Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVK9EHD)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase-like protein 2; GalNAc-T-like protein 2; pp-GaNTase-like protein 2; Polypeptide N-acetylgalactosaminyltransferase-like protein 2; Protein-UDP acetylgalactosaminyltransferase-like protein 2; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-like protein 2
• Gene Name: GALNT15
• Related Disease: Colorectal carcinoma
• UniProt ID: GLT15_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MLLRKRYRHRPCRLQFLLLLLMLGCVLMMVAMLHPPHHTLHQTVTAQASKHSPEARYRLD
  FGESQDWVLEAEDEGEEYSPLEGLPPFISLREDQLLVAVALPQARRNQSQGRRGGSYRLI
  KQPRRQDKEAPKRDWGADEDGEVSEEEELTPFSLDPRGLQEALSARIPLQRALPEVRHPL
  CLQQHPQDSLPTASVILCFHDEAWSTLLRTVHSILDTVPRAFLKEIILVDDLSQQGQLKS
  ALSEYVARLEGVKLLRSNKRLGAIRARMLGATRATGDVLVFMDAHCECHPGWLEPLLSRI
  AGDRSRVVSPVIDVIDWKTFQYYPSKDLQRGVLDWKLDFHWEPLPEHVRKALQSPISPIR
  SPVVPGEVVAMDRHYFQNTGAYDSLMSLRGGENLELSFKAWLCGGSVEILPCSRVGHIYQ
  NQDSHSPLDQEATLRNRVRIAETWLGSFKETFYKHSPEAFSLSKAEKPDCMERLQLQRRL
  GCRTFHWFLANVYPELYPSEPRPSFSGKLHNTGLGLCADCQAEGDILGCPMVLAPCSDSR
  QQQYLQHTSRKEIHFGSPQHLCFAVRQEQVILQNCTEEGLAIHQQHWDFQENGMIVHILS
  GKCMEAVVQENNKDLYLRPCDGKARQQWRFDQINAVDER
• 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. Although it displays a much weaker activity toward all substrates tested compared to GALNT2, it is able to transfer up to seven GalNAc residues to the Muc5AC peptide, suggesting that it can fill vicinal Thr/Ser residues in cooperation with other GALNT proteins. Prefers Muc1a as substrate.
• Tissue Specificity: Widely expressed. Highly expressed in small intestine, placenta, spleen, cerebral cortex and ovary. Expressed at intermediate level in uterus, mammary gland, stomach, cerebellum and whole brain. Weakly expressed in fetal brain, bone marrow, thyroid gland, thymus, heart, skeletal muscle, lung, liver, colon, pancreas, kidney and testis. Not expressed in leukocyte. Expressed in both normal and osteoarthritic cartilage. Expressed at low level in chondrocytes in all zones of both normal and osteoarthritic cartilage.
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Disputed	Genetic Variation	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15) affects the response to substance of Temozolomide.	[8]
DTI-015	DMXZRW0	Approved	Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15) affects the response to substance of DTI-015.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[2]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 15 (GALNT15).	[6]

References

• [1] Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins.BMC Cancer. 2011 Aug 5;11:339. doi: 10.1186/1471-2407-11-339.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [5] 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.
• [6] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [7] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [8] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.