2.4.1.222: O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
This is an abbreviated version!
For detailed information about O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, go to the full flat file.
Word Map on EC 2.4.1.222
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2.4.1.222
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notch
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glycosyltransferases
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somite
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mesoderm
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n-glycans
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presomitic
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n-acetylglucosamine
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somitogenesis
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udp-n-acetylglucosamine
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galactosyltransferase
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delta1
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jagged1
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paraxial
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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
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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
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pomgnt1s
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poly-n-acetyllactosamine
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o-fucosyltransferase
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tetraantennary
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gnt-ivs
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o-mannosylated
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synthesis
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medicine
- 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
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o-mannosylated
- synthesis
- medicine
Reaction
Synonyms
acetylglucosaminylferase, uridine diphosphoacetylglucosamine:fucosyglycoprotein beta1-3-, beta-1,3-N-acetyl-glucosaminyltransferase, beta-1,3-N-acetylglucosaminyltransferase, beta1,3-acetylglucosaminyltransferase, beta1,3-N-acetylglucosaminyltransferase, beta1,3-N-acetylglucosaminyltransferase-2, beta1,3-N-acetylglusoaminyltransferase, Dfng, FNG, Fringe, fringe beta1,3 N-acetylglucosaminyltransferase, fringe glycosyltransferase, Fringe O-fucose-beta1,3-N-acetylglucosaminyltransferase, Fringe protein, glycosyltransferase Fringe, LFNG, Lunatic Fringe, lunatic fringe glycosyltransferase, Maniac Fringe, Manic fringe, manic fringe glycosyltransferase, MFng, N-acetylglucosaminyltransferase, O-fucose-beta1,3-N-acetylglucosaminyltransferase, O-fucosylpeptide beta-1,3-N-acetylglucosaminyltransferase, O-fucosylpeptide-3-beta-N-acetylglucosaminyltransferase, Radical Fringe, radical fringe glycosyltransferase, Rfng, UDP-acetylglucosamine:fucosylglycoprotein, UDP-D-GlcNAc:O-L-fucosylpeptide 3-beta-N-acetyl-D-glucosaminyltransferase, UDP-GlcNAc:fucose beta1,3 N-acetylglucosaminyltransferase, UDP-glucose:O-linked fucose beta1,3-glucosyltransferase
ECTree
2.4.1.222 O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferaseAdvanced search results
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General Information on EC 2.4.1.222 - O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
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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
metabolism
physiological function
additional information
malfunction
deletion of gene lfng impairs myofibroblast differentiation and alveogenesis, alveolar developmental defect in Lfng mutants with altered elastogenesis and collagen deposition in Lfng mutant lungs, phenotype, overview
malfunction
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eliminating any of three highly conserved O-fucose sites at EGF 12, 26, or 27 within mouse Notch1 alters the activity in cell-based Notch signaling assays. EGF 12 is part of the ligand-binding region of Notch, a mouse line carrying a point mutation in the O-fucosylation site of EGF 12 in endogenous Notch1 shows loss of this site which results in a mild Notch phenotype with defects in T cell development
malfunction
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impact of Lfng deficiency on beta-selection, decreasing Lfng expression during the DN3-DP transition minimizes the potent leukemogenic potential of Notch1 signaling
malfunction
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Lfng depletion does not affect the balance between neuronally committed cells and selfrenewing progenitors, irrespective of the cell density of Lfng-depleted cells, and causes no obvious defects in brain development, but in vivo overexpression of Lfng shows that it strongly augments Notch signaling mediated by Delta-like 1 but not Jagged 1, phenotypes, overview
malfunction
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Lfng modification of EGF12 in the Notch1 ligand-binding domain contributes to, but is not solely responsible for, the cell-nonautonomous inhibition of T cell development caused by transgenic Lfng expression in double-positive thymocytes. O-fucose site in the Notch1 ligand binding domain is partly responsible for the effects of Lfng overexpression
malfunction
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Lfng overexpression results in significantly decreased Th2 cytokine production in asthma, which is the same effect as the gamma-secretase inhibitor GSI treatment alone, but has an increased effect on Th1 cytokines than GSI treatment
malfunction
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the NOTCH signaling effect through MFNG is abolished by a DDD to DDA mutation in MFNG that inactivates its GlcNAc transferase activity
malfunction
deletion of Lfng in mice causes altered Notch activation in the prostate, associated with elevated accumulation of Notch1, Notch2, and Notch4 intracellular domains, decreased levels of the putative Notch3 intracellular fragment, as well as increased expression of Hes1, Hes5, and Hey2. Loss of Lfng results in expansion of the basal layer, increased proliferation of both luminal and basal cells, and ultimately, prostatic intraepithelial neoplasia. The Lfng-null prostate shows down-regulation of prostatic tumor suppressor gene NKX3.1 and increased androgen receptor expression. Deletion of Lfng caused dysregulation of Notch signaling in the prostate. Increased epithelial proliferation and prostatic intraepithelial neoplasia in the Lfng-null mutant gland
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
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
loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack the enzyme lunatic fringe. Embryos double homozygous for null mutations in Dll3 and Lfng are phenotypically indistinguishable from the single mutants supporting a potential common function. Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3 can still inhibit Notch in cis in vitro. In contrast to wild type DLL3, O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3 during somitogenesis in the embryo
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
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
metabolism
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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. The structure GlcNAcbeta1-3Fucalpha1-OSer/Thr can be further elongated in mammals to the tetrasaccharide by sequential action of a beta1-4galactosyltransferase and an alpha2-3 or alpha2-6sialyltransferase
physiological function
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isoform manic fringe expression is not required for embryonic development. Despite significant overlap in expression patterns, there are no obvious synergistic defects in mice in the absence of two, or all three, fringe genes during development of the axial skeleton, limbs, hindbrain, and cranial nerves
physiological function
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isoforms lunatic fringe and manic fringe cooperatively enhance the Delta-like-1-Notch2 interaction to promote splenic marginal zone B cell development
physiological function
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Lfng is required cell autonomously in neural epithelial cells to limit the amount of neurogenesis and to maintain progenitors. Lfng is not required for the role of Notch in interneuronal fate choice, which is mediated by Notch1a. The expression of Lfng does not require Notch activity, but rather is regulated downstream of proneural genes that are widely expressed by neural progenitors
physiological function
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Fringe modulates Notch receptor expression and promotes the Notch signaling pathway through receptor-ligand binding, essential role of Fringe, overview. Notch signaling is more activated in asthmatic naive CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibit Notch signaling in asthmatic naive CD4+T lymphocytes
physiological function
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Fringe proteins are glycosyltransferases that add N-acetylglucosamine to O-fucose moieties to the extracellular domains of Notch receptors. In the immune system, Lunatic Fringe, Lfng, plays a key role in the early stages of T-lymphocyte development, critically enhancing DL4/Notch1-dependent suppression of alternative B-lineage potential and promoting T-lineage specification. Furthermore, Lfng and Manic Fringe cooperatively enhance DL1-induced Notch2 activation to promote marginal zone B-cell development. Lfng enhances Notch1 activation by Delta-like 4 to promote Notch1-dependent T-lineage commitment of thymus-seeding progenitors. Lfng temporally sustains Delta-like-induced Notch1 signaling to prolong proliferative self-renewal of pre-DP thymocytes. Pre-TCR signaling greatly augments Notch trophic functions to promote robust proliferation of pre-double positive progenitors. In the absence of DL/Notch signaling, pre-TCR expressing progenitors rapidly atrophy and differentiate into double positive thymocytes
physiological function
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LFNG and MFNG are both required for the optimal generation of MZB cells in spleen consistent with a synergistic action on Notch. Differential modification of EGF repeats on Notch by LFNG versus MFNG: MFNG promotes DLL1-induced NOTCH signaling better in the absence of Gal than in its presence, the effect is reversed in Lec8 cells corrected by expression of a UDP-Gal transporter cDNA. MFNG activity is required to enhance DLL1-induced Notch signaling in Lec8 cells. In co-culture Notch signaling assays, LFNG generally enhances DLL1-induced Notch signaling, but not in either Lec8 or Lec20 CHO mutants lacking Gal on O-fucose glycans. LFNG generally inhibits JAG1-induced Notch signaling, but in mutant CHO cells that do not add galactose to the GlcNAc transferred by Fringe, JAG1-induced Notch signaling is not inhibited by LFNG or MFNG, roles for Gal in LFNG and MFNG modulation of DLL1-induced Notch signaling in CHO cells, overview
physiological function
Lunatic Fringe, Lfng, is a beta1-3 N-acetylglucosamine transferase that modifies Notch receptors to facilitate their activation by Delta-like (Dll1/4) ligands, Lfng functions to enhance Notch-dependent induction of myofibroblast differentiation during embryonic lung development in the mouse
physiological function
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Notch signaling is essential for the self-renewal of mammalian neural progenitor cells. A variety of mechanisms modulate Notch signaling to balance the self-renewal and differentiation of progenitor cells. Fringe is a major Notch regulator and promotes or suppresses Notch signaling, depending on the Notch ligands. Lfng potentiates Notch signaling cell autonomously in neural progenitor cells of developinmg brain. Lfng and Notch intracellular domain affect embryonic self-renewing progenitor cell identity and cell proliferation in a similar way
physiological function
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Notch1 activation by Delta-like Notch ligands is essential to induce T cell commitment and to suppress B cell development from thymus-seeding progenitors. Thymus-seeding progenitor competition for Delta-like ligand DL4 is critically regulated by Lunatic Fringe, which glycosylates epidermal growth factor repeats in the Notch1 extracellular domain to enhance binding avidity for Delta-like ligands. Notch1 activation is also essential for the process of beta-selection, which drives TCRbeta+ CD4/CD8 double-negative 3 precursors to proliferate and generate a large pool of CD4/CD8 double-positive thymocytes. Lunatic Fringe enhances competition for delta-like Notch ligands but does not overcome defective pre-TCR signaling during thymocyte beta-selection in vivo, importance of Lfng-Notch1 interactions in regulating competition of preselection and postselection DN3 thymocytes for DL ligands in vivo, overview. Transgenic Lfng confers a competitive advantage to wild-type but not Rag2-/- DN3 thymocytes. Lfng improves the competitive fitness of Lck-deficient and Ptcra-deficient DN3beta thymocytes
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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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. Mammalian Fringe modification also alters ligand binding. Elongation beyond GlcNAc to the trisaccharide (Galbeta1-4GlcNAcbeta1-3-Fucosealpha1-O-Ser/Thr) is necessary to see a Fringe effect in a mammalian cell system
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
physiological function
enzyme lunatic fringe is a glycosyltransferase involved in modifying Notch signaling. modification of DLL3 by O-linked fucose via the action of enzyme lunatic fringe is essential for its function during somitogenesis
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
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
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)
physiological function
Drosophila sp. (in: flies)
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the enzyme (Fringe) regulates fly Notch signaling by adding GlcNAc to O-fucose on Notch EGF8, -9, and -12. Fringe-modified EGF8, -9, and -12 promote Delta-Notch signaling in wing vein formation. Fringe-modified EGF8 and -12 prevent cis-inhibition of Serrate by Notch in vivo
additional information
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Fringe elongation to the GlcNAc-beta1,3-fucose causes a significant conformational shift of several residues within the O-fucose consensus region. This may provide a mechanism for how Fringe modification indirectly exerts its effects on Notch activity at EGF 12
additional information
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Lfng overexpression enhances proliferative expansion of DN3 and DN4 thymocytes in response to Delta-like ligands in vitro. Lfng overexpression augments binding of Delta-like 1 and Delta-like 4 by double negative and double positive thymocytes
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
