Protein: Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (PIP5K1-alpha) (PtdIns(4)P-5-kinase 1 alpha) (EC 2.7.1.68) (68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha) (Phosphatidylinositol 4-phosphate 5-kinase type I alpha) (PIP5KIalpha) (Q99755)
Organism: Homo sapiens (Human)
Function: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility. PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can also use phosphatidylinositol (PtdIns) as substrate in vitro. Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (By similarity). Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (By similarity). 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, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation. Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity). Together with PIP5K1C has a role during embryogenesis (By similarity). Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane. Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs.
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P70182}. Cytoplasm {ECO:0000250|UniProtKB:P70182}. Nucleus {ECO:0000269|PubMed:15157668}. Nucleus speckle {ECO:0000269|PubMed:18288197}. Cell projection, ruffle {ECO:0000269|PubMed:20660631}. Cell projection, lamellipodium {ECO:0000269|PubMed:15157668}. Note=Colocalizes with RAC1 at actin-rich membrane ruffles (PubMed:20660631). Localizes to nuclear speckles and associates with TUT1 to regulate polyadenylation of selected mRNAs (PubMed:18288197). {ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:20660631}.
Interaction partners:
- Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma
- Phosphatidylinositol 4-kinase beta
- ADP-ribosylation factor 6
- Phosphatidylinositol 4-kinase type 2-alpha
- Phosphatidylinositol 4-phosphate 5-kinase-like protein 1
- Phosphatidylinositol 4-kinase alpha
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- Phosphatidylinositol 4-kinase type 2-beta
- Phosphatidylinositol 4-phosphate 5-kinase type-1 beta
- Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
Sequence:
MASASSGPSSSVGFSSFDPAVPSCTLSSAASGIKRPMASEVLEARQDSYISLVPYASGMPIKKIGHRSVDSSGETTYKKTTSSALKGAIQLGITHTVGSLSTKPERDVLMQDFYVVESIFFPSEGSNLTPAHHYNDFRFKTYAPVAFRYFRELFGIRPDDYLYSLCSEPLIELCSSGASGSLFYVSSDDEFIIKTVQHKEAEFLQKLLPGYYMNLNQNPRTLLPKFYGLYCVQAGGKNIRIVVMNNLLPRSVKMHIKYDLKGSTYKRRASQKEREKPLPTFKDLDFLQDIPDGLFLDADMYNALCKTLQRDCLVLQSFKIMDYSLLMSIHNIDHAQREPLSSETQYSVDTRRPAPQKALYSTAMESIQGEARRGGTMETDDHMGGIPARNSKGERLLLYIGIIDILQSYRFVKKLEHSWKALVHDGDTVSVHRPGFYAERFQRFMCNTVFKKIPLKPSPSKKFRSGSSFSRRAGSSGNSCITYQPSVSGEHKAQVTTKAEVEPGVHLGRPDVLPQTPPLEEISEGSPIPDPSFSPLVGETLQMLTTSTTLEKLEVAESEFTH