Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO3RO36)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 1; GalNAc-T1; pp-GaNTase 1; Protein-UDP acetylgalactosaminyltransferase 1; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1
• Gene Name: GALNT1
• Related Disease:
  Bladder cancer
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Gastric cancer
  Hepatocellular carcinoma
  Stomach cancer
  Artery stenosis
  Congenital heart disease
  Ebola virus infection
  Epithelial ovarian cancer
• UniProt ID: GALT1_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRKFAYCKVVLATSLIWVLLDMFLLLYFSECNKCDEKKERGLPAGDVLEPVQKPHEGPGE
  MGKPVVIPKEDQEKMKEMFKINQFNLMASEMIALNRSLPDVRLEGCKTKVYPDNLPTTSV
  VIVFHNEAWSTLLRTVHSVINRSPRHMIEEIVLVDDASERDFLKRPLESYVKKLKVPVHV
  IRMEQRSGLIRARLKGAAVSKGQVITFLDAHCECTVGWLEPLLARIKHDRRTVVCPIIDV
  ISDDTFEYMAGSDMTYGGFNWKLNFRWYPVPQREMDRRKGDRTLPVRTPTMAGGLFSIDR
  DYFQEIGTYDAGMDIWGGENLEISFRIWQCGGTLEIVTCSHVGHVFRKATPYTFPGGTGQ
  IINKNNRRLAEVWMDEFKNFFYIISPGVTKVDYGDISSRVGLRHKLQCKPFSWYLENIYP
  DSQIPRHYFSLGEIRNVETNQCLDNMARKENEKVGIFNCHGMGGNQVFSYTANKEIRTDD
  LCLDVSKLNGPVTMLKCHHLKGNQLWEYDPVKLTLQHVNSNQCLDKATEEDSQVPSIRDC
  NGSRSQQWLLRNVTLPEIF
• 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 a broad spectrum of substrates such as apomucin-, MUC5AC-, MUC1- and MUC2-derived peptides.
• Tissue Specificity: Widely expressed. Expressed in all 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)
  Maturation of protein 3a (R-HSA-9683673)
  Maturation of protein 3a (R-HSA-9694719)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
• BioCyc Pathway: MetaCyc:HS06826-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Artery stenosis	DISQU4Q5	Limited	Genetic Variation	[6]
Congenital heart disease	DISQBA23	Limited	Biomarker	[6]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) affects the response to substance of Topotecan.	[19]

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 1 (GALNT1).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[14]
Nicotinamide mononucleotide	DMW1LKP	Preclinical	Nicotinamide mononucleotide increases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[17]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[18]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[15]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Nicotinamide-Adenine-Dinucleotide increases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[15]
Deamido-NAD	DMDFRTI	Investigative	Deamido-NAD increases the expression of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1).	[16]

References

• [1] ppGalNAc T1 as a potential novel marker for human bladder cancer.Asian Pac J Cancer Prev. 2012;13(11):5653-7. doi: 10.7314/apjcp.2012.13.11.5653.
• [2] MiR30-GALNT1/2 Axis-Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts.J Am Heart Assoc. 2017 Feb 10;6(2):e003601. doi: 10.1161/JAHA.116.003601.
• [3] LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1.Cell Death Dis. 2018 Jun 18;9(7):722. doi: 10.1038/s41419-018-0759-7.
• [4] Increased sensitivity of gastric cancer cells to natural killer and lymphokine-activated killer cells by antisense suppression of N-acetylgalactosaminyltransferase.J Immunol. 1997 Sep 15;159(6):2645-51.
• [5] Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling.Oncotarget. 2015 Mar 20;6(8):5650-65. doi: 10.18632/oncotarget.3117.
• [6] Galnt1 is required for normal heart valve development and cardiac function.PLoS One. 2015 Jan 23;10(1):e0115861. doi: 10.1371/journal.pone.0115861. eCollection 2015.
• [7] Site-specific glycosylation of Ebola virus glycoprotein by human polypeptide GalNAc-transferase 1 induces cell adhesion defects.J Biol Chem. 2018 Dec 21;293(51):19866-19873. doi: 10.1074/jbc.RA118.005375. Epub 2018 Nov 2.
• [8] Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium.Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):600-4. doi: 10.1158/1055-9965.EPI-09-0861.
• [9] 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.
• [10] 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.
• [11] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [12] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [13] 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.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol. 2018 Aug;118:880-888.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.