Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGRLC4C)

• DOT Name: Alpha-2,8-sialyltransferase 8E (ST8SIA5)
• Synonyms: EC 2.4.99.-; Sialyltransferase 8E; SIAT8-E; Sialyltransferase St8Sia V; ST8SiaV
• Gene Name: ST8SIA5
• UniProt ID: SIA8E_HUMAN
• EC Number: 2.4.99.-
• Pfam ID: PF00777
• Sequence:
  MRYADPSANRDLLGSRTLLFIFICAFALVTLLQQILYGRNYIKRYFEFYEGPFEYNSTRC
  LELRHEILEVKVLSMVKQSELFDRWKSLQMCKWAMNISEANQFKSTLSRCCNAPAFLFTT
  QKNTPLGTKLKYEVDTSGIYHINQEIFRMFPKDMPYYRSQFKKCAVVGNGGILKNSRCGR
  EINSADFVFRCNLPPISEKYTMDVGVKTDVVTVNPSIITERFHKLEKWRRPFYRVLQVYE
  NASVLLPAFYNTRNTDVSIRVKYVLDDFESPQAVYYFHPQYLVNVSRYWLSLGVRAKRIS
  TGLILVTAALELCEEVHLFGFWAFPMNPSGLYITHHYYDNVKPRPGFHAMPSEIFNFLHL
  HSRGILRVHTGTCSCC
• Function: Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively.
• Tissue Specificity: .Expressed in fetal and adult brain, adult heart and skeletal muscle.; [Isoform 2]: Expressed in fetal and adult brain, not detected in adult heart and skeletal muscle.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - ganglio series (hsa00604)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

4 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-2,8-sialyltransferase 8E (ST8SIA5).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-2,8-sialyltransferase 8E (ST8SIA5).	[2]
Marinol	DM70IK5	Approved	Marinol increases the expression of Alpha-2,8-sialyltransferase 8E (ST8SIA5).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-2,8-sialyltransferase 8E (ST8SIA5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Alpha-2,8-sialyltransferase 8E (ST8SIA5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-2,8-sialyltransferase 8E (ST8SIA5).	[5]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] 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.
• [4] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [5] 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.
• [6] 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.