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EC Tree
IUBMB 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.
The taxonomic range for the selected organisms is: Drosophila melanogaster 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, maniac fringe,
more
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beta1,3-N-acetylglucosaminyltransferase
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acetylglucosaminylferase, uridine diphosphoacetylglucosamine:fucosyglycoprotein beta1-3-
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beta-1,3-N-acetylglucosaminyltransferase
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beta1,3-acetylglucosaminyltransferase
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beta1,3-N-acetylglusoaminyltransferase
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fringe beta1,3 N-acetylglucosaminyltransferase
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fringe glycosyltransferase
lunatic fringe glycosyltransferase
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manic fringe glycosyltransferase
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N-acetylglucosaminyltransferase
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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 glycosyltransferase
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fringe glycosyltransferase
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UDP-N-acetyl-alpha-D-glucosamine + [protein with EGF-like domain]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine) = UDP + [protein with EGF-like domain]-3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl]-(L-serine/L-threonine)
UDP-N-acetyl-alpha-D-glucosamine + [protein with EGF-like domain]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine) = UDP + [protein with EGF-like domain]-3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl]-(L-serine/L-threonine)
mechanism
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UDP-N-acetyl-alpha-D-glucosamine + [protein with EGF-like domain]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine) = UDP + [protein with EGF-like domain]-3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl]-(L-serine/L-threonine)
co-expressing of Notch and Fringe in Drosophila SL2 cells results in an increase of binding of ligand Delta to Notch
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UDP-N-acetyl-alpha-D-glucosamine + [protein with EGF-like domain]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine) = UDP + [protein with EGF-like domain]-3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-alpha-L-fucosyl]-(L-serine/L-threonine)
GlcNAc-transfer activity of Fringe is essential for it to modulate Notch signalling
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hexosyl group transfer
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hexosyl group transfer
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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.
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
epidermal growth factor-like sequence repeats-O-fucose + UDP-GlcNAc
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Drosophila Fringe, Lunic Fringe, Manic Fringe
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factor VII EGF repeat + UDP-D-GlcNAc
beta-D-glucosaminyl-factor VII EGF repeat + UDP
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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
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L-fucose + GlcNAc
GlcNAc-beta-1,3-fucitol
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
Notch1 + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch1 + UDP
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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
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O-fucose residues on Delta Notch ligand + UDP-GlcNAc
GlcNAc-beta-1,3-fucitol-Delta Notch
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in vitro
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O-fucose residues on Serrate Notch ligand + UDP-GlcNAc
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in vitro
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O-linked fucose on the epidermal growth factor-like sequence repeats of Notch + GlcNAc
GlcNAc-beta-1,3-fucitol-Notch
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p-nitrophenyl-alpha-L-fucose + UDP-GlcNAc
GlcNAc-beta-1,3-fucitol + p-nitrophenol + UDP
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p-nitrophenyl-alpha-L-fucose structurally mimics O-linked fucose, Lunic Fringe, Manic Fringe, Drosophila Fringe
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UDP-beta-D-GlcNAc + fucosyl-protein
UDP + O-beta-D-GlcNAc-fucosyl-protein
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[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
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additional information
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
enzyme modulates signaling through Notch receptors by modifying O-linked fucose on epidermal growth factor-like domains
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
Notch protein is O-fucosylated at a serine or threonine residue in the epidermal growth factor-like domain
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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enzyme completely inhibits binding of Notch protein to its serrate ligands by capping of O-fucose sites, regulation of enzyme activity via expression level in correspondance to the expression level of protein O-fucosyltransferase
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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enzyme plays a key role in the specification of boundaries during development by modulating the ability of Notch ligands to activate Notch receptors
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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Fringe and protein O-fucosyltransferase regulate Notch signaling via binding to cell surface Notch receptors, overview
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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Notch protein is O-fucosylated at a serine or threonine residue in epidermal growth factor-like repeats, identification of glycosylation sites
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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Notch protein is O-fucosylated at a serine or threonine residue in the epidermal growth factor-like domain
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additional information
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further substrate: recombinant epidermal growth factor repeat from the serum protein factor VII modified with O-linked fucose
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additional information
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no substrates: p-nitrophenyl-galactose, p-nitrophenyl-glucose
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additional information
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activity on different factor VII EGF repeat containing protein fragments, overview
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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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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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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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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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O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255
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additional information
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Drosophila Fringe glycosyltransferase adds GlcNAc specifically to the O-fucose residues of Notch transmembrane proteins
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
enzyme modulates signaling through Notch receptors by modifying O-linked fucose on epidermal growth factor-like domains
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP
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additional information
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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enzyme completely inhibits binding of Notch protein to its serrate ligands by capping of O-fucose sites, regulation of enzyme activity via expression level in correspondance to the expression level of protein O-fucosyltransferase
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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enzyme plays a key role in the specification of boundaries during development by modulating the ability of Notch ligands to activate Notch receptors
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Notch + UDP-D-GlcNAc
beta-D-glucosaminyl-Notch + UDP
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Fringe and protein O-fucosyltransferase regulate Notch signaling via binding to cell surface Notch receptors, overview
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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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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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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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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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O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255
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additional information
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Drosophila Fringe glycosyltransferase adds GlcNAc specifically to the O-fucose residues of Notch transmembrane proteins
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iroquois transcription factor
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Iro
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sloppy-paired transcription factor
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Slp
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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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additional information
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Lunic Fringe has a higher specific activity than either Drosophila Fringe and Manic Fringe
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SwissProt
brenda
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brenda
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brenda
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brenda
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brenda
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brenda
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ventral eye disc cell
brenda
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brenda
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microsomal fraction enriched for Golgi membrane
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brenda
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malfunction
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Fringe-dependent Notch signaling is disrupted in a nac and Efr double mutant, reduction of Notch signaling may account for the developmental defects associated with CDG IIc
metabolism
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Fringe-dependent Notch signaling, overview
physiological function
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the O-fucose and O-glucose glycans on Notch occur at specific consensus sequences within the context of EGF repeats, which make up the majority of the Notch extracellulr domain. O-GlcNAc modification, a third form of O-glycosylation, occurs on EGF repeats, on hydroxy amino acids between the fifth and sixth conserved Cys of an EGF repeat. Similar to O-fucosylation, the major effect of Fringe-mediated O-fucose elongation appears to be modulation of Notch-ligand binding, whereby Delta activation of Notch is potentiated, while signaling via Serrate is inhibited. GlcNAc is the terminal sugar added to O-fucose residues on Drosophila Notch, and the disaccharide is sufficient for observing a Fringe effect, In vitro extension to trisaccharide causes no change in in vitro ligand binding as assessed in vitro
physiological function
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Drosophila Fringe is a glycosyltransferase, which adds GlcNAc specifically to the O-fucose residues on EGF-like repeats of Notch protein. The O-fucose is important as an acceptor for GlcNAc. The GlcNAc modification modulates the binding between Notch and two different ligands for Notch. This modulation of Notch-ligand interaction is required for region-specific activation of Notch signaling, which is essential for morphogenesis of various organs
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DSOR1_DROME
396
0
43870
Swiss-Prot
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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
additional information
construction and genetic analysis of mutated alleles, several mutants with introduced stop codons, mutant phenotypes analysis, mutants show altered wing vein numbers and structure, overview
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on a His-Select nickel affinity gel
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gene fng, DNA and amino acid sequence determination and analysis
expressed in Drosophila S2 cells
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full-length, His-tagged FNG is expressed in S2 cells from a pMTHy vector construct
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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
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Moloney, D.J.; Panin, V.M.; Johnston, S.H.; Chen, J.; Shao, U.; Wilson, R.; Wang, Y.; Stanley, P.; Irvine, K.D.; Haltwanger, R.S.; Vogt, T.F.
Fringe is a glycosyltransferase that modifies Notch
Nature
406
369-375
2000
Drosophila melanogaster, Mammalia
brenda
Bruckner, K.; Perez, L.; Clausen, H.; Cohen, S.
Glycosyltransferase activity of Fringe modulates Notch-Delta interactions
Nature
406
411-415
2000
Drosophila melanogaster
brenda
Panin, V.M.; Shao, L.; Lei, L.; Moloney, D.J.; Irvine, K.D.; Haltiwanger, R.S.
Notch ligands are substrates for protein O-fucosyltransferase-1 and Fringe
J. Biol. Chem.
277
29945-29952
2002
Drosophila melanogaster, Mammalia
brenda
Okajima, T.; Xu, A.; Irvine, K.D.
Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe
J. Biol. Chem.
278
42340-42345
2003
Drosophila melanogaster
brenda
Shao, L.; Moloney, D.J.; Haltiwanger, R.
Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region
J. Biol. Chem.
278
7775-7782
2003
Drosophila melanogaster
brenda
Xu, A.; Lei, L.; Irvine, K.D.
Regions of Drosophila Notch that contribute to ligand binding and the modulatory influence of Fringe
J. Biol. Chem.
280
30158-30165
2005
Drosophila melanogaster
brenda
Correia, T.; Papayannopoulos, V.; Panin, V.; Woronoff, P.; Jiang, J.; Vogt, T.F.; Irvine, K.D.
Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila
Proc. Natl. Acad. Sci. USA
100
6404-6409
2003
Drosophila melanogaster (Q24324)
brenda
Okajima, T.; Reddy, B.; Matsuda, T.; Irvine, K.D.
Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling
BMC Biol.
6
1-10
2008
Drosophila melanogaster
brenda
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
brenda
Sato, A.; Tomlinson, A.
Dorsal-ventral midline signaling in the developing Drosophila eye
Development
134
659-667
2007
Drosophila melanogaster
brenda
Xu, A.; Haines, N.; Dlugosz, M.; Rana, N.A.; Takeuchi, H.; Haltiwanger, R.S.; Irvine, K.D.
In vitro reconstitution of the modulation of Drosophila Notch-ligand binding by Fringe
J. Biol. Chem.
282
35153-35162
2007
Drosophila melanogaster
brenda
Rana, N.A.; Haltiwanger, R.S.
Fringe benefits: functional and structural impacts of O-glycosylation on the extracellular domain of Notch receptors
Curr. Opin. Struct. Biol.
21
583-589
2011
Drosophila melanogaster, Mus musculus
brenda
Matsumoto, K.; Ishio, A.; Matsuno, K.
O-Fucose glycan in Drosophila Notch signaling
Glycosci. Biol. Med.
2015
841-847
2015
Drosophila melanogaster
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brenda