Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMF0W2U)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase-like protein 3; GalNAc-T-like protein 3; pp-GaNTase-like protein 3; Protein-UDP acetylgalactosaminyltransferase-like protein 3; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-like protein 3; Williams-Beuren syndrome chromosomal region 17 protein
• Gene Name: GALNT17
• Related Disease:
  Autism spectrum disorder
  Asthma
• UniProt ID: GLT17_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MASLRRVKVLLVLNLIAVAGFVLFLAKCRPIAVRSGDAFHEIRPRAEVANLSAHSASPIQ
  DAVLKRLSLLEDIVYRQLNGLSKSLGLIEGYGGRGKGGLPATLSPAEEEKAKGPHEKYGY
  NSYLSEKISLDRSIPDYRPTKCKELKYSKDLPQISIIFIFVNEALSVILRSVHSAVNHTP
  THLLKEIILVDDNSDEEELKVPLEEYVHKRYPGLVKVVRNQKREGLIRARIEGWKVATGQ
  VTGFFDAHVEFTAGWAEPVLSRIQENRKRVILPSIDNIKQDNFEVQRYENSAHGYSWELW
  CMYISPPKDWWDAGDPSLPIRTPAMIGCSFVVNRKFFGEIGLLDPGMDVYGGENIELGIK
  VWLCGGSMEVLPCSRVAHIERKKKPYNSNIGFYTKRNALRVAEVWMDDYKSHVYIAWNLP
  LENPGIDIGDVSERRALRKSLKCKNFQWYLDHVYPEMRRYNNTVAYGELRNNKAKDVCLD
  QGPLENHTAILYPCHGWGPQLARYTKEGFLHLGALGTTTLLPDTRCLVDNSKSRLPQLLD
  CDKVKSSLYKRWNFIQNGAIMNKGTGRCLEVENRGLAGIDLILRSCTGQRWTIKNSIK
• Function: May catalyze the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
• Tissue Specificity: Highly expressed in brain and heart. Weakly expressed in kidney, liver, lung and spleen.
• 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
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 17 (GALNT17).	[11]

References

• [1] A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3.Eur J Hum Genet. 2017 Feb;25(2):234-239. doi: 10.1038/ejhg.2016.153. Epub 2016 Nov 23.
• [2] Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma.PLoS One. 2015 Jun 17;10(6):e0129385. doi: 10.1371/journal.pone.0129385. eCollection 2015.
• [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] 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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] 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.
• [11] 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.