Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTANT9E6)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 11; GalNAc-T11; pp-GaNTase 11; Protein-UDP acetylgalactosaminyltransferase 11; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 11
• Gene Name: GALNT11
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Small lymphocytic lymphoma
• UniProt ID: GLT11_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MGSVTVRYFCYGCLFTSATWTVLLFVYFNFSEVTQPLKNVPVKGSGPHGPSPKKFYPRFT
  RGPSRVLEPQFKANKIDDVIDSRVEDPEEGHLKFSSELGMIFNERDQELRDLGYQKHAFN
  MLISDRLGYHRDVPDTRNAACKEKFYPPDLPAASVVICFYNEAFSALLRTVHSVIDRTPA
  HLLHEIILVDDDSDFDDLKGELDEYVQKYLPGKIKVIRNTKREGLIRGRMIGAAHATGEV
  LVFLDSHCEVNVMWLQPLLAAIREDRHTVVCPVIDIISADTLAYSSSPVVRGGFNWGLHF
  KWDLVPLSELGRAEGATAPIKSPTMAGGLFAMNRQYFHELGQYDSGMDIWGGENLEISFR
  IWMCGGKLFIIPCSRVGHIFRKRRPYGSPEGQDTMTHNSLRLAHVWLDEYKEQYFSLRPD
  LKTKSYGNISERVELRKKLGCKSFKWYLDNVYPEMQISGSHAKPQQPIFVNRGPKRPKVL
  QRGRLYHLQTNKCLVAQGRPSQKGGLVVLKACDYSDPNQIWIYNEEHELVLNSLLCLDMS
  ETRSSDPPRLMKCHGSGGSQQWTFGKNNRLYQVSVGQCLRAVDPLGQKGSVAMAICDGSS
  SQQWHLEG
• Function: Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1. O-glycosylation of NOTCH1 promotes activation of NOTCH1, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). Polypeptide N-acetylgalactosaminyltransferases catalyze the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays the same enzyme activity toward MUC1, MUC4, and EA2 than GALNT1. Not involved in glycosylation of erythropoietin (EPO).
• Tissue Specificity: Highly expressed in kidney. Expressed at intermediate level in brain, heart and skeletal muscle. Weakly expressed other tissues. In kidney, it is strongly expressed in tubules but not expressed in glomeruli.
• 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
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[8]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[12]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[13]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the acetylation of Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11).	[16]

References

• [1] Treatment of cancer stem cells from human colon adenocarcinoma cell line HT-29 with resveratrol and sulindac induced mesenchymal-endothelial transition rate.Cell Tissue Res. 2019 Jun;376(3):377-388. doi: 10.1007/s00441-019-02998-9. Epub 2019 Feb 13.
• [2] Contribution of rare germline copy number variations and common susceptibility loci in Lynch syndrome patients negative for mutations in the mismatch repair genes.Int J Cancer. 2016 Apr 15;138(8):1928-35. doi: 10.1002/ijc.29948. Epub 2015 Dec 28.
• [3] GALNT11 as a new molecular marker in chronic lymphocytic leukemia.Gene. 2014 Jan 1;533(1):270-9. doi: 10.1016/j.gene.2013.09.052. Epub 2013 Sep 27.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [14] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [17] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.