Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCV61V1)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 5; GalNAc-T5; pp-GaNTase 5; Protein-UDP acetylgalactosaminyltransferase 5; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 5
• Gene Name: GALNT5
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Metastatic malignant neoplasm
  Gastric cancer
  Pancreatic cancer
  Stomach cancer
  Pancreatic ductal carcinoma
  Neoplasm
• UniProt ID: GALT5_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MNRIRKFFRGSGRVLAFIFVASVIWLLFDMAALRLSFSEINTRVIKEDIVRRERIGFRVQ
  PDQGKIFYSSIKEMKPPLRGHGKGAWGKENVRKTEESVLKVEVDLDQTQRERKMQNALGR
  GKVVPLWHPAHLQTLPVTPNKQKTDGRGTKPEASSHQGTPKQTTAQGAPKTSFIAAKGTQ
  VVKISVHMGRVSLKQEPRKSHSPSSDTSKLAAERDLNVTISLSTDRPKQRSQAVANERAH
  PASTAVPKSGEAMALNKTKTQSKEVNANKHKANTSLPFPKFTVNSNRLRKQSINETPLGS
  LSKDDGARGAHGKKLNFSESHLVIITKEEEQKADPKEVSNSKTKTIFPKVLGKSQSKHIS
  RNRSEMSSSSLAPHRVPLSQTNHALTGGLEPAKINITAKAPSTEYNQSHIKALLPEDSGT
  HQVLRIDVTLSPRDPKAPGQFGRPVVVPHGKEKEAERRWKEGNFNVYLSDLIPVDRAIED
  TRPAGCAEQLVHNNLPTTSVIMCFVDEVWSTLLRSVHSVINRSPPHLIKEILLVDDFSTK
  DYLKDNLDKYMSQFPKVRILRLKERHGLIRARLAGAQNATGDVLTFLDSHVECNVGWLEP
  LLERVYLSRKKVACPVIEVINDKDMSYMTVDNFQRGIFVWPMNFGWRTIPPDVIAKNRIK
  ETDTIRCPVMAGGLFSIDKSYFFELGTYDPGLDVWGGENMELSFKVWMCGGEIEIIPCSR
  VGHIFRNDNPYSFPKDRMKTVERNLVRVAEVWLDEYKELFYGHGDHLIDQGLDVGNLTQQ
  RELRKKLKCKSFKWYLENVFPDLRAPIVRASGVLINVALGKCISIENTTVILEDCDGSKE
  LQQFNYTWLRLIKCGEWCIAPIPDKGAVRLHPCDNRNKGLKWLHKSTSVFHPELVNHIVF
  ENNQQLLCLEGNFSQKILKVAACDPVKPYQKWKFEKYYEA
• 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 EA2 peptide substrate, but has a weak activity toward Muc2 or Muc1b substrates.
• 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

8 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	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	moderate	Biomarker	[2]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[3]
Stomach cancer	DISKIJSX	moderate	Biomarker	[2]
Pancreatic ductal carcinoma	DIS26F9Q	Disputed	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[11]

10 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 5 (GALNT5).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[14]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[16]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5).	[17]

References

• [1] miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.Clin Cancer Res. 2017 Sep 1;23(17):5255-5266. doi: 10.1158/1078-0432.CCR-17-0023. Epub 2017 May 22.
• [2] GALNT5 uaRNA promotes gastric cancer progression through its interaction with HSP90.Oncogene. 2018 Aug;37(33):4505-4517. doi: 10.1038/s41388-018-0266-4. Epub 2018 May 10.
• [3] The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer.FEBS Lett. 2019 Oct;593(19):2751-2761. doi: 10.1002/1873-3468.13532. Epub 2019 Jul 21.
• [4] Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma.Math Biosci Eng. 2019 Nov 6;17(1):910-927. doi: 10.3934/mbe.2020048.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] 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.
• [15] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.