PIK3C2A
The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq]
Full Name
phosphoinositide-3-kinase, class 2, alpha polypeptide
Function
Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465).
Biological Process
Cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Clathrin coat assemblyManual Assertion Based On ExperimentTAS:UniProtKB
EndocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Epidermal growth factor receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
ExocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Insulin receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Membrane organizationTAS:Reactome
Phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIBA:GO_Central
Phosphatidylinositol biosynthetic processManual Assertion Based On ExperimentTAS:ProtInc
Phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Phosphatidylinositol-3-phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Phosphatidylinositol-mediated signalingManual Assertion Based On ExperimentIBA:GO_Central
Platelet-derived growth factor receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of autophagyManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of cell migration involved in sprouting angiogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Vascular associated smooth muscle contractionManual Assertion Based On ExperimentTAS:UniProtKB
Cellular Location
Cell membrane
Cytoplasmic vesicle, clathrin-coated vesicle
Nucleus
Cytoplasm
Golgi apparatus, trans-Golgi network
Inserts preferentially into membranes containing PtdIns(4,5)P2 (PubMed:17038310).
Associated with RNA-containing structures (PubMed:11606566).
Involvement in disease
Oculoskeletodental syndrome (OCSKD):
An autosomal recessive syndrome characterized by congenital cataracts, short stature, dysmorphic features with coarse facies, dental anomalies, multiple skeletal abnormalities, and neurological manifestations. Other recurrent features include hearing loss, secondary glaucoma, and nephrocalcinosis.
PTM
Phosphorylated upon insulin stimulation; which may lead to enzyme activation (By similarity).
Phosphorylated on Ser-259 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation. Ser-259 phosphorylation may be mediated by CDK1 or JNK, depending on the physiological state of the cell.