Information on EC 2.4.1.132 - GDP-Man:Man1GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.4.1.132
-
RECOMMENDED NAME
GeneOntology No.
GDP-Man:Man1GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GDP-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
show the reaction diagram
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexosyl group transfer
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
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N-Glycan biosynthesis
-
-
protein N-glycosylation (eukaryotic, high mannose)
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Various types of N-glycan biosynthesis
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dolichyl-diphosphooligosaccharide biosynthesis
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-
SYSTEMATIC NAME
IUBMB Comments
GDP-D-mannose:D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol 3-alpha-mannosyltransferase
The biosynthesis of asparagine-linked glycoproteins utilizes a dolichyl diphosphate-linked glycosyl donor, which is assembled by the series of membrane-bound glycosyltransferases that comprise the dolichol pathway. Alg2 mannosyltransferase from Saccharomyces cerevisiae 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 (cf. EC 2.4.1.257), to form the first branched pentasaccharide intermediate of the dolichol pathway [1,2].
CAS REGISTRY NUMBER
COMMENTARY hide
81181-76-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
calf
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-
Manually annotated by BRENDA team
pathogenic fungus
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-
Manually annotated by BRENDA team
recombinant AceA
-
-
Manually annotated by BRENDA team
gene ALG2
UniProt
Manually annotated by BRENDA team
gene ALG2
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GDP-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
show the reaction diagram
GDPmannose + acceptor containing mannose alpha-1,3-linked at the non-reducing terminus
?
show the reaction diagram
-
-
-
-
?
GDPmannose + alpha-1,3-dimannoside acceptor
GDP + alpha-1,3-trimannoside product
show the reaction diagram
-
-
-
-
?
GDPmannose + Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)(Manalpha(1-6))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
GDP + Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)(Manalpha(1-3)Manalpha(1-6))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
show the reaction diagram
GDPmannose + Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
GDP + Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-PP-dolichol
show the reaction diagram
-
-
-
?
GDPmannose + ManGlcNAc2-PP-dolichol
GDP + Manalpha(1-3)ManGlcNAc2-PP-dolichol
show the reaction diagram
hALG2
-
?
GDPmannose + phytanyl-pyrophosphate-linked cellobiose
?
show the reaction diagram
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synthetic substrate for recombinant alpha-1,3-mannosyltransferase AceA, product is a trisaccharide
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-
?
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
show the reaction diagram
GDPmannose + undecaprenyl-pyrophosphate-linked cellobiose
?
show the reaction diagram
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natural substrate
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-
-
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GDP-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
show the reaction diagram
GDPmannose + tetrasaccharide-diphosphoryl-lipid
GDP + mannosyl-alpha-1,3-tetrasaccharide-diphosphoryl-lipid
show the reaction diagram
GDPmannose + undecaprenyl-pyrophosphate-linked cellobiose
?
show the reaction diagram
-
natural substrate
-
-
-
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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activation, about 60% as effective as Mg2+
Co2+
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activation, about 4% as effective as Mg2+
Mn2+
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activation, about 40% as effective as Mg2+
additional information
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no require of divalent cations
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
GDPglucose
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glycerol
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1-2% v/v
GMP
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50% inhibition at 0.094 mM
GTP
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50% inhibition at 0.006 mM
mannose-1-phosphate
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Phospholipids
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stable bilayer forming, e.g. phosphatidylcholine, restorable by addition of cholesterol, dolichol and dolichol-derivatives
UDP-N-acetylglucosamine
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weak
UDPglucose
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weak
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cardiolipin
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activation, 35% as effective as phosphatidylethanolamine
dolichol
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stimulates enzyme in the presence of inhibitory concentrations of phosphatidylcholine
dolichyl phosphate
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stimulates enzyme in the presence of inhibitory concentrations of phosphatidylcholine
Nonidet P-40
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activation, up to 0.0225% v/v
phosphatidylethanolamine
phosphatidylserine
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activation, 16-43% as effective as phosphatidylethanolamine
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00065 - 0.00142
GDPmannose
0.00021 - 0.00096
tetrasaccharide-diphosphoryl-lipid
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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distribution of ALG2 in mouse muscle sections by immunohistochemic analysis, Alg2 is enriched at endplate regions of the muscle sections, the region of the alpha-bungarotoxin binding
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
85000
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SDS-PAGE
98500
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SDS-PAGE, MW slowly increases due to glycosylation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
no glycoprotein
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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5 min, in 0.0225% Nonidet P-40 without substrate, about 80% loss of activity. In phosphatidylethanolamine without substrate: at least 5 min stable, after 25 min about 15% loss of activity
additional information
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phosphatidylethanolamine increases heat-stability
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol, 0.5% v/v, stabilizes during storage and purification
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, in 0.1% v/v Nonidet P-40 and 10% v/v glycerol, at least 3 months
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0-4°C, in 0.1% v/v Nonidet P-40 and 10% v/v glycerol, 24 h
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glycerol, 10% v/v, stabilizes during storage
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; hALG2 encodes an alpha-1,3-mannosyltransferase resulting in Manalpha(1-3)ManGlcNAc2-PP-dolichol
ALG2 gene encodes GDP-Man:Dol-PP-GlcNAc2Man2 alpha-1,3-mannosyltransferase, amino acid sequence
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alg3 encodes enzyme responsible for the alpha-1,3-Man middle-arm addition, MNN1 encoded enzyme adds at least the penultimate alpha-1,3-linked Man of the terminal Manalpha(1-3)Manalpha(1-3)-disaccharide on O-linked glycans
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gene ALG2, expression analysis by quantitative RT-PCR, coexpression of Alg2 and Runx2 in COS-7 cells, both localizing to different compartments
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gene ALG2, recombinant expression of wild-type and mutat V68G enzymes in HEK-293 cells
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MNN1 gene encoding Mnn1p is cloned and sequenced
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MNN1, MNT2 and MNT3 genes encode alpha-1,3-mannosyltransferases, wild type and mutants carrying single and multiple combinations of the disrupted gene
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overexpression in Escherichia coli. Two Alg2 constructs are expressed and isolated, one with the N-terminal TRX domain and C-terminal His and V5 epitope tags and the other with only an N-terminal His tag
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wild type and mutant that lacks NH2-terminal cytoplasmic tail
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
knockdown of human immunodeficiency virus type 1 enhancer-binding protein 3, Hivep3, downregulates Alg2 expression. Expression of the Alg2 gene is reduced upon knockdown of Hivep3 in osteoblastic cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G393T/DELTAG1040
mutation in a patient with a congenital disorders of glycosylation designated CDG-Ii caused by ALG2 deficiency
D203A
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mutation has no influence on Alg2 function
D248A
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mutation has no influence on Alg2 function
E264A
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mutation has no influence on Alg2 function
E335A/E343A
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significant lower level of product formation, identical to that of the E335A mutant
G337A
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mutation has no influence on Alg2 function
G337E
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nonfunctional enzyme variant
G337R
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nonfunctional enzyme variant
G338A
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mutation has no influence on Alg2 function
H336A
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mutation has no influence on Alg2 function
K206A
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mutation has no influence on Alg2 function
K210A
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mutation has no influence on Alg2 function
K229A
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mutation has no effect on growth and glycosylation
K230A
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mutation causes loss of Alg2 activity
K251A
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mutation has no influence on Alg2 function
N231A
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mutation has no effect on growth and glycosylation
N392A
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mutation has no influence on Alg2 function
P192A
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mutation has no influence on Alg2 function
P359A
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mutation has no influence on Alg2 function
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
hALG2 is the cause of a new type of congenital disorders of glycosylation designated CDG-Ii
pharmacology