Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTENME7S)

• DOT Name: CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4)
• Synonyms: EC 2.4.3.-; Alpha-2,8-sialyltransferase 8D; Polysialyltransferase; Polysialyltransferase-1; Sialyltransferase 8D; SIAT8-D; Sialyltransferase St8Sia IV; ST8SiaIV
• Gene Name: ST8SIA4
• UniProt ID: SIA8D_HUMAN
• PDB ID: 5Y22; 5Y3U; 6AHZ
• EC Number: 2.4.3.-
• Pfam ID: PF00777
• Sequence:
  MRSIRKRWTICTISLLLIFYKTKEIARTEEHQETQLIGDGELSLSRSLVNSSDKIIRKAG
  SSIFQHNVEGWKINSSLVLEIRKNILRFLDAERDVSVVKSSFKPGDVIHYVLDRRRTLNI
  SHDLHSLLPEVSPMKNRRFKTCAVVGNSGILLDSECGKEIDSHNFVIRCNLAPVVEFAAD
  VGTKSDFITMNPSVVQRAFGGFRNESDREKFVHRLSMLNDSVLWIPAFMVKGGEKHVEWV
  NALILKNKLKVRTAYPSLRLIHAVRGYWLTNKVPIKRPSTGLLMYTLATRFCDEIHLYGF
  WPFPKDLNGKAVKYHYYDDLKYRYFSNASPHRMPLEFKTLNVLHNRGALKLTTGKCVKQ
• Function: Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan protein acceptor through alpha-2,8-linkages. Therefore, participates in polysialic acid synthesis on various sialylated N-acetyllactosaminyl oligosaccharides, including NCAM1 N-glycans, FETUB N-glycans and AHSG. It is noteworthy that alpha-2,3-linked sialic acid is apparently a better acceptor than alpha-2,6-linked sialic acid.
• Tissue Specificity: Highly expressed in fetal brain, lung and kidney and in adult heart, spleen and thymus . Present to a lesser extent in adult brain, placenta, lung, large and small intestine and peripheral blood leukocytes .
• Reactome Pathway:
  NCAM1 interactions (R-HSA-419037)
  Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

2 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 CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[10]

11 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 CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[9]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase (ST8SIA4).	[12]

References

• [1] 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.
• [2] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [5] 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.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.