Gene Symbol: PIP5K1A
Description: phosphatidylinositol-4-phosphate 5-kinase type 1 alpha
Alias: phosphatidylinositol 4-phosphate 5-kinase type-1 alpha, 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha, PIP5K1-alpha, PIP5KIalpha, phosphatidylinositol 4-phosphate 5-kinase type I alpha, ptdIns(4)P-5-kinase 1 alpha
Species: human
Products:     PIP5K1A

Top Publications

  1. Loijens J, Anderson R. Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. J Biol Chem. 1996;271:32937-43 pubmed
    ..Using peptide sequences from the erythroid 68-kDa PIP5KI, we have isolated cDNAs encoding PIP5KIalpha from human brain...
  2. Xie Z, Chang S, Pennypacker S, Liao E, Bikle D. Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular calcium-induced keratinocyte differentiation. Mol Biol Cell. 2009;20:1695-704 pubmed publisher
    ..This signaling pathway is critical for Cao-induced generation of the second messengers IP3 and Cai and keratinocyte differentiation. ..
  3. Kisseleva M, Feng Y, Ward M, Song C, Anderson R, Longmore G. The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha. Mol Cell Biol. 2005;25:3956-66 pubmed
    ..Thus, in addition to its effects upon Rac activity Ajuba can also influence cell migration through regulation of PI(4,5)P2 synthesis through direct activation of PIPKIalpha enzyme activity. ..
  4. Doughman R, Firestone A, Wojtasiak M, Bunce M, Anderson R. Membrane ruffling requires coordination between type Ialpha phosphatidylinositol phosphate kinase and Rac signaling. J Biol Chem. 2003;278:23036-45 pubmed
    ..Combined, these data support a model where the localized production of PIP2 by PIPKIalpha is necessary for actin remodeling, whereas formation of membrane ruffles required Rac signaling. ..
  5. Choi S, Chen M, Cryns V, Anderson R. A nuclear phosphoinositide kinase complex regulates p53. Nat Cell Biol. 2019;21:462-475 pubmed publisher
    ..and mutant p53 is regulated by the type I phosphatidylinositol phosphate kinase (PIPKI-α (also known as PIP5K1A)) and its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)...
  6. Adhikari H, Counter C. Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability. Nat Commun. 2018;9:3646 pubmed publisher
    ..Using this strategy, we identify phosphatidylinositol phosphate kinase PIP5K1A as a KRAS-specific interactor and show that PIP5K1A binds to a unique region in KRAS...
  7. Sarwar M, Syed Khaja A, Aleskandarany M, Karlsson R, Althobiti M, Ødum N, et al. The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor. Oncogene. 2019;38:375-389 pubmed publisher
    ..011 and for mRNA expression, p = 0.028, log-rank test). 29% of triple-negative BC had PIP5K1A gene amplification. Elevated level of PIP5K1α increased expression of pSer-473 AKT (p < 0...
  8. Doumatey A, Xu H, Huang H, Trivedi N, Lei L, Elkahloun A, et al. Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans. J Endocrinol Metab. 2015;5:199-210 pubmed
    ..Telomere extension by telomerase (HNRNPA1, TNKS2), D-myo-inositol (1, 4, 5)-trisphosphate biosynthesis (PIP5K1A, PIP4K2A), and regulation of actin-based motility by Rho (ARPC3) were the most significant canonical pathways and ..
  9. Callegaro G, Forcella M, Melchioretto P, Frattini A, Gribaldo L, Fusi P, et al. Toxicogenomics applied to in vitro Cell Transformation Assay reveals mechanisms of early response to cadmium. Toxicol In Vitro. 2018;48:232-243 pubmed publisher
    ..to be up-regulated in the first 24?h following Cd administration: phospatidylinositol-4-phospate 5-kinase alpha (Pip5k1a), glutathione S-transferase (Gst? 1-3), Gdf15 and aldolase...

More Information


  1. Płóciennikowska A, Zdioruk M, Traczyk G, Świątkowska A, Kwiatkowska K. LPS-induced clustering of CD14 triggers generation of PI(4,5)P2. J Cell Sci. 2015;128:4096-111 pubmed publisher
    ..of PI(4,5)P2 and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region...
  2. Hu J, Yuan Q, Kang X, Qin Y, Li L, Ha Y, et al. Resolution of structure of PIP5K1A reveals molecular mechanism for its regulation by dimerization and dishevelled. Nat Commun. 2015;6:8205 pubmed publisher
    ..Here we report the crystal structure of the catalytic domain of zebrafish PIP5K1A at 3.3 Å resolution. This molecule forms a side-to-side dimer...
  3. Luo B, Prescott S, Topham M. Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. Cell Signal. 2004;16:891-7 pubmed
    ..Here we show that expression of DGKzeta significantly enhances PIP5KIalpha activity in thrombin-stimulated HEK293 cells, and DGK activity is required for this stimulation...
  4. Divecha N, Roefs M, Halstead J, D Andrea S, Fernandez Borga M, Oomen L, et al. Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity. EMBO J. 2000;19:5440-9 pubmed
    ..We show that the physiological requirement of PLD enzymes for PtdIns(4,5)P(2) is critical and that PLD2 activity can be regulated solely by the levels of this key intracellular lipid. ..
  5. Halstead J, van Rheenen J, Snel M, Meeuws S, Mohammed S, D Santos C, et al. A role for PtdIns(4,5)P2 and PIP5Kalpha in regulating stress-induced apoptosis. Curr Biol. 2006;16:1850-6 pubmed
    ..These observations demonstrate that certain apoptotic stimuli initiate an essential signaling pathway during cell death, and this pathway leads to caspase-independent downregulation of PIP5Kalpha and its product PtdIns(4,5)P(2). ..
  6. van den Bout I, Divecha N. PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions. J Cell Sci. 2009;122:3837-50 pubmed publisher
    ..In this Commentary, we review how PIP5Ks are modulated to achieve regulated PtdIns(4,5)P(2) production, and discuss the role of these proteins in different cellular processes. ..
  7. Jones D, Morris J, Morgan C, Kondo H, Irvine R, Cockcroft S. Type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the golgi compartment. J Biol Chem. 2000;275:13962-6 pubmed
    ..ARF1 increased Type I PIP 5-kinase activity in a guanine nucleotide-dependent manner, identifying this enzyme as a direct effector for ARF1. ..
  8. Saito K, Tolias K, Saci A, Koon H, Humphries L, Scharenberg A, et al. BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity. Immunity. 2003;19:669-78 pubmed
    ..This enzyme-enzyme interaction provides a shuttling mechanism that allows BTK to stimulate the production of the substrate required by both its upstream activator, PI3K, and its downstream target, PLC-gamma2. ..
  9. Chao W, Daquinag A, Ashcroft F, Kunz J. Type I PIPK-alpha regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation. J Cell Biol. 2010;190:247-62 pubmed publisher
    ..Thus, our study defines the role of PIPKI-alpha in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration. ..
  10. Gonzales M, Mellman D, Anderson R. CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs. J Biol Chem. 2008;283:12665-73 pubmed publisher
    ..The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs. ..
  11. Mellman D, Gonzales M, Song C, Barlow C, Wang P, Kendziorski C, et al. A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature. 2008;451:1013-7 pubmed publisher
    ..The results reveal a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression. ..
  12. Chang J, Field S, Rameh L, Carpenter C, Cantley L. Identification and characterization of a phosphoinositide phosphate kinase homolog. J Biol Chem. 2004;279:11672-9 pubmed
    ..These results suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P(3). ..
  13. Szymańska E, Korzeniowski M, Raynal P, Sobota A, Kwiatkowska K. Contribution of PIP-5 kinase Ialpha to raft-based FcgammaRIIA signaling. Exp Cell Res. 2009;315:981-95 pubmed publisher
    ..The data suggest that activation of FcgammaRIIA leads to membrane rafts coalescing into signaling platforms containing PIP5-kinase Ialpha and PI(4,5)P(2). ..
  14. Choi S, Hedman A, Sayedyahossein S, Thapa N, Sacks D, Anderson R. Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nat Cell Biol. 2016;18:1324-1335 pubmed publisher
    ..Blockade of IQGAP1 interaction with PIPKI? or PI(3)K inhibited PtdIns(3,4,5)P3 generation and signalling, and selectively diminished cancer cell survival, revealing a target for cancer chemotherapy. ..
  15. Chakrabarti R, Bhowmick D, Bhargava V, Bhar K, Siddhanta A. Nuclear pool of phosphatidylinositol 4 phosphate 5 kinase 1? is modified by polySUMO-2 during apoptosis. Biochem Biophys Res Commun. 2013;439:209-14 pubmed publisher
    ..Moreover, this SUMOylated pool of PIP5K increased during apoptosis. PolySUMO-2 chain conjugated PIP5K was detected by pull-down experiment using affinity-tagged RNF4, a polySUMO-2 binding protein, during late apoptosis. ..
  16. Chakrabarti R, Sanyal S, Ghosh A, Bhar K, Das C, Siddhanta A. Phosphatidylinositol-4-phosphate 5-Kinase 1α Modulates Ribosomal RNA Gene Silencing through Its Interaction with Histone H3 Lysine 9 Trimethylation and Heterochromatin Protein HP1-α. J Biol Chem. 2015;290:20893-903 pubmed publisher
    ..This study, for the first time, demonstrates that PIP5K, an enzyme actively associated with lipid modification pathway, has additional roles in rDNA silencing. ..
  17. Nelson C, Kovacs J, Nobles K, Whalen E, Lefkowitz R. Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor. J Biol Chem. 2008;283:21093-101 pubmed publisher
    ..Collectively, these data support a model in which beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization. ..
  18. Yamaguchi H, Yoshida S, Muroi E, Kawamura M, Kouchi Z, Nakamura Y, et al. Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells. Cancer Sci. 2010;101:1632-8 pubmed publisher
    ..is mainly mediated by type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5KI) family proteins, which include PIP5KIalpha, Ibeta, and Igamma...
  19. Muscolini M, Camperio C, Capuano C, Caristi S, Piccolella E, Galandrini R, et al. Phosphatidylinositol 4-phosphate 5-kinase ? activation critically contributes to CD28-dependent signaling responses. J Immunol. 2013;190:5279-86 pubmed publisher
    ..Our findings elucidate a novel mechanism that involves PIP5K? as a key modulator of CD28 costimulatory signals. ..
  20. Shrestha C, Tang Y, Fan H, Li L, Zeng Q, Pennypacker S, et al. Phosphoprotein Phosphatase 1 Is Required for Extracellular Calcium-Induced Keratinocyte Differentiation. Biomed Res Int. 2016;2016:3062765 pubmed publisher
  21. Anitei M, Stange C, Czupalla C, Niehage C, Schuhmann K, Sala P, et al. Spatiotemporal Control of Lipid Conversion, Actin-Based Mechanical Forces, and Curvature Sensors during Clathrin/AP-1-Coated Vesicle Biogenesis. Cell Rep. 2017;20:2087-2099 pubmed publisher
    ..These include PIP5K1A and phospholipase C-beta 3 controlling the conversion of PI[4]P into diacylglycerol...
  22. Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, et al. Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell. 1999;99:521-32 pubmed
  23. Micucci F, Capuano C, Marchetti E, Piccoli M, Frati L, Santoni A, et al. PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway. Blood. 2008;111:4165-72 pubmed
    ..Our findings delineate a novel mechanism implicating PI5KIalpha and PI5KIgamma isoforms in the synthesis of PIP2 pools critically required for IP3-dependent Ca(2+) response and lytic granule release. ..
  24. Im Y, Perera I, Brglez I, Davis A, Stevenson Paulik J, Phillippy B, et al. Increasing plasma membrane phosphatidylinositol(4,5)bisphosphate biosynthesis increases phosphoinositide metabolism in Nicotiana tabacum. Plant Cell. 2007;19:1603-16 pubmed
    ..Furthermore, expressing Hs PIPKIalpha increased sugar use and oxygen uptake. Our results demonstrate that PIPK is flux limiting and that this high rate of PI metabolism increased the energy demands in these cells. ..
  25. Xie Y, Zhu L, Zhao G. Assignment of type I phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) to human chromosome bands 1q22--> q24 by in situ hybridization. Cytogenet Cell Genet. 2000;88:197-9 pubmed
  26. Barrero Villar M, Barroso González J, Cabrero J, Gordón Alonso M, Alvarez Losada S, Munoz Fernandez M, et al. PI4P5-kinase Ialpha is required for efficient HIV-1 entry and infection of T cells. J Immunol. 2008;181:6882-8 pubmed
    ..These data indicate that PI4P5-K Ialpha-mediated PIP(2) production is crucial for HIV-1 entry and the early steps of infection in permissive lymphocytes. ..
  27. Tsai M, Katagiri N, Ohbayashi N, Iwasaki K, Ohkohchi N, Ding S, et al. Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP2-producing enzyme PIP5K1A. Sci Rep. 2017;7:9438 pubmed publisher
    ..and liver regeneration through the phosphatidylinositol 4,5-bisphosphate (PIP2)-producing enzyme PIP5K1A. We find that knockdown of Arf6 and PIP5K1A in HepG2 cells inhibits HGF-stimulated proliferation, Akt activation, ..
  28. Carpenter C. Btk-dependent regulation of phosphoinositide synthesis. Biochem Soc Trans. 2004;32:326-9 pubmed
    ..This complex provides a novel shuttling mechanism that allows Btk to regulate the production of the substrate required by both its upstream activator phosphoinositide 3-kinase and its downstream target phospholipase Cgamma2. ..
  29. Niiro H, Clark E. Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1. Immunity. 2003;19:637-40 pubmed
    ..Recent studies of Bam32-/- and Carma1-/- mice suggest that each adaptor controls a distinct conduit regulating either only proliferation (Bam32) or both the proliferation and survival of B cells (Carma1). ..
  30. Mejillano M, Yamamoto M, Rozelle A, Sun H, Wang X, Yin H. Regulation of apoptosis by phosphatidylinositol 4,5-bisphosphate inhibition of caspases, and caspase inactivation of phosphatidylinositol phosphate 5-kinases. J Biol Chem. 2001;276:1865-72 pubmed
    ..Overexpression of phosphatidylinositol phosphate 5-kinase alpha (PIP5KIalpha), which synthesizes PIP2, suppressed apoptosis, whereas a kinase-deficient mutant did not...