Target Information
| Target General Information | Top | |||||
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| Target ID |
T53103
(Former ID: TTDS00495)
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| Target Name |
Alpha-N-acetylglucosaminidase (NAGLU)
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| Synonyms |
UFHSD1; NAGLU; NAG; N-acetyl-alpha-glucosaminidase; Alpha-N-acetylglucosaminidase82 kDa form; Alpha-N-acetylglucosaminidase77 kDa form
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| Gene Name |
NAGLU
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Diabetes mellitus [ICD-11: 5A10] | |||||
| Function |
Involved in the degradation of heparan sulfate.
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| BioChemical Class |
Glycosylase
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| UniProt ID | ||||||
| EC Number |
EC 3.2.1.50
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| Sequence |
MEAVAVAAAVGVLLLAGAGGAAGDEAREAAAVRALVARLLGPGPAADFSVSVERALAAKP
GLDTYSLGGGGAARVRVRGSTGVAAAAGLHRYLRDFCGCHVAWSGSQLRLPRPLPAVPGE LTEATPNRYRYYQNVCTQSYSFVWWDWARWEREIDWMALNGINLALAWSGQEAIWQRVYL ALGLTQAEINEFFTGPAFLAWGRMGNLHTWDGPLPPSWHIKQLYLQHRVLDQMRSFGMTP VLPAFAGHVPEAVTRVFPQVNVTKMGSWGHFNCSYSCSFLLAPEDPIFPIIGSLFLRELI KEFGTDHIYGADTFNEMQPPSSEPSYLAAATTAVYEAMTAVDTEAVWLLQGWLFQHQPQF WGPAQIRAVLGAVPRGRLLVLDLFAESQPVYTRTASFQGQPFIWCMLHNFGGNHGLFGAL EAVNGGPEAARLFPNSTMVGTGMAPEGISQNEVVYSLMAELGWRKDPVPDLAAWVTSFAA RRYGVSHPDAGAAWRLLLRSVYNCSGEACRGHNRSPLVRRPSLQMNTSIWYNRSDVFEAW RLLLTSAPSLATSPAFRYDLLDLTRQAVQELVSLYYEEARSAYLSKELASLLRAGGVLAY ELLPALDEVLASDSRFLLGSWLEQARAAAVSEAEADFYEQNSRYQLTLWGPEGNILDYAN KQLAGLVANYYTPRWRLFLEALVDSVAQGIPFQQHQFDKNVFQLEQAFVLSKQRYPSQPR GDTVDLAKKIFLKYYPRWVAGSW Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | N-Acetyl-D-glucosamine | Drug Info | Approved | Autoimmune diabetes | [2] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | ABO-101 | Drug Info | Phase 1/2 | Mucopolysaccharidosis | [3] | |
| 2 | BMN 250 | Drug Info | Phase 1/2 | Mucopolysaccharidosis type IIIB | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | N-Acetyl-D-glucosamine | Drug Info | [1], [5] | |||
| Replacement | [+] 1 Replacement drugs | + | ||||
| 1 | BMN 250 | Drug Info | [6] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 1-Phosphono-L-histidine | Ligand Info | |||||
| Structure Description | Crystal structure of the human N-acetyl-alpha-glucosaminidase | PDB:4XWH | ||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | No | [7] |
| PDB Sequence |
DEAREAAAVR
33 ALVARLLGPG43 PAADFSVSVE53 RALAAKPGLD63 TYSLGGGGAA73 RVRVRGSTGV 83 AAAAGLHRYL93 RDFCGCHVAW103 SGSQLRLPRP113 LPAVPGELTE123 ATPNRYRYYQ 133 NVCTQSYSFV143 WWDWARWERE153 IDWMALNGIN163 LALAWSGQEA173 IWQRVYLALG 183 LTQAEINEFF193 TGPAFLAWGR203 MGNLHTWDGP213 LPPSWHIKQL223 YLQHRVLDQM 233 RSFGMTPVLP243 AFAGHVPEAV253 TRVFPQVNVT263 KMGSWGHFNC273 SYSCSFLLAP 283 EDPIFPIIGS293 LFLRELIKEF303 GTDIYGADTF314 NEMQPPSSEP324 SYLAAATTAV 334 YEAMTAVDTE344 AVWLLQGWLF354 QHQPQFWGPA364 QIRAVLGAVP374 RGRLLVLDLF 384 AESQPVYTRT394 ASFQGQPFIW404 CMLHNFGGNH414 GLFGALEAVN424 GGPEAARLFP 434 NSTMVGTGMA444 PEGISQNEVV454 YSLMAELGWR464 KDPVPDLAAW474 VTSFAARRYG 484 VSHPDAGAAW494 RLLLRSVYNC504 SGEACRGHNR514 SPLVRRPSLQ524 MNTSIWYNRS 534 DVFEAWRLLL544 TSAPSLATSP554 AFRYDLLDLT564 RQAVQELVSL574 YYEEARSAYL 584 SKELASLLRA594 GGVLAYELLP604 ALDEVLASDS614 RFLLGSWLEQ624 ARAAAVSEAE 634 ADFYEQNSRY644 QLTLWGPEGN654 ILDYANKQLA664 GLVANYYTPR674 WRLFLEALVD 684 SVAQGIPFQQ694 HQFDKNVFQL704 EQAFVLSKQR714 YPSQPRGDTV724 DLAKKIFLKY 734 YPRWVAGSW
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| Ligand Name: Xylitol | Ligand Info | |||||
| Structure Description | Crystal structure of the human N-acetyl-alpha-glucosaminidase | PDB:4XWH | ||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | No | [7] |
| PDB Sequence |
DEAREAAAVR
33 ALVARLLGPG43 PAADFSVSVE53 RALAAKPGLD63 TYSLGGGGAA73 RVRVRGSTGV 83 AAAAGLHRYL93 RDFCGCHVAW103 SGSQLRLPRP113 LPAVPGELTE123 ATPNRYRYYQ 133 NVCTQSYSFV143 WWDWARWERE153 IDWMALNGIN163 LALAWSGQEA173 IWQRVYLALG 183 LTQAEINEFF193 TGPAFLAWGR203 MGNLHTWDGP213 LPPSWHIKQL223 YLQHRVLDQM 233 RSFGMTPVLP243 AFAGHVPEAV253 TRVFPQVNVT263 KMGSWGHFNC273 SYSCSFLLAP 283 EDPIFPIIGS293 LFLRELIKEF303 GTDIYGADTF314 NEMQPPSSEP324 SYLAAATTAV 334 YEAMTAVDTE344 AVWLLQGWLF354 QHQPQFWGPA364 QIRAVLGAVP374 RGRLLVLDLF 384 AESQPVYTRT394 ASFQGQPFIW404 CMLHNFGGNH414 GLFGALEAVN424 GGPEAARLFP 434 NSTMVGTGMA444 PEGISQNEVV454 YSLMAELGWR464 KDPVPDLAAW474 VTSFAARRYG 484 VSHPDAGAAW494 RLLLRSVYNC504 SGEACRGHNR514 SPLVRRPSLQ524 MNTSIWYNRS 534 DVFEAWRLLL544 TSAPSLATSP554 AFRYDLLDLT564 RQAVQELVSL574 YYEEARSAYL 584 SKELASLLRA594 GGVLAYELLP604 ALDEVLASDS614 RFLLGSWLEQ624 ARAAAVSEAE 634 ADFYEQNSRY644 QLTLWGPEGN654 ILDYANKQLA664 GLVANYYTPR674 WRLFLEALVD 684 SVAQGIPFQQ694 HQFDKNVFQL704 EQAFVLSKQR714 YPSQPRGDTV724 DLAKKIFLKY 734 YPRWVAGSW
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TYR65
3.656
ALA86
4.579
ALA87
2.839
GLY88
4.720
HIS90
3.172
ARG91
3.682
ARG94
2.909
CYS136
3.955
TYR140
2.511
LEU159
2.653
ASN160
2.364
GLY161
4.587
TRP201
3.035
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Glycosaminoglycan degradation | hsa00531 | Affiliated Target |
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| Class: Metabolism => Glycan biosynthesis and metabolism | Pathway Hierarchy | ||
| Lysosome | hsa04142 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 7.57E-02 | Radiality | 6.18E+00 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 18 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Glycosaminoglycan degradation | |||||
| 2 | Metabolic pathways | |||||
| 3 | Lysosome | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | HS-GAG degradation | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Glycosaminoglycan metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Development of bFGF-Chitosan Matrices and Their Interactions with Human Dermal Fibroblast Cells. J Biomater Sci Polym Ed. 2009;20(10):1335-51. | |||||
| REF 2 | Drug information of N-Acetyl-D-glucosamine, 2008. eduDrugs. | |||||
| REF 3 | Clinical pipeline report, company report or official report of Abeona Therapeutics. | |||||
| REF 4 | Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B. Drug Deliv Transl Res. 2020 Apr;10(2):425-439. | |||||
| REF 5 | Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation. Cell Mol Life Sci. 2004 May;61(9):1025-41. | |||||
| REF 6 | Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B. Drug Deliv Transl Res. 2020 Apr;10(2):425-439. | |||||
| REF 7 | Structural characterization of the Alpha-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B. J Struct Biol. 2019 Mar 1;205(3):65-71. | |||||
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