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MGP003540

UniProt Annotations

Entry Information
Gene Namephosphatidylinositol-4-phosphate 5-kinase, type I, alpha
Protein EntryPI51A_HUMAN
UniProt IDQ99755
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=PIP5KIalpha2; IsoId=Q99755-1; Sequence=Displayed; Name=2; Synonyms=PIP5KIalpha3; IsoId=Q99755-2; Sequence=VSP_016007, VSP_016008; Name=3; IsoId=Q99755-3; Sequence=VSP_016007; Name=4; IsoId=Q99755-4; Sequence=VSP_041912, VSP_041913;
Catalytic ActivityATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
CautionThere is confusion in the literature with phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due to the fact that frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5-kinase type I alpha. {ECO:0000305}.
FunctionCatalyzes the phosphorylation of phosphatidylinositol 4- phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as actin cytoskeleton organization, cell adhesion, migration and phagocytosis. Required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of RAC1 to the plasma membrane. Together with PIP5K1C is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle ingestion by activating WAS that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B is required after stimulation of G-protein coupled receptors for stable platelet adhesion. Plays a role during calcium-induced keratinocyte differentiation. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate that mobilize internal calcium and drive keratinocyte differentiation. Together with PIP5K1C have a role during embryogenesis. Functions also in the nucleus where acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs. {ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393, ECO:0000269|PubMed:20660631}.
SimilarityContains 1 PIPK domain. {ECO:0000255|PROSITE- ProRule:PRU00781}.
Subcellular LocationCell membrane. Cytoplasm {ECO:0000250}. Nucleus speckle. Cell projection, ruffle. Note=Colocalizes with RAC1 at actin-rich membrane ruffles. Localizes to nuclear speckles and associates with TUT1 to regulate polyadenylation of selected mRNAs.
SubunitInteracts with RAC1 (By similarity). Interacts with TUT1. Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane upon calcium stimulation. {ECO:0000250, ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393}.
Tissue SpecificityHighly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in brain, lung and liver.
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