MGP Database

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MGP002286

UniProt Annotations

Entry Information
Gene Namephosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Protein EntryP3C2A_HUMAN
UniProt IDO00443
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O00443-1; Sequence=Displayed; Name=2; IsoId=O00443-2; Sequence=VSP_056158; Note=No experimental confirmation available.;
Biophysicochemical PropertiesKinetic parameters: KM=122 uM for PtdIns (in the absence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; KM=64 uM for PtdIns (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; KM=25 uM for PtdIns4P (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; KM=15 uM for ATP (with PtdIns as substrate) (in the absence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; KM=32 uM for ATP (with PtdIns as substrate) (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; KM=54 uM for ATP (with PtdIns4P as substrate) (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=990 pmol/min/mg enzyme with PtdIns as substrate (in the absence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=200 pmol/min/mg enzyme with PtdIns as substrate (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=240 pmol/min/mg enzyme with PtdIns4P as substrate (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=6800 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the absence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=805 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Vmax=880 pmol/min/mg enzyme toward ATP with PtdIns4P as substrate (in the presence of phosphatidylserine) {ECO:0000269|PubMed:9337861}; Note=In the absence of the carrier phosphatidylserine, enzymatic kinetics toward PtdIns4P are non-linear.;
Catalytic ActivityATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate.
CofactorName=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:9337861}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:9337861}; Note=Ca(2+) or Mg(2+). Mn(2+) cannot be used. {ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:9337861};
Enzyme RegulationActivated by insulin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by clathrin. {ECO:0000250, ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:9337861}.
FunctionGenerates 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. {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:9337861}.
PtmPhosphorylated 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. {ECO:0000250, ECO:0000269|PubMed:11606566, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
SimilarityBelongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-ProRule:PRU00879, ECO:0000255|PROSITE- ProRule:PRU00880}.
SimilarityContains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}.
SimilarityContains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE- ProRule:PRU00880}.
SimilarityContains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}.
SimilarityContains 1 PI3K-RBD domain. {ECO:0000255|PROSITE- ProRule:PRU00879}.
SimilarityContains 1 PIK helical domain. {ECO:0000255|PROSITE- ProRule:PRU00878}.
SimilarityContains 1 PX (phox homology) domain. {ECO:0000255|PROSITE-ProRule:PRU00147}.
Subcellular LocationCell membrane. Golgi apparatus. Cytoplasmic vesicle, clathrin-coated vesicle. Nucleus. Cytoplasm. Note=According to PubMed:10766823 and PubMed:11239472, it is found in the cell membrane, the Golgi apparatus and in clathrin-coated vesicles. According to PubMed:17038310 it inserts preferentially into membranes containing PtdIns(4,5)P2. According to PubMed:11606566, it is nuclear and cytoplasmic. Associated with RNA-containing structures. According to PubMed:14563213, it is mainly cytoplasmic.
SubunitPart of a complex with ERBB2 and EGFR. Interacts with clathrin trimers. {ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:16215232}.
Tissue SpecificityExpressed in columnar and transitional epithelia, mononuclear cells, smooth muscle cells, and endothelial cells lining capillaries and small venules (at protein level). Ubiquitously expressed, with highest levels in heart, placenta and ovary, and lowest levels in the kidney. Detected at low levels in islets of Langerhans from type 2 diabetes mellitus individuals. {ECO:0000269|PubMed:14563213, ECO:0000269|PubMed:21127054, ECO:0000269|PubMed:9337861}.
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