PIK3C2A
Description
The PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) is a protein-coding gene located on chromosome 11.
Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the PIK3C2A gene. 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 PI 3-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 wortmannin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling.
== Clinical significance == Three families have been reported with homozygous loss of function mutations in this gene. The clinical features of this syndrome include short stature, coarse facial features, cataracts with secondary glaucoma, multiple skeletal abnormalities and neurological manifestations. Abnormalities of cilial function were also noted.
PIK3C2A generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), acting as second messengers. It plays a crucial role in intracellular trafficking events, particularly in insulin signaling and secretion. PIK3C2A facilitates the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, enabling glucose uptake in response to insulin-mediated RHOQ activation. It regulates insulin secretion through two mechanisms: firstly, by participating in glucose-induced insulin secretion downstream of the insulin receptor via AKT1 activation and TBC1D4/AS160 phosphorylation; secondly, by playing a role in the late stages of insulin granule exocytosis, potentially involving insulin granule fusion. PIK3C2A also synthesizes PtdIns3P in response to insulin signaling and functions in the formation and distribution of clathrin-coated endocytic vesicles. Furthermore, it regulates dynamin-independent endocytosis, possibly by recruiting EEA1 to internalizing vesicles. In neurosecretory cells, PIK3C2A synthesizes PtdIns3P on large dense core vesicles. It 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. PIK3C2A might also be involved in the EGF signaling cascade, mitosis, and UV-induced damage response. It is required for the maintenance of normal renal structure and function by supporting normal podocyte function. PIK3C2A is involved in the regulation of ciliogenesis and the trafficking of ciliary components. It forms a complex with ERBB2 and EGFR and interacts with clathrin trimers and SBF2/MTMR13.
PIK3C2A is also known as CPK, OCSKD, PI3-K-C2(ALPHA), PI3-K-C2A, PI3K-C2-alpha, PI3K-C2alpha.
