Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR0B67G)

DOT Name N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA)
Synonyms EC 3.1.4.45; Mannose 6-phosphate-uncovering enzyme; Phosphodiester alpha-GlcNAcase
Gene Name NAGPA
Related Disease
Mucolipidosis type II ( )
Mucolipidosis type III, alpha/beta ( )
Mucopolysaccharidosis type 3B ( )
Specific language impairment ( )
UniProt ID
NAGPA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.4.45
Pfam ID
PF09992
Sequence
MATSTGRWLLLRLALFGFLWEASGGLDSGASRDDDLLLPYPRARARLPRDCTRVRAGNRE
HESWPPPPATPGAGGLAVRTFVSHFRDRAVAGHLTRAVEPLRTFSVLEPGGPGGCAARRR
ATVEETARAADCRVAQNGGFFRMNSGECLGNVVSDERRVSSSGGLQNAQFGIRRDGTLVT
GYLSEEEVLDTENPFVQLLSGVVWLIRNGSIYINESQATECDETQETGSFSKFVNVISAR
TAIGHDRKGQLVLFHADGQTEQRGINLWEMAEFLLKQDVVNAINLDGGGSATFVLNGTLA
SYPSDHCQDNMWRCPRQVSTVVCVHEPRCQPPDCHGHGTCVDGHCQCTGHFWRGPGCDEL
DCGPSNCSQHGLCTETGCRCDAGWTGSNCSEECPLGWHGPGCQRPCKCEHHCPCDPKTGN
CSVSRVKQCLQPPEATLRAGELSFFTRTAWLALTLALAFLLLISTAANLSLLLSRAERNR
RLHGDYAYHPLQEMNGEPLAAEKEQPGGAHNPFKD
Function
Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases.
Tissue Specificity Isoform 2 may be brain-specific.
KEGG Pathway
Lysosome (hsa04142 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mucolipidosis type II DISUNVXN Strong Biomarker [1]
Mucolipidosis type III, alpha/beta DISU1TGJ Strong Biomarker [1]
Mucopolysaccharidosis type 3B DIS1RN28 Strong Genetic Variation [2]
Specific language impairment DISEKRML Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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 N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [9]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [6]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [8]
Decitabine DMQL8XJ Approved Decitabine affects the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [7]
Propanoic Acid DM9TN2W Investigative Propanoic Acid decreases the expression of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (NAGPA). [10]
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⏷ Show the Full List of 6 Drug(s)

References

1 Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.Eur J Hum Genet. 2016 Apr;24(4):529-34. doi: 10.1038/ejhg.2015.154. Epub 2015 Jul 1.
2 BMN 250, a fusion of lysosomal alpha-N-acetylglucosaminidase with IGF2, exhibits different patterns of cellular uptake into critical cell types of Sanfilippo syndrome B disease pathogenesis.PLoS One. 2019 Jan 18;14(1):e0207836. doi: 10.1371/journal.pone.0207836. eCollection 2019.
3 A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering.Neurobiol Dis. 2014 Sep;69:23-31. doi: 10.1016/j.nbd.2014.04.019. Epub 2014 May 5.
4 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.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 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.
7 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
8 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
9 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.
10 Propionic acid induces mitochondrial dysfunction and affects gene expression for mitochondria biogenesis and neuronal differentiation in SH-SY5Y cell line. Neurotoxicology. 2019 Dec;75:116-122. doi: 10.1016/j.neuro.2019.09.009. Epub 2019 Sep 14.