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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.

• GO:0007092 : activation of mitotic anaphase-promoting complex activity
• GO:0007568 : aging
• GO:0001525 : angiogenesis
• GO:0006915 : apoptotic process
• GO:0048854 : brain morphogenesis
• GO:0060070 : canonical Wnt signaling pathway
• GO:0048738 : cardiac muscle tissue development
• GO:0016477 : cell migration
• GO:0008283 : cell proliferation
• GO:0007417 : central nervous system development
• GO:0032286 : central nervous system myelin maintenance
• GO:0021955 : central nervous system neuron axonogenesis
• GO:0060997 : dendritic spine morphogenesis
• GO:0021542 : dentate gyrus development
• GO:0043542 : endothelial cell migration
• GO:0007173 : epidermal growth factor receptor signaling pathway
• GO:0038095 : Fc-epsilon receptor signaling pathway
• GO:0008543 : fibroblast growth factor receptor signaling pathway
• GO:0048853 : forebrain morphogenesis
• GO:0007507 : heart development
• GO:0045087 : innate immune response
• GO:0046855 : inositol phosphate dephosphorylation
• GO:0043647 : inositol phosphate metabolic process
• GO:0007611 : learning or memory
• GO:0045475 : locomotor rhythm
• GO:0007626 : locomotory behavior
• GO:0060292 : long term synaptic depression
• GO:0060291 : long-term synaptic potentiation
• GO:0060179 : male mating behavior
• GO:0042711 : maternal behavior
• GO:0007613 : memory
• GO:0033555 : multicellular organismal response to stress
• GO:0043066 : negative regulation of apoptotic process
• GO:0050771 : negative regulation of axonogenesis
• GO:0090344 : negative regulation of cell aging
• GO:0030336 : negative regulation of cell migration
• GO:0008285 : negative regulation of cell proliferation
• GO:0045792 : negative regulation of cell size
• GO:0031658 : negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
• GO:0061002 : negative regulation of dendritic spine morphogenesis
• GO:0050680 : negative regulation of epithelial cell proliferation
• GO:0090394 : negative regulation of excitatory postsynaptic membrane potential
• GO:0051895 : negative regulation of focal adhesion assembly
• GO:2000134 : negative regulation of G1/S transition of mitotic cell cycle
• GO:0031642 : negative regulation of myelination
• GO:0046621 : negative regulation of organ growth
• GO:0050765 : negative regulation of phagocytosis
• GO:0014067 : negative regulation of phosphatidylinositol 3-kinase signaling
• GO:0051898 : negative regulation of protein kinase B signaling
• GO:0001933 : negative regulation of protein phosphorylation
• GO:0090071 : negative regulation of ribosome biogenesis
• GO:2000808 : negative regulation of synaptic vesicle clustering
• GO:0007270 : neuron-neuron synaptic transmission
• GO:0048011 : neurotrophin TRK receptor signaling pathway
• GO:0035335 : peptidyl-tyrosine dephosphorylation
• GO:0006661 : phosphatidylinositol biosynthetic process
• GO:0046856 : phosphatidylinositol dephosphorylation
• GO:0048015 : phosphatidylinositol-mediated signaling
• GO:0006644 : phospholipid metabolic process
• GO:0048008 : platelet-derived growth factor receptor signaling pathway
• GO:0043065 : positive regulation of apoptotic process
• GO:2001235 : positive regulation of apoptotic signaling pathway
• GO:0008284 : positive regulation of cell proliferation
• GO:2000463 : positive regulation of excitatory postsynaptic membrane potential
• GO:2000060 : positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
• GO:0051091 : positive regulation of sequence-specific DNA binding transcription factor activity
• GO:0097107 : postsynaptic density assembly
• GO:0060134 : prepulse inhibition
• GO:0097105 : presynaptic membrane assembly
• GO:0060736 : prostate gland growth
• GO:0006470 : protein dephosphorylation
• GO:0043491 : protein kinase B signaling
• GO:0050821 : protein stabilization
• GO:0002902 : regulation of B cell apoptotic process
• GO:0032535 : regulation of cellular component size
• GO:0000079 : regulation of cyclin-dependent protein serine/threonine kinase activity
• GO:0033032 : regulation of myeloid cell apoptotic process
• GO:0010975 : regulation of neuron projection development
• GO:0031647 : regulation of protein stability
• GO:0046685 : response to arsenic-containing substance
• GO:0033198 : response to ATP
• GO:0042493 : response to drug
• GO:0032355 : response to estradiol
• GO:0045471 : response to ethanol
• GO:0009749 : response to glucose
• GO:0007584 : response to nutrient
• GO:0010043 : response to zinc ion
• GO:0060024 : rhythmic synaptic transmission
• GO:0044281 : small molecule metabolic process
• GO:0035176 : social behavior
• GO:0007416 : synapse assembly
• GO:0060074 : synapse maturation
• GO:0050852 : T cell receptor signaling pathway

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/