Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXIBF4D)

• DOT Name: Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2)
• Synonyms: Alpha 2,6-ST 2; EC 2.4.3.1; CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,6-sialyltransferase 2; ST6Gal II; ST6GalII; hST6Gal II; Sialyltransferase 2
• Gene Name: ST6GAL2
• Related Disease:
  Breast cancer
  Thyroid gland follicular carcinoma
  Neoplasm of esophagus
• UniProt ID: SIAT2_HUMAN
• EC Number: 2.4.3.1
• Pfam ID: PF00777
• Sequence:
  MKPHLKQWRQRMLFGIFAWGLLFLLIFIYFTDSNPAEPVPSSLSFLETRRLLPVQGKQRA
  IMGAAHEPSPPGGLDARQALPRAHPAGSFHAGPGDLQKWAQSQDGFEHKEFFSSQVGRKS
  QSAFYPEDDDYFFAAGQPGWHSHTQGTLGFPSPGEPGPREGAFPAAQVQRRRVKKRHRRQ
  RRSHVLEEGDDGDRLYSSMSRAFLYRLWKGNVSSKMLNPRLQKAMKDYLTANKHGVRFRG
  KREAGLSRAQLLCQLRSRARVRTLDGTEAPFSALGWRRLVPAVPLSQLHPRGLRSCAVVM
  SAGAILNSSLGEEIDSHDAVLRFNSAPTRGYEKDVGNKTTIRIINSQILTNPSHHFIDSS
  LYKDVILVAWDPAPYSANLNLWYKKPDYNLFTPYIQHRQRNPNQPFYILHPKFIWQLWDI
  IQENTKEKIQPNPPSSGFIGILIMMSMCREVHVYEYIPSVRQTELCHYHELYYDAACTLG
  AYHPLLYEKLLVQRLNMGTQGDLHRKGKVVLPGFQAVHCPAPSPVIPHS
• Function: Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates. Has alpha-2,6-sialyltransferase activity toward oligosaccharides that have the Gal-beta-1,4-GlcNAc sequence at the non-reducing end of their carbohydrate groups, but it has weak or no activities toward glycoproteins and glycolipids.
• Tissue Specificity: Weakly expressed in some tissues, such as small intestine, colon and fetal brain.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Other types of O-glycan biosynthesis (hsa00514)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Altered Expression	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Beta-galactoside alpha-2,6-sialyltransferase 2 (ST6GAL2).	[11]

References

• [1] Triple-negative and HER2-overexpressing breast cancer cell sialylation impacts tumor microenvironment T-lymphocyte subset recruitment: a possible mechanism of tumor escape.Cancer Manag Res. 2018 May 4;10:1051-1059. doi: 10.2147/CMAR.S162932. eCollection 2018.
• [2] LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge.Cell Death Dis. 2018 Mar 7;9(3):372. doi: 10.1038/s41419-018-0382-7.
• [3] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] 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.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.