Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT03PU29)

DOT Name Lysosomal alpha-glucosidase (GAA)
Synonyms EC 3.2.1.20; Acid maltase; Aglucosidase alfa
Gene Name GAA
Related Disease
Glycogen storage disease type II ( )
Glycogen storage disease due to acid maltase deficiency, infantile onset ( )
Glycogen storage disease due to acid maltase deficiency, late-onset ( )
UniProt ID
LYAG_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5KZW; 5KZX; 5NN3; 5NN4; 5NN5; 5NN6; 5NN8; 7P2Z; 7P32
EC Number
3.2.1.20
Pfam ID
PF13802 ; PF01055 ; PF21365 ; PF00088
Sequence
MGVRHPPCSHRLLAVCALVSLATAALLGHILLHDFLLVPRELSGSSPVLEETHPAHQQGA
SRPGPRDAQAHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGA
QMGQPWCFFPPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLH
FTIKDPANRRYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLF
FADQFLQLSTSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLA
LEDGGSAHGVFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGY
PFMPPYWGLGFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDG
FRDFPAMVQELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKV
WPGSTAFPDFTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELEN
PPYVPGVVGGTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISR
STFAGHGRYAGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVR
WTQLGAFYPFMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAG
ETVARPLFLEFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPV
EALGSLPPPPAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQP
MALAVALTKGGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQ
LQKVTVLGVATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
Function Essential for the degradation of glycogen in lysosomes. Has highest activity on alpha-1,4-linked glycosidic linkages, but can also hydrolyze alpha-1,6-linked glucans.
KEGG Pathway
Galactose metabolism (hsa00052 )
Starch and sucrose metabolism (hsa00500 )
Metabolic pathways (hsa01100 )
Lysosome (hsa04142 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Glycogen breakdown (glycogenolysis) (R-HSA-70221 )
Glycogen storage disease type II (GAA) (R-HSA-5357609 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glycogen storage disease type II DISXZPBC Definitive Autosomal recessive [1]
Glycogen storage disease due to acid maltase deficiency, infantile onset DISQE1VS Supportive Autosomal recessive [2]
Glycogen storage disease due to acid maltase deficiency, late-onset DISKE80D Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Lysosomal alpha-glucosidase (GAA). [3]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Lysosomal alpha-glucosidase (GAA). [9]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Lysosomal alpha-glucosidase (GAA). [14]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Lysosomal alpha-glucosidase (GAA). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Lysosomal alpha-glucosidase (GAA). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Lysosomal alpha-glucosidase (GAA). [6]
Quercetin DM3NC4M Approved Quercetin increases the expression of Lysosomal alpha-glucosidase (GAA). [7]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Lysosomal alpha-glucosidase (GAA). [8]
Menadione DMSJDTY Approved Menadione affects the expression of Lysosomal alpha-glucosidase (GAA). [8]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Lysosomal alpha-glucosidase (GAA). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Lysosomal alpha-glucosidase (GAA). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Lysosomal alpha-glucosidase (GAA). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Lysosomal alpha-glucosidase (GAA). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Lysosomal alpha-glucosidase (GAA). [13]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Lysosomal alpha-glucosidase (GAA). [15]
PP-242 DM2348V Investigative PP-242 increases the expression of Lysosomal alpha-glucosidase (GAA). [16]
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⏷ Show the Full List of 13 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
3 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.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
9 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.
10 Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
11 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
12 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.
13 Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model. Front Cell Dev Biol. 2023 Aug 16;11:1236243. doi: 10.3389/fcell.2023.1236243. eCollection 2023.
14 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
15 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
16 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.