Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOQQVH1)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 6; GalNAc-T6; pp-GaNTase 6; Protein-UDP acetylgalactosaminyltransferase 6; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 6
• Gene Name: GALNT6
• Related Disease:
  Adenocarcinoma
  Breast neoplasm
  Carcinoma
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometrial carcinoma
  Endometriosis
  Epithelial ovarian cancer
  Gastric cancer
  Lung adenocarcinoma
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Serous cystadenocarcinoma
  Ductal breast carcinoma in situ
• UniProt ID: GALT6_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MRLLRRRHMPLRLAMVGCAFVLFLFLLHRDVSSREEATEKPWLKSLVSRKDHVLDLMLEA
  MNNLRDSMPKLQIRAPEAQQTLFSINQSCLPGFYTPAELKPFWERPPQDPNAPGADGKAF
  QKSKWTPLETQEKEEGYKKHCFNAFASDRISLQRSLGPDTRPPECVDQKFRRCPPLATTS
  VIIVFHNEAWSTLLRTVYSVLHTTPAILLKEIILVDDASTEEHLKEKLEQYVKQLQVVRV
  VRQEERKGLITARLLGASVAQAEVLTFLDAHCECFHGWLEPLLARIAEDKTVVVSPDIVT
  IDLNTFEFAKPVQRGRVHSRGNFDWSLTFGWETLPPHEKQRRKDETYPIKSPTFAGGLFS
  ISKSYFEHIGTYDNQMEIWGGENVEMSFRVWQCGGQLEIIPCSVVGHVFRTKSPHTFPKG
  TSVIARNQVRLAEVWMDSYKKIFYRRNLQAAKMAQEKSFGDISERLQLREQLHCHNFSWY
  LHNVYPEMFVPDLTPTFYGAIKNLGTNQCLDVGENNRGGKPLIMYSCHGLGGNQYFEYTT
  QRDLRHNIAKQLCLHVSKGALGLGSCHFTGKNSQVPKDEEWELAQDQLIRNSGSGTCLTS
  QDKKPAMAPCNPSDPHQLWLFV
• 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. May participate in synthesis of oncofetal fibronectin. Has activity toward MUC1A, MUC2, EA2 and fibronectin peptides. Glycosylates FGF23.
• Tissue Specificity: Expressed in placenta and trachea. Weakly expressed in brain and pancreas. Expressed in fibroblast. Weakly or not expressed in lung, liver, muscle, kidney, spleen, thymus, prostate, testis, ovary, intestine, colon, leukocyte, stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland and bone marrow.
• 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

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Colon adenocarcinoma	DISDRE0J	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[5]
Endometriosis	DISX1AG8	Strong	Altered Expression	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[9]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[7]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[7]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[10]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[10]
Serous cystadenocarcinoma	DISVK716	moderate	Altered Expression	[11]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Biomarker	[12]

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 Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6).	[23]

References

• [1] De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium.J Biol Chem. 2018 Jan 26;293(4):1298-1314. doi: 10.1074/jbc.M117.812826. Epub 2017 Nov 29.
• [2] UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow-disseminated breast cancer cells.Int J Cancer. 2006 Sep 15;119(6):1383-8. doi: 10.1002/ijc.21959.
• [3] Glycosyltransferase Gene Expression Identifies a Poor Prognostic Colorectal Cancer Subtype Associated with Mismatch Repair Deficiency and Incomplete Glycan Synthesis.Clin Cancer Res. 2018 Sep 15;24(18):4468-4481. doi: 10.1158/1078-0432.CCR-17-3533. Epub 2018 May 29.
• [4] GALNT6 suppresses progression of colorectal cancer.Am J Cancer Res. 2018 Dec 1;8(12):2419-2435. eCollection 2018.
• [5] GalNAc-T6 in the relationship with invasion ability of endometrial carcinomas and prognostic significance.Am J Cancer Res. 2017 May 1;7(5):1188-1197. eCollection 2017.
• [6] Correlation of polypeptide N-acetylgalactosamine transferases-3 and -6 to different stages of endometriosis.Arch Gynecol Obstet. 2017 Jun;295(6):1413-1419. doi: 10.1007/s00404-017-4344-6. Epub 2017 Apr 5.
• [7] GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity.Oncotarget. 2017 Jun 27;8(26):42588-42601. doi: 10.18632/oncotarget.16585.
• [8] Polypeptide N-acetylgalactosaminyltransferase-6 expression in gastric cancer.Onco Targets Ther. 2017 Jul 7;10:3337-3344. doi: 10.2147/OTT.S138590. eCollection 2017.
• [9] Epithelial-mesenchymal transition markers screened in a cell-based model and validated in lung adenocarcinoma.BMC Cancer. 2019 Jul 11;19(1):680. doi: 10.1186/s12885-019-5885-9.
• [10] GALNT6 Promotes Tumorigenicity and Metastasis of Breast Cancer Cell via -catenin/MUC1-C Signaling Pathway.Int J Biol Sci. 2019 Jan 1;15(1):169-182. doi: 10.7150/ijbs.29048. eCollection 2019.
• [11] Expression of Polypeptide N-Acetylgalactosaminyltransferase-6 in Epithelial Ovarian Carcinoma.Anticancer Res. 2017 Jul;37(7):3911-3915. doi: 10.21873/anticanres.11773.
• [12] N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.Pathol Oncol Res. 2019 Apr;25(2):759-768. doi: 10.1007/s12253-019-00593-5. Epub 2019 Jan 28.
• [13] 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.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] 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.
• [16] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [20] 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.
• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [23] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.