Information on EC 3.1.3.36 - phosphoinositide 5-phosphatase and Organism(s) Homo sapiens and UniProt Accession P32019

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UNIPROT: P32019
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.1.3.36
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RECOMMENDED NAME
GeneOntology No.
phosphoinositide 5-phosphatase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide degradation
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Inositol phosphate metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
phosphatidyl-myo-inositol-4,5-bisphosphate 4-phosphohydrolase
These enzymes can also remove the 5-phosphate from Ins(1,4,5)P3 and/or Ins(1,3,4,5)P4. They are a diverse family of enzymes, with differing abilities to catalyse two or more of the four reactions listed. They are thought to use inositol lipids rather than inositol phosphates as substrates in vivo. All of them can use either or both of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates; this is the main property that distinguishes them from EC 3.1.3.56, inositol-polyphosphate 5-phosphatase.
CAS REGISTRY NUMBER
COMMENTARY hide
9036-01-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
the enzyme negatively regulates myogenesis through inhibition of insulin-like growth factor-II production and attenuation of the insulin-like growth factor-II-Akt-mTOR signaling pathway
physiological function
additional information
-
GTP-bound, active Rab35 directly interacts with OCRL and controls its localization at the intercellular bridge
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate
show the reaction diagram
-
-
-
-
?
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate
show the reaction diagram
-
-
-
-
?
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O
1D-myo-inositol 1,3,4-trisphosphate + phosphate
show the reaction diagram
1D-myo-inositol 1,3,4,5-tetrasphosphate + H2O
1D-myo-inositol 1,3,4-trisphosphate + phosphate
show the reaction diagram
-
-
-
-
?
1D-myo-inositol 1,4,5-trisphosphate + H2O
1D-myo-inositol 1,4-bisphosphate + phosphate
show the reaction diagram
-
-
-
-
?
7-nitrobenz-2-oxa-1,3-diazole 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
7-nitrobenz-2-oxa-1,3-diazole 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
-
fluorescence-labeled substrate
-
-
?
D(+)-sn-1,2-di-O-hexadecanoylglyceryl 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O
D(+)-sn-1,2-di-O-hexadecanoylglyceryl 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate
show the reaction diagram
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3-O-phospho-linked
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-
?
D(+)-sn-1,2-di-O-hexadecanoylglyceryl 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
D(+)-sn-1,2-di-O-hexadecanoylglyceryl 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
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3-O-phospho-linked, best substrate for synaptojanin2
-
-
?
D-myo-phosphatidylinositol 3,4,5-trisphosphate
D-myo-phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
D-myo-phosphatidylinositol 4,5-bisphosphate
D-myo-phosphatidylinositol 4-phosphate
show the reaction diagram
-
-
-
-
?
inositol 1,3,4,5-tetrakisphosphate + H2O
inositol 1,3,4-trisphosphate + phosphate
show the reaction diagram
myo-inositol 1,4,5-trisphosphate + H2O
inositol 1,4-diphosphate + phosphate
show the reaction diagram
myo-inositol 3,4,5-trisphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
phosphatidyl-myo-inositol 4,5-bisphosphate + H2O
phosphatidylinositol 4-phosphate + phosphate
show the reaction diagram
phosphatidylinositol 4,5-bisphosphate + H2O
phosphatidylinositol 4-phosphate + phosphate
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
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate
show the reaction diagram
-
-
-
-
?
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the enzyme reduces the Ca2+ flux in the cell
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-benzyl-oxybenzene 1,2,4-trisphosphate
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3-hydroxybenzene 1,2,4-trisphosphate
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4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazolo(3,4-d)pyrimidine
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inhibits translocation of SHIP1 to the plasma membrane and tyrsine phosphorylation
ammonyx LO
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benzene 1,2,3,4-tetrakisphosphate
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benzene 1,2,3,5-tetrakisphosphate
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benzene 1,2,3-trisphosphate
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benzene 1,2,4,5-tetrakisphosphate
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benzene 1,2,4-trisphosphate
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benzene 1,3,5-trisphosphate
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biphenyl 2,3',4,5',6-pentakisphosphate
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Ca2+
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competitive with Mg2+ in presence of optimal concentrations of Mg2+
hemoglobin
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at concentrations higher than 1% W/v
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neomycin
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inhibits only in absence of Triton X-100
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
phosphatidylcholine
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vesicles of phosphatidylcholine only stimulate SHIP2 activity by 2fold. This effect is specific for di-C8 and di-C16 fatty acids of D-myo-phosphatidylinositol 3,4,5-trisphosphate as substrate
phosphatidylserine
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vesicles of phosphatidylserine (PtdSer) greatly stimulate SHIP2. This effect is specific for di-C8 and di-C16 fatty acids of D-myo-phosphatidylinositol 3,4,5-trisphosphate as substrate
potassium bisperoxo (1,10-phenanthroline) oxovanadate (V)
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protein phosphatase inhibitor bpV(phen), a cell permeable derivative, enhances the activity of PtdIns3P3 5-phosphatase, particularly SHIP2
Sodium vanadate
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protein phosphatase inhibitor enhances the activity of PtdIns3P3 5-phosphatase, particularly SHIP2
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.028
Inositol 1,3,4,5-tetrakisphosphate
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0.123
Inositol 1,4,5-trisphosphate
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0.25 - 0.27
phosphatidyl-myo-inositol 4,5-bisphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.068
3-benzyl-oxybenzene 1,2,4-trisphosphate
Homo sapiens;
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0.021
3-hydroxybenzene 1,2,4-trisphosphate
Homo sapiens;
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0.098
benzene 1,2,3,4-tetrakisphosphate
Homo sapiens;
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0.078
benzene 1,2,3,5-tetrakisphosphate
Homo sapiens;
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0.086
benzene 1,2,3-trisphosphate
Homo sapiens;
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0.004
benzene 1,2,4,5-tetrakisphosphate
Homo sapiens;
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0.014
benzene 1,2,4-trisphosphate
Homo sapiens;
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0.016
benzene 1,3,5-trisphosphate
Homo sapiens;
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0.001
biphenyl 2,3',4,5',6-pentakisphosphate
Homo sapiens;
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.765
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additional information
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the adaptor protein APS, which specifically interacts with SHIP2, increases the PtdIns(3,4,5)P3 5-phosphatase activity of SHIP2 (76.7% at 3 microM APS and by 111.3% at 6 microM APS)
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
activity declines sharply at temperatures above 37°C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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lowest expression
Manually annotated by BRENDA team
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highest expression
Manually annotated by BRENDA team
additional information
-
ubiquitously expressed
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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subcellular localisation found in Golgi apparatus and ER-to-Golgi intermediate compartment (ERGIC). INPP5B binds to specific RAB proteins within the secretory pathway, and mutational analysis indicates that RAB binding is required for efficient Golgi targeting of INPP5B
Manually annotated by BRENDA team
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multicolor total internal reflection fluorescence microscopy (TIRFM) is used to visualize the spatial-temporal recruitment of SJ1, and its binding partner endophilin to clathrin-coated-pits. Differential temporal recruitment of the two major SJ1 splice variants to clathrin-coated-pits is observed. SJ1-145 is rapidly recruited as a burst, together with its binding partner endophilin, at a late stage of clathrin-coated-pit formation; multicolor total internal reflection fluorescence microscopy (TIRFM) is used to visualize the spatialtemporal recruitment of SJ1, and its binding partner endophilin to clathrin-coated-pits. Differential temporal recruitment of the two major SJ1 splice variants to clathrin-coated-pits is observed. SJ1-170 is present at all stages of CCP formation
Manually annotated by BRENDA team
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SKIP localizes to the ER in HuH-7 cells
Manually annotated by BRENDA team
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enzyme is associated with the lysosomal membrane
Manually annotated by BRENDA team
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in HuH-7 cells overexpressing SKIP and infected with hepatitis B virus (HBV), SKIP localizes to nucleus in addition to endoplasmic reticulum and suppresses HBV gene expression and replication. SKIP loses its nuclear localization and suppressive effect during replication of a core-negative HBV mutant
Manually annotated by BRENDA team
both isoforms a and b predominantly localize to the perinuclear region
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Manually annotated by BRENDA team
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OCRL1 accumulates on Legionella-containing vacuoles in wild-type Legionella pneumophilia infected Dictyostelium discoideum
Manually annotated by BRENDA team
additional information
OCRL1a is significantly more abundant in the cytoplasmic puncta, and there is less diffuse cytosolic staining compared to isoform b in NRK- and HeLa cells
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
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x * 100000, SDS-PAGE
104000
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gel filtration
145000
-
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170000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method
sitting drop vapor diffusion method
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
half-life: about 1 day
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivated by freezing
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Triton X-100 stabilizes
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, half-life: about 1 day
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
immobilized metal ion affinity chromatography (Co2+), gel filtration
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Ni2+-colums
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partial
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recombinant GST-tagged catalytic domains of synaptojanin2 and OCRL from Escherichia coli strain DH5alpha by glutathione affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
full-length human INPP5B cDNA is cloned into pEGFP-C3 with an N-terminal FLAG tag for in vivo expression. INPP5B cDNA is cloned into pGBKT7 for yeast two-hybrid experiments and pBAC2 for expression of recombinant protein in insect cells. DNA encoding the N-terminal 229 amino acids of INPP5B is cloned into pET41EK-LIC for expression of GST-tagged protein in Escherichia coli
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DNA and amino acid sequence detremination and analysis, expression of GFP-tagged synaptojanin-1 in CHO cells
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expressed as a HIS-tagged fusion protein in 3T3-L1 adipocytes and in CHO-IR cells (Chinese hamster ovary cells stably transfected with the insulin receptor)
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expressed in COS-7 cells and in Saccharomyces cerevisiae
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expressed in Dictyostelium discoideum
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expressed in Escherichia coli as a GST-fusion protein and as a Flag-tagged fusion protein in human hepatoma HuH-7 cells
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expressed in Escherichia coli as a GST-tagged protein
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expressed in HEK293 cells
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expressed in murine 3T3-L1 preadipocytes
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expressed in Saccharomyces cerevisiae and in NRK- and HeLa cells
expression in baculovirus-infected Sf9 cells
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expression of GST-tagged catalytic domains, comprising residues D474-R959 of synaptojanin2 and residues V202-E618 of OCRL, in Escherichia coli strain DH5alpha
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full-length SJ1-145 is cloned into the peGFP-C1 vector; full-length SJ1-170 is cloned into the peGFP-C1 vector
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SH2 domain; SH2 domain, a maltose-binding protein fusion protein and a His-tagged version expressed in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression, which is markedly elevated during cell differentiation
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isoform INPP5E is overexpressed in cervical cancer, non-Hodgkin’s lymphoma, and uterine leiomyosarcoma
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the enzyme is downregulated in human melanoma
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C910A
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mutation of the C-terminal cysteine (C910A), which abolishes prenylation of INPP5B does not affect cellular targeting of INPP5B
D524A
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mutation of the aspartic acid within the conserved sequence PAWCDRIL in the 5-phosphatase domain which renders INPP5B catalytically inactive, has no effect on the targeting of INPP5B to the Golgi apparatus, ERGIC or endosomes
C383S
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mutant with an almost entirely eliminated 3-phosphatase and 4-phosphatase activity, but a maintained 5-phosphatase activity also fails to rescue the endocytic defects in synj1-/- neurons
C392S
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site-directed mutagenesis, inactivating mutation in the conserved CX5R(T/S) motif of the Sac domain
C641A
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site-directed mutagenesis, the mutation removes the prenylation site of the enzyme
D192A
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to assess the role of catalytic activity of SKIP on its suppressive effect, a phosphatase-negative mutant D192A is generated: 5-phosphatase activity is not required for the suppressive effect
D193/E195A
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binding activity is much lower compared to wild-type fragment consisting of amino acids 124-314. Binding activity for active RhoA is dramatically reduced compared to wild-type
D223/K224A
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binding activity is much lower compared to wild-type fragment consisting of amino acids 124-314
D556A
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site-directed mutagenesis, inactivating point mutation of the conserved DRVL motif of INPP5E
D730A
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mutant with a deficient 5-phosphatase activity fails to rescue the endocytic defects in synj1-/- neurons
DELTA1-885/1186-1258
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the effects of SHIP2 on c-Jun NH2-terminal kinase (JNK) activity and JIP1 (JNK-interacting protein 1) tyrosine phosphorylation are independent of the SHIP2 phosphoinositide 5-phosphatase activity, as similar results are obtained when using a SHIP2 catalytic inactive mutant instead of wild-type SHIP2
DELTA237-893
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the N-terminal domain of OCRL1 is localized throughout the host cytoplasm and it binds Legionella pneumophila LpnE, a Sel1-like repeat protein involved in Legionella-containing vacuoles formation, which localizes to Legionella-containing vacuoles and selectively binds PtdIns(3)P
DELTA73-77
deletion of this LIDIA sequence motif within the N-terminal region of OCRL1 reveals that this sequence motif functions as a second clathrin binding domain in both isoforms
DELTAPIP2
expression of OCRL1 isoform a, but not isoform b, lacking the 5-phosphatase domain impairs transferrin endocytosis
G664D
G664D mutation shows little effect on binding to clathrin, alpha-adaptin, Rac1 or APPL1, while binding to Rabs 5 and 6 is almost completely abolished. The effects of G664D mutation are the same for both OCRL1 isoforms
P105E
-
Glu in SHIP1 SH2 domain, faster association kinetics for binding to immobilized peptide VApYSYL
P686A/D690A/R691A
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catalytically inactive dominant-negative mutant inhibits proliferation of preadipocytes more potently than wild-type SHIP2. Phospho-Akt, phospho-ERK1/2, and PDGF receptor (PDGFR) levels are reduced in mutant-expressing preadipocytes. The inhibition of PDGF-activated mitogenic pathways by SHIP2 mutant is consistent with a decrease in PDGFR phosphorylation caused by a drop in receptor levels in SHIP2 mutant-expressing cells. SHIP2 mutant promotes ubiquitination of the PDGFR and its degradation via the lysosomal pathway independently of the association between the E3 ubiquitin ligase c-Cbl and PDGFR
P88S
-
Ser in SHIP1 SH2 domain, faster association kinetics for binding to immobilized peptide VApYSYL
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
molecular biology
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results suggest a role for INPP5B in retrograde ER-to-Golgi intermediate compartment (ERGIC) transport
medicine
-
examination of patients with Lowe oculocerebrorenal syndrome, MIM 309000, and their families for mutations in enzyme gene
molecular biology