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Information on EC 5.1.3.14 - UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) and Organism(s) Homo sapiens and UniProt Accession Q9Y223

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IUBMB Comments
This bacterial enzyme catalyses the reversible interconversion of UDP-GlcNAc and UDP-ManNAc. The latter is used in a variety of bacterial polysaccharide biosyntheses. cf. EC 3.2.1.183, UDP-N-acetylglucosamine 2-epimerase (hydrolysing).
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Homo sapiens
UNIPROT: Q9Y223
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
udp-n-acetylglucosamine 2-epimerase/n-acetylmannosamine kinase, udp-glcnac 2-epimerase, udp-n-acetylglucosamine 2-epimerase, udp-n-acetylglucosamine-2-epimerase/n-acetylmannosamine kinase, udp-glcnac 2-epimerase/mannac kinase, gne/mnk, cap5p, udp-glcnac-2-epimerase, udp-n-acetylglucosamine-2-epimerase, nmsaca, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Epimerase, uridine diphosphoacetylglucosamine 2-
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GNE/MNK
UDP-GlcNAc 2'-epimerase
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UDP-GlcNAc 2-epimerase
UDP-GlcNAc 2-epimerase/ManAc kinase
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bifunctional enzyme
UDP-GlcNAc 2-epimerase/ManNAc kinase
UDP-GlcNAc 2-epimerase/ManNAc kinase gene
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UDP-GlcNAc-2-epimerase
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UDP-N-acetylglucosamine 2'-epimerase
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UDP-N-acetylglucosamine 2-epimerase
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UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase
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Uridine diphosphate-N-acetylglucosamine-2'-epimerase
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Uridine diphospho-N-acetylglucosamine 2'-epimerase
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Uridine diphosphoacetylglucosamine 2'-epimerase
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additional information
bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
epimerization
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SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-alpha-D-glucosamine 2-epimerase
This bacterial enzyme catalyses the reversible interconversion of UDP-GlcNAc and UDP-ManNAc. The latter is used in a variety of bacterial polysaccharide biosyntheses. cf. EC 3.2.1.183, UDP-N-acetylglucosamine 2-epimerase (hydrolysing).
CAS REGISTRY NUMBER
COMMENTARY hide
9037-71-2
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
UDP-GlcNAc
ManNAc + UDP
show the reaction diagram
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sialic acid biosynthetic pathway
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-
?
UDP-N-acetyl-D-glucosamine
?
show the reaction diagram
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enzyme of the N-acetylneuraminic acid metabolic pathway
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-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
show the reaction diagram
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
show the reaction diagram
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-GlcNAc
ManNAc + UDP
show the reaction diagram
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sialic acid biosynthetic pathway
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-
?
UDP-N-acetyl-D-glucosamine
?
show the reaction diagram
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enzyme of the N-acetylneuraminic acid metabolic pathway
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-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
show the reaction diagram
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reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles
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-
?
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
show the reaction diagram
additional information
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CMP-Neu5Ac
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feedback inhibition
CMP-sialic acid
GNE/MNK is feedback inhibited by binding of the downstream product, CMP-sialic acid, in its allosteric site. The allosteric regulation by CMP-sialic acid involves residues D255, E260, R263, R266, K268, and N275
additional information
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UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bisubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
HIV-infected. Downregulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in hyposialylated HIV-infected T cells
Manually annotated by BRENDA team
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skin
Manually annotated by BRENDA team
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human epithel, HEK AD293
Manually annotated by BRENDA team
additional information
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GNE2 and GNE3 display tissue-specific expression patterns
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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associated with the cytoplasmic side
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
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the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GLCNE_HUMAN
722
0
79275
Swiss-Prot
-
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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recombinant splice variant hGNE1, mixture of tetramers and dimers in ratio of 3:1. Recombinant splice variant hGNE2, dimer. Gel filtration expreriments
tetramer
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recombinant splice variant hGNE1, mixture of tetramers and dimers in ratio of 3:1, gel filtration
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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phosphorylation of GNE by protein kinase C
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A630T
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mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 70-80% of wild-type activity
A631V
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a naturally occuring missense mutation in exon 11 of the GNE gene of a patient with hereditary inclusion body myopathy
C303V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
C303X
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D176V
D177C
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mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
D225N
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D378Y
E2G
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a naturally occuring missense mutation in exon 2 of the GNE gene of a patient with hereditary inclusion body myopathy
G135V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
G135V/R246W
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mutation in patients with hereditary inclusion body myopathy: G135V/R246W (GNE/GNE domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 38% of wild-type, N-acetylmannosamine kinase activity is 72% of wild-type
G206S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
G708S
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mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 50% of wild-type activity
G89R
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
H132Q
I142T
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a naturally occuring missense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
I200F
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
I241S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
I298T
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a naturally occuring missense mutation in exon 5 of the GNE gene of a patient with hereditary inclusion body myopathy
I472T
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mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 50% of wild-type activity
L379H
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
L556S
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a naturally occuring missense mutation in exon 10 of the GNE gene of a patient with hereditary inclusion body myopathy
M171V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
M29T
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
M712T
M712T/M712T
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M712T/M712T (MNK/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 83% of wild-type, N-acetylmannosamine kinase activity is 55% of wild-type
P27S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
P283S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
P36L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
Q436X
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a naturally occuring nonsense mutation in exon 8 of the GNE gene of a patient with hereditary inclusion body myopathy
R11W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R129Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R162C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R177C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R202L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R246Q
R246W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R263L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R266Q
R266W
R277C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R306Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R335W
R71W
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a naturally occuring missense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
R8X
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a naturally occuring nonsense mutation in exon 2 of the GNE gene of a patient with hereditary inclusion body myopathy
S615X
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a naturally occuring nonsense mutation in exon 11 of the GNE gene of a patient with hereditary inclusion body myopathy
V216A
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V216A/A631V
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V216A/A631V (GNE/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 48% of wild-type, N-acetylmannosamine kinase activity is 63% of wild-type
V331A
V367I
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V572L
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mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 70-80% of wild-type activity
V696M
W204X
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a naturally occuring nonsense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
Y675H
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a naturally occuring missense mutation in exon 12 of the GNE gene of a patient with hereditary inclusion body myopathy
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequencing of the GNE coding region of 64 symptomatic patients with autosomal recessive hereditary inclusion body myopathy, genotyping-phenotyping of patients from different ethnics, overview
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expression in Escherichia coli
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expression of M712T mutant enzyme in Sf9 insect cells
expression of wild-type and mutant enzymes (C13S, H132Q, D176V, D177C, V331A, I472T, G708S, A631V, V572L and A630T) in COS-7 cells
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splice variant hGNE2, expression in insect and mammalian cells. Splice variant hGNE3, expression in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase interacts with the non-muscle form of alpha-actinin, alpha-actinin-1, in mature skeletal muscle cells. No significant difference in the binding of alpha-actinin-1 with either wild-type or mutant enzyme, and therefore no conclusions wether and how the interaction is relevant to the muscle-restricted pathology of hereditary inclusion body myopathy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Scocca, J.R.
Identification of N-acetylhexosamines produced by enzymes of the N-acetylneuraminic acid metabolic pathway by borate complex anion-exchange chromatography of the corresponding N-acetylhexosaminitols
Anal. Biochem.
156
61-66
1986
Homo sapiens
Manually annotated by BRENDA team
Lucka, L.; Krause, M.; Danker, K.; Reutter, W.; Horstkorte, R.
Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis
FEBS Lett.
454
341-344
1999
Homo sapiens (Q9Y223)
Manually annotated by BRENDA team
Keppler, O.T.; Hinderlich, S.; Langner, J.; Schwartz-Albiez, R.; Reutter, W.; Pawlita, M.
UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation
Science
284
1372-1376
1999
Homo sapiens
Manually annotated by BRENDA team
Krause, S.; Hinderlich, S.; Amsili, S.; Horstkorte, R.; Wiendl, H.; Argov, Z.; Mitrani-Rosenbaum, S.; Lochmueller, H.
Localization of UDP-GlcNAc 2-epimerase/ManAc kinase (GNE) in the Golgi complex and the nucleus of mammalian cells
Exp. Cell Res.
304
365-379
2005
Homo sapiens
Manually annotated by BRENDA team
Giordanengo, V.; Ollier, L.; Lanteri, M.; Lesimple, J.; March, D.; Thyss, S.; Lefebvre, J.C.
Epigenetic reprogramming of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) in HIV-1-infected CEM T cells
FASEB J.
18
1961-1963
2004
Homo sapiens (Q9Y223)
Manually annotated by BRENDA team
Hinderlich, S.; Salama, I.; Eisenberg, I.; Potikha, T.; Mantey, L.R.; Yarema, K.J.; Horstkorte, R.; Argov, Z.; Sadeh, M.; Reutter, W.; Mitrani-Rosenbaum, S.
The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy
FEBS Lett.
566
105-109
2004
Homo sapiens (Q9Y223), Homo sapiens
Manually annotated by BRENDA team
Sparks, S.E.; Ciccone, C.; Lalor, M.; Orvisky, E.; Klootwijk, R.; Savelkoul, P.J.; Dalakas, M.C.; Krasnewich, D.M.; Gahl, W.A.; Huizing, M.
Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy
Glycobiology
15
1102-1110
2005
Homo sapiens
Manually annotated by BRENDA team
Noguchi, S.; Keira, Y.; Murayama, K.; Ogawa, M.; Fujita, M.; Kawahara, G.; Oya, Y.; Imazawa, M.; Goto, Y.I.; Hayashi, Y.K.; Nonaka, I.; Nishino, I.
Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles
J. Biol. Chem.
279
11402-11407
2004
Homo sapiens
Manually annotated by BRENDA team
Reinke, S.O.; Hinderlich, S.
Prediction of three different isoforms of the human UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
FEBS Lett.
581
3327-3331
2007
Homo sapiens (Q9Y223), Homo sapiens, Mus musculus (Q3UW64)
Manually annotated by BRENDA team
Wang, Z.; Sun, Z.; Li, A.V.; Yarema, K.J.
Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation
J. Biol. Chem.
281
27016-27028
2006
Homo sapiens
Manually annotated by BRENDA team
Reinke, S.O.; Eidenschink, C.; Jay, C.M.; Hinderlich, S.
Biochemical characterization of human and murine isoforms of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE)
Glycoconj. J.
26
415-422
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Amsili, S.; Zer, H.; Hinderlich, S.; Krause, S.; Becker-Cohen, M.; MacArthur, D.G.; North, K.N.; Mitrani-Rosenbaum, S.
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) binds to alpha-actinin 1: novel pathways in skeletal muscle?
PLoS ONE
3
e2477
2008
Homo sapiens
Manually annotated by BRENDA team
Reinke, S.O.; Lehmer, G.; Hinderlich, S.; Reutter, W.
Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
Biol. Chem.
390
591-599
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Voermans, N.C.; Guillard, M.; Doedee, R.; Lammens, M.; Huizing, M.; Padberg, G.W.; Wevers, R.A.; van Engelen, B.G.; Lefeber, D.J.
Clinical features, lectin staining, and a novel GNE frameshift mutation in hereditary inclusion body myopathy
Clin. Neuropathol.
29
71-77
2010
Homo sapiens
Manually annotated by BRENDA team
Saechao, C.; Valles-Ayoub, Y.; Esfandiarifard, S.; Haghighatgoo, A.; No, D.; Shook, S.; Mendell, J.R.; Rosales-Quintero, X.; Felice, K.J.; Morel, C.F.; Pietruska, M.; Darvish, D.
Novel GNE mutations in hereditary inclusion body myopathy patients of non-Middle Eastern descent
Genet. Test. Mol. Biomarkers
14
157-162
2010
Homo sapiens
Manually annotated by BRENDA team
Kurochkina, N.; Yardeni, T.; Huizing, M.
Molecular modeling of the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase and predictions of structural effects of mutations associated with HIBM and sialuria
Glycobiology
20
322-337
2010
Homo sapiens (Q9Y223), Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team