adams-Oliver syndrome
  Aplasia cutis congenita
• UniProt ID: EOGT_HUMAN
• EC Number: 2.4.1.255
• Pfam ID: PF04577
• Sequence:
  MLMLFVFGVLLHEVSLSGQNEAPPNTHSIPGEPLYNYASIRLPEEHIPFFLHNNRHIATV
  CRKDSLCPYKKHLEKLKYCWGYEKSCKPEFRFGYPVCSYVDMGWTDTLESAEDIFWKQAD
  FGYARERLEEMHVLCQPKETSDSSLVCSRYLQYCRATNLYLDLRNIKRNHDRFKEDFFQS
  GEIGGHCKLDIRTLTSEGQRKSPLQSWFAELQSYTQLNFRPIEDAKCDIVIEKPTYFMKL
  DAGVNMYHHFCDFINLYITQHVNNSFSTDVYIVMWDTSSYGYGDLFSDTWNAFTDYDVIH
  LKTYDSKRVCFKEAVFSLLPRMRYGLFYNTPLISGCQNTGLFRAFAQHVLHRLNITQEGP
  KDGKIRVTILARSTEYRKILNQNELVNALKTVSTFEVQIVDYKYRELGFLDQLRITHNTD
  IFIGMHGAGLTHLLFLPDWAAVFELYNCEDERCYLDLARLRGVHYITWRRQNKVFPQDKG
  HHPTLGEHPKFTNYSFDVEEFMYLVLQAADHVLQHPKWPFKKKHDEL
• Function: Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in extracellular proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Specifically glycosylates the Thr residue located between the fifth and sixth conserved cysteines of folded EGF-like domains.
• KEGG Pathway: Other types of O-glycan biosynthesis (hsa00514)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adams-Oliver syndrome 1	DISC3I62	Strong	Genetic Variation	[1]
Adams-Oliver syndrome 4	DIST0BJH	Strong	Autosomal recessive	[2]
Corpus callosum, agenesis of	DISO9P40	Strong	Genetic Variation	[3]
Adams-Oliver syndrome	DISQO525	Supportive	Autosomal dominant	[2]
Aplasia cutis congenita	DISMDAYM	Limited	Genetic Variation	[3]

12 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 EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[13]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[7]

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 decreases the methylation of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT).	[11]

References

• [1] Adams-Oliver syndrome caused by mutations of the EOGT gene.Am J Med Genet A. 2019 Nov;179(11):2246-2251. doi: 10.1002/ajmg.a.61313. Epub 2019 Jul 31.
• [2] Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome. Am J Hum Genet. 2013 Apr 4;92(4):598-604. doi: 10.1016/j.ajhg.2013.02.012. Epub 2013 Mar 21.
• [3] Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.Hum Mutat. 2018 Sep;39(9):1246-1261. doi: 10.1002/humu.23567. Epub 2018 Jul 4.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] 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.
• [12] 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.
• [13] 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.