Information on EC 3.1.4.50 - glycosylphosphatidylinositol phospholipase D

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.1.4.50
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RECOMMENDED NAME
GeneOntology No.
glycosylphosphatidylinositol phospholipase D
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O = 6-(alpha-D-glucosaminyl)-1D-myo-inositol + 3-sn-phosphatidate
show the reaction diagram
this enzyme is also active when O-4 of the glucosamine is substituted by carrying the oligosaccharide that can link a protein to the structure. It therefore cleaves proteins from the lipid part of the glycosylphosphatidylinositol anchors, but does so by hydrolysis, whereas glycosylphosphatidylinositol diacylglycerol-lyase, EC 4.6.1.14, does so by elimination. It acts on plasma membranes only after solubilization of the substrate with detergents or solvents, but it may act on intracellular membranes
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric diester
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
glycoprotein-phosphatidylinositol phosphatidohydrolase
This enzyme is also active when O-4 of the glucosamine is substituted by carrying the oligosaccharide that can link a protein to the structure. It therefore cleaves proteins from the lipid part of the glycosylphosphatidylinositol (GPI) anchors, but does so by hydrolysis, whereas glycosylphosphatidylinositol diacylglycerol-lyase (EC 4.6.1.14) does so by elimination. It acts on plasma membranes only after solubilization of the substrate with detergents or solvents, but it may act on intracellular membranes.
CAS REGISTRY NUMBER
COMMENTARY hide
113756-14-2
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127737-50-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
C57BL/6 mice
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
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the enzyme may participate in regulating inflammation in atherosclerosis
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-O-alpha-D-galactosaminyl-1-phosphatidyl-D-chiro-inositol + H2O
?
show the reaction diagram
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-
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?
2-O-alpha-D-glucosaminyl-1-phosphatidyl-D-chiro-inositol + H2O
?
show the reaction diagram
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-
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?
3-O-alpha-D-galactosaminyl-2-phosphatidyl-L-chiro-inositol + H2O
?
show the reaction diagram
3-O-alpha-D-glycosaminyl-2-phosphatidyl-L-chiro-inositol + H2O
?
show the reaction diagram
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?
5'-nucleotidase + H2O
?
show the reaction diagram
6-O-alpha-D-glucosaminylphosphatidylinositol + H2O
?
show the reaction diagram
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-
?
alkaline phosphatase + H2O
?
show the reaction diagram
glycosylphosphatidylinositol-anchor intermediates + H2O
?
show the reaction diagram
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?
glycosylphosphatidylinositol-anchored placental alkaline phosphatase + H2O
?
show the reaction diagram
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?
glycosylphosphatidylinositol-anchored protein + H2O
?
show the reaction diagram
glycosylphosphatidylinositol-anchored proteins
phosphatidic acid + variant membrane protein
show the reaction diagram
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GPI-PLD is highly specific for the GPI anchor
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ir
glycosylphosphatidylinositol-membrane anchor of Cripto-1
soluble Cripto-1 + phosphatidic acid
show the reaction diagram
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ir
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
show the reaction diagram
membrane-anchored form of urokinase plasminogen activator + H2O
soluble form of urokinase plasminogen activator
show the reaction diagram
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i.e. uPAR or CD 87
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?
membrane-bound carcinoembryonic antigen + H2O
?
show the reaction diagram
membrane-bound mucin binding protein + H2O
free mucin binding protein
show the reaction diagram
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?
myristate-labelled membrane form of variant surface glycoprotein from Trypanosoma brucei + H2O
?
show the reaction diagram
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?
phosphatidylinositol + H2O
diacylglycerol + inositol phosphate
show the reaction diagram
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phosphatidylinositol-glycan-anchored membrane form of acetylcholinesterase + H2O
soluble acetylcholinesterase + phosphatidic acid
show the reaction diagram
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isolated from bovine erythrocyte membranes
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?
Zn2+-glycerophosphocholine cholinephosphodiesterase, amphiphilic form + H2O
Zn2+-glycerophosphocholine cholinephosphodiesterase, hydrophilic form
show the reaction diagram
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
glycosylphosphatidylinositol-anchored protein + H2O
?
show the reaction diagram
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GPI-PDL can influence the steady-state levels of glycosylphosphatidylinositol-anchored proteins by hydrolysing the anchor before and after its attachment to proteins
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?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
show the reaction diagram
membrane-bound carcinoembryonic antigen + H2O
?
show the reaction diagram
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cleavage enhances the metastatic potential in colorectal carcinoma cells
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?
phosphatidylinositol-glycan-anchored membrane form of acetylcholinesterase + H2O
soluble acetylcholinesterase + phosphatidic acid
show the reaction diagram
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isolated from bovine erythrocyte membranes
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
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about 10 atoms per enzyme molecule
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
2,2'-dipyridyl
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Ca2+ does not protect
Bicarbonate buffer
Ca2+
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slight decrease of activity above 1 mM, activation at 0.0001-0.01 mM
Chloropromazine
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partial
cholesteryl ester
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strong
ganglioside
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strong
lipid A
lysophosphatidic acid
lysophosphatidylcholine
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50% inhibition at 0.05 mM
NaHCO3
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kinetics, pH-dependent: at pH 7.5, not at pH 5.5, reversible
NaOCN
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kinetics, pH-dependent, reversible
p-Hydroxymercuriphenylsulfonic acid
phosphatidic acid
phosphatidylglycerol
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strong
phosphatidylinositol
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strong
phosphatidylserine
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strong
sphingomyelin
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strong
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
monoacylglycerol
monodecanoylglycerol
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n-butanol
Nonidet P-40
phosphatidylethanolamine
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activation
suramin
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activates
Triton X-100
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activation, best at 1-2 mM
Trypsin
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during cleavage enzymatic activity increases 3-4fold
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additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001
phosphatidylinositol-glycan-anchor of membrane form of acetylcholinesterase
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37°C, pH 7.4
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
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higher activity at low ionic strength, increasing amounts of NaCl, KCl, Na2SO4 or sodium phosphate decrease activity
6.6
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7
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about 60% of maximal activity at pH 5 and about half-maximal activity at pH 7, no activity above pH 8.5
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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expression during embryonic ossification. GPI-PLD is observed during both intramembraneous and endochondral ossification and localized predominantly to the extracellular matrix of chondrocytes and to primary trabecular of the skeleton
Manually annotated by BRENDA team
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localized predominantly to the extracellulat matrix of chondrocytes and to primary trabeculae of the skeleton
Manually annotated by BRENDA team
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SW620, SW837, Colo201, Colo320 and SW1736
Manually annotated by BRENDA team
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the serum GPI-PLD activities, the GPI-PLD protein expression levels, and the protein and mRNA levels of GPI-PLD in hepatocellular carcinoma are decreased by 40%, 60%, and 56%, respectively
Manually annotated by BRENDA team
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GPI-PDL activities and their mRNA copies in patients with chronic myeloid leukemia are significantly lower than those in healthy adults
Manually annotated by BRENDA team
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culture of buccal mucosa
Manually annotated by BRENDA team
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islet amyloid
Manually annotated by BRENDA team
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macrophage cell line
Manually annotated by BRENDA team
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localized predominantly to the extracellulat matrix of chondrocytes and to primary trabeculae of the skeleton
Manually annotated by BRENDA team
additional information
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GPI-PLD is expressed in nearly all tissues and cells types, but the liver has the highest level of GPI-PLD expression and is the primary source of circulating GPI-PLD. GPI-PLD is a minor high-density lipoprotein-associated protein. It is elevated in patients with insulin resistance or high triglycerides
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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murine pancreatic enzyme is recombinantly expressed in Hela cells
Manually annotated by BRENDA team
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murine pancreatic enzyme is recombinantly expressed in Hela cells
Manually annotated by BRENDA team
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murine pancreatic enzyme is recombinantly expressed in Hela cells
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
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gel filtration
103000
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x * 103000, SDS-PAGE
110000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 103000, SDS-PAGE
monomer
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1 * 110000
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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different oligosaccharide processing of enzyme after expression in mammalian CHO cells and insect H5 cells affecting immunoreactive and enzymatic properties
phosphoprotein
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wild-type enzyme and mutant enzymes H81N, H98N, H125N, H133N and H158N are phosphorylated
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
sensitive to ionic detergents
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serum triglycerides alter GPI-PLD activity in vitro
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stable over a range of 0.01-0.1% detergent, ionic detergents such as SDS are inhibitory, and bicarbonate buffer is inhibitory
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Hep-G2 cells
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overexpression of GPI-PLD in the insulinoma cell line betaTC6f7 enhances glucose-stimulated insulin secretion 4fold, but does not affect the preproinsulin mRNA levels. Overexpressing GPI-PLD using adenovirus-mediated gene transfer in C57BL/6 mice, associated with a decrease in fasting glucose as well as an improvement in glucose tolerance
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overview
wild-type and mutant enzymes are expressed in COS-I cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
hepatic GPI-PLD messenger RNA and serum GPI-PLD levels are increased in patients with nonalcoholic fatty liver disease
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H125N
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inactive mutant enzyme
H133N
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inactive mutant enzyme
H158N
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inactive mutant enzyme
H29N
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inactive mutant enzyme
H56N
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inactive mutant enzyme
H88N
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inactive mutant enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
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the enzyme might be a diagnostic predictive marker for abdominal aortic aneurysm
medicine
additional information
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GPI-PLD predicts the change in insulin resistance in subjects randomized to the low-fat diet, but not in response to those randomized to the very low carbohydrate diet