Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV9EDZB)

• DOT Name: Procollagen galactosyltransferase 2 (COLGALT2)
• Synonyms: EC 2.4.1.50; Collagen beta(1-O)galactosyltransferase 2; ColGalT 2; Glycosyltransferase 25 family member 2; Hydroxylysine galactosyltransferase 2
• Gene Name: COLGALT2
• Related Disease: Tourette syndrome
• UniProt ID: GT252_HUMAN
• EC Number: 2.4.1.50
• Pfam ID: PF13704 ; PF01755
• Sequence:
  MAARPAATLAWSLLLLSSALLREGCRARFVAERDSEDDGEEPVVFPESPLQSPTVLVAVL
  ARNAAHTLPHFLGCLERLDYPKSRMAIWAATDHNVDNTTEIFREWLKNVQRLYHYVEWRP
  MDEPESYPDEIGPKHWPTSRFAHVMKLRQAALRTAREKWSDYILFIDVDNFLTNPQTLNL
  LIAENKTIVAPMLESRGLYSNFWCGITPKGFYKRTPDYVQIREWKRTGCFPVPMVHSTFL
  IDLRKEASDKLTFYPPHQDYTWTFDDIIVFAFSSRQAGIQMYLCNREHYGYLPIPLKPHQ
  TLQEDIENLIHVQIEAMIDRPPMEPSQYVSVVPKYPDKMGFDEIFMINLKRRKDRRDRML
  RTLYEQEIEVKIVEAVDGKALNTSQLKALNIEMLPGYRDPYSSRPLTRGEIGCFLSHYSV
  WKEVIDRELEKTLVIEDDVRFEHQFKKKLMKLMDNIDQAQLDWELIYIGRKRMQVKEPEK
  AVPNVANLVEADYSYWTLGYVISLEGAQKLVGANPFGKMLPVDEFLPVMYNKHPVAEYKE
  YYESRDLKAFSAEPLLIYPTHYTGQPGYLSDTETSTIWDNETVATDWDRTHAWKSRKQSR
  IYSNAKNTEALPPPTSLDTVPSRDEL
• Function: Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of collagen.
• Tissue Specificity: Expressed in brain and skeletal muscle.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Other types of O-glycan biosynthesis (hsa00514)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
• BioCyc Pathway: MetaCyc:G66-33947-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

13 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 Procollagen galactosyltransferase 2 (COLGALT2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Procollagen galactosyltransferase 2 (COLGALT2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Procollagen galactosyltransferase 2 (COLGALT2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Procollagen galactosyltransferase 2 (COLGALT2).	[11]

References

• [1] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] 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] 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] 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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] 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.
• [14] 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.