Details of Drug Off-Target (DOT)

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

• DOT Name: N-acetylgalactosaminyltransferase 7 (GALNT7)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 7; GalNAc-T7; pp-GaNTase 7; Protein-UDP acetylgalactosaminyltransferase 7; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 7
• Gene Name: GALNT7
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Advanced cancer
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Laryngeal squamous cell carcinoma
  Nasopharyngeal carcinoma
  Neoplasm
• UniProt ID: GALT7_HUMAN
• PDB ID: 6IWQ; 6IWR
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRLKIGFILRSLLVVGSFLGLVVLWSSLTPRPDDPSPLSRMREDRDVNDPMPNRGGNGLA
  PGEDRFKPVVPWPHVEGVEVDLESIRRINKAKNEQEHHAGGDSQKDIMQRQYLTFKPQTF
  TYHDPVLRPGILGNFEPKEPEPPGVVGGPGEKAKPLVLGPEFKQAIQASIKEFGFNMVAS
  DMISLDRSVNDLRQEECKYWHYDENLLTSSVVIVFHNEGWSTLMRTVHSVIKRTPRKYLA
  EIVLIDDFSNKEHLKEKLDEYIKLWNGLVKVFRNERREGLIQARSIGAQKAKLGQVLIYL
  DAHCEVAVNWYAPLVAPISKDRTICTVPLIDVINGNTYEIIPQGGGDEDGYARGAWDWSM
  LWKRVPLTPQEKRLRKTKTEPYRSPAMAGGLFAIEREFFFELGLYDPGLQIWGGENFEIS
  YKIWQCGGKLLFVPCSRVGHIYRLEGWQGNPPPIYVGSSPTLKNYVRVVEVWWDEYKDYF
  YASRPESQALPYGDISELKKFREDHNCKSFKWFMEEIAYDITSHYPLPPKNVDWGEIRGF
  ETAYCIDSMGKTNGGFVELGPCHRMGGNQLFRINEANQLMQYDQCLTKGADGSKVMITHC
  NLNEFKEWQYFKNLHRFTHIPSGKCLDRSEVLHQVFISNCDSSKTTQKWEMNNIHSV
• Function: Glycopeptide transferase involved in O-linked oligosaccharide biosynthesis, which catalyzes the transfer of an N-acetyl-D-galactosamine residue to an already glycosylated peptide. In contrast to other proteins of the family, it does not act as a peptide transferase that transfers GalNAc onto serine or threonine residue on the protein receptor, but instead requires the prior addition of a GalNAc on a peptide before adding additional GalNAc moieties. Some peptide transferase activity is however not excluded, considering that its appropriate peptide substrate may remain unidentified.
• Tissue Specificity: Widely expressed. Expressed in uterus, retina, kidney, small intestine, omentum, stomach and CNS.
• 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Definitive	Biomarker	[1]
Cervical carcinoma	DIST4S00	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Altered Expression	[5]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	N-acetylgalactosaminyltransferase 7 (GALNT7) affects the response to substance of Cisplatin.	[13]
Paclitaxel	DMLB81S	Approved	N-acetylgalactosaminyltransferase 7 (GALNT7) affects the response to substance of Paclitaxel.	[13]

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 N-acetylgalactosaminyltransferase 7 (GALNT7).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-acetylgalactosaminyltransferase 7 (GALNT7).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-acetylgalactosaminyltransferase 7 (GALNT7).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of N-acetylgalactosaminyltransferase 7 (GALNT7).	[10]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of N-acetylgalactosaminyltransferase 7 (GALNT7).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of N-acetylgalactosaminyltransferase 7 (GALNT7).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of N-acetylgalactosaminyltransferase 7 (GALNT7).	[12]

References

• [1] MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by targeting UDP-N-acetyl--D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7.J Biol Chem. 2012 Apr 20;287(17):14301-9. doi: 10.1074/jbc.M111.337642. Epub 2012 Mar 7.
• [2] High expression of GALNT7 promotes invasion and proliferation of glioma cells.Oncol Lett. 2018 Nov;16(5):6307-6314. doi: 10.3892/ol.2018.9498. Epub 2018 Sep 25.
• [3] Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression.J Hematol Oncol. 2018 Jul 3;11(1):89. doi: 10.1186/s13045-018-0632-2.
• [4] miR-214 inhibits invasion and migration via downregulating GALNT7 in esophageal squamous cell cancer.Tumour Biol. 2016 Nov;37(11):14605-14614. doi: 10.1007/s13277-016-5320-7. Epub 2016 Sep 12.
• [5] MiR-154 inhibits the growth of laryngeal squamous cell carcinoma by targeting GALNT7.Biochem Cell Biol. 2018 Dec;96(6):752-760. doi: 10.1139/bcb-2018-0047. Epub 2018 Jun 6.
• [6] GALNT7, a target of miR-494, participates in the oncogenesis of nasopharyngeal carcinoma.Tumour Biol. 2016 Apr;37(4):4559-67. doi: 10.1007/s13277-015-4281-6. Epub 2015 Oct 27.
• [7] 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.
• [8] 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.
• [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] 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.
• [11] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] 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.