Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GDP-alpha-D-mannose + beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphosphodolichol
GDP + alpha-D-Man-(1->3)-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphosphodolichol
hALG2
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
GDP-alpha-D-mannose + decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose
GDP + ?
GDP-alpha-D-mannose + Man-(beta1,4)-Gn-(beta1,4)-Gn-PP-phytanyl
GDP + Man-(alpha1,3)[Man-(alpha1,6)]-Man1Gn2-PPhy
GDP-alpha-D-mannose + Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
GDP + Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
-
-
-
?
GDP-alpha-D-mannose + P1-[11- (anthracen-9-ylmethoxy) undecyl]-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl) diphosphate
GDP + ?
GDPmannose + acceptor containing mannose alpha-1,3-linked at the non-reducing terminus
?
-
-
-
-
?
GDPmannose + phytanyl-pyrophosphate-linked cellobiose
?
-
synthetic substrate for recombinant alpha-1,3-mannosyltransferase AceA, product is a trisaccharide
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
GDPmannose + undecaprenyl-pyrophosphate-linked cellobiose
?
-
natural substrate
-
-
?
additional information
?
-
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
in eukaryotes, biosynthesis of N-glycans starts with the assembly of the common core oligosaccharide precursor Glc3Man9 GlcNAc2-PP-Dol, the glycan moiety of which is subsequently transferred onto selected Asn-Xaa-(Ser/Thr) acceptor sites of the nascent polypeptide chain by the oligosaccharyl-transferase complex
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
the biosynthesis of asparagine-linked glycoproteins utilizes a dolichylpyrophosphate-linked glycosyl donor, which is assembled by the series of membrane-bound glycosyltransferases that comprise the dolichol pathway. Alg2 carries out an alpha1,3-mannosylation of D-Man-beta-(1-4)-D-GlcNAc-beta-(1-4)-D-GlcNAc-diphosphodolichol, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the dolichol pathway
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
Alg2 carries out an alpha1,3-mannosylation of Man-beta1,4-GlcNAc-beta1,4-GlcNAc-diphosphodolichol, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the dolichol pathway
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
Alg2 is able to catalyze both the addition of the alpa1,3- and alpha1,6-linked mannose residue to Man1GlcNAc2-PP-Dol, forming Man2GlcNAc2-PP-Dol (cf EC 2.4.1.132) and subsequently to Man3GlcNAc2-PP-Dol
-
-
?
GDP-alpha-D-mannose + decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose
GDP + ?
i.e. synthetic acceptor GlcNAc-PP-De
-
-
?
GDP-alpha-D-mannose + decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose
GDP + ?
i.e. synthetic acceptor GlcNAc-PP-De
-
-
?
GDP-alpha-D-mannose + Man-(beta1,4)-Gn-(beta1,4)-Gn-PP-phytanyl
GDP + Man-(alpha1,3)[Man-(alpha1,6)]-Man1Gn2-PPhy
synthesis of acceptor phytanyl oligosaccharide, Man1Gn2-PPhy, from Gn-(beta1,4)-Gn-PP-phytanyl (Gn2-PPhy) using yeast Alg1. Recombinant scAlg2 transfers 2 Man residues to the beta1,4-Man of the Man1Gn2-PPhy substrate with alpha1,6 and alpha1,3-linkages, yielding Man-(alpha1,3)[Man-(alpha1,6)]-Man1Gn2-PPhy, cf. EC 2.4.1.257
-
-
?
GDP-alpha-D-mannose + Man-(beta1,4)-Gn-(beta1,4)-Gn-PP-phytanyl
GDP + Man-(alpha1,3)[Man-(alpha1,6)]-Man1Gn2-PPhy
synthesis of acceptor phytanyl oligosaccharide, Man1Gn2-PPhy, from Gn-(beta1,4)-Gn-PP-phytanyl (Gn2-PPhy) using yeast Alg1. Recombinant scAlg2 transfers 2 Man residues to the beta1,4-Man of the Man1Gn2-PPhy substrate with alpha1,6 and alpha1,3-linkages, yielding Man-(alpha1,3)[Man-(alpha1,6)]-Man1Gn2-PPhy, cf. EC 2.4.1.257
-
-
?
GDP-alpha-D-mannose + P1-[11- (anthracen-9-ylmethoxy) undecyl]-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl) diphosphate
GDP + ?
i.e. GlcNAc-PP-AnthrU
-
-
?
GDP-alpha-D-mannose + P1-[11- (anthracen-9-ylmethoxy) undecyl]-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl) diphosphate
GDP + ?
i.e. GlcNAc-PP-AnthrU
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
no acceptor is dolichol-phosphate
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
involved in the biosynthesis of asparagine-linked saccharide chains of mammalian glycoproteins
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
the 1,3-linked mannosyl residue in mammalian lipid-linked oligosaccharide of the structure Glc3Man9GlcNAc2 is produced by this enzyme
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
-
?
additional information
?
-
-
role in the synthesis of the glucuronoxylomannan of the capsule
-
-
?
additional information
?
-
enzyme WfcD is expressed in Escherichia coli strain BL21(DE3), and the enzymatic product is identified by liquid chromatography-mass spectrometry (LC-MS), collision-induced dissociation electrospray ionization ion trap multiple tandem MS (CID-ESI-IT-MSn), and glycosidase digestion using the donor substrate GDP-Man and the synthetic acceptor substrate decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose (GlcNAc-PP-De). Analysis of donor substrate specificity of WfcD, overview. WfcD is an alpha-1,3-ManT that catalyzes the Man(alpha1-3)-GlcNAc-R linkage formation. No activity with GlcNAc-GlcNAc-PP-De, Glc-PP-De, UDP-GlcNAc, GlcNAc, and GlcNAc-NP
-
-
-
additional information
?
-
enzyme WfcD is expressed in Escherichia coli strain BL21(DE3), and the enzymatic product is identified by liquid chromatography-mass spectrometry (LC-MS), collision-induced dissociation electrospray ionization ion trap multiple tandem MS (CID-ESI-IT-MSn), and glycosidase digestion using the donor substrate GDP-Man and the synthetic acceptor substrate decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose (GlcNAc-PP-De). Analysis of donor substrate specificity of WfcD, overview. WfcD is an alpha-1,3-ManT that catalyzes the Man(alpha1-3)-GlcNAc-R linkage formation. No activity with GlcNAc-GlcNAc-PP-De, Glc-PP-De, UDP-GlcNAc, GlcNAc, and GlcNAc-NP
-
-
-
additional information
?
-
-
hALG2: early steps of dolichol-linked oligosaccharide biosynthesis
-
-
?
additional information
?
-
hALG2: early steps of dolichol-linked oligosaccharide biosynthesis
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
-
-
?
additional information
?
-
-
Mnn1p has 2 conserved aspartate residues necessary for activity
-
-
?
additional information
?
-
-
Mnn1p family of alpha-1,3-mannosyltransferases is responsible for adding the terminal mannose residues of O-linked oligosaccharides, MNT2 and MNT3 genes in combination with MNN1 have overlapping roles in the addition of the fourth and fifth alpha-1,3-linked mannose residues to form Man4 and Man5 oligosaccharides
-
-
?
additional information
?
-
-
primary and secondary structure of the ALG2 protein
-
-
?
additional information
?
-
-
Mnn1p is required for the complex glycosylation of secreted proteins
-
-
?
additional information
?
-
Alg2 shows no activity with D-Man-beta-(1-4)-D-GlcNAc-beta-(1-4)-D-GlcNAc-diphosphodolichol
-
-
?
additional information
?
-
unique bifunctionality of Alg2 during lipid-linked oligosaccharide (LLO) synthesis
-
-
-
additional information
?
-
-
Mnn1p family of alpha-1,3-mannosyltransferases is responsible for adding the terminal mannose residues of O-linked oligosaccharides, MNT2 and MNT3 genes in combination with MNN1 have overlapping roles in the addition of the fourth and fifth alpha-1,3-linked mannose residues to form Man4 and Man5 oligosaccharides
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
Mnn1p is required for the complex glycosylation of secreted proteins
-
-
?
additional information
?
-
-
Mnn1p has 2 conserved aspartate residues necessary for activity
-
-
?
additional information
?
-
-
primary and secondary structure of the ALG2 protein
-
-
?
additional information
?
-
unique bifunctionality of Alg2 during lipid-linked oligosaccharide (LLO) synthesis
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
GDPmannose + undecaprenyl-pyrophosphate-linked cellobiose
?
-
natural substrate
-
-
?
additional information
?
-
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
-
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
in eukaryotes, biosynthesis of N-glycans starts with the assembly of the common core oligosaccharide precursor Glc3Man9 GlcNAc2-PP-Dol, the glycan moiety of which is subsequently transferred onto selected Asn-Xaa-(Ser/Thr) acceptor sites of the nascent polypeptide chain by the oligosaccharyl-transferase complex
-
-
?
GDP-alpha-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol
GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol
the biosynthesis of asparagine-linked glycoproteins utilizes a dolichylpyrophosphate-linked glycosyl donor, which is assembled by the series of membrane-bound glycosyltransferases that comprise the dolichol pathway. Alg2 carries out an alpha1,3-mannosylation of D-Man-beta-(1-4)-D-GlcNAc-beta-(1-4)-D-GlcNAc-diphosphodolichol, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the dolichol pathway
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
involved in the biosynthesis of asparagine-linked saccharide chains of mammalian glycoproteins
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
the 1,3-linked mannosyl residue in mammalian lipid-linked oligosaccharide of the structure Glc3Man9GlcNAc2 is produced by this enzyme
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
-
-
-
-
?
additional information
?
-
-
role in the synthesis of the glucuronoxylomannan of the capsule
-
-
?
additional information
?
-
-
hALG2: early steps of dolichol-linked oligosaccharide biosynthesis
-
-
?
additional information
?
-
hALG2: early steps of dolichol-linked oligosaccharide biosynthesis
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
-
-
?
additional information
?
-
-
Mnn1p is required for the complex glycosylation of secreted proteins
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
Mnn1p is required for the complex glycosylation of secreted proteins
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
malfunction
deficiency of GDP-Man:Man1GlcNAc2-PP-dolichol mannosyltransferase, is the cause of a congenital disorders of glycosylation designated CDG-Ii. The patients are normal at birth but develop in the 1st year of life a multisystemic disorder with mental retardation, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities. An accumulation of Man1GlcNAc2-PP-dolichol and Man2GlcNAc2-PP-dolichol is observed in skin fibroblasts of the patient. Incubation of patient fibroblast extracts with Man1GlcNAc2-PP-dolichol and GDP-mannose reveals a severely reduced activity of the mannosyltransferase elongating Man1GlcNAc2-PP dolichol
malfunction
enzyme mutations are linked to congenital myasthenic syndrome
malfunction
loss of Alg2 promotes osteoblast differentiation in ST-2 cells without affecting the protein level of Runx2. Alg2 knockdown does not affect endoplasmic reticulum stress or bone morphogenetic protein, BMP, signaling in ST-2 cells. Atf4,also known as CCAAT/enhancer-binding protein homologous protein (Chop), is mildly upregulated by sAlg2, but only in BMP-2-treated cells. The expression of a target of the Atf6 pathway, heat shock protein 5 (Hspa5), is not altered by loss of Alg2
malfunction
cells deleted for ALG2 are inviable. Mutant alg2 alleles display intraallelic complementation
malfunction
-
loss of Alg2 promotes osteoblast differentiation in ST-2 cells without affecting the protein level of Runx2. Alg2 knockdown does not affect endoplasmic reticulum stress or bone morphogenetic protein, BMP, signaling in ST-2 cells. Atf4,also known as CCAAT/enhancer-binding protein homologous protein (Chop), is mildly upregulated by sAlg2, but only in BMP-2-treated cells. The expression of a target of the Atf6 pathway, heat shock protein 5 (Hspa5), is not altered by loss of Alg2
-
malfunction
-
cells deleted for ALG2 are inviable. Mutant alg2 alleles display intraallelic complementation
-
metabolism
ALG2 is an alpha-1,3-mannosyltransferase that catalyses the second and third mannosylation steps in the N-linked glycosylation pathway
metabolism
ALG2 is an alpha-1,3-mannosyltransferase that catalyses the second and third mannosylation steps in the N-linked glycosylation pathway
metabolism
asparagine-linked glycosylation (ALG) is one of the most common protein modification reactions in eukaryotic cells, as many proteins that are translocated across or integrated into the rough endoplasmic reticulum carry N-linked oligosaccharides. Linkage between an asparagine-linked glycosylation mannosyltransferase gene and osteochondrogenesis
metabolism
the fourth and fifth steps of lipid-linked oligosaccharide (LLO) synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities
metabolism
-
asparagine-linked glycosylation (ALG) is one of the most common protein modification reactions in eukaryotic cells, as many proteins that are translocated across or integrated into the rough endoplasmic reticulum carry N-linked oligosaccharides. Linkage between an asparagine-linked glycosylation mannosyltransferase gene and osteochondrogenesis
-
metabolism
-
the fourth and fifth steps of lipid-linked oligosaccharide (LLO) synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities
-
physiological function
human immunodeficiency virus type 1 enhancer-binding protein 3, Hivep3 or Schnurri-3, Zas3, and Krc, is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation. Alg2 suppresses osteoblast differentiation by inhibiting the activity of Runx2. Alg2 silencing suppresses the expression of Creb3l2 and chondrogenesis. Enzyme ALG2 is associated with osteochondrogenesis, Alg2 is a downstream mediator of Hivep3 and suppresses osteogenesis, whereas it promotes chondrogenesis. Regulation analysis, overview
physiological function
the enzyme transfers D-mannosyl units to endoplasmic reticulum membrane-bound N-acetylglucosaminyl dolichyl-phosphates
physiological function
the enzyme transfers D-mannosyl units to endoplasmic reticulum membrane-bound N-acetylglucosaminyl dolichyl-phosphates
physiological function
asparagine (N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-diphosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum. The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities. Alg2 adds both an alpha1,3- and alpha1,6-mannose ontoManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol. Alg2-dependent Man3GlcNAc2-PDol production relies on net-neutral lipids with a propensity to form bilayers
physiological function
WfcD is the first characterized bacterial mannosyltransferase that acts on the Man-alpha-(1->3)-GlcNAc linkage
physiological function
-
human immunodeficiency virus type 1 enhancer-binding protein 3, Hivep3 or Schnurri-3, Zas3, and Krc, is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation. Alg2 suppresses osteoblast differentiation by inhibiting the activity of Runx2. Alg2 silencing suppresses the expression of Creb3l2 and chondrogenesis. Enzyme ALG2 is associated with osteochondrogenesis, Alg2 is a downstream mediator of Hivep3 and suppresses osteogenesis, whereas it promotes chondrogenesis. Regulation analysis, overview
-
physiological function
-
WfcD is the first characterized bacterial mannosyltransferase that acts on the Man-alpha-(1->3)-GlcNAc linkage
-
physiological function
-
asparagine (N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-diphosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum. The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities. Alg2 adds both an alpha1,3- and alpha1,6-mannose ontoManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol. Alg2-dependent Man3GlcNAc2-PDol production relies on net-neutral lipids with a propensity to form bilayers
-
additional information
the conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo. Alg2 immunoprecipitates from extracts of yeast microsomal membranes also displays both alpha1,3- and alpha1,6-mannosyltransferase (MTase) activities. The conserved Val62 residue is required for yeast Alg2 function. The first E (E335) and His-336 are partially required for alpha1,6-mannosylation, and importance of both E335 and E343 of the EX7E domain for Alg2 function in vivo. Identification of three conserved G-rich motifs in scAlg2, located in the N-terminal cytosolic short tail, in the middle of Alg2, and in the C-terminal domain. Residues G17, G19, and G20 are within the N-terminal cytosolic tail of Alg2, importance of this domain for Alg2 function
additional information
-
the conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo. Alg2 immunoprecipitates from extracts of yeast microsomal membranes also displays both alpha1,3- and alpha1,6-mannosyltransferase (MTase) activities. The conserved Val62 residue is required for yeast Alg2 function. The first E (E335) and His-336 are partially required for alpha1,6-mannosylation, and importance of both E335 and E343 of the EX7E domain for Alg2 function in vivo. Identification of three conserved G-rich motifs in scAlg2, located in the N-terminal cytosolic short tail, in the middle of Alg2, and in the C-terminal domain. Residues G17, G19, and G20 are within the N-terminal cytosolic tail of Alg2, importance of this domain for Alg2 function
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
G393T/DELTAG1040
mutation in a patient with a congenital disorders of glycosylation designated CDG-Ii caused by ALG2 deficiency
D203A
mutation has no influence on Alg2 function
D248A
mutation has no influence on Alg2 function
E264A
mutation has no influence on Alg2 function
E335A/E343A
significant lower level of product formation, identical to that of the E335A mutant
F337A
site-directed mutagenesis, Trx-scAlg2F337A produces 26% Man3Gn2 product compared to wild-type enzyme
G337A
mutation has no influence on Alg2 function
G337E
nonfunctional enzyme variant
G337R
nonfunctional enzyme variant
G338A
mutation has no influence on Alg2 function
G377R
site-directed mutagenesis, a temperature-sensitive alg2-1 mutant containing a single missense mutation, catalytically inactive
K206A
mutation has no influence on Alg2 function
K210A
mutation has no influence on Alg2 function
K229A
mutation has no effect on growth and glycosylation
K230A
mutation causes loss of Alg2 activity
K251A
mutation has no influence on Alg2 function
N231A
mutation has no effect on growth and glycosylation
N392A
mutation has no influence on Alg2 function
P192A
mutation has no influence on Alg2 function
P359A
mutation has no influence on Alg2 function
V62G
site-directed mutagenesis, Trx-scAlg2V62G produces 25% Man3Gn2 product compared to wild-type enzyme. The HA-tagged mutant allele (3HAscAlg2V62G) fails to complement the lethality of the alg2DELTA LSY2 when grown on 5-FOA
E335A
-
site-directed mutagenesis, Trx-scAlg2E335A produces only no final product and only 32% of intermediate Man2Gn2 compared to wild-type enzyme
-
E343A
-
site-directed mutagenesis, inactive mutant
-
F337A
-
site-directed mutagenesis, Trx-scAlg2F337A produces 26% Man3Gn2 product compared to wild-type enzyme
-
H336A
-
site-directed mutagenesis, Trx-scAlg2H336A produces 8% Man3Gn2 product compared to wild-type enzyme
-
V68G
naturally occuring mutation, a non-conservative change, a pathogenic mutation causing a rare congenital disorder such as congenital myasthenic syndrome, CMS
V68G
site-directed mutagenesis, the mutant shows reduced expression in muscle
E335A
mutant has some residual activity
E335A
significant lower level of product formation
E335A
site-directed mutagenesis, Trx-scAlg2E335A produces only no final product and only 32% of intermediate Man2Gn2 compared to wild-type enzyme
E343A
no activity
E343A
inactive mutant enzyme
E343A
site-directed mutagenesis, inactive mutant
H336A
mutation has no influence on Alg2 function
H336A
site-directed mutagenesis, Trx-scAlg2H336A produces 8% Man3Gn2 product compared to wild-type enzyme
additional information
-
ALG2 mutant with severely reduced enzyme activity
additional information
ALG2 mutant with severely reduced enzyme activity
additional information
variant c.214_226delinsAGTCCCCGGC, p.72_75delinsSPR, removes a highly conserved GDWL motif of the glycosyltransferase 4-like domain, and inserts three different amino acids
additional information
-
variant c.214_226delinsAGTCCCCGGC, p.72_75delinsSPR, removes a highly conserved GDWL motif of the glycosyltransferase 4-like domain, and inserts three different amino acids
additional information
ALG2 downregulation in ST-2 cells by siRNA transfection
additional information
-
ALG2 downregulation in ST-2 cells by siRNA transfection
-
additional information
-
ALG2 mutant with severely reduced enzyme activity
additional information
ALG2 mutant with severely reduced enzyme activity
additional information
-
mutagenesis of Mnn1p by altering either of the 2 conserved aspartates eliminates all enzymic activity, but does not affect the overall folding and assembly of Mnn1p
additional information
-
Mnn1 mutant strain
additional information
-
lumenal domain retention mutants of Mnn1p
additional information
mutational analysis of Alg2 and identification of amino acids required for its activity. None of the four domains (predicted as transmembrane-spanning helices) is essential for transferase activity because truncated Alg2 variants can exert their function as long as Alg2 is associated with the endaplasmic reticulum by either its N- or C-terminal hydrophobic regions
additional information
site-directed mutagenesis of conserved EX7E motif. Trx-scAlg2E335A, mutated in the first E, has significantly decreased activity, producing no final product and only 32% of intermediate Man2Gn2. Trx-scAlg2E343A, mutated in the second E, has no detectable activity. The intervening amino acids of the EX7E are also important, though less than either E335 or E343. Trx-scAlg2H336A and Trx-scAlg2F337A produce 8% and 26% of Man3Gn2 product, respectively, compared to wild-type. Cells deleted for ALG2 are inviable, a plasmid shuffling technique is used to measure complementation. Mutant alg2 alleles display intraallelic complementation. Mutations (changed to proline) in five of the glycines (G19, G20, G256, G357, G358) result in complete loss of activity, while two of them (G17, G257) are significantly decreased
additional information
-
ALG2 mutant with severely reduced enzyme activity
-
additional information
-
Mnn1 mutant strain
-
additional information
-
lumenal domain retention mutants of Mnn1p
-
additional information
-
mutagenesis of Mnn1p by altering either of the 2 conserved aspartates eliminates all enzymic activity, but does not affect the overall folding and assembly of Mnn1p
-
additional information
-
site-directed mutagenesis of conserved EX7E motif. Trx-scAlg2E335A, mutated in the first E, has significantly decreased activity, producing no final product and only 32% of intermediate Man2Gn2. Trx-scAlg2E343A, mutated in the second E, has no detectable activity. The intervening amino acids of the EX7E are also important, though less than either E335 or E343. Trx-scAlg2H336A and Trx-scAlg2F337A produce 8% and 26% of Man3Gn2 product, respectively, compared to wild-type. Cells deleted for ALG2 are inviable, a plasmid shuffling technique is used to measure complementation. Mutant alg2 alleles display intraallelic complementation. Mutations (changed to proline) in five of the glycines (G19, G20, G256, G357, G358) result in complete loss of activity, while two of them (G17, G257) are significantly decreased
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Jensen, J.W.; Schutzbach, J.S.
The biosynthesis of oligosaccharide-lipids. Partial purification and characterization of mannosyltransferase II
J. Biol. Chem.
256
12899-12904
1981
Oryctolagus cuniculus
brenda
Jensen, J.W.; Schutzbach, J.S.
Activation of mannosyltransferase II by nonbilayer phospholipids
Biochemistry
23
1115-1119
1984
Oryctolagus cuniculus
-
brenda
Jensen, J.W.; Schutzbach, J.S.
The biosynthesis of oligosaccharide-lipids. Activation of mannosyltransferase II by specific phospholipids
J. Biol. Chem.
257
9025-9029
1982
Oryctolagus cuniculus
brenda
Graham, T.R.; Krasnov, V.A.
Sorting of yeast alpha 1,3 mannosyltransferase is mediated by a lumenal domain interaction, and a transmembrane domain signal that can confer clathrin-dependent Golgi localization to a secreted protein
Mol. Biol. Cell
6
809-824
1995
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Graham, T.R.; Seeger, M.; Payne, G.S.; MacKay, V.L.; Emr, S.D.
Clathrin-dependent localization of alpha 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae
J. Cell. Biol.
127
667-678
1994
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Romero, P.A.; Lussier, M.; Veronneau, S.; Sdicu, A.M.; Herscovics, A.; Bussey, H.
Mnt2p and Mnt3p of Saccharomyces cerevisiae are members of the Mnn1p family of alpha-1,3-mannosyltransferases responsible for adding the terminal mannose residues of O-linked oligosaccharides
Glycobiology
9
1045-1051
1999
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Thiel, C.; Schwarz, M.; Peng, J.; Grzmil, M.; Hasilik, M.; Braulke, T.; Kohlschuetter, A.; von Figura, K.; Lehle, L.; Koerner, C.
A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis
J. Biol. Chem.
278
22498-22505
2003
Saccharomyces cerevisiae, Saccharomyces cerevisiae (P43636), Homo sapiens, Homo sapiens (Q9H553), Saccharomyces cerevisiae A
brenda
Lellouch, A.C.; Watt, G.M.; Geremia, R.A.; Flitsch, S.L.
Phytanyl-pyrophosphate-linked substrate for a bacterial alpha-mannosyltransferase
Biochem. Biophys. Res. Commun.
272
290-292
2000
Komagataeibacter xylinus
brenda
Doering, T.
alpha-1,3-Mannosyltransferase from Cryptococcus neoformans and other pathogenic fungi and method of screening for alpha-1,3-mannosyltransferase inhibitors and anti-fungal therapeutics
PCT Int. Appl.
2000
38pp
2000
Cryptococcus neoformans
-
brenda
Yip, C.L.; Welch, S.K.; Klebl, F.; Gilbert, T.; Seidel, P.; Grant, F.; O'Hara, P.J.; MacKay, V.L.
Cloning and analysis of the Saccharomyces cerevisiae MNN9 and MNN1 genes required for complex glycosylation of secreted proteins
Proc. Natl. Acad. Sci. USA
91
2723-2727
1994
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Doering, T.
A unique alpha-1,3-mannosyltransferase of the pathogenic fungus Cryptococcus neoformans
J. Bacteriol.
181
5482-5488
1999
Cryptococcus neoformans
brenda
Reynolds, T.B.; Hopkins, B.D.; Lyons, M.R.; Graham, T.R.
The high osmolarity glycerol response (HOG) MAP kinase pathway controls localization of a yeast Golgi glycosyltransferase
J. Cell Biol.
143
935-946
1998
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Wiggins, C.A.R.; Munro, S.
Activity of the yeast MNN1 alpha-1,3-mannosyltransferase requires a motif conserved in many other families of glycosyltransferases
Proc. Natl. Acad. Sci. USA
95
7945-7940
1998
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Shpakov, A.O.; Derkach, K.V.
Yeast dolichol-coupled mannosyltransferases. Theoretical analysis of primary structure and identification of sites homologous to other enzymes of the dolichol cycle
Zh. Evol. Biokhim. Fiziol.
32
3-18
1996
Saccharomyces cerevisiae, Saccharomyces cerevisiae A
brenda
Herscovics, A.; Warren, C.D.; Jeanloz, R.W.
Solubilization of an alpha-(1-3)-D-mannosyltransferase from pancreas which utilizes synthetic dolichyl pyrophosphate trisaccharide beta-Man-(1-4)-beta-GlcNAc-(1-4)-GlcNAc as substrate
FEBS Lett.
156
298-302
1983
Bos taurus
brenda
Gao, X.D.; Nishikawa, A.; Dean, N.
Physical interactions between the Alg1, Alg2, and Alg11 mannosyltransferases of the endoplasmic reticulum
Glycobiology
14
559-570
2004
Saccharomyces cerevisiae
brenda
O'Reilly, M.K.; Zhang, G.; Imperiali, B.
In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis
Biochemistry
45
9593-9603
2006
Saccharomyces cerevisiae (P43636)
brenda
Kmpf, M.; Absmanner, B.; Schwarz, M.; Lehle, L.
Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional alpha1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis
J. Biol. Chem.
284
11900-11912
2009
Saccharomyces cerevisiae (P43636)
brenda
Cossins, J.; Belaya, K.; Hicks, D.; Salih, M.A.; Finlayson, S.; Carboni, N.; Liu, W.W.; Maxwell, S.; Zoltowska, K.; Farsani, G.T.; Laval, S.; Seidhamed, M.Z.; Seidhamed, M.Z.; Donnelly, P.; Bentley, D.; McGowan, S.J.; Mueller, J.; Palace, J.; Lochmueller, H.; Beeson, D.
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14
Brain
136
944-956
2013
Mus musculus (Q9DBE8), Homo sapiens (Q9H553), Homo sapiens
brenda
Imamura, K.; Maeda, S.; Kawamura, I.; Matsuyama, K.; Shinohara, N.; Yahiro, Y.; Nagano, S.; Setoguchi, T.; Yokouchi, M.; Ishidou, Y.; Komiya, S.
Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation
J. Biol. Chem.
289
9865-9879
2014
Mus musculus (Q9DBE8), Mus musculus C57/BL6J (Q9DBE8)
brenda
Chen, C.; Hou, X.; Utkina, N.; Danilov, L.; Zhou, D.; Torgov, V.; Veselovsky, V.; Liu, B.; Feng, L.
Identification and biochemical characterization of a novel alpha-1,3-mannosyltransferase WfcD from Escherichia coli O141
Carbohydr. Res.
443-444
78-86
2017
Escherichia coli (A6MF03), Escherichia coli O141 (A6MF03)
brenda
Li, S.-T.; Wang, N.; Xu, X.-X.; Fujita, M.; Nakanishi, H.; Kitajima, T.; Dean, N.; Gao, X.-D.
Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase
FASEB J.
32
2492-2506
2018
Saccharomyces cerevisiae (P43636), Saccharomyces cerevisiae ATCC 204508 (P43636)
brenda