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Information on EC 3.1.4.50 - glycosylphosphatidylinositol phospholipase D and Organism(s) Homo sapiens and UniProt Accession P80108
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3.1.4.50 glycosylphosphatidylinositol phospholipase DIUBMB Comments
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.
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Word Map
- 3.1.4.50
-
gpi-anchored
- medicine
-
gpi-phospholipase
- gpi-plc
-
glycosyl-phosphatidylinositol
-
3hmyristate-labeled
-
3hethanolamine
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
gpi-pld, glycosylphosphatidylinositol-specific phospholipase d, gpld1, gpi-specific phospholipase d, glycosylphosphatidylinositol phospholipase d, pi-g pld, phosphatidylinositol-specific phospholipase d, glycosylphosphatidylinositol-phospholipase d, glycoprotein phospholipase d, phosphatidylinositol phospholipase d, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
glycoprotein phospholipase D
-
-
-
-
glycosylphosphatidylinositol-specific phospholipase D
-
-
GPI-PLD
phosphatidylinositol phospholipase D
-
-
-
-
phosphatidylinositol-specific phospholipase D
-
-
-
-
phospholipase D, phosphatidylinositol
-
-
-
-
PI-G PLD
-
-
-
-
GPI-PLD
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric diester
-
-
-
-
PATHWAY SOURCE
PATHWAYS
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
113756-14-2
-
127737-50-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
glycosylphosphatidylinositol-anchored placental alkaline phosphatase + H2O
?
-
-
-
-
?
glycosylphosphatidylinositol-anchored proteins
phosphatidic acid + variant membrane protein
-
GPI-PLD is highly specific for the GPI anchor
-
-
ir
glycosylphosphatidylinositol-membrane anchor of Cripto-1
soluble Cripto-1 + phosphatidic acid
-
-
-
-
ir
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
membrane-anchored form of urokinase plasminogen activator + H2O
soluble form of urokinase plasminogen activator
-
i.e. uPAR or CD 87
-
?
myristate-labelled membrane form of variant surface glycoprotein from Trypanosoma brucei + H2O
?
-
-
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
-
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
cleaves phosphodiester linkage to diacylglycerol
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
specific for glycosyl-phosphatidylinositol structure, i.e. the anchoring domain of cell surface proteins
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
phospholipase D-type hydrolysis
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
phospholipase D-type hydrolysis
-
?
membrane-bound carcinoembryonic antigen + H2O
?
-
cleavage enhances the metastatic potential in colorectal carcinoma cells
-
-
?
additional information
?
-
cleavage of the glycan-phosphatidylinositol linkage of GPI-anchored proteins
-
-
?
additional information
?
-
-
no substrate: phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol derived from HNO2-cleaved mfVSG, overview on substrate specificity
-
-
?
additional information
?
-
-
enzyme catalyzed cleavage of glycosylphosphatidylinositol anchor is a potential source of diacylglycerol production to activate protein kinase Calpha
-
-
?
additional information
?
-
-
GPI-PDL activities and their mRNA copies in patients with chronic myeloid leukemia are significantly lower than those in healthy adults. The decreased GPI-PLD expression may reduce the release of GPI-anchored CD55 and CD59 in leukemia cells and finally decrease complement mediated killing of these cells in chronic phase of chronic myeloid leukemia
-
-
?
additional information
?
-
-
GPI-PLD may play a role in islet amyloid formation in type 2 diabetes
-
-
?
additional information
?
-
-
involvement of endogenous GPI-PDI in spontaneous elevated release of carcinoembryonic antigen from human colon cancer cells
-
-
?
additional information
?
-
-
the enzyme plays an active role in lipoprotein metabolism and may contribute to the dyslipidemia of insulin resistant patients
-
-
?
additional information
?
-
-
patients with non-alcoholic fatty liver disease have elevated serum levels and hepatic expression of glycosylphosphatidylinositol-specific phospholipase D. The enzyme may play a role in the pathogenesis of non-alcoholic fatty liver disease and/or its metabolic features
-
-
?
additional information
?
-
-
cleavage of GPI-membrane anchor of carcinoembryonic antigen enhances the metastatic potential in colorectal carcinoma cells
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
membrane-bound carcinoembryonic antigen + H2O
?
-
cleavage enhances the metastatic potential in colorectal carcinoma cells
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
-
-
?
membrane form of variant-surface-glycoprotein + H2O
phosphatidic acid + variant-surface-glycoprotein inositol
-
-
-
?
additional information
?
-
-
enzyme catalyzed cleavage of glycosylphosphatidylinositol anchor is a potential source of diacylglycerol production to activate protein kinase Calpha
-
-
?
additional information
?
-
-
GPI-PDL activities and their mRNA copies in patients with chronic myeloid leukemia are significantly lower than those in healthy adults. The decreased GPI-PLD expression may reduce the release of GPI-anchored CD55 and CD59 in leukemia cells and finally decrease complement mediated killing of these cells in chronic phase of chronic myeloid leukemia
-
-
?
additional information
?
-
-
GPI-PLD may play a role in islet amyloid formation in type 2 diabetes
-
-
?
additional information
?
-
-
involvement of endogenous GPI-PDI in spontaneous elevated release of carcinoembryonic antigen from human colon cancer cells
-
-
?
additional information
?
-
-
the enzyme plays an active role in lipoprotein metabolism and may contribute to the dyslipidemia of insulin resistant patients
-
-
?
additional information
?
-
-
patients with non-alcoholic fatty liver disease have elevated serum levels and hepatic expression of glycosylphosphatidylinositol-specific phospholipase D. The enzyme may play a role in the pathogenesis of non-alcoholic fatty liver disease and/or its metabolic features
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
n-butanol
-
activation, at pH 5, membrane form of variant-surface-glycoprotein as substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
-
GPI-PDL activities and their mRNA copies in patients with chronic myeloid leukemia are significantly lower than those in healthy adults
additional information
-
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
-
plasma enzyme levels are significantly lower in patients with ruptured compared nonruptured abdominal aortic aneurysm which is a result of hemodilution due to hemorrhage in patients with ruptured abdominal aortic aneurysm. The plasma enzyme levels are similar in patients with nonruptured abdominal aortic aneurysm compared to the controls without aneurysm
-
hepatic GPI-PLD messenger RNA and serum GPI-PLD levels are increased in patients with nonalcoholic fatty liver disease
-
the baseline level of plasma GPI-PLD in the cohort of obese women on low-carbohydrate and low-fat weight loss diets is nearly twice that of a cohort with nonalcoholic fatty liver disease, but similar to that of a cohort with type 2 diabetes mellitus and low HDL
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
serum GPI-PLD level is strongly and independently associated with serum alanine transaminase and triglyceride levels in human male subjects
malfunction
physiological function
-
the enzyme may participate in regulating inflammation in atherosclerosis
malfunction
-
GPI-PLD is elevated in patients with insulin resistance or high triglycerides, and in patients with nonalcoholic fatty liver disease, overview
malfunction
-
plasma enzyme levels are significantly lower in patients with ruptured compared nonruptured abdominal aortic aneurysm which is a result of hemodilution due to hemorrhage in patients with ruptured abdominal aortic aneurysm. The plasma enzyme levels are similar in patients with nonruptured abdominal aortic aneurysm compared to the controls without aneurysm
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PHLD_HUMAN
840
0
92336
Swiss-Prot
Secretory Pathway (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
different oligosaccharide processing of enzyme after expression in mammalian CHO cells and insect H5 cells affecting immunoreactive and enzymatic properties
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the hepatic mRNA level and circulating concentration of GPI-PLD are significantly augmented in diabetic mice
hepatic GPI-PLD messenger RNA and serum GPI-PLD levels are increased in patients with nonalcoholic fatty liver disease
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
diagnostics
-
the enzyme might be a diagnostic predictive marker for abdominal aortic aneurysm
medicine
additional information
-
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
medicine
in samples from steatohepatitis and hepatocellular carcinoma patients, serum GPI-PLD activity is increased 4fold, while its tissue activity is reduced by 60%. c-Myc influences GPI-AP signaling transcriptionally and posttranslationally and represses GPI-AP anti-proliferative signaling in tumors
medicine
the expression of GPI-PLD is dramatically down-regulated in both the brain and cerebrospinal fluids of Creutzfeldt-Jakob disease patients, while no differences in expression are observed in either the brains or cerebrospinal fluids specimens from Alzheimer's disease patients
medicine
the hepatic mRNA level and circulating concentration of GPI-PLD are significantly augmented in diabetic mice
medicine
-
patients with liver disease have lower activites, those with renal disease have higher activities than healthy controls
medicine
-
enzyme may be involved in generation of circulating prognostic markers in cancer
medicine
-
serum enzyme activity is positively correlated with inflammatory markers and counts of monocytes and stab cells
medicine
-
baseline GPI-PLD levels correlate with the change in insulin sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity correlates with the change in insulin sensitivity in response to the lowcarbohydrate diet, plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Malik, A.S.; Low, M.G.
Conversion of human placental alkaline phosphatase from a high Mr form to a low Mr form during butanol extraction. An investigation of the role of endogenous phosphoinositide-specific phospholipases
Biochem. J.
240
519-527
1986
Homo sapiens
Low, M.G.; Prasad, A.R.S.
A phospholipase D specific for the phosphatidylinositol anchor of cell-surface proteins is abundant in plasma
Proc. Natl. Acad. Sci. USA
85
980-984
1988
Bos taurus, Canis lupus familiaris, Equus caballus, Gallus gallus, Homo sapiens, Oryctolagus cuniculus, Rattus norvegicus
Deeg, M.A.; Davitz, M.A.
Glycosylphosphatidylinositol-phospholipase D: a tool for glycosylphosphatidylinositol structural analysis
Methods Enzymol.
250
630-640
1995
Bos taurus, Homo sapiens
Maguire, G.A.; Gossner, A.
Glycosyl phosphatidyl inositol phospholipase D activity in human serum
Ann. Clin. Biochem.
32
74-78
1995
Homo sapiens
Rhode, H.; Schulze, M.; Cumme, G.A.; Gohlert, A.; Blume, E.; Bublitz, R.; Schilling, K.; Horn, A.
Glycosylphosphatidylinositol-specific phospholipase D of human serum--activity modulation by naturally occurring amphiphiles
Biol. Chem.
381
471-485
2000
Homo sapiens
Rhode, H.; Lopatta, E.; Schulze, M.; Pascual, C.; Schulze, H.P.; Schubert, K.; Schubert, H.; Reinhart, K.; Horn, A.
Glycosylphosphatidylinositol-specific phospholipase D in blood serum: is the liver the only source of the enzyme?
Clin. Chim. Acta
281
127-145
1999
Homo sapiens, Rattus norvegicus
Schofield, J.N.; Stephens, J.W.; Hurel, S.J.; Bell, K.M.; deSouza, J.B.; Rademacher, T.W.
Insulin reduces serum glycosylphosphatidylinositol phospholipase D levels in human type I diabetic patients and streptozotocin diabetic rats
Mol. Genet. Metab.
75
154-161
2002
Homo sapiens, Rattus norvegicus (Q8R2H5)
Tsujioka, H.; Takami, N.; Misumi, Y.; Ikehara, Y.
Intracellular cleavage of glycosylphosphatidylinositol by phospholipase D induces activation of protein kinase Calpha
Biochem. J.
342
449-455
1999
Homo sapiens
Tsujioka, H.; Misumi, Y.; Takami, N.; Ikehara, Y.; Tujioka, H.
Posttranslational modification of glycosylphosphatidylinositol (GPI)-specific phospholipase D and its activity in cleavage of GPI anchors
Biochem. Biophys. Res. Commun.
251
737-743
1998
Homo sapiens
Wilhelm, O.G.; Wilhelm, S.; Escott, G.M.; Lutz, V.; Magdolen, V.; Schmitt, M.; Rifkin, D.B.; Wilson, E.L.; Graeff, H.; Brunner, G.
Cellular glycosylphosphatidylinositol-specific phospholipase D regulates urokinase receptor shedding and cell surface expression
J. Cell. Physiol.
180
225-235
1999
Homo sapiens
Yamamoto, Y.; Hirakawa, E.; Mori, S.; Hamada, Y.; Kawaguchi, N.; Matsuura, N.
Cleavage of carcinoembryonic antigen induces metastatic potential in colorectal carcinoma
Biochem. Biophys. Res. Commun.
333
223-229
2005
Homo sapiens
Naghibalhossaini, F.; Ebadi, P.
Evidence for CEA release from human colon cancer cells by an endogenous GPI-PLD enzyme
Cancer Lett.
234
158-167
2006
Homo sapiens
Jian-Hua, T.; Xiao-Jie, Z.; Yi-Dan, W.; Wen-Kai, L.; Wang-Jiao, H.; Cheng-Hong, W.; Gui-Yuan, L.
Effect of glycosylphosphatidylinositol specific phospholipase D gene expression levels on complement mediated killing of leukemic cells in patients with chronic myeloid leukemia
Clin. Chim. Acta
359
115-124
2005
Homo sapiens
Larson, D.M.; Kennedy, M.A.; Bowen, R.F.; Verchere, C.B.; Deeg, M.A.
Glycosylphosphatidylinositol-specific phospholipase D immunoreactivity is present in islet amyloid in type 2 diabetes
J. Pathol.
203
961-967
2004
Homo sapiens
Kurtz, T.A.; Fineberg, N.S.; Considine, R.V.; Deeg, M.A.
Insulin resistance is associated with increased serum levels of glycosylphosphatidylinositol-specific phospholipase D
Metabolism
53
138-139
2004
Homo sapiens
Chalasani, N.; Vuppalanchi, R.; Raikwar, N.S.; Deeg, M.A.
Glycosylphosphatidylinositol-specific phospholipase D in non-alcoholic fatty liver disease: a preliminary study
J. Clin. Endocrinol. Metab.
91
2279-2285
2006
Homo sapiens
Watanabe, K.; Bianco, C.; Strizzi, L.; Hamada, S.; Mancino, M.; Bailly, V.; Mo, W.; Wen, D.; Miatkowski, K.; Gonzales, M.; Sanicola, M.; Seno, M.; Salomon, D.S.
Growth factor induction of Cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration
J. Biol. Chem.
282
31643-31655
2007
Homo sapiens
Song, K.; Sun, X.; Wang, J.; Zhou, S.; Zeng, H.; Chen, F.
Role of glycosylphosphatidylinositol-specific phospholipase D in the homing of umbilical cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic stem/progenitor cells
Leuk. Res.
31
1701-1707
2007
Homo sapiens (P80108)
Song, K.; Sun, X.; Wang, J.; Chen, F.
How Glycosylphosphatidylinositol-phospholipase D acts in homing of hematopoietic stem/progenitor cells?
Med. Hypotheses
69
660-665
2007
Homo sapiens
Deeg, M.A.; Raikwar, N.S.; Johnson, C.; Williams, C.D.
Statin therapy reduces serum levels of glycosylphosphatidylinositol-specific phospholipase D
Transl. Res.
150
153-157
2007
Homo sapiens
Jian-Hua, T.; Wang-Jiao, H.; He, H.; Chao-Chao, T.; Qiong, D.; Kai-Jia, W.; Xian-Yu, Y.; Xu-Jin, Z.
Important roles of glycosylphosphatidylinositol (GPI)-specific phospholipase D and some GPI-anchored proteins in the pathogenesis of hepatocellular carcinoma
Clin. Biochem.
42
400-407
2009
Homo sapiens
Gray, D.L.; OBrien, K.D.; DAlessio, D.A.; Brehm, B.J.; Deeg, M.A.
Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women
Metab. Clin. Exp.
57
473-478
2008
Homo sapiens
Lindqvist, M.; Wallinder, J.; Bergstroem, J.; Henriksson, A.E.
Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal aortic aneurysm
Int. J. Clin. Exp. Med.
5
306-309
2012
Homo sapiens
Masuda, S.; Fujishima, Y.; Maeda, N.; Tsugawa-Shimizu, Y.; Nakamura, Y.; Tanaka, Y.; Obata, Y.; Fukuda, S.; Nagao, H.; Kita, S.; Nishizawa, H.; Shimomura, I.
Impact of glycosylphosphatidylinositol-specific phospholipase D on hepatic diacylglycerol accumulation, steatosis, and insulin resistance in diet-induced obesity
Am. J. Physiol. Endocrinol. Metab.
316
E239-E250
2019
Homo sapiens (P80108), Homo sapiens, Mus musculus (Q7TNZ4), Rattus norvegicus (Q8R2H5)
Ritorto, M.S.; Rhode, H.; Vogel, A.; Borlak, J.
Regulation of glycosylphosphatidylinositol-anchored proteins and GPI-phospholipase D in a c-Myc transgenic mouse model of hepatocellular carcinoma and human HCC
Biol. Chem.
397
1147-1162
2016
Homo sapiens (P80108), Homo sapiens, Mus musculus (O70362), Mus musculus
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