Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9PBQVT)

• DOT Name: Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2)
• Synonyms: EC 2.4.3.3; GalNAc alpha-2,6-sialyltransferase II; ST6GalNAc II; ST6GalNAcII; SThM; Sialyltransferase 7B; SIAT7-B
• Gene Name: ST6GALNAC2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  IgA nephropathy
  Major depressive disorder
  Advanced cancer
  Melanoma
  Thyroid gland follicular carcinoma
  Neoplasm
• UniProt ID: SIA7B_HUMAN
• PDB ID: 6APJ; 6APL
• EC Number: 2.4.3.3
• Pfam ID: PF00777
• Sequence:
  MGLPRGSFFWLLLLLTAACSGLLFALYFSAVQRYPGPAAGARDTTSFEAFFQSKASNSWT
  GKGQACRHLLHLAIQRHPHFRGLFNLSIPVLLWGDLFTPALWDRLSQHKAPYGWRGLSHQ
  VIASTLSLLNGSESAKLFAPPRDTPPKCIRCAVVGNGGILNGSRQGPNIDAHDYVFRLNG
  AVIKGFERDVGTKTSFYGFTVNTMKNSLVSYWNLGFTSVPQGQDLQYIFIPSDIRDYVML
  RSAILGVPVPEGLDKGDRPHAYFGPEASASKFKLLHPDFISYLTERFLKSKLINTHFGDL
  YMPSTGALMLLTALHTCDQVSAYGFITSNYWKFSDHYFERKMKPLIFYANHDLSLEAALW
  RDLHKAGILQLYQR
• Function: Catalyzes the transfer of N-acetylneuraminyl groups onto glycan chains in glycoproteins. Shows a preference for N-acetylgalactosamine (GalNAc) residues already modified by the addition of galactose or galactose followed by sialic acid in alpha-2,3 linkage.
• Tissue Specificity: Expressed in skeletal muscle, heart, kidney, placenta, lung and leukocytes.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Maturation of protein 3a (R-HSA-9683673)
  Maturation of spike protein (R-HSA-9694548)
  Maturation of protein 3a (R-HSA-9694719)
  Termination of O-glycan biosynthesis (R-HSA-977068)
  Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[4]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Melanoma	DIS1RRCY	moderate	Biomarker	[7]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[9]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) affects the response to substance of Etoposide.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[14]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2).	[18]

References

• [1] ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF-B signaling pathway.IUBMB Life. 2014 Apr;66(4):300-8. doi: 10.1002/iub.1268. Epub 2014 Apr 23.
• [2] Identification and functional characterization of a human GalNAc [alpha]2,6-sialyltransferase with altered expression in breast cancer.Mol Med. 2002 Jan;8(1):42-55.
• [3] miR-182 and miR-135b Mediate the Tumorigenesis and Invasiveness of Colorectal Cancer Cells via Targeting ST6GALNAC2 and PI3K/AKT Pathway.Dig Dis Sci. 2017 Dec;62(12):3447-3459. doi: 10.1007/s10620-017-4755-z. Epub 2017 Oct 13.
• [4] Interaction between variants of two glycosyltransferase genes in IgA nephropathy.Kidney Int. 2009 Jul;76(2):190-8. doi: 10.1038/ki.2009.99. Epub 2009 Apr 8.
• [5] Altered plasma protein glycosylation in a mouse model of depression and in patients with major depression.J Affect Disord. 2018 Jun;233:79-85. doi: 10.1016/j.jad.2017.08.057. Epub 2017 Aug 19.
• [6] Sticking to sugars at the metastatic site: sialyltransferase ST6GalNAc2 acts as a breast cancer metastasis suppressor.Cancer Discov. 2014 Mar;4(3):275-7. doi: 10.1158/2159-8290.CD-14-0075.
• [7] Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential.J Invest Dermatol. 2015 Jul;135(7):1849-1862. doi: 10.1038/jid.2015.95. Epub 2015 Mar 10.
• [8] ST6GalNAcII mediates tumor invasion through PI3K/Akt/NF-B signaling pathway in follicular thyroid carcinoma.Oncol Rep. 2016 Apr;35(4):2131-40. doi: 10.3892/or.2016.4590. Epub 2016 Jan 22.
• [9] An in vivo functional screen identifies ST6GalNAc2 sialyltransferase as a breast cancer metastasis suppressor.Cancer Discov. 2014 Mar;4(3):304-17. doi: 10.1158/2159-8290.CD-13-0287. Epub 2014 Feb 11.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line. Nucl Med Biol. 2006 Oct;33(7):875-82. doi: 10.1016/j.nucmedbio.2006.07.004.
• [12] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [15] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] 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.
• [18] 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.
• [19] 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.