Information on EC 2.4.1.222 - O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.4.1.222
-
RECOMMENDED NAME
GeneOntology No.
O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
transfers a beta-D-GlcNAc residue from UDP-D-GlcNAc to the fucose residue of a fucosylated protein acceptor
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexosyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Other types of O-glycan biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-D-GlcNAc:O-L-fucosylpeptide 3-beta-N-acetyl-D-glucosaminyltransferase
O-Fucosylpeptide 3-beta-N-acetylglucosaminyltransferases are the products of fringe genes. O-linked fucose is an unusual form of glycosylation where the fucose is attached directly to proteins through the hydroxy groups of Ser or Thr residues.
CAS REGISTRY NUMBER
COMMENTARY hide
299203-70-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
sea urchin
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the family of glycosyltransferases. Binding to UDP and presence of DxD motif are two significant characteristics of glycosyltransferases; the enzyme belongs to the family of glycosyltransferases. Binding to UDP and presence of DxD motif are two significant characteristics of glycosyltransferases; the enzyme belongs to the family of glycosyltransferases. Binding to UDP and presence of DxD motif are two significant characteristics of glycosyltransferases
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
epidermal growth factor-like sequence repeats-O-fucose + UDP-GlcNAc
?
show the reaction diagram
factor VII EGF repeat + UDP-D-GlcNAc
beta-D-glucosaminyl-factor VII EGF repeat + UDP
show the reaction diagram
-
Manic fringe modifies O-fucose on mouse Notch1 at extracellular epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region expressed in Lec1 cells
-
-
?
L-fucose + GlcNAc
GlcNAc-beta-1,3-fucitol
show the reaction diagram
-
-
-
-
?
Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
show the reaction diagram
Notch1 + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch1 + UDP
show the reaction diagram
-
Manic fringe modifies O-fucose on mouse Notch1 at extracellular epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region expressed in Lec1 cells
-
-
?
O-fucose residues on Delta Notch ligand + UDP-GlcNAc
GlcNAc-beta-1,3-fucitol-Delta Notch
show the reaction diagram
O-fucose residues on Jagged1 Notch ligand + UDP-GlcNAc
GlcNAc-beta1,3-fucitol-Jagged1 Notch
show the reaction diagram
-
human Jagged1 ligand, exogenous expressed in Chinese hamster ovary Lec1 cells, experiment in vivo
-
?
O-fucose residues on Serrate Notch ligand + UDP-GlcNAc
?
show the reaction diagram
-
in vitro
-
-
?
O-linked fucose on the epidermal growth factor-like sequence repeats of Notch + GlcNAc
GlcNAc-beta-1,3-fucitol-Notch
show the reaction diagram
p-nitrophenyl-alpha-L-fucose + UDP-beta-D-GlcNAc
GlcNAc-beta-1,3-fucitol + p-nitrophenol + UDP
show the reaction diagram
-
-
-
?
p-nitrophenyl-alpha-L-fucose + UDP-GlcNAc
GlcNAc-beta-1,3-fucitol + p-nitrophenol + UDP
show the reaction diagram
UDP-beta-D-GlcNAc + fucosyl-protein
UDP + O-beta-D-GlcNAc-fucosyl-protein
show the reaction diagram
[factor VII]-fucose + UDP-alpha-D-N-acetylglucosamine
[factor VII]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
show the reaction diagram
-
residues on EGF repeat from factor VII
-
-
?
[factor VII]-fucose + UDP-alpha-N-acetyl-2-amino-2-deoxy-D-glucose
[factor VII]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
show the reaction diagram
-
residues on EGF repeat from factor VII
-
-
?
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
show the reaction diagram
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Manganese
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-galactose
-
Gal is required for the enhancement of Notch signaling by LFNG, whereas Gal inhibits the enhancement of DLL1-induced NOTCH signaling by MFNG
iroquois transcription factor
-
Iro
-
additional information
-
enzyme expression is perturbed by injection of fringe morpholino antisense oligonucleotide resulting in a reduced number of secondary mesenchym cells and altered endoderm and mesoderm specification, as well as decreased and delayed archenteron invagination
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-galactose
-
Gal is required for the enhancement of Notch signaling by LFNG, whereas Gal inhibits the enhancement of DLL1-induced NOTCH signaling by MFNG
sloppy-paired transcription factor
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Slp
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additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00116 - 0.129
p-nitrophenyl-alpha-L-fucose
0.0343 - 0.0707
UDP-beta-D-GlcNAc
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.08
UDP-beta-D-GlcNAc
Mus musculus
O09008
wild-type, pH 6.8, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
UDP
wild-type, pH 6.8, 37C
0.096
UMP
wild-type, pH 6.8, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29
-
enzyme assay
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
in the developing brain, Lfng is expressed in self-renewing progenitors
Manually annotated by BRENDA team
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manic fringe is highly expressed in claudin-low breast cancer
Manually annotated by BRENDA team
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expression is relatively constant during germ layer development and occurs in all cells, but becomes restricted during gastrulation
Manually annotated by BRENDA team
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isoform lunatic fringe Lfng is expressed by progenitors in neurogenic regions and downregulated in cells that have initiated neuronal differentiation
Manually annotated by BRENDA team
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Lfng is expressed in the distal lung during saccular development
Manually annotated by BRENDA team
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during Drosophila oogenesis
Manually annotated by BRENDA team
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expression levels of three Fringe homologues in naive CD4+T cells in asthmatic rats, overview. Radical Fringe (Rfng) is highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) are expressed at low levels
Manually annotated by BRENDA team
additional information
-
distribution, Fringe is expressed in both the signaling and the receiving cells during the first Delta-Notch signal
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
fringe is a secreted protein; fringe is a secreted protein; fringe is a secreted protein
-
Manually annotated by BRENDA team
-
apical and surface membranes
Manually annotated by BRENDA team
-
microsomal fraction enriched for Golgi membrane
-
Manually annotated by BRENDA team
additional information
-
secreted protein
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33000
-
x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
34100
-
predicted size of the fully processed, mature fragment
35000
-
determined by SDS-PAGE and Western Blot analysis
43600
-
predicted size of full-length unprocessed LFNG protein
53000
-
x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
additional information
enzyme structure homology modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview; enzyme structure homology modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview; enzyme structure homology modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
presence of two N-linked glycans
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of mouse Manic Fringe bound to UDP and Mn2+
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sitting-drop vapour diffusion method. Abolishing the glycosylation sites by site-directed mutagenesis was necessary in order to obtain orthorhombic crystals that diffracted to 1.8 A resolution. Crystals belonged to space group P2(1)2(1)2. The unit-cell parameters (a = 162.6, b = 41.4, c = 38.8 A) are consistent with the presence of one molecule in the asymmetric unit
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
on a His-Select nickel affinity gel
-
recombinant enzyme
-
recombinant fusion protein galectin-1-hum-MFng from Escherichia coli strain Rosetta (DE3) pLysS, the fusion protein is cleaved with Tev protease to release the MFng protein, further purification by UDP-agarose chromatography
-
recombinant His-tagged enzyme by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalytic domain of murine Manic Fringe is expressed in the baculovirus/insect-cell system as a secreted protein
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coexpression of Flag-tagged DLL3 and HA-tagged LFNG in CHO cells, the two proteins coprecipitate
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DNA acid sequence determination and analysis, expression as insoluble His-tagged protein in Escherichia coli strain XL1-Blue
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expressed in Drosophila S2 cells
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expression of MFeng as soluble protein in fusion with galectin-1 from pLgals1-hum-MFng in Escherichia coli Rosetta (DE3) pLysS
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expression of Radical Fringe, Lunatic Fringe, and Manic Fringe in HEK 293T cells and NIH 3T3 cells
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full-length, His-tagged FNG is expressed in S2 cells from a pMTHy vector construct
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gene fng, DNA and amino acid sequence determination and analysis
gene Lfng, Lfng is located at 7p22 arm of human chromosome; gene Mfng, Mfng maps to human chromosome 22q13.1; gene Rfng, Rfng is localized at 17q25 arm of human chromosome
gene LFNG, quantitative RT-PCR enzyme expression analysis
genes lfng and mfng, expression in wild-type CHO cells, in Lec1.3C, Lec2.6A, Lec8.3D, and Lec20.15C CHO glycosylation mutant lines, and in Lec8 and Lec20 CHO mutant lines
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Lfng overexpression in transgenic mouse model
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Lunatic Fringe and Manic Fringe expressed in Chinese hamster ovary Lec1 cells
-
Manic Fringe stable expressed in Chinese hamster ovary Lec1 cells
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mouse FRINGE coding sequences are ligated into pcDNA3 for transfection of NIH3T3 cells
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Notch alone or Fringe alone expressed in Drosophila SL2 cells or Notch and Fringe co-expressed in Drosophila SL2 cells
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overexpression in S2 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the expression of Lfng does not require Notch activity, but rather is regulated downstream of proneural genes that are widely expressed by neural progenitors
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D327N
EMS mutagenesis, transheterozygote, mutation on allele 14, lethal phenotype
E220K
EMS mutagenesis, transheterozygote, mutation on allele 3, lethal phenotype
G295D
EMS mutagenesis, transheterozygote, mutation on allele L81, lethal phenotype
K196E
EMS mutagenesis, transheterozygote, mutation on allele 11, lethal phenotype
K196N
EMS mutagenesis, transheterozygote, mutation on allele 11, lethal phenotype
L213F
EMS mutagenesis, transheterozygote, mutation on allele L83, lethal phenotype
L398Q
EMS mutagenesis, transheterozygote, mutation on allele 2, phenotype overview
S350T
EMS mutagenesis, transheterozygote, mutation on allele 1, lethal phenotype
T184M
EMS mutagenesis, transheterozygote, phenotype overview
A175V
short loop mutant
A235Y
long loop mutant
C290S
active site mutant to short loop side of residue D289
D288A
active site mutant to short loop side of residue D289, activity too low to measure
D289E
active site mutant, catalytically inactive
E237A
long loop mutant
F251S
active site mutant, catalytically inactive
F251Y
active site mutant to short loop side of residue D289
G254A
active site mutant to short loop side of residue D289
G334H
donor specificity mutant, 94.6% of wild-type UDP-beta-D-GlcNAc utilization, 78.0% of wild-type UDP-Glc utilization
H171A
short loop mutant
H171D
short loop mutant
H313A
donor specificity mutant, 6.2% of wild-type UDP-beta-D-GlcNAc utilization, 75.9% of wild-type UDP-Glc utilization
H313A/G334H
donor specificity mutant, 3.1% of wild-type UDP-beta-D-GlcNAc utilization, 34.7% of wild-type UDP-Glc utilization
I233A
long loop mutant
L176A
short loop mutant
L229Q
long loop mutant
L314R
donor specificity mutant, 21.7% of wild-type UDP-beta-D-GlcNAc utilization, 119.5% of wild-type UDP-Glc utilization
S128V
short loop mutant
S168A
short loop mutant
S228A
active site mutant to short loop side of residue D289
S228L
active site mutant, catalytically inactive
s228T
active site mutant to short loop side of residue D289
S228Y
active site mutant, catalytically inactive
S312T
donor specificity mutant, 1.9% of wild-type UDP-beta-D-GlcNAc utilization, 18.1% of wild-type UDP-Glc utilization
T253A
active site mutant, catalytically inactive
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
the Notch signaling pathway is involved in numerous developmental cascades in mammals, mutations in the pathway have been implicated in a variety of Human diseases, like CADASIL, spondylocostal dysostosis, alagille syndrome, cancer and multiple sclerosis
synthesis
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use of manic fringe in engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae for production of O-fucosylated epidermal growth factor domains. In the system, manic fringe facilitates the addition of N-acetylglucosamine to the EGF domain from factor IX but not from factor VII
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