General Information of Drug Off-Target (DOT) (ID: OTH91ETM)

DOT Name Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5)
Synonyms EC 2.4.99.-; GD1 alpha synthase; GalNAc alpha-2,6-sialyltransferase V; ST6GalNAc V; ST6GalNAcV; Sialyltransferase 7E; SIAT7-E
Gene Name ST6GALNAC5
Related Disease
Glioma ( )
Neoplasm ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cervical Intraepithelial neoplasia ( )
Cervix disorder ( )
Rheumatoid arthritis ( )
Acute myelogenous leukaemia ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Lymphoma ( )
UniProt ID
SIA7E_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.4.99.-
Pfam ID
PF00777
Sequence
MKTLMRHGLAVCLALTTMCTSLLLVYSSLGGQKERPPQQQQQQQQQQQQASATGSSQPAA
ESSTQQRPGVPAGPRPLDGYLGVADHKPLKMHCRDCALVTSSGHLLHSRQGSQIDQTECV
IRMNDAPTRGYGRDVGNRTSLRVIAHSSIQRILRNRHDLLNVSQGTVFIFWGPSSYMRRD
GKGQVYNNLHLLSQVLPRLKAFMITRHKMLQFDELFKQETGKDRKISNTWLSTGWFTMTI
ALELCDRINVYGMVPPDFCRDPNHPSVPYHYYEPFGPDECTMYLSHERGRKGSHHRFITE
KRVFKNWARTFNIHFFQPDWKPESLAINHPENKPVF
Function
Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of GM1b. GD1alpha is a critical molecule in the communication and interaction between neuronal cells and their supportive cells, particularly in brain tissues, and functions as an adhesion molecule in the process of metastasis. Also shows activity towards sialyl Lc4Cer (N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl-sphing-4-enine) generating disialyl Lc4Cer, which can lead to the synthesis of disialyl Lewis a (Le(a)), suggested to be a cancer-associated antigen.
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

14 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioma DIS5RPEH Definitive Altered Expression [1]
Neoplasm DISZKGEW Definitive Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Cervical cancer DISFSHPF Strong Biomarker [4]
Cervical carcinoma DIST4S00 Strong Biomarker [4]
Cervical Intraepithelial neoplasia DISXP757 Strong Biomarker [4]
Cervix disorder DIS1HG31 Strong Biomarker [4]
Rheumatoid arthritis DISTSB4J Strong Biomarker [5]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [6]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [7]
Coronary heart disease DIS5OIP1 Limited Biomarker [7]
Lymphoma DISN6V4S Limited Biomarker [8]
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⏷ Show the Full List of 14 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [9]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [12]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [5]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [14]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [15]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [18]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [19]
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⏷ Show the Full List of 10 Drug(s)
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-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5). [16]
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References

1 Overexpression of ST6GalNAcV, a ganglioside-specific alpha2,6-sialyltransferase, inhibits glioma growth in vivo.Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12646-51. doi: 10.1073/pnas.0909862107. Epub 2010 Jun 28.
2 Genes that mediate breast cancer metastasis to the brain.Nature. 2009 Jun 18;459(7249):1005-9. doi: 10.1038/nature08021. Epub 2009 May 6.
3 Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9.Phytother Res. 2018 Jul;32(7):1373-1381. doi: 10.1002/ptr.6071. Epub 2018 Mar 13.
4 Detection of hypermethylated genes as markers for cervical screening in women living with HIV.J Int AIDS Soc. 2018 Aug;21(8):e25165. doi: 10.1002/jia2.25165.
5 Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
6 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
7 Mutation in ST6GALNAC5 identified in family with coronary artery disease.Sci Rep. 2014 Jan 8;4:3595. doi: 10.1038/srep03595.
8 Expression analysis of 0-series gangliosides in human cancer cell lines with monoclonal antibodies generated using knockout mice of ganglioside synthase genes.Glycobiology. 2016 Sep;26(9):984-998. doi: 10.1093/glycob/cww049. Epub 2016 Apr 21.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 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.
11 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.
12 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
13 Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
14 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.
15 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
16 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.
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 changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.