Details of Drug Off-Target (DOT)

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

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 18; GalNAc-T18; Polypeptide GalNAc transferase-like protein 4; GalNAc-T-like protein 4; pp-GaNTase-like protein 4; Polypeptide N-acetylgalactosaminyltransferase-like protein 4; Protein-UDP acetylgalactosaminyltransferase-like protein 4; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-like protein 4
• Gene Name: GALNT18
• Related Disease:
  Gastric adenocarcinoma
  Rheumatoid arthritis
• UniProt ID: GLT18_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MVCTRKTKTLVSTCVILSGMTNIICLLYVGWVTNYIASVYVRGQEPAPDKKLEEDKGDTL
  KIIERLDHLENVIKQHIQEAPAKPEEAEAEPFTDSSLFAHWGQELSPEGRRVALKQFQYY
  GYNAYLSDRLPLDRPLPDLRPSGCRNLSFPDSLPEVSIVFIFVNEALSVLLRSIHSAMER
  TPPHLLKEIILVDDNSSNEELKEKLTEYVDKVNSQKPGFIKVVRHSKQEGLIRSRVSGWR
  AATAPVVALFDAHVEFNVGWAEPVLTRIKENRKRIISPSFDNIKYDNFEIEEYPLAAQGF
  DWELWCRYLNPPKAWWKLENSTAPIRSPALIGCFIVDRQYFQEIGLLDEGMEVYGGENVE
  LGIRVWQCGGSVEVLPCSRIAHIERAHKPYTEDLTAHVRRNALRVAEVWMDEFKSHVYMA
  WNIPQEDSGIDIGDITARKALRKQLQCKTFRWYLVSVYPEMRMYSDIIAYGVLQNSLKTD
  LCLDQGPDTENVPIMYICHGMTPQNVYYTSSQQIHVGILSPTVDDDDNRCLVDVNSRPRL
  IECSYAKAKRMKLHWQFSQGGPIQNRKSKRCLELQENSDLEFGFQLVLQKCSGQHWSITN
  VLRSLAS
• Function: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Other types of O-glycan biosynthesis (hsa00514)
  Metabolic pathways (hsa01100)
• Reactome Pathway: O-linked glycosylation of mucins (R-HSA-913709)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 18 (GALNT18).	[18]

References

• [1] GalNAc-T15 in gastric adenocarcinoma: Characterization according to tissue architecture and cellular location.Eur J Histochem. 2018 Jun 14;62(2):2931. doi: 10.4081/ejh.2018.2931.
• [2] Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] 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.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] 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.
• [20] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.