Information on EC 2.4.1.83 - dolichyl-phosphate beta-D-mannosyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Archaea, artificial sequences

EC NUMBER
COMMENTARY
2.4.1.83
-
RECOMMENDED NAME
GeneOntology No.
dolichyl-phosphate beta-D-mannosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
GDP-mannose + dolichyl phosphate = GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
sequential mechanism
-
GDP-mannose + dolichyl phosphate = GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
dolichyl-diphosphooligosaccharide biosynthesis
-
Metabolic pathways
-
N-Glycan biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
GDP-mannose:dolichyl-phosphate beta-D-mannosyltransferase
Acts only on long-chain polyprenyl phosphates and alpha-dihydropolyprenyl phosphates that are larger than C35.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
AglD
Haloferax volcanii WR536 (H53)
-
-
-
bDPM1
-
-
D-P-M
-
-
Dol-P Man synthase
-
-
Dol-P-Man synthase
-
-
Dol-P-Man synthase
-
-
Dol-P-Man synthase1
-
-
Dol-P-Man-synthase
-
-
-
-
Dol-P-Mansynthase
-
-
-
-
dolichol phosphate mannose synthase
-
-
-
-
dolichol phosphate mannose synthase
-
-
dolichol phosphate mannose synthase
-
-
dolichol phosphate mannose synthase
Haloferax volcanii WR536 (H53)
-
-
-
dolichol phosphate mannose synthase
-
-
dolichol phosphoryl mannose synthase
-
-
dolichol phosphoryl mannose synthase
-
-
dolichol phosphoryl mannose synthase
Saccharomyces cerevisiae SF402-4D
-
-
-
dolichol-P-mannose synthase
-
-
dolicholphosphate mannose synthase
-
-
dolichyl mannosyl phosphate synthase
-
-
-
-
dolichyl phosphate mannosyltransferase
-
-
-
-
dolichyl-phosphate mannose synthase
-
-
-
-
dolichyl-phosphate mannosyltransferase
-
-
dolichyl-phospho-mannose synthase
-
-
-
-
DPM
Saccharomyces cerevisiae SF402-4D
-
-
-
DPM synthase
-
-
DPM synthase
-
-
DPM1
-
gene name
DPMS
-
-
-
-
GDP-Man:DolP mannosyltransferase
-
-
-
-
GDP-mannose-dolichol phosphate mannosyltransferase
-
-
-
-
GDPMan:DolP mannosyltransferase
-
-
-
-
GDPmannose-dolichylmonophosphate mannosyltransferase
-
-
-
-
GDPmannose:dolichyl-phosphate mannosyltransferase
-
-
-
-
mannosylphospho dolichol synthase
-
-
mannosylphosphodolichol synthase
-
-
-
-
mannosylphosphodolichol synthase
-
-
mannosylphosphodolichol synthase
-
-
mannosylphosphoryldolichol synthase
-
-
-
-
mannosyltransferase, guanosine diphosphomannose-dolichol phosphate
-
-
-
-
MPD synthase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
62213-44-9
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
loss-of-function mutations and RNA interference-mediated reduction of DPMS1 expression in Arabidopsis causes a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that is manifested by extensive chlorosis and a strong reduction of root growth
metabolism
-
dolichyl phosphate mannose synthase is a key enzyme in the O-glycosylation pathway
physiological function
-
high level of expression of (GlcNAc-beta-(1,4)-GlcNAc) 1-4-beta-GlcNAc-NeuAc glycans on the external surface of the capillary endothelial cells overexpressing DPMS. Increased cellular proliferation and accelerated healing of the wound induced by mechanical stress of the DPMS-overexpressing clone unequivocally supports a role of DPMS in angiogenesis
physiological function
-
overexpression of DPMS accelerates angiogenesis, a higher rate of cellular proliferation in DPMS overexpressing cells compared to the pEGFP-N1 vector and the parental cells
physiological function
-
elevated activity of overexpressed Saccharomyces cerevisiae dolichyl phosphate mannose synthase enhances biocontrol abilities of Trichoderma atroviride
physiological function
-
overexpression of DPMS1 in Arabidopsis thaliana results in disorganized stem morphology and vascular bundle arrangements, wrinkled seed coat, and constitutive ER stress response
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6Z,10E,14E,18E,22E)-3,7,15,19,23,27-hexamethyl-11-[(naphthalen-1-ylamino)methyl]octacosa-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
(6Z,10Z,14Z,18Z,22E,26E)-3,7,11,15,19,23,27-heptamethyl-30-(naphthalen-1-ylamino)triaconta-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
(6Z,10Z,14Z,18Z,22Z,26Z,30E,34E,38E)-3,7,11,15,19,23,27,31,35,39-decamethyl-42-(naphthalen-1-ylamino)dotetraconta-6,10,14,18,22,26,30,34,38-nonaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
GDP-mannose + C110-dolichyl phosphate
GDP + C110-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C120-dolichyl phosphate
GDP + C120-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C55-undecaprenyl phosphate
GDP + C55-undecaprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C85-dolichyl phosphate
GDP + C85-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
P14020
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
cAMP-dependent protein kinase is essential for upregulating the Dol-P-Man synthase activity and consequently the Glc3Man9GlcNAc-PP-Dol biosymthesis and protein N-glycosylation in cAMP-responsive cells
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
the enzyme transfers mannose from the water soluble cytoplasmic donor GDP-Man, to the membrane bound, extremely hydrophobic, and long-chain polyisoprenoid acceptor, dolichyl-phosphate, or synthetic analogs of dolichyl phosphate
-
-
?
GDPmannose + (S)-3-methyloctadecanyl phosphate
GDP + (S)-3-methyloctadecanyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C100 alpha-dihydropolyprenyl phosphate
GDP + C100 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C55 alpha-dihydropolyprenyl phosphate
GDP + C55 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C55-polyisoprenol
GDP + D-mannosyl-C55-polyisopropenol
show the reaction diagram
-
-
-
-
?
GDPmannose + C80 alpha-dihydropolyprenyl phosphate
GDP + C80 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + cetyl phosphate
GDP + cetyl D-mannosyl phosphate
show the reaction diagram
-
less efficient than dolichol phosphate
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
O60762
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
r
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
r
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
essential enzyme in glycoprotein biosynthesis
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
the enzyme is involved in glycoconjugate biosynthesis
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
cAMP-mediated protein phosphorylation of microsomal membranes increases mannosylphosphodolichol synthase activity
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
synthesis of dolichol-phosphate mannose, a key mannosyl donor for the biosynthesis of N-linked oligosaccharides as well as for O-linked oligosaccharides on yeast glycoproteins
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
Hypocrea jecorina QM 9414
-
-
-
?
GDPmannose + farnesyl phosphate
GDP + farnesyl D-mannosyl phosphate
show the reaction diagram
-
less efficient than dolichol phosphate
-
-
?
GDPmannose + phytanyl phosphate
GDP + phytanyl D-mannosyl phosphate
show the reaction diagram
-
at 60-70% of the activity with dolichyl phosphate
-
-
?
additional information
?
-
-
activities of fluorescent labeled dolichyl-phosphate derivatives
-
-
-
additional information
?
-
-
branching of lipid phosphates is essential for substrates of the enzyme, transfer of mannose occurs even if only branching at C3 is present
-
-
-
additional information
?
-
-
increased availability of GDP-mannose corrects glycosylation defects in the endoplasmic reticulum, such as dolichyl D-mannosyl phosphate formation in dolichyl-phosphate beta-D-mannosyltransferase mutants of Saccharomyces cerevisiae
-
-
-
additional information
?
-
-
glycosylphosphatidylinositol anchor biosynthesis
-
-
-
additional information
?
-
-
two binding proteins, DPMS2 and DPMS3 serve as membrane anchors for DPMS1 or provide catalytic assistance. Recombinant DPMS1 alone does not catalyze dolichyl D-mannosyl phosphate synthesis
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
cAMP-dependent protein kinase is essential for upregulating the Dol-P-Man synthase activity and consequently the Glc3Man9GlcNAc-PP-Dol biosymthesis and protein N-glycosylation in cAMP-responsive cells
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
the enzyme transfers mannose from the water soluble cytoplasmic donor GDP-Man, to the membrane bound, extremely hydrophobic, and long-chain polyisoprenoid acceptor, dolichyl-phosphate
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
essential enzyme in glycoprotein biosynthesis
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
the enzyme is involved in glycoconjugate biosynthesis
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
cAMP-mediated protein phosphorylation of microsomal membranes increases mannosylphosphodolichol synthase activity
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
-
synthesis of dolichol-phosphate mannose, a key mannosyl donor for the biosynthesis of N-linked oligosaccharides as well as for O-linked oligosaccharides on yeast glycoproteins
-
-
?
additional information
?
-
-
increased availability of GDP-mannose corrects glycosylation defects in the endoplasmic reticulum, such as dolichyl D-mannosyl phosphate formation in dolichyl-phosphate beta-D-mannosyltransferase mutants of Saccharomyces cerevisiae
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
5 mM, divalent metal required, 90% of the activation with 5 mM Mn2+
Co2+
-
less efficient in activation than Mn2+
Mg2+
-
Km: 1.31 mM
Mg2+
-
Mg2+ and Mn2+ up to a concentration of 5 mM result in the same activation
Mg2+
-
5 mM, divalent metal required, 70% of the activation with 5 mM Mn2+
Mg2+
-
stimulation by addition of divalent cations, maximal stimulation at 5 mM
Mg2+
-
optimal stimulation at 3 mM
Mg2+
-
less efficient than Mn2+ in activation
Mg2+
-
optimally stimulated, 1.7fold, by 10 mM
Mg2+
-
divalent cation required for dolichol phosphate mannose: 2.5-7.5 mM Mg2+ or 2-3 mM Mn2+. Mg2+ is a better activator than Mn2+ in the reverse reaction
Mg2+
-
stimulated by MgCl2, optimal concentration: 20 mM
Mg2+
-
-
Mg2+
-
required
Mn2+
-
Mg2+ and Mn2+ up to a concentration of 5 mM result in the same activation
Mn2+
-
5 mM, divalent cation required, highest activation with Mn2+
Mn2+
-
divalent cation required, maximal stimulation at 2.5 mM Mn2+
Mn2+
-
stimulation by divalent cation, Mn2+ is less effective than Mg2+
Mn2+
-
divalent cation required, maximal activity with Mn2+
Mn2+
-
divalent cation required for synthesis of dolichyl D-mannosyl phosphate: 2.5-7.5 mM Mg2+ or 2-3 mM Mn2+. Mg2+ is a better activator than Mn2+ in the reverse reaction
Mn2+
-
required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
Amphomycin
-
0.03 mg/ml, 50% inhibition
GDP
-
0.0013 mM, 50% inhibition
GDP
-
0.1 mM, 75% inhibition
GDP
-
0.01 mM, 81% inhibition
GDP-2-deoxy-D-glucose
-
-
GDP-3-deoxy-D-mannose
-
-
GDP-4-deoxy-D-mannose
-
-
GDP-6-deoxy-D-mannose
-
-
GDP-D-glucose
-
0.01 mM, 50% inhibition
GMP
-
0.016 mM, 50% inhibition
GMP
-
1 mM, 75% inhibition
GMP
-
1 mM, 84% inhibition; competitive
GTP
-
0.003 mM, 50% inhibition
lucifer yellow iodoacetamide
-
-
Nonidet P-40
-
0.01%, 50% inhibition
p-hydroxymercuribenzoate
-
0.003 mM, 50% inhibition
p-hydroxymercuribenzoate
-
-
phosphatidylinositol
-
relative activity: 70%
Tunicamycin
-
-
[(5Z)-4-oxo-5-(phenylmethylidene)-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
42% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
23% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates
[(5Z)-5-[(3-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
90% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-chlorophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
86% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-cyanophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
73% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-ethynylphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
94% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
70% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates
[(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
20% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates
[(5Z)-5-[[3-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
23% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
10% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates
additional information
-
GDP, GTP, IDP or GMP provide protection against inactivation by thiol reagents
-
additional information
-
DPMS inhibitors prevent the biosynthesis of glycosylphosphatidylinositol anchors, and possess trypanocidal activity against live trypanosomes
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
8-bromo-cAMP
-
capillary endothelial cells treated with the cAMP enhancer 8-bromo-cAMP show a 20% and 30% higher activity after 24h and 32h, respectively
phosphatidylcholine
-
activates
phosphatidylcholine
-
increases activity 1.3fold at the optimal concentration
phosphatidylcholine
-
relative activity: 122%
phosphatidylethanolamine
-
increases activity 2.3fold at the optimal concentration
phosphatidylethanolamine
-
relative activity: 125%
phosphatidylglycerol
-
relative activity: 356%
phosphatidylinositol
-
increases activity 2.3fold at the optimal concentration
phosphatidylinositol
-
relative activity: 70%
phosphatidylserine
-
relative activity: 342%
Phospholipid
-
no absolute requirement for phospholipid, the phospholipid is required for interaction of the enzyme with the long chain polyisoprenol substrate dolichyl phosphate
sphingomyelin
-
activates
lysophosphatidylcholine
-
activates
additional information
-
optimally active in a phospholipid matrix that contains some component phospholipids that prefer non-bilayer structural organization in isolation
-
additional information
-
the activity of dolichyl-phosphate beta-D-mannosyltransferase is subject to activation by a cAMP-dependent protein kinase in vitro
-
additional information
-
the enzyme is activated by cAMP-dependent protein kinase
-
additional information
-
cAMP-dependent protein kinase is essential for upregulating the Dol-P-Man synthase activity and consequently the Glc3Man9GlcNAc-PP-Dol biosynthesis and protein N-glycosylation in cAMP-responsive cells
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0751
-
(6Z,10E,14E,18E,22E)-3,7,15,19,23,27-hexamethyl-11-[(naphthalen-1-ylamino)methyl]octacosa-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate
-
pH 7.5
0.0246
-
(6Z,10Z,14Z,18Z,22E,26E)-3,7,11,15,19,23,27-heptamethyl-30-(naphthalen-1-ylamino)triaconta-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate
-
pH 7.5
0.0248
-
(6Z,10Z,14Z,18Z,22Z,26Z,30E,34E,38E)-3,7,11,15,19,23,27,31,35,39-decamethyl-42-(naphthalen-1-ylamino)dotetraconta-6,10,14,18,22,26,30,34,38-nonaen-1-yl dihydrogen phosphate
-
pH 7.5
0.00059
-
C110-dolichyl phosphate
-
-
0.00159
-
C120-dolichyl phosphate
-
-
0.00117
-
C55-undecaprenyl phosphate
-
-
0.0023
-
C85-dolichyl phosphate
-
-
0.0003
-
dolichyl phosphate
-
-
0.0025
-
dolichyl phosphate
-
wild-type enzyme reconstituted with phosphatidylethanolamine
0.0026
-
dolichyl phosphate
-
-
0.0027
-
dolichyl phosphate
-
wild-type enzyme reconstituted with phosphatidylethanolamine
0.0033
-
dolichyl phosphate
-
-
0.0106
-
dolichyl phosphate
-
wild-type enzyme assayed in solution of Nonidet P-40
0.0143
-
dolichyl phosphate
-
-
0.00018
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, wild-type enzyme
0.00029
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate,enzyme from cAMP-dependent protein kinase-deficient mutant 10215
0.00032
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, wild-type enzyme
0.00045
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate,enzyme from cAMP-dependent protein kinase-deficient mutant 10215
0.00048
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10260
0.00076
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10248
0.00082
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10260
0.00093
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10248
0.0011
-
GDP-mannose
P14020
phosphorylated enzyme, 37C, pH 7.0
0.0012
-
GDP-mannose
P14020
non-phosphorylated enzyme, 37C, pH 7.0
0.00025
-
GDPmannose
-
-
0.00036
-
GDPmannose
-
-
0.00043
-
GDPmannose
-
-
0.00069
-
GDPmannose
-
-
0.00133
-
GDPmannose
-
-
0.0015
-
GDPmannose
-
wild-type enzyme assayed in solution of Nonidet P-40
0.00173
-
GDPmannose
-
-
0.0041
-
GDPmannose
-
-
0.005
-
GDPmannose
-
unphosphorylated enzyme
0.0065
-
GDPmannose
-
phosphorylated enzyme
0.007
-
GDPmannose
-
-
additional information
-
additional information
P14020
the KM-values for dolichyl phosphate do not differ between the invitro phosphorylated and the control enzyme
-
additional information
-
additional information
-
KM-values for synthetic dolichyl phosphate analogs
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0000023
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, wild-type enzyme
0.0000029
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, wild-type enzyme
0.0000049
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, with or without dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10215
0.0000063
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10260
0.0000069
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10260
0.0000089
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, without dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10248
0.0000095
-
GDP-mannose
-
37C, pH 7.0, wild-type enzyme, in presence of dolichyl phosphate, enzyme from cAMP-dependent protein kinase-deficient mutant 10248
12.1
-
GDP-mannose
P14020
non-phosphorylated enzyme, 37C, pH 7.0
70.9
-
GDP-mannose
P14020
phosphorylated enzyme, 37C, pH 7.0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.018
-
GDP
-
-
0.056
-
GDP
-
-
0.0013
-
GDP-2-deoxy-D-glucose
-
-
0.001
-
GDP-3-deoxy-D-mannose
-
-
0.0031
-
GDP-4-deoxy-D-mannose
-
-
0.0004
-
GDP-6-deoxy-D-mannose
-
-
0.235
-
GMP
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000285
-
-
-
0.0016
-
-
-
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.1
-
-
Mes buffer or sodium/potassium phosphate buffer
7
-
-
-
7
-
-
assay at
7.2
-
-
-
7.5
8
-
potassium phosphate or Tris-HCl buffer
7.5
9.5
-
-
8.5
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
8
-
pH 5.8: about 35% of maximal activity, pH 8.0: about 60% of maximal activity
6.5
8.5
-
pH 6.5: about 80% of maximal activity, pH 8.5: about 54% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
15
35
-
15C: about 60% of maximal activity, 35C: about 30% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
capillary endothelial cell
Manually annotated by BRENDA team
-
higher level of expression in mature female worms, as compared to immature and male worms
Manually annotated by BRENDA team
-
Lec15.1 cell have a single point mutation within the coding region of DPM2 gene. The cDNA of the mutant DPM2 subunit is expressed at a drastically reduced amount of DPM2 protein
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
enzyme is closely associated with membranes of the endoplasmic reticulum
Manually annotated by BRENDA team
-
DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by the small membrane protein DPM3
Manually annotated by BRENDA team
-
enzyme is anchored with both its N-termini and C-termini in the membrane, while the main part of the protein is oriented towards the lumen of the endoplasmic reticulum
Manually annotated by BRENDA team
-
enzyme is closely associated with membranes of the endoplasmic reticulum
Manually annotated by BRENDA team
-
of the endoplasmic reticulum
Manually annotated by BRENDA team
-
N-terminal domain is membrane-bound
Manually annotated by BRENDA team
-
DPMS has one membrane spanning region
Manually annotated by BRENDA team
-
following isopycnic centrifugation of plasma membrane-free extracts, microsomes enrich dolichol-P-mannose synthase
-
Manually annotated by BRENDA team
Hypocrea jecorina QM 9414
-
-
-
-
Manually annotated by BRENDA team
-
cytosolic face of the outer membrane
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
41010
-
-
deduced from cDNA
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 30000, SDS-PAGE
?
-
x * 30000, SDS-PAGE
?
-
x * 42000, SDS-PAGE under reducing conditions
?
-
x * 33000, recombinant His-tag DPMS, SDS-PAGE
?
-
x * 85000, Clostridium thermocellum cellulose-binding domain-fusion protein, SDS-PAGE
?
Haloferax volcanii WR536 (H53)
-
x * 85000, Clostridium thermocellum cellulose-binding domain-fusion protein, SDS-PAGE
-
additional information
-
enzyme consists of three subunits: DPM1, DPM2 and DPM3. DPM3 is stabilized by DPM2 and DPM3, in turn stabilizes the catalytic subunit DPM1
additional information
-
enzyme consists of three subunits: DPM1, DPM2, and DPM3
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
alignment of the amino acid sequence of bDPM1 with that of Homo sapiens, Schizosaccharomyces pombe, Saccharomyces cerevisiae and Ustilago maydis indicates the presence of a cAMP-dependent phosphorylation motif
phosphoprotein
-
the enzyme can be regulated by phosphorylation and dephosphorylation
phosphoprotein
P14020
in vitro phosphorylation by cAMP-dependent protein kinase up-regulates recombinant Saccharomyces cerevisiae mannosylphosphodolichol synthase
phosphoprotein
-
the enzyme contains a potential site for phosphorylation by cAMP-dependent protein kinase
additional information
-
no glycosylation
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
20 min, complete inactivation, in presence of mitochondrial extract 40% loss of activity, stable for 30 min in presence of sphingomyelin and dolichyl phosphate
40
-
-
20 min, 50% loss of activity in presence of sphingomyelin and dolichyl phosphate
75
-
-
protein shows thermostability up to 75C
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reducing agents positively influence stability
-
in combination dolichyl phosphate and phospholipids are effective in stabilization
-
unstable in presence of detergent
-
the enzyme is resistant to inactivation by incubation with trypsin unless Triton is present
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, loss of a third of the activity after 2 weeks
-
-70C, 2 weeks, no loss of activity
-
0C, 3 days, 50% loss of activity
-
-40C, stable for about a month with 20% loss of activity
-
during solubilization the enzyme is stabilized by the presence of lipophilic substrate dilochylphosphate and phospholipids as well as by protease inhibitors
-
4C, enzyme is relatively stable when stored overnight in phosphate buffer and retains full activity when stored within liposomes
-
4C, stable for more than 24 h
-
-20C, phosphate buffer, pH 6.0, 20 mM Mg2+, 0.2% polidocanol, 20% glycerol, stable for 2 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DEAE-cellulose column chromatography, gel filtration
-
His-tag fusion protein purified using ProBond purification system, more than 97% pure
-
one-step purification
-
solubilized with Triton X-100 and purified to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DPMS (KB-3) gene cloned into the pcDNA3.1/His A vector at the KpnI and XhoI site and transformed into DH5alpha cells. Cloned into Xho I and BamH I sites of pEGFP-N1 to obtain pEGFP-N1-DPMS overexpression plasmid. Transfection of capillary endothelial cells with pEGFP-N1-DPMS overexpression plasmid and pEGFP-N1 vector
-
DPM1 cDNA from wild-type and Lec15.1 cells is identical
-
gene can complement a lethal null mutation in Schizosaccharomyces pombe
O60762
expressed in Escherichia coli
-
full-length protein is expressed in Escherichia coli and the N-terminal domain is expressed in Saccharomyces cerevisiae
-
expressed in Trichoderma atroviride strain P1
-
functionally active mutant enzyme S141A is expressed in Escherichia coli
P14020
gene can complement a lethal null mutation in Schizosaccharomyces pombe
-
glycoprotein hypersecretion alters the cell wall in Trichoderma reesei strains expressing the Saccharomyces cerevisiae dolichylphosphate mannose synthase gene
-
the cDNA is amplified in mature males and females
-
cDNA fragments containing the start and stop codons amplified and subcloned into the EcoRV site of the pBluescript II SK(-) cloning vector
-
capillary endothelial cell clone overexpressing the gene encoding DPMS
-
full-length DPMS expressed in Escherichia coli
-
functionally expressed in yeast strain DPM 1-6 and Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
capillary endothelial cells harboring DPMS overexpressing plasmid express DPMS higher than pEGFP-N1 vector and the parental cells
-
compared with the mock line, the temporary PEC(Z)/PB lines show a decreased mRNA expression for D-P-M and a clear destruction of porcine endogenous retrovirus infectivity to human cells in the Lac Z pseudotype assay. Compared with parental and mock cells, all PEC(Z)/PB cells transfected with siRNA show a decreased mRNA expression for the D-P-M by one-fifth
-
the DPMS-overexpressing clone has a high level of DPMS mRNA, expresses nearly 4times more DPMS protein than the clone transfected with pEGFP-N1 vector only and has 108% higher DPMS activity than the vector control
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D38A
-
5.8% of the activity of wild-type
D39A
-
2% of the activity of wild-type
D89A
-
0.09% of the activity of wild-type
D91A
-
0.17% of the activity of wild-type
C172S
-
specific activity similar to the wild-type enzyme
C259S
-
specific activity similar to the wild-type enzyme
C93S
-
specific activity similar to the wild-type enzyme
G10E
-
Lec15.1 cell have a single point mutation within the coding region of DPM2 gene. The mutant DPM2 cDNA is expresses a drastically reduced amount of DPM2 protein
additional information
-
cloned Pfdpm1 gene fails to complement a Saccharomyces cerevisiae mutant indicating that the parasite gene does not belong to the bakers yeast group. Furthermore, Pfdpm1 is unable to complement a mouse mutant deficient in DPM but efficiently complements the Schizosaccharomyces pombe fission yeast mutant, indicating a difference between fission yeast and mammalian DPM genes
I253N
-
higher value for the apparent Km-value for dolichyl phosphate when assayed in detergent solution, mutation has no effect on Km-value when the enzyme is reconstituted with phosphatidylethanolamine
additional information
-
mutant enzymes containing successive deletions or mutations of the hydrophobic region exhibit decreased transferase activity in vitro compared to the wild type enzyme, but the sequence is not essential for growth or for protein glycosylation. Although deletion of the entire hydrophobic region results in a soluble protein, mutant proteins containing 3 or 8 hydrophobic residues are still membrane-associated
additional information
-
DPM synthase mutants have an aberrant cell wall composition and ultrastructure. Mutant is oversensitive to Calcofluor white, an agent interacting with the cell wall chitin. Chemical analysis of the cell wall alkali-insoluble fraction indicates an increased amount of chitin and changes in the quantity of beta1,6- and beta1,3-glucan in dpm1-6 mutants. Cell wall defect is suppressed by an increased dolichol availability caused by the RER2 (cis-prenyl transferase-encoding) gene overexpression and subsequent upregulation of DolPPGlcNAc2 synthesis. This is concomitant with an increase in glycosylation and stability of the plasma membrane protein Gas1 and rearrangement of the cell wall components
S141A
P14020
functionally active mutant enzyme with more than 50% reduction in catalytic activity compared to wild-type enzyme
additional information
Saccharomyces cerevisiae SF402-4D
-
DPM synthase mutants have an aberrant cell wall composition and ultrastructure. Mutant is oversensitive to Calcofluor white, an agent interacting with the cell wall chitin. Chemical analysis of the cell wall alkali-insoluble fraction indicates an increased amount of chitin and changes in the quantity of beta1,6- and beta1,3-glucan in dpm1-6 mutants. Cell wall defect is suppressed by an increased dolichol availability caused by the RER2 (cis-prenyl transferase-encoding) gene overexpression and subsequent upregulation of DolPPGlcNAc2 synthesis. This is concomitant with an increase in glycosylation and stability of the plasma membrane protein Gas1 and rearrangement of the cell wall components
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
increased DPMS activity through protein phosphorylation is a driving force for angiogenesis
medicine
-
D-P-M enzyme activity represents a potentially useful approach to address the problem of porcine endogenous retrovirus infections in clinical xenotransplantations
drug development
-
inhibition of DPMS is a promising strategy for the development of anti-trypanosomal agents. Thiazolidinones [(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid, [(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid and [(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid in particular are promising candidates for further development because of their respective activities against trypanosomal DPMS and GPI anchor biosynthesis