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evolution
CePOFUT1 is a member of the GT65 family and contains four conserved disulfide bridges through the GT65 family
evolution
POFUT2 belongs to the classical GT-B fold family of glycosyltransferases with two closely interacting Rossmann-like domains. POFUT2 shows a variation of the classical GT-B fold
evolution
the highly correlated presence of POFUT1 and fucosylatable hEGFs has accompanied animal evolution
malfunction
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CHO cells lacking Pofut1 express Notch receptors on the cell surface at similar levels to wild-type cells
malfunction
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deletion of Pofut1 leads to global defects in Notch signaling and death of mice at E9.5, with a phenotype consistent with inactivation of signaling by the four Notch receptors. Embryonic stem cells lacking Pofut1 express Notch receptors on the cell surface at similar levels to wild-type cells. In mouse somites, there is evidence of altered Notch trafficking in the absence of Pofut1, consistent with reduced cell surface expression
malfunction
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embryonic stem cells lacking Pofut1 are deficient in Notch ligand binding, have wild-type levels of cell surface Notch receptors. Pofut1-/- embryonic stem cells do not bind Notch ligands or exhibit Notch signaling. Overexpression of fucosyltransferase-defective Pofut1 R245A in Pofut1-/- cells partially rescues ligand binding and Notch signaling, but this effect is not specific. Under certain conditions, mammalian Notch receptors can bind Notch ligands and transduce a Notch signal in the absence of Pofut1 and O-fucose
malfunction
Drosophila sp. (in: flies)
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in ofut1 mutant cells, Notch goes to the membrane, is internalized and accumulates in an uncharacterized endocytic compartment. Knockdown of Ofut1 using doublestranded RNA in cultured cells inhibits the secretion of a soluble version of the Notch extracellular domain. In ofut1 mutant cells, Notch does not accumulate at adherens junctions but instead accumulates into intracellular dots. A low level of Notch is also present at the surface of ofut1 mutant cells
malfunction
Drosophila sp. (in: flies)
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loss of OFUT1 results in the phenotype that is characteristic of Notch loss of function. Loss of OFUT1 leads to the loss of cell surface expression and the intracellular accumulation of Notch receptors. Secretion of Notch is impaired in OFUT1-depleted S2 cells and the abnormal endoplasmic reticulum accumulation of Notch receptors is observed in Ofut1 mutant clones in Drosophila wing imaginal discs
malfunction
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loss of Pofut1 results in the phenotype that is characteristic of Notch loss of function
malfunction
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neural crest cell-specific Pofut1-knockout mice die within 1 day of birth, accompanied by a defect of enteric nervous system development. Sox10 expression is decreased in Pofut1-null enteric neural crest cells, whereas the number of enteric neural crest cells that express Mash1, a potent repressor of Sox10, is increased in the Pofut1-null mouse. Enteric neural crest cells lacking Pofut1 show premature neurogenesis and a decrease in the number of glial progenitors
malfunction
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Pofut1 deletion inactivates Notch signaling, giving rise to smaller but viable mice. Dysplastic foci in Pofut1-deficient small intestine with occasional progression to tumor formation. Inactivation of Pofut1 leads to intestinal inflammation. Mucus hypersecretion upon Pofut1 inactivation is accompanied by alteration of the mucus-associated flora, which likely contributes to the development of enterocolitis
malfunction
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Pofut1-null mouse shows a similar phenotype to the RBP-Jk null mouse. Cardiac development in the Pofut1-/- mice is severely affected in valve formation, which is characterized in the lack of mesenchymal cells as seen in RBP-Jk null embryos and embryonic development is arrested at E9.0. Pofut1-null cells do not possess normally localized Notch1 receptors. Abnormal accumulation of the Notch1 receptor in the endoplasmic reticulum and cytoplasm in Pofut1-null mouse embryos
malfunction
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siRNAs eliminating Pofut1 transcripts in CHO cells. CHO cells deficient in Pofut1 have reduced Notch signaling and ligand binding. Under certain conditions, mammalian Notch receptors can bind Notch ligands and transduce a Notch signal in the absence of Pofut1 and O-fucose
malfunction
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elimination of Pofut1 in mice causes embryonic lethality with Notch-like phenotypes, elimination of Pofut2 results in an early embryonic lethal phenotype in mice
malfunction
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elimination of Pofut1 in mice has a profound effect on ligand binding in both embryonic stem cells and lymphoid cells. A small decrease in cell surface expression of Notch proteins is seen in embryonic stem cells lacking Pofut1 and in somites from mice with a hypomorphic allele of Pofut1, cax
malfunction
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mice lacking Pofut1 show myeloid hyperplasia and impaired lymphopoiesis. Mx-Cre/Pofut1F/F mice splenomegaly show in the bone marrow a decrease in T and B lymphocytes and an expansion of mature granulocytes and myeloid progenitors, mutant mice phenotypes, detailed overview. Mx-Cre/Pofut1F/F marrow progenitors have defective T lymphopoiesis and enhanced myeloid development in vitro that is correlated with decreased Notch ligand binding.. Defective T-cell development and myeloid hyperplasia are rescued by reinstating Notch1 signaling. Heterozygosity of Pofut1 affects rescue of FX-/- mice myeloid hyperplasia by exogenous fucose
malfunction
cell proliferation of POFUT1 knockdown cells is significantly inhibited compared with that of control cells, phenotypes, overview
malfunction
knockdown and overexpression of Pofut1 inhibits and accelerates the growth, migration and invasion of hepatocellular carcinoma cells, respectively
malfunction
phenotype of Pofut1-/- mouse embryos resembles embryos lacking downstream components of Notch signaling, like CBF1/RBP-Jkappa. Mutation on the O-fucosylation site in mouse Notch1 EGF12 results in a hypomorphic allele affecting the Notch-ligand interaction. Pofut1 knockdown decreases Pax7 and disrupts the expression of myogenic markers. Downregulation of gene Pofut1 significantly lowers the quantity of cleaved Notch intracellular domain and the expression levels of genes Rbpj and Hes1 but without modification of the cell surface expression pattern of Notch1, phenotype, overview
malfunction
CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signaling are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation
malfunction
genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice
malfunction
heterozygous mutations in POFUT1 are linked to a rare skin condition, Dowling-Degos Disease. Amplification of POFUT1 is associated with several types of cancer
malfunction
loss-of-function mutants display impaired sexual reproduction that is linked to a defective male gamete. oft1 Mutant pollen tubes are ineffective at penetrating the stigma-style interface leading to a drastic reduction in seed set and a nearly 2000-fold reduction in pollen transmission
physiological function
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is essential for Notch signalling
physiological function
Drosophila sp. (in: flies)
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is essential for Notch signalling. Ability of OFUT1 to promote Notch secretion does not depend on its enzyme activity, suggesting the chaperon-like role of OFUT1
physiological function
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Notch receptors require Pofut1 for the generation of optimally functional Notch receptors, but Pofut1 is not required for stable cell surface expression of Notch
physiological function
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Notch receptors require Pofut1 for the generation of optimally functional Notch receptors, but Pofut1 is not required for stable cell surface expression of Notch
physiological function
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Pofut1 is required for Notch signaling upstream of NICD1
physiological function
Drosophila sp. (in: flies)
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roles in the folding of Notch in the endoplasmic reticulum, in Notch-ligand binding and in endocytic trafficking of Notch. The carboxy-terminal extremity of Ofut1 contains a Lys-Asp-Glu-Leu (KDEL)-like motif that is dispensable for its catalytic activity but is required for both endoplasmic reticulum retention and function. Ofut1 is required only for Fringe-dependent signaling events
physiological function
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Notch is a transmembrane receptor that shares homology with proteins containing epidermal growth factor-like repeats and mediates the cell-cell interactions necessary for many cell fate decisions. O-fucosyltransferase 1 catalyzes the O-fucosylation of these epidermal growth factor-like repeats. This O-fucose elongates, resulting in an O-linked tetrasaccharide that regulates the signaling activities of Notch. Fucosylation occurs in the lumen of the endoplasmicreticulum and Golgi. GDP-fucose uptake into the ER and Golgi is essential for fucosylation, Efr, a multifunctional nucleotide sugar transporter, and Golgi GDP-fucose transporter Gfr are involved in the biosynthesis of heparan sulfate-glycosaminoglycan chains and the O-fucosylation of Notch. Gfr but not Efr is crucial for the fucosylation of N-glycans, overview
physiological function
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O-fucosylation is universally required for all Notch signaling. 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 extracellular domain. Molecular mechanisms by which O-fucose and O-glucose glycans affect Notch function
physiological function
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O-fucosylation is universally required for all Notch signaling. 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 extracellular domain. Ofut1 might have a chaperone-like activity in Drosophila that is required for cell-surface expression of Notch in flies. Molecular mechanisms by which O-fucose and O-glucose glycans affect Notch function, overview
physiological function
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O-fucosylation of Notch is essential for its function
physiological function
protein O-fucosyltransferase 2 catalyzes the protein O-fucosylation, a post-translational modification found on serine/threonine residues of thrombospondin type 1 repeats
physiological function
critical role of Pofut1 on Notch pathway activation during myogenic differentiation, overview. Both active Pofut1 and O-fucosylation of Notch are required for the canonical Notch signaling by Delta1 or Jagged1
physiological function
protein O-fucosyltransferase 2 is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats
physiological function
the enzyme adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. ENzyme POFUT1 expression can contribute to cancer progression
physiological function
the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. Pofut1 overexpression accelerates cell proliferation and migration in hepatocellular carcinoma cells and it promotes the binding of Notch ligand Dll1 to Notch receptor, and hence activates Notch signaling pathway in hepatocellular carcinoma cells
physiological function
AtOFT1 plays a critical role in pollen tube penetration through the stigma/style in Arabidopsis
physiological function
both POFUT1 and POFUT2 are proposed to participate in non-canonical endoplasmic reticulum quality control pathways for the folding of Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs), respectively
physiological function
both POFUT1 and POFUT2 participate in non-canonical endoplasmic reticulum quality control pathways for the folding of Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs), respectively
physiological function
protein O-fucosylation is an important glycosylation modification and plays an important role in embryonic development. Protein O-fucosyltransferase 1 promotes trophoblast cell proliferation through activation of MAPK and PI3K/Akt signaling pathways
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
physiological function
the enzyme (Pofut1), which transfers O-fucose to the EGF domains of the Notch1 receptor, is indispensable for Notch signaling activation
physiological function
the enzyme activates nuclear growth repressor DELLA. SPY-dependent protein O-fucosylation plays a key role in regulating plant development
physiological function
the enzyme is responsible for O-glycosylating of the sporozoite surface proteins CSP and TRAP. The enzyme (POFUT2) ensures the trafficking of Plasmodium thrombospondin repeat proteins as part of a non-canonical glycosylation-dependent endoplasmic reticulum protein quality control mechanism
physiological function
the enzyme O-glycosylates micronemal protein 2 (MIC2). This glycan is dispensable in Toxoplasma gondii tachyzoites and for Toxoplasma gondii infectivity
physiological function
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the enzyme O-glycosylates micronemal protein 2 (MIC2). This glycan is dispensable in Toxoplasma gondii tachyzoites and for Toxoplasma gondii infectivity
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additional information
GDP-fucose is bound in a conserved cavity formed mainly by amino acids from the C-terminal domain, it is localised in the interface where the two domains face each other, localisation of EGF repeat binding site in CePOFUT1, active site and ligand binding structure analysis, detailed overview
additional information
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O-glycome of Drosophila melanogaster by mass spectrometry, using beta-elimination to release the O-linked sugar modifications from total protein extracts of fly embryos, overview
additional information
recognition of a small conserved 3D structural motif and mechanism of enzyme-protein substrate specificity. POFUT2 features a unique loop, residues 265-285, located on the opposite side of the large cleft, which protrudes from the C-terminal domain and which is attached to the N-terminal domain via a completely conserved tryptophan residue, W273 is involved in controlling movements of the N- and C-terminal domain relative to each other during the catalytic cycle, and 90% activity is lost in mutant W273A. Structure-function analysis of POFUT2 and comparison to POFUT1
additional information
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recognition of a small conserved 3D structural motif and mechanism of enzyme-protein substrate specificity. POFUT2 features a unique loop, residues 265-285, located on the opposite side of the large cleft, which protrudes from the C-terminal domain and which is attached to the N-terminal domain via a completely conserved tryptophan residue, W273 is involved in controlling movements of the N- and C-terminal domain relative to each other during the catalytic cycle, and 90% activity is lost in mutant W273A. Structure-function analysis of POFUT2 and comparison to POFUT1
additional information
enzyme in complex with GDP and human thrombospondin type 1 repeat shows an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the thrombospondin type 1 repeat is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex, role of interstitial water in the complex interface, water-mediated interactions, overview
additional information
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enzyme in complex with GDP and human thrombospondin type 1 repeat shows an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the thrombospondin type 1 repeat is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex, role of interstitial water in the complex interface, water-mediated interactions, overview