Details of Drug Off-Target (DOT)

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

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 16; GalNAc-T16; Polypeptide GalNAc transferase-like protein 1; GalNAc-T-like protein 1; pp-GaNTase-like protein 1; Polypeptide N-acetylgalactosaminyltransferase-like protein 1; Protein-UDP acetylgalactosaminyltransferase-like protein 1; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-like protein 1
• Gene Name: GALNT16
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: GLT16_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRKIRANAIAILTVAWILGTFYYLWQDNRAHAASSGGRGAQRAGRRSEQLREDRTIPLIV
  TGTPSKGFDEKAYLSAKQLKAGEDPYRQHAFNQLESDKLSPDRPIRDTRHYSCPSVSYSS
  DLPATSVIITFHNEARSTLLRTVKSVLNRTPANLIQEIILVDDFSSDPEDCLLLTRIPKV
  KCLRNDRREGLIRSRVRGADVAAATVLTFLDSHCEVNTEWLPPMLQRVKEDHTRVVSPII
  DVISLDNFAYLAASADLRGGFDWSLHFKWEQIPLEQKMTRTDPTRPIRTPVIAGGIFVID
  KSWFNHLGKYDAQMDIWGGENFELSFRVWMCGGSLEIVPCSRVGHVFRKRHPYNFPEGNA
  LTYIRNTKRTAEVWMDEYKQYYYEARPSAIGKAFGSVATRIEQRKKMNCKSFRWYLENVY
  PELTVPVKEALPGIIKQGVNCLESQGQNTAGDFLLGMGICRGSAKNPQPAQAWLFSDHLI
  QQQGKCLAATSTLMSSPGSPVILQMCNPREGKQKWRRKGSFIQHSVSGLCLETKPAQLVT
  SKCQADAQAQQWQLLPHT
• Function: Catalyzes 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.
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]

1 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 16 (GALNT16).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[9]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[9]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16).	[14]

References

• [1] Evaluation of GALNT16 polymorphisms to breast cancer risk in Chinese population.Mol Genet Genomic Med. 2019 Aug;7(8):e848. doi: 10.1002/mgg3.848. Epub 2019 Jul 8.
• [2] A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
• [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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [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] 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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [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.
• [14] 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.