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Information on EC 2.4.1.222 - O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase and Organism(s) Homo sapiens and UniProt Accession O00587
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2.4.1.222 O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferaseIUBMB Comments
The enzyme, found in animals and plants, is involved in the biosynthesis of the tetrasaccharides alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-alpha-L-Fuc and alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-alpha-L-Fuc, which are attached to L-Ser or L-Thr residues within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser/Thr-Cys in EGF-like domains in Notch and Factor-X proteins, respectively. The substrate is provided by EC 2.4.1.221, peptide-O-fucosyltransferase.
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Word Map
- 2.4.1.222
- notch
- glycosyltransferases
- somite
- mesoderm
- n-glycans
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presomitic
- n-acetylglucosamine
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somitogenesis
- udp-n-acetylglucosamine
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galactosyltransferase
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delta1
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jagged1
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paraxial
- dll1
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delta-like
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bisect
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fucose-specific
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unsegmented
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o-fucosylation
- n-acetyllactosamine
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o-mannose
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glcnac-ts
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delta-notch
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n-acetylglucosaminylated
- pomgnt1s
- poly-n-acetyllactosamine
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o-fucosyltransferase
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tetraantennary
- gnt-ivs
-
o-mannosylated
- synthesis
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
n-acetylglucosaminyltransferase, lunatic fringe, radical fringe, manic fringe, beta1,3-n-acetylglucosaminyltransferase, beta-1,3-n-acetylglucosaminyltransferase, fringe protein, glycosyltransferase fringe, beta1,3-n-acetylglucosaminyltransferase-2, fringe glycosyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetylglucosaminylferase, uridine diphosphoacetylglucosamine:fucosyglycoprotein beta1-3-
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beta1,3-acetylglucosaminyltransferase
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Fringe
fringe beta1,3 N-acetylglucosaminyltransferase
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fringe glycosyltransferase
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lunatic fringe glycosyltransferase
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manic fringe glycosyltransferase
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O-fucose-beta1,3-N-acetylglucosaminyltransferase
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O-fucosylpeptide beta-1,3-N-acetylglucosaminyltransferase
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radical fringe glycosyltransferase
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UDP-acetylglucosamine:fucosylglycoprotein
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UDP-D-GlcNAc:O-L-fucosylpeptide 3-beta-N-acetyl-D-glucosaminyltransferase
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UDP-GlcNAc:fucose beta1,3 N-acetylglucosaminyltransferase
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UDP-glucose:O-linked fucose beta1,3-glucosyltransferase
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Fringe
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
hexosyl group transfer
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-alpha-D-glucosamine:[protein with EGF-like domain]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine) 3-beta-N-acetyl-D-glucosaminyltransferase (configuration-inverting)
The enzyme, found in animals and plants, is involved in the biosynthesis of the tetrasaccharides alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-alpha-L-Fuc and alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-alpha-L-Fuc, which are attached to L-Ser or L-Thr residues within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser/Thr-Cys in EGF-like domains in Notch and Factor-X proteins, respectively. The substrate is provided by EC 2.4.1.221, peptide-O-fucosyltransferase.
CAS REGISTRY NUMBER
COMMENTARY
299203-70-6
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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
[factor VII]-fucose + UDP-alpha-D-N-acetylglucosamine
[factor VII]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
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residues on EGF repeat from factor VII
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?
[factor VII]-fucose + UDP-alpha-N-acetyl-2-amino-2-deoxy-D-glucose
[factor VII]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
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residues on EGF repeat from factor VII
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?
additional information
?
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the enzyme modifies EGF repeats in the Notch extracellular domain
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?
additional information
?
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the enzyme modifies EGF repeats in the Notch extracellular domain
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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transfers a beta-D-GlcNAc residue from UDP-D-GlcNAc to the fucose residue of a fucosylated protein acceptor
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?
additional information
?
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MFng transfers GlcNAc in beta1-3-linkage to O-fucose residues present on the EGF repeats. Free MFng shows a specific activity with fucose and with 4 mM 4-nitrophenyl-2-fucose as acceptors. Transfer of C2-keto-glucose to fucose residues on EGF repeat from factor VII by the hum-MFng, substrate specificity, overview
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?
additional information
?
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the enzyme adds N-acetylglucosamine to O-linked fucose residues on epidermal growth factor repeats of Notch
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?
additional information
?
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the enzyme adds N-acetylglucosamine to O-linked fucose residues on epidermal growth factor repeats of Notch
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
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
additional information
?
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the enzyme modifies EGF repeats in the Notch extracellular domain
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?
additional information
?
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the enzyme modifies EGF repeats in the Notch extracellular domain
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
-
the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
-
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?
additional information
?
-
the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
additional information
?
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transfers a beta-D-GlcNAc residue from UDP-D-GlcNAc to the fucose residue of a fucosylated protein acceptor
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?
additional information
?
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the enzyme adds N-acetylglucosamine to O-linked fucose residues on epidermal growth factor repeats of Notch
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?
additional information
?
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the enzyme adds N-acetylglucosamine to O-linked fucose residues on epidermal growth factor repeats of Notch
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?
additional information
?
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the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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-
?
additional information
?
-
the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
-
-
?
additional information
?
-
the enzyme transfers beta-D-N-acetylglucosaminyl residues to EGF repeats of Notch proteins, Notch receptors and ligands are transmembrane proteins
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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fringe requires a properly folded EGF repeat modified by O-fucose for its enzymatic activity
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
free MFng shows a specific activity of 0.5 pmol/min/mg of protein with 100 mM fucose as an acceptor and 0.6 pmol/min/mg of protein with 4 mM 4-nitrophenyl-2-fucose as an acceptor
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
manic fringe is highly expressed in claudin-low breast cancer
expression of Lfng in the prostate is relatively low compared with manic fringe and radical fringe but more restricted to basal epithelium
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme belongs to the family of glycosyltransferases. Binding to UDP and presence of DxD motif are two significant characteristics of glycosyltransferases
malfunction
Mfng silencing in claudin-low breast cancer CLBC cell lines reduces cell migration, tumorsphere formation, and in vivo tumorigenicity associated with a decrease in the stem-like cell population. Lfng deficiency induces basal-like breast cancer
physiological function
evolution
the enzyme belongs to the family of glycosyltransferases. Binding to UDP and presence of DxD motif are two significant characteristics of glycosyltransferases
malfunction
physiological function
additional information
physiological function
manic fringe promotes a claudin-low breast cancer phenotype through notch-mediated phosphoinositide kinase PIK3CG induction. The enzyme functions as an oncogen in claudin-low breast cancer. Phosphoinossitide kinase Pik3cg is a direct target of enzyme Mfng-enhanced Notch signaling in claudin-low breast cancer
physiological function
the enzyme adds N-acetylglucoseamine to O-linked fucose on epidermal growth factor repeats of Notch. Fringe is a Golgi resident glycosyltransferase that requires a specific DxD active site motif to function. It specifically binds to uridinediphosphate (UDP)
malfunction
knockdown of LFNG in DU-145 prostate cancer cells leads to expansion of CD44+CD24- and CD49f+CD24- stem/progenitor-like cell population associated with enhanced prostatosphere-forming capacity. The Lfng-null prostate shows down-regulation of prostatic tumor suppressor gene NKX3.1 and increased androgen receptor expression
malfunction
a Japanese Spondylocostal dysostosis case with multiple severe vertebral anomalies from cervical to sacral spine is a compound heterozygote for c.372delG (p.K124Nfs*) and c.601G>A (p.D201N) variants of the enzyme (LFNG), which encodes a glycosyltransferase (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase). The missense variant is in the DxD motif, an active-site motif of the glycosyltransferase, and its loss of the enzyme function is confirmed by an in vitro enzyme assay
physiological function
fringe genes code for O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferases that can add N-acetylglucosamine to O-linked fucose residues on epidermal growth factor repeats of Notch. This modification modulates specificity and sensitivity of Notch receptors for different ligands. Therefore, fringes are powerful regulators of ligand-mediated Notch signaling. Tumor-suppressive activity of lunatic fringe in prostate through differential modulation of Notch receptor activation. The enzyme plays a critical role in regulation of prostate epithelial differentiation and proliferation, as well as in prostate tumor suppression
physiological function
the enzyme adds N-acetylglucoseamine to O-linked fucose on epidermal growth factor repeats of Notch. Fringe is a Golgi resident glycosyltransferase that requires a specific DxD active site motif to function. It specifically binds to uridinediphosphate (UDP)
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
enzyme structure modelling using Mus musculus manic fringe crystal structure, PDB ID 2J0A, as template, comparison with the other human fringe enzymes, overview. Homology modeling and molecular dynamics simulation, overview
additional information
expression of LFNG and NKX3.1 are positively correlated in publically available human prostate cancer data sets
additional information
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expression of LFNG and NKX3.1 are positively correlated in publically available human prostate cancer data sets
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). MFNG_HUMAN
321
0
36202
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
33000
-
x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
53000
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x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
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x * 53000, recombinant galectin-1-hum-MFng fusion protein, SDS-PAGE, x * 33000, recombinant detagged MFng, SDS-PAGE
additional information
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
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
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
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
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
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
enzyme knockout by LFNG-small hairpin RNA (shRNA) construct in retroviral red fluorescent protein (RFP) vector targeting 5'-AGCAGGTGACGCTGAGCTACGGTATGTTT- 3' sequences of the human LFNG gene
additional information
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enzyme knockout by LFNG-small hairpin RNA (shRNA) construct in retroviral red fluorescent protein (RFP) vector targeting 5'-AGCAGGTGACGCTGAGCTACGGTATGTTT- 3' sequences of the human LFNG gene
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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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gene Lfng, Lfng is located at 7p22 arm of human chromosome
gene Rfng, Rfng is localized at 17q25 arm of human chromosome
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rampal, R.; Luther, K.B.; Haltiwanger, R.S.
Notch signaling in normal and disease States: possible therapies related to glycosylation
Curr. Mol. Med.
7
427-445
2007
Drosophila melanogaster, Homo sapiens, Mammalia
Chigira, Y.; Oka, T.; Okajima, T.; Jigami, Y.
Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains
Glycobiology
18
303-314
2008
Homo sapiens
Pasek, M.; Ramakrishnan, B.; Boeggeman, E.; Mercer, N.; Dulcey, A.E.; Griffiths, G.L.; Qasba, P.K.
The N-acetyl-binding pocket of N-acetylglucosaminyltransferases also accommodates a sugar analog with a chemical handle at C2
Glycobiology
22
379-388
2012
Homo sapiens
Zhang, S.; Chung, W.C.; Wu, G.; Egan, S.E.; Miele, L.; Xu, K.
Manic fringe promotes a claudin-low breast cancer phenotype through notch-mediated PIK3CG induction
Cancer Res.
75
1936-1943
2015
Homo sapiens (O00587), Homo sapiens
Azam, S.; Akhunzada, M.
Structure and dynamic studies of lunatic, manic and radical fringe
J. Mol. Liq.
188
186-195
2013
Homo sapiens (O00587), Homo sapiens (Q8NES3), Homo sapiens (Q9Y644)
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Zhang, S.; Chung, W.C.; Wu, G.; Egan, S.E.; Xu, K.
Tumor-suppressive activity of lunatic fringe in prostate through differential modulation of Notch receptor activation
Neoplasia
16
158-167
2014
Mus musculus (O09008), Homo sapiens (Q8NES3), Homo sapiens
Otomo, N.; Mizumoto, S.; Lu, H.F.; Takeda, K.; Campos-Xavier, B.; Mittaz-Crettol, L.; Guo, L.; Takikawa, K.; Nakamura, M.; Yamada, S.; Matsumoto, M.; Watanabe, K.; Ikegawa, S.
Identification of novel LFNG mutations in spondylocostal dysostosis
J. Hum. Genet.
64
261-264
2019
Homo sapiens (Q8NES3)
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