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Information on EC 3.2.1.183 - UDP-N-acetylglucosamine 2-epimerase (hydrolysing) and Organism(s) Homo sapiens and UniProt Accession Q9Y223
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3.2.1.183 UDP-N-acetylglucosamine 2-epimerase (hydrolysing)IUBMB Comments
The enzyme is found in mammalian liver, as well as in some pathogenic bacteria including Neisseria meningitidis and Staphylococcus aureus. It catalyses the first step of sialic acid (N-acetylneuraminic acid) biosynthesis. The initial product formed is the alpha anomer, which rapidly mutarotates to a mixture of anomers . The mammalian enzyme is bifunctional and also catalyses EC 2.7.1.60, N-acetylmannosamine kinase.
cf. EC 5.1.3.14, UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing).
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
bifunctional udp-n-acetylglucosamine 2-epimerase/n-acetylmannosamine kinase, bifunctional udp-glcnac 2-epimerase/mannac kinase, uridine diphosphate-n-acetylglucosamine-2-epimerase, uridine diphosphate-n-acetylglucosamine 2-epimerase/n-acetylmannosamine kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
bifunctional enzyme UDP-Nacetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
GNE
neuC
-
-
-
-
siaA
-
-
-
-
UDP-GlcNAc-2-epimerase/ManAc kinase
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase
uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
UniProt
GNE
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-N-acetyl-alpha-D-glucosamine + H2O = N-acetyl-D-mannosamine + UDP
catalytic and regulatory mechanisms
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-alpha-D-glucosamine hydrolase (2-epimerising)
The enzyme is found in mammalian liver, as well as in some pathogenic bacteria including Neisseria meningitidis and Staphylococcus aureus. It catalyses the first step of sialic acid (N-acetylneuraminic acid) biosynthesis. The initial product formed is the alpha anomer, which rapidly mutarotates to a mixture of anomers [2]. The mammalian enzyme is bifunctional and also catalyses EC 2.7.1.60, N-acetylmannosamine kinase.
cf. EC 5.1.3.14, UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing).
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
-
?
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
?
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
?
additional information
?
-
-
bifunctional enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase consisting of an N-terminal epimerase and a C-terminal kinase domain. The epimerase domain converts UDP-GlcNAc to ManNAc and the kinase domain phosphorylates ManNAc to ManNAc-P
-
-
?
additional information
?
-
analysis of interaction between GNE and alpha-actinin 2, overview. Enzyme GNE shows a much higher affinity for alpha-actinin 2 than to alpha-actinin 1, protein-protein interaction, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
-
?
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
?
UDP-N-acetyl-alpha-D-glucosamine + H2O
N-acetyl-D-mannosamine + UDP
-
-
-
?
additional information
?
-
-
bifunctional enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase consisting of an N-terminal epimerase and a C-terminal kinase domain. The epimerase domain converts UDP-GlcNAc to ManNAc and the kinase domain phosphorylates ManNAc to ManNAc-P
-
-
?
additional information
?
-
analysis of interaction between GNE and alpha-actinin 2, overview. Enzyme GNE shows a much higher affinity for alpha-actinin 2 than to alpha-actinin 1, protein-protein interaction, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CMP-Neu5Ac
feedback-inhibits the UDPGlcNAc 2-epimerase activity of GNE by binding to its allosteric site
CMP-Neu5Ac
feedback inhibition, cooperative binding mode and binding structure, overview
CMP-Neu5Ac
the downstream product CMP-Neu5Ac also acts as a feed-back inhibitor to regulate the GNE activity. The feedback inhibitor binds to the dimer-dimer interface and locks the tetramer into a tightly closed and inactive conformation. This is distinct from the activation mechanism of the non-hydrolyzing enzyme through a closed conformation
UDP
the binding mode of UDP reveals unique interactions with the hydrolyzing epimerase, binding structure, overview. The base is sandwiched between the side chains of Arg19 and Phe287, while making two hydrogen bonds to the backbone of Val282. The two hydroxyl groups of ribose are hydrogen bonded to the side chains of Ser23 and Glu307. The diphosphate forms salt bridges to Arg19, Arg113 and Arg321. It also interacts with His220 and Asn253 through hydrogen bonds, as well as the two consecutive Ser301 and Ser302 at the N-terminus of helix alpha12
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active
-
additional information
-
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0005
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant D112A, pH 7.5, 37°C
0.0121
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant S302A, pH 7.5, 37°C
0.0331
UDP-N-acetyl-alpha-D-glucosamine
recombinant wild-type enzyme, pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.076
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant D112A, pH 7.5, 37°C
0.791
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant S302A, pH 7.5, 37°C
11.8
UDP-N-acetyl-alpha-D-glucosamine
recombinant wild-type enzyme, pH 7.5, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
65.4
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant S302A, pH 7.5, 37°C
152
UDP-N-acetyl-alpha-D-glucosamine
recombinant mutant D112A, pH 7.5, 37°C
356.5
UDP-N-acetyl-alpha-D-glucosamine
recombinant wild-type enzyme, pH 7.5, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
quantitative real-time PCR.expression and tissue localization analysis of isozymes GNE1-GNE8, isozymes hGNE1 and hGNE6 is localized ubiquitously in all tissues examined
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
hereditary inclusion body myopathy (GNE myopathy) is a neuromuscular disorder due to mutation in key sialic acid biosynthetic enzyme gene, GNE, D176V and V572L. Mutation in GNE affects beta1-integrin-mediated cell adhesion process in GNE mutant cells
malfunction
isozymes hGNE3 and hGNE8 contain a 53-residue N-terminal deletion, epimerase enzymatic activity of isozymes GNE3 and GNE8 is likely absent, because the deleted fragment contains important substrate binding residues in homologous bacterial epimerases. Isozymes hGNE5-hGNE8 have a 53-residue deletion, which was assigned a role in substrate UDP-GlcNAc binding
malfunction
defective GNE inhibition by CMP-Neu5Ac causes cytoplasmic accumulation and increased excretion of free sialic acid. Sialuria is an autosomal dominant disorder which is related to GNE mutation in one of the two arginine residues 263 and 266 (R263L, R266Q or R266W), the mutations in Arg263 and Arg266 can cause sialuria by hindering the enzyme inhibition through CMP-Neu5Ac binding
malfunction
distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive genetic disease characterized by weakness of the anterior compartment of the lower limbs, sparing the quadriceps muscle, and rimmed vacuoles in muscle biopsies. The disease is caused by a mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene located on chromosome 9p13.3. We present two cases of Chinese patients with progressive lower extremity weakness, phenotypes, overview
malfunction
hereditary inclusion body myopathy (GNE myopathy) is a neuromuscular disorder due to mutation in key sialic acid biosynthetic enzyme, GNE. The subcellular distribution of recombinant GNE and its mutant shows differential localization in the cell. The enzyme mutation leads to hyposialylation of cell membrane receptor, beta1-integrin. Hyposialylated beta1-integrin localized to internal vesicles that is restored upon supplementation with sialic acid. Fibronectin stimulation causes migration of hyposialylated beta1-integrin to the cell membrane and colocalization with focal adhesion kinase (FAK) leading to increased focal adhesion formation. This further activates FAK and Src, downstream signaling molecules and leads to increased cell adhesion. The mutation in GNE affects beta1-integrin-mediated cell adhesion process in GNE mutant cells. Activation of endoplasmic reticulum stress response due to accumulation of misfolded mutated GNE protein
malfunction
impaired feed-back inhibition of the enzyme by CMP-Neu5Ac to regulate the GNE activity can result in sialuria
malfunction
mutation M743T of enzyme GNE leads to GNE myopathy (i.e. hereditary inclusion body myopathy, HIBM), a unique muscle pathophysiology disorder
malfunction
phenotype-genotype analysis of GNE myopathy index patients of a kohort, overview
metabolism
the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid. Two distinct human disorders, sialuria and hereditary inclusion body myopathy, are associated with predominantly missense mutations in GNE
metabolism
bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase, GNE, is key sialic acid biosynthetic enzyme
metabolism
sialic acid biosynthesis in mammals starts by converting UDP-GluNAc into UDP and ManNAc, followed by phosphorylation of ManNAc at the sixth position, catalysis of both reactions is carried out by the bifunctional enzyme GNE. Regulation of cell-surface sialyation level by binding to the downstream product CMP-Neu5Ac. The feedback inhibition is highly positively cooperative and it does not affect the ManNAc kinase activity
metabolism
the biosynthesis of sialic acids starts with hydrolytic epimerization of N-acetyl glucosamine (GlcNAc), catalyzed by UDP-GlcNAc 2-epimerase and producing N-acetyl mannosamine (ManNAc), which then reacts with phosphoenolpyruvate to form Neu5Ac. Whereas the substrate for non-hydrolyzing epimerase and hydrolyzing epimerase is the same, in this case, UDP-GlcNAc, the product of the former is UDP-ManNAc, and that of the latter is alpha-ManNAc plus UDP
physiological function
-
the enzyme is involved in sialic acid synthesis and other cellular functions, it plays a role in beta1-integrin-mediated cell adhesion, overview
physiological function
UDP-GlcNAc 2-epimerase/ManNAc kinase catalyzes the first two committed steps in sialic acid synthesis. Isozyme hGNE1 is the ubiquitously expressed major isoform, while the isozymes hGNE2-hGNE8 isoforms are differentially expressed and may act as tissue-specific regulators of sialylation
physiological function
biosynthesis of sialic acid is regulated by a 79-kDa bifunctional enzyme UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase (GNE), consisting of N-terminal epimerase and C-terminal kinase domain. The epimerase domain converts UDP-GlcNAc to ManNAc and kinase domain phosphorylates ManNAc to ManNAc phosphate
physiological function
the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production. It is different from the non-hydrolyzing enzymes for bacterial cell wall biosynthesis, and it is feedback inhibited by the downstream product CMP-Neu5Ac. Being a key enzyme that catalyzes the rate-limiting step of sialic acid biosynthesis, GNE plays an important role in regulation of cell-surface sialyation level by binding to the downstream product CMP-Neu5Ac. Regulation of cell-surface sialyation level by binding to the downstream product CMP-Neu5Ac. The feedback inhibition is highly positively cooperative and it does not affect the ManNAc kinase activity. By mediating cell-cell recognition, sialic acids are important in the development of nervous system. Structure and biosynthesis of sialic acid, overview
additional information
in the dimeric state GNE possess only kinase activity, in the hexameric state it displays both the epimerase and kinase activities while no activity is observed when GNE is present as a monomer
additional information
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active. Residue D143 is essential for catalytic activity
additional information
-
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active. Residue D143 is essential for catalytic activity
additional information
the comparison of the UDP-binding modes of the non-hydrolyzing and hydrolyzing UDP-GlcNAc epimerases might explain the mechanistic difference. While the epimerization reactions of both enzymes are similar, Arg113 and Ser302 of GNE are likely involved in product hydrolysis. Full-length modelling suggests a channel for ManNAc trafficking within the bifunctional enzyme, possible epimerase-kinase channel
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GLCNE_HUMAN
722
0
79275
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
additional information
additional information
isozyme sequence comparisons, secondary structures, and structure modeling, overview. Isozymes hGNE2 and hGNE7 display a 31-residue N-terminal extension compared to isozyme hGNE1, isozymes hGNE3 and hGNE8 contain a 53-residue N-terminal deletion and a 50-residue N-terminal extension compared to hGNE1
additional information
in the dimeric state GNE possess only kinase activity, in the hexameric state it displays both the epimerase and kinase activities while no activity is observed when GNE is present as a monomer
additional information
the epimerase part of the bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) folds into two Rossmann-like domains and forms dimers and tetramers
additional information
-
the epimerase part of the bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) folds into two Rossmann-like domains and forms dimers and tetramers
additional information
the full-length enzyme can form a dimer or tetramer, depending on the presence of UDP-GlcNAc and CMP-Neu5Ac. GNE forms a closed tetramer in the presence of UDP-GlcNAc and CMP-Neu5Ac. The complex crystal structure of the N-terminal epimerase part of human GNE shows a tetramer in which UDP binds to the active site and CMP-Neu5Ac binds to the dimer-dimer interface. The enzyme is locked in a tightly closed conformation. Each dimer further forms a tetramer with a crystallographic dyad-related dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with UDP-GlcNAc, X-ray diffraction crystal structure determination and analysis at 2.7 A resolution. Only UDP is observed in the active site of each monomer despite the use of UDP-GlcNAc in crystallization, presumably the substrate has been converted to ManNAc and UDP before it is trapped in the crystal
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A287V
naturally occuring mutation, pathogenic variant with possible effect on splicing, severe phenotype
C13S
naturally occuring heterozygous missense mutation of a Chinese distal myopathy (DMRV) patient, phenotype, overview. A c.131G->C homozygous missense mutation on exon 3, leading to a C13S amino acid change
C612F
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
C617Y
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
D112A
site-directed mutagenesis, the mutant shows 97.7% reduced activity compared to the wild-type enzyme
D143A
D176V
D227Y
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
D239E
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, , mild phenotype
D239N
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, mild phenotype
D244V
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, moderate phenotype
D316H
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
E33G
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, severe phenotype
G237S
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, moderate phenotype
G395R
naturally occuring mutation, pathogenic variant, effect on splicing is uncertain, severe phenotype
G576R
naturally occuring heterozygous missense mutation of a Chinese distal myopathy (DMRV) patient, phenotype, overview. A c.1726G->C heterozygous missense mutation, located on exon 10, resulting in a G576R amino acid change
G590R
naturally occuring mutation, pathogenic variant with possible effect on splicing, severe phenotype
G700R
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, severe phenotype
H179Q
naturally occuring mutation, pathogenic variant with possible effect on splicing, severe phenotype
H251P
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
K406N
naturally occuring mutation, pathogenic variant without effect on splicing, moderate phenotype
L682R
naturally occuring mutation, pathogenic variant without effect on splicing, severe phenotype
M60R
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, severe phenotype
M743T
a naturally occuring GNE myopathy mutant, located at the last exon 13 of the gene
M91V
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, mild phenotype
R512P
naturally occuring mutation, pathogenic variant without effect on splicing, moderate phenotype
R90X
naturally occuring mutation, pathogenic variant with possible effect on splicing, severe phenotype
S302A
site-directed mutagenesis, the mutant shows 87.1% reduced activity compared to the wild-type enzyme
V572L
Y465C
naturally occuring mutation, pathogenic variant with predicted deleterious effects on splicing, moderate phenotype
additional information
D176V
-
naturally occuring mutation involved in hereditary inclusion body myopathy, the mutant enzyme shows 83% reduced UDP-N-acetyl alpha-D-glucosamine epimerase activity compared to the wild-type, N-acetyl mannosamine kinase activity is also reduced but to a lesser extent
D176V
naturally occuring mutation in hereditary inclusion body myopathy (GNE myopathy) patients, phenotype, detailed overview. The mutant enzyme shows 85% reduced activity of the epimerase compared to the wild-type enzyme
V572L
-
naturally occuring mutation involved in hereditary inclusion body myopathy, the mutant enzyme shows 44% reduced UDP-N-acetyl alpha-D-glucosamine epimerase activity compared to the wild-type, N-acetyl mannosamine kinase activity is laos reduced to a higher extent
V572L
naturally occuring mutation in hereditary inclusion body myopathy (GNE myopathy) patients, phenotype, detailed overview. The mutant enzyme shows 44% reduced activity of the epimerase compared to the wild-type enzyme
additional information
-
efficient metabolic oligosaccharide engineering of glycoproteins by GNE enzyme knockdown by specific shRNAs in HEK293 cells. Stable GNE knockout via RNAi dramatically increases incorporation of N-acetylmannosamine analogues into glycoproteins of HEK293 cells. By means of these GNE-deficient cells highly sialylated glycoproteins can efficiently be decorated with reactive functional groups, which can be employed in bioorthogonal functionalization strategies for fluorescence labelling or biotinylation
additional information
-
endogenous GNE is knocked down in HEK-293 cells using GNE-specific shRNA
additional information
endogenous GNE is knocked down from normal HEK cells using shRNA, sialic acid quantitation in GNE overexpressed and knockdown cells, overview. Presence of r-wt-GNE and r-V572L-GNE proteins in nucleus while r-D176V-GNE primarily in the cytoplasm suggesting that mutation in the epimerase domain might prevent nuclear localization of GNE. Activation of endoplasmic reticulum stress response due to accumulation of misfolded mutated GNE protein. Hyposialylation caused due to mutation in GNE is affecting the membrane localization of beta1-integrin
additional information
genotyping of GNE myopathy index patients of a kohort, overview. Functional analysis of possibly abnormal splicing caused by c.717T>G mutation using an in vitro minigene splicing assay. Phenotype modelling
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene gne, genotyping, transcriptional analysis of the GNE variant c.717T>G, recombinant expression of splicing mutant c.717T>G in HEK 293 cells
gene gne, overexpresion of wild-type and mutant enzymes in HEK-293 cells, the endogenous GNE is knocked down in HEK-293 cells using GNE-specific shRNA
gene gne, recombinant expression of N-terminally FLAG3-tagged wild-type and mutant M743T in HEK-293 cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
a GNE-deficient HEK293 cell line proves its potential for the production of glycoproteins with modified sialylation, gaining therapeutic and diagnostic glycoproteins, and efficient application of metabolic oligosaccharide engineering
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moeller, H.; Boehrsch, V.; Lucka, L.; Hackenberger, C.P.; Hinderlich, S.
Efficient metabolic oligosaccharide engineering of glycoproteins by UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) knock-down
Mol. Biosyst.
7
2245-2251
2011
Homo sapiens
Yardeni, T.; Choekyi, T.; Jacobs, K.; Ciccone, C.; Patzel, K.; Anikster, Y.; Gahl, W.A.; Kurochkina, N.; Huizing, M.
Identification, tissue distribution, and molecular modeling of novel human isoforms of the key enzyme in sialic acid synthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase
Biochemistry
50
8914-8925
2011
Homo sapiens (Q9Y223)
Grover, S.; Arya, R.
Role of UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase (GNE) in beta1-integrin-mediated cell adhesion
Mol. Neurobiol.
50
257-273
2014
Homo sapiens
Ko, T.P.; Lai, S.J.; Hsieh, T.J.; Yang, C.S.; Chen, Y.
The tetrameric structure of sialic-acid-synthesizing UDP-GlcNAc 2-epimerase from Acinetobacter baumannii a comparative study with human GNE
J. Biol. Chem.
293
10119-10127
2018
Homo sapiens (Q9Y223), Homo sapiens
Grover, S.; Arya, R.
Role of UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase (GNE) in beta-integrin-mediated cell adhesion
Mol. Neurobiol.
50
257-273
2014
Homo sapiens (Q9Y223)
Harazi, A.; Becker-Cohen, M.; Zer, H.; Moshel, O.; Hinderlich, S.; Mitrani-Rosenbaum, S.
The interaction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) and alpha-actinin 2 is altered in GNE myopathy M743T mutant
Mol. Neurobiol.
54
2928-2938
2017
Homo sapiens (Q9Y223)
Liu, N.; Wang, Z.K.; Wang, H.X.; Li, Y.; Niu, Z.H.; Yu, X.F.
Muscle biopsy and UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene mutation analysis in two Chinese patients with distal myopathy with rimmed vacuoles
NeuroReport
26
598-601
2015
Homo sapiens (Q9Y223)
Chen, S.C.; Huang, C.H.; Lai, S.J.; Yang, C.S.; Hsiao, T.H.; Lin, C.H.; Fu, P.K.; Ko, T.P.; Chen, Y.
Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis
Sci. Rep.
6
23274
2016
Homo sapiens (Q9Y223)
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