Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT650121)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 13; GalNAc-T13; pp-GaNTase 13; Protein-UDP acetylgalactosaminyltransferase 13; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 13
• Gene Name: GALNT13
• Related Disease:
  Chronic obstructive pulmonary disease
  Lung cancer
  Neoplasm
  Sickle-cell anaemia
• UniProt ID: GLT13_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRRFVYCKVVLATSLMWVLVDVFLLLYFSECNKCDDKKERSLLPALRAVISRNQEGPGEM
  GKAVLIPKDDQEKMKELFKINQFNLMASDLIALNRSLPDVRLEGCKTKVYPDELPNTSVV
  IVFHNEAWSTLLRTVYSVINRSPHYLLSEVILVDDASERDFLKLTLENYVKNLEVPVKII
  RMEERSGLIRARLRGAAASKGQVITFLDAHCECTLGWLEPLLARIKEDRKTVVCPIIDVI
  SDDTFEYMAGSDMTYGGFNWKLNFRWYPVPQREMDRRKGDRTLPVRTPTMAGGLFSIDRN
  YFEEIGTYDAGMDIWGGENLEMSFRIWQCGGSLEIVTCSHVGHVFRKATPYTFPGGTGHV
  INKNNRRLAEVWMDEFKDFFYIISPGVVKVDYGDVSVRKTLRENLKCKPFSWYLENIYPD
  SQIPRRYYSLGEIRNVETNQCLDNMGRKENEKVGIFNCHGMGGNQVFSYTADKEIRTDDL
  CLDVSRLNGPVIMLKCHHMRGNQLWEYDAERLTLRHVNSNQCLDEPSEEDKMVPTMQDCS
  GSRSQQWLLRNMTLGT
• 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. Generates GalNAc-O-Ser/Thr structure also known as Tn antigen, which itself is immunogenic but also serves as a precursor for the synthesis of different mucin-type O-glycan core structures. Contributes to the synthesis of O-linked glycans on mucins and proteoglycans of the central nervous system. May promote neurogenesis through glycosylation and stabilization of PDPN ; [Isoform 1]: Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC, specifically on Thr-3 of non-glycosylated MUC5AC peptide, on Thr-12 and Thr-13 of preglycosylated MUC5AC at Thr-3 (MUC5AC-3), on Thr-3 of preglycosylated MUC5AC at Thr-13 (MUC5AC-13) and on Thr-12 of preglycosylated MUC5AC at Thr-3 and Thr-13 (MUC5AC-3,13). Transfers GalNAc to three consecutive serine/threonine residues on SDC3 forming a triplet-Tn epitope expressed in Purkinje cells of the developing brain; [Isoform 3]: Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC, specifically on Thr-3 of non-glycosylated MUC5AC peptide, on Thr-12 and Thr-13 of preglycosylated MUC5AC at Thr-3 (MUC5AC-3), on Thr-3 of preglycosylated MUC5AC at Thr-13 (MUC5AC-13) and on Thr-12 of preglycosylated MUC5AC at Thr-3 and Thr-13 (MUC5AC-3,13).
• Tissue Specificity: Specifically expressed in neuronal cells. Expressed in fetal brain, whole adult brain, cerebral cortex and cerebellum. Not expressed in other tissues tested.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Limited	Altered Expression	[2]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[2]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13).	[10]

References

• [1] A genome-wide analysis of the response to inhaled 2-agonists in chronic obstructive pulmonary disease.Pharmacogenomics J. 2016 Aug;16(4):326-35. doi: 10.1038/tpj.2015.65. Epub 2015 Oct 27.
• [2] Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis.Int J Oncol. 2016 Oct;49(4):1369-76. doi: 10.3892/ijo.2016.3638. Epub 2016 Jul 29.
• [3] A novel molecular signature for elevated tricuspid regurgitation velocity in sickle cell disease.Am J Respir Crit Care Med. 2012 Aug 15;186(4):359-68. doi: 10.1164/rccm.201201-0057OC. Epub 2012 Jun 7.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [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] 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.
• [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] 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.