Target Information
| Target General Information | Top | |||||
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| Target ID |
T42065
(Former ID: TTDI02080)
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| Target Name |
N-acetylmannosamine kinase (GNE)
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| Synonyms |
UDPGlcNAc2epimerase/ManAc kinase; GNE; Bifunctional UDPNacetylglucosamine 2epimerase/Nacetylmannosamine kinase
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| Gene Name |
GNE
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Muscle disorder [ICD-11: FB32-FB3Z] | |||||
| Function |
Regulates and initiates biosynthesis of N- acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development. Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. {ECO:0000250, ECO:0000269|PubMed:10334995}.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| Sequence |
MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYGNTYRM
IEQDDFDINTRLHTIVRGEDEAAMVESVGLALVKLPDVLNRLKPDIMIVHGDRFDALALA TSAALMNIRILHIEGGEVSGTIDDSIRHAITKLAHYHVCCTRSAEQHLISMCEDHDRILL AGCPSYDKLLSAKNKDYMSIIRMWLGDDVKSKDYIVALQHPVTTDIKHSIKMFELTLDAL ISFNKRTLVLFPNIDAGSKEMVRVMRKKGIEHHPNFRAVKHVPFDQFIQLVAHAGCMIGN SSCGVREVGAFGTPVINLGTRQIGRETGENVLHVRDADTQDKILQALHLQFGKQYPCSKI YGDGNAVPRILKFLKSIDLQEPLQKKFCFPPVKENISQDIDHILETLSALAVDLGGTNLR VAIVSMKGEIVKKYTQFNPKTYEERINLILQMCVEAAAEAVKLNCRILGVGISTGGRVNP REGIVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAALAERKFGQGKGLENFVTL ITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREA KKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNAKAQSILRTAGTALGLGVVNILHTM NPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRR IY Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | GNE Lipoplex | Drug Info | Phase 1 | Myopathy | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | GNE Lipoplex | Drug Info | [1] | |||
| 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: CMP-sialic acid | Ligand Info | |||||
| Structure Description | Crystal structure of UDP-GlcNAc 2-epimerase | PDB:4ZHT | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [3] |
| PDB Sequence |
NRKLRVCVAT
16 CNRADYSKLA26 PIFGIKTEPE37 FFELDVVVLG47 SHLIDDYGNT57 YRIEQDDFDI 68 NTRLHTIVRG78 EDEAAVESVG89 LALVKLPDVL99 NRLKPDIIVH110 GDRFDALALA 120 TSAALNIRIL131 HIEGGEVSGT141 IDDSIRHAIT151 KLAHYHVCCT161 RSAEQHLISC 172 EDHDRILLAG182 CPSYDKLLSA192 KNKDYSIIRW204 LGDDVKSKDY214 IVALQHPVTT 224 DIKHSIKFEL235 TLDALISFNK245 RTLVLFPNID255 AGSKEVRVRK267 KGIEHHPNFR 277 AVKHVPFDQF287 IQLVAHAGCI298 GNSSCGVREV308 GAFGTPVINL318 GTRQIGRETG 328 ENVLHVRDAD338 TQDKILQALH348 LQFGKQYPCS358 KIYGDGNAVP368 RILKFLKSID 378 LQEPLQKKFC388 FP
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| Ligand Name: Uridine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of UDP-GlcNAc 2-epimerase | PDB:4ZHT | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [3] |
| PDB Sequence |
NRKLRVCVAT
16 CNRADYSKLA26 PIFGIKTEPE37 FFELDVVVLG47 SHLIDDYGNT57 YRIEQDDFDI 68 NTRLHTIVRG78 EDEAAVESVG89 LALVKLPDVL99 NRLKPDIIVH110 GDRFDALALA 120 TSAALNIRIL131 HIEGGEVSGT141 IDDSIRHAIT151 KLAHYHVCCT161 RSAEQHLISC 172 EDHDRILLAG182 CPSYDKLLSA192 KNKDYSIIRW204 LGDDVKSKDY214 IVALQHPVTT 224 DIKHSIKFEL235 TLDALISFNK245 RTLVLFPNID255 AGSKEVRVRK267 KGIEHHPNFR 277 AVKHVPFDQF287 IQLVAHAGCI298 GNSSCGVREV308 GAFGTPVINL318 GTRQIGRETG 328 ENVLHVRDAD338 TQDKILQALH348 LQFGKQYPCS358 KIYGDGNAVP368 RILKFLKSID 378 LQEPLQKKFC388 FP
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ARG19
2.761
ALA20
3.600
SER23
2.811
LYS24
3.101
ARG113
3.038
LEU218
3.477
HIS220
2.495
LEU250
3.241
ASN253
2.802
LYS280
4.671
HIS281
3.312
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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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| Amino sugar and nucleotide sugar metabolism | hsa00520 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 1.54E-03 |
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| Closeness centrality | 1.92E-01 | Radiality | 1.33E+01 | Clustering coefficient | 2.00E-01 |
| Neighborhood connectivity | 6.00E+00 | Topological coefficient | 2.33E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | CMP-N-acetylneuraminate biosynthesis I (eukaryotes) | |||||
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Amino sugar and nucleotide sugar metabolism | |||||
| 2 | Metabolic pathways | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Amino Sugar Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Sialic acid metabolism | |||||
| References | Top | |||||
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| REF 1 | Hereditary inclusion body myopathy: single patient response to intravenous dosing of GNE gene lipoplex. Hum Gene Ther. 2011 Nov;22(11):1331-41. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034673) | |||||
| REF 3 | Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis. Sci Rep. 2016 Mar 16;6:23274. | |||||
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