ID:PI51A_HUMAN DESCRIPTION: RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha; Short=PIP5K1-alpha; Short=PtdIns(4)P-5-kinase 1 alpha; EC=2.7.1.68; AltName: Full=68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha; AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I alpha; Short=PIP5KIalpha; FUNCTION: Catalyzes 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. CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. SUBUNIT: Interacts 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. SUBCELLULAR LOCATION: Cell membrane. Cytoplasm (By similarity). 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. TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in brain, lung and liver. SIMILARITY: Contains 1 PIPK domain. CAUTION: There 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.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99755
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_rhoPathway - Rho cell motility signaling pathway
Reactome (by CSHL, EBI, and GO)
Protein Q99755 (Reactome details) participates in the following event(s):
R-HSA-1676082 PI4P is phosphorylated to PI(4,5)P2 by PIP5K1A-C at the plasma membrane R-HSA-1675773 PI(3,4)P2 is phosphorylated to PI(3,4,5)P3 by PIP5K1A-C at the plasma membrane R-HSA-1676145 PI3P is phosphorylated to PI(3,4)P2 by PIP4K2/5K1 at the plasma membrane R-HSA-1676134 PI3P is phosphorylated to PI(3,5)P2 by PIP5K1A/B at the plasma membrane R-HSA-1675810 PI is phosphorylated to PI5P by PIP5K1A/B at the plasma membrane R-HSA-1660499 Synthesis of PIPs at the plasma membrane R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1483255 PI Metabolism R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-1483257 Phospholipid metabolism R-HSA-1257604 PIP3 activates AKT signaling R-HSA-556833 Metabolism of lipids R-HSA-9006925 Intracellular signaling by second messengers R-HSA-1430728 Metabolism R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
