Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ6FDOL)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 10; GalNAc-T10; pp-GaNTase 10; Protein-UDP acetylgalactosaminyltransferase 10; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 10
• Gene Name: GALNT10
• Related Disease:
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Schizophrenia
• UniProt ID: GLT10_HUMAN
• PDB ID: 2D7I; 2D7R
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRRKEKRLLQAVALVLAALVLLPNVGLWALYRERQPDGTPGGSGAAVAPAAGQGSHSRQK
  KTFFLGDGQKLKDWHDKEAIRRDAQRVGNGEQGRPYPMTDAERVDQAYRENGFNIYVSDK
  ISLNRSLPDIRHPNCNSKRYLETLPNTSIIIPFHNEGWSSLLRTVHSVLNRSPPELVAEI
  VLVDDFSDREHLKKPLEDYMALFPSVRILRTKKREGLIRTRMLGASVATGDVITFLDSHC
  EANVNWLPPLLDRIARNRKTIVCPMIDVIDHDDFRYETQAGDAMRGAFDWEMYYKRIPIP
  PELQKADPSDPFESPVMAGGLFAVDRKWFWELGGYDPGLEIWGGEQYEISFKVWMCGGRM
  EDIPCSRVGHIYRKYVPYKVPAGVSLARNLKRVAEVWMDEYAEYIYQRRPEYRHLSAGDV
  AVQKKLRSSLNCKSFKWFMTKIAWDLPKFYPPVEPPAAAWGEIRNVGTGLCADTKHGALG
  SPLRLEGCVRGRGEAAWNNMQVFTFTWREDIRPGDPQHTKKFCFDAISHTSPVTLYDCHS
  MKGNQLWKYRKDKTLYHPVSGSCMDCSESDHRIFMNTCNPSSLTQQWLFEHTNSTVLEKF
  NRN
• 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. Has activity toward Muc5Ac and EA2 peptide substrates.
• Tissue Specificity: Widely expressed. Expressed at high level in small intestine, and at intermediate levels in stomach, pancreas, ovary, thyroid gland and spleen. Weakly expressed in other tissues.
• 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
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10) affects the response to substance of Progesterone.	[26]

2 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 10 (GALNT10).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[22]

21 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 10 (GALNT10).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[17]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10).	[25]

References

• [1] Decreased expression of hepatocyte nuclear factor 4 (Hnf4)/microRNA-122 (miR-122) axis in hepatitis B virus-associated hepatocellular carcinoma enhances potential oncogenic GALNT10 protein activity.J Biol Chem. 2015 Jan 9;290(2):1170-85. doi: 10.1074/jbc.M114.601203. Epub 2014 Nov 24.
• [2] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [10] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] 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.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [15] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [19] 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.
• [20] 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.
• [21] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [22] 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.
• [23] 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.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [26] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.