Functional Description
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In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (By similarity). Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability.Functional Description
In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (By similarity). Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. |
| Gene Ontology |
GO:0016324--C:apical plasma membrane
GO:0042995--C:cell projection
GO:0005737--C:cytoplasm
GO:0009898--C:cytoplasmic side of plasma membrane
GO:0043197--C:dendritic spine
GO:0005739--C:mitochondrion
GO:0035749--C:myelin sheath adaxonal region
GO:0043005--C:neuron projection
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0016605--C:PML body
GO:0045211--C:postsynaptic membrane
GO:0043220--C:Schmidt-Lanterman incisure
GO:0010997--F:anaphase-promoting complex binding
GO:0019899--F:enzyme binding
GO:0042802--F:identical protein binding
GO:0051717--F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
GO:0000287--F:magnesium ion binding
GO:0030165--F:PDZ domain binding
GO:0016314--F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO:0051800--F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
GO:0004438--F:phosphatidylinositol-3-phosphatase activity
GO:0004721--F:phosphoprotein phosphatase activity
GO:0019901--F:protein kinase binding
GO:0004722--F:protein serine/threonine phosphatase activity
GO:0004725--F:protein tyrosine phosphatase activity
GO:0008138--F:protein tyrosine/serine/threonine phosphatase activity
GO:0007092--P:activation of APC-Cdc20 complex activity
GO:0030534--P:adult behavior
GO:0007568--P:aging
GO:0001525--P:angiogenesis
GO:0006915--P:apoptotic process
GO:0048854--P:brain morphogenesis
GO:0060070--P:canonical Wnt signaling pathway
GO:0048738--P:cardiac muscle tissue development
GO:0016477--P:cell migration
GO:0036294--P:cellular response to decreased oxygen levels
GO:0071456--P:cellular response to hypoxia
GO:0007417--P:central nervous system development
GO:0032286--P:central nervous system myelin maintenance
GO:0021955--P:central nervous system neuron axonogenesis
GO:0060997--P:dendritic spine morphogenesis
GO:0021542--P:dentate gyrus development
GO:0043542--P:endothelial cell migration
GO:0048853--P:forebrain morphogenesis
GO:0007507--P:heart development
GO:0046855--P:inositol phosphate dephosphorylation
GO:0007611--P:learning or memory
GO:0045475--P:locomotor rhythm
GO:0007626--P:locomotory behavior
GO:0060292--P:long term synaptic depression
GO:0060291--P:long-term synaptic potentiation
GO:0060179--P:male mating behavior
GO:0042711--P:maternal behavior
GO:0007613--P:memory
GO:0033555--P:multicellular organismal response to stress
GO:0043066--P:negative regulation of apoptotic process
GO:0050771--P:negative regulation of axonogenesis
GO:0090344--P:negative regulation of cell aging
GO:0030336--P:negative regulation of cell migration
GO:0008285--P:negative regulation of cell proliferation
GO:0045792--P:negative regulation of cell size
GO:0031658--P:negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
GO:0061002--P:negative regulation of dendritic spine morphogenesis
GO:0050680--P:negative regulation of epithelial cell proliferation
GO:0090394--P:negative regulation of excitatory postsynaptic potential
GO:0051895--P:negative regulation of focal adhesion assembly
GO:2000134--P:negative regulation of G1/S transition of mitotic cell cycle
GO:0031642--P:negative regulation of myelination
GO:0046621--P:negative regulation of organ growth
GO:0050765--P:negative regulation of phagocytosis
GO:0051898--P:negative regulation of protein kinase B signaling
GO:0001933--P:negative regulation of protein phosphorylation
GO:0090071--P:negative regulation of ribosome biogenesis
GO:2000808--P:negative regulation of synaptic vesicle clustering
GO:0007270--P:neuron-neuron synaptic transmission
GO:0035335--P:peptidyl-tyrosine dephosphorylation
GO:0046856--P:phosphatidylinositol dephosphorylation
GO:0048008--P:platelet-derived growth factor receptor signaling pathway
GO:2001235--P:positive regulation of apoptotic signaling pathway
GO:0008284--P:positive regulation of cell proliferation
GO:0070374--P:positive regulation of ERK1 and ERK2 cascade
GO:2000463--P:positive regulation of excitatory postsynaptic potential
GO:2000060--P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0051091--P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:0097107--P:postsynaptic density assembly
GO:0060134--P:prepulse inhibition
GO:0097105--P:presynaptic membrane assembly
GO:0060736--P:prostate gland growth
GO:0006470--P:protein dephosphorylation
GO:0043491--P:protein kinase B signaling
GO:0050821--P:protein stabilization
GO:0048679--P:regulation of axon regeneration
GO:0002902--P:regulation of B cell apoptotic process
GO:0051726--P:regulation of cell cycle
GO:0032535--P:regulation of cellular component size
GO:0060341--P:regulation of cellular localization
GO:0033032--P:regulation of myeloid cell apoptotic process
GO:0010975--P:regulation of neuron projection development
GO:0031647--P:regulation of protein stability
GO:0032228--P:regulation of synaptic transmission, GABAergic
GO:0046685--P:response to arsenic-containing substance
GO:0033198--P:response to ATP
GO:0042493--P:response to drug
GO:0032355--P:response to estradiol
GO:0045471--P:response to ethanol
GO:0009749--P:response to glucose
GO:0007584--P:response to nutrient
GO:0010043--P:response to zinc ion
GO:0060024--P:rhythmic synaptic transmission
GO:0035176--P:social behavior
GO:0007416--P:synapse assembly
GO:0060074--P:synapse maturation
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