Gene Symbol: PIP5K1C
Description: phosphatidylinositol-4-phosphate 5-kinase type 1 gamma
Alias: LCCS3, PIP5K-GAMMA, PIP5K1-gamma, PIP5Kgamma, phosphatidylinositol 4-phosphate 5-kinase type-1 gamma, diphosphoinositide kinase, phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, ptdIns(4)P-5-kinase 1 gamma, type I PIP kinase
Species: human
Products:     PIP5K1C

Top Publications

  1. Sun Y, Turbin D, Ling K, Thapa N, Leung S, Huntsman D, et al. Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer. Breast Cancer Res. 2010;12:R6 pubmed publisher
    ..The results reveal a significant correlation between PIPKIgamma expression and the progression of breast cancer. This is consistent with PIPKIgamma 's role in breast cancer cell migration, invasion, and proliferation. ..
  2. Wang Y, Li W, Wang J, Xu K, Dong P, Luo X, et al. Critical role of PIP5KI{gamma}87 in InsP3-mediated Ca(2+) signaling. J Cell Biol. 2004;167:1005-10 pubmed
    ..Therefore, PIP5KIgamma87's PIP(2) pool that supports GPCR-mediated Ca(2+) signaling is functionally compartmentalized from those generated by the other PIP5KIs. ..
  3. Sun Y, Ling K, Wagoner M, Anderson R. Type I gamma phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. J Cell Biol. 2007;178:297-308 pubmed
    ..These interactions in turn define the spatial and temporal generation of PI4,5P(2) and derived messengers required for directional migration. ..
  4. Wenk M, Pellegrini L, Klenchin V, Di Paolo G, Chang S, Daniell L, et al. PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse. Neuron. 2001;32:79-88 pubmed
    ..These results implicate PIPKIgamma in the synthesis of a PI(4,5)P(2) pool that acts as a positive regulator of clathrin coat recruitment and actin function at the synapse. ..
  5. Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, et al. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature. 2002;420:85-9 pubmed
    ..These findings define an interaction that has a regulatory role in cell adhesion and suggest new similarities between molecular interactions underlying synaptic junctions and general mechanisms of cell adhesion. ..
  6. 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. ..
  7. Krauss M, Kinuta M, Wenk M, De Camilli P, Takei K, Haucke V. ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma. J Cell Biol. 2003;162:113-24 pubmed
    ..These data suggest a model according to which activation of PIPKIgamma by ARF6-GTP facilitates clathrin-coated pit assembly at the synapse. ..
  8. Krauss M, Kukhtina V, Pechstein A, Haucke V. Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes. Proc Natl Acad Sci U S A. 2006;103:11934-9 pubmed
    ..These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2mu, and PIPK type I which may provide a specific pool of PI(4,5)P(2) dedicated to clathrin/AP-2-dependent receptor internalization. ..
  9. Nakano Kobayashi A, Yamazaki M, Unoki T, Hongu T, Murata C, Taguchi R, et al. Role of activation of PIP5Kgamma661 by AP-2 complex in synaptic vesicle endocytosis. EMBO J. 2007;26:1105-16 pubmed
    ..These findings provide evidence for the molecular mechanism through which PIP5Kgamma661 locally generates PI(4,5)P2 in hippocampal neurons and suggest a model in which the interaction trigger SV endocytosis. ..

More Information


  1. Ling K, Bairstow S, Carbonara C, Turbin D, Huntsman D, Anderson R. Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J Cell Biol. 2007;176:343-53 pubmed
  2. Ling K, Doughman R, Firestone A, Bunce M, Anderson R. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature. 2002;420:89-93 pubmed
    ..This defines a mechanism for spatial generation of PtdIns(4,5)P(2) at focal adhesions. ..
  3. Ishihara H, Shibasaki Y, Kizuki N, Wada T, Yazaki Y, Asano T, et al. Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J Biol Chem. 1998;273:8741-8 pubmed
    ..Here, we report the cloning of the third member (PIP5Kgamma) and the characterization of members of the type I PIP5K family...
  4. 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. ..
  5. Bairstow S, Ling K, Su X, Firestone A, Carbonara C, Anderson R. Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis. J Biol Chem. 2006;281:20632-42 pubmed
    ..Collectively, this evidence implies an important role for PIPKIgamma661 in the AP2-mediated endocytosis of transferrin. ..
  6. Uličná L, Rohozkova J, Hozak P. Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis. Int J Mol Sci. 2018;19: pubmed publisher
    ..elegans hermaphrodite. The depletion of PIP2 by type I PIP kinase (PPK-1) kinase RNA interference results in an altered chromosome structure and leads to various defects ..
  7. Waugh M. Chromosomal Instability and Phosphoinositide Pathway Gene Signatures in Glioblastoma Multiforme. Mol Neurobiol. 2016;53:621-630 pubmed publisher
    ..phosphoinositide phosphatase genes OCRL, MTM1 and MTMR8; copy number amplifications for the chromosome 19 genes PIP5K1C, AKT2 and PIK3R2, and also for the phospholipase C genes PLCB1, PLCB4 and PLCG1 on chromosome 20...
  8. Wright B, Simpson C, Stashko M, Kireev D, Hull Ryde E, Zylka M, et al. Development of a High-Throughput Screening Assay to Identify Inhibitors of the Lipid Kinase PIP5K1C. J Biomol Screen. 2015;20:655-62 pubmed publisher
    ..Here, we report a novel, high-throughput, microfluidic mobility shift assay to identify inhibitors of PIP5K1C. This assay uses fluorescently labeled phosphatidylinositol 4-phosphate as the substrate and recombinant human ..
  9. Zeng X, Uyar A, Sui D, Donyapour N, Wu D, Dickson A, et al. Structural insights into lethal contractural syndrome type 3 (LCCS3) caused by a missense mutation of PIP5Kγ. Biochem J. 2018;475:2257-2269 pubmed publisher
  10. 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
    ..and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region...
  11. Tan X, Sun Y, Thapa N, Liao Y, Hedman A, Anderson R. LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. EMBO J. 2015;34:475-90 pubmed publisher
    ..These results reveal an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2 signaling, and the ESCRT complex and define a mechanism by which the oncoprotein LAPTM4B can transform cells and promote tumor progression. ..
  12. Zhang X, Dong R, Zhang Y, Zhang J, Luo Z, Zhang J, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res. 2016;26:1277-87 pubmed publisher
  13. Narkis G, Ofir R, Landau D, Manor E, Volokita M, Hershkowitz R, et al. Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 2007;81:530-9 pubmed
    ..Of these genes, 30 candidates were sequenced, which identified a single homozygous mutation in PIP5K1C. PIP5K1C encodes phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (PIPKI gamma ), an enzyme that ..
  14. Auvinen E, Kivi N, Vaheri A. Regulation of ezrin localization by Rac1 and PIPK in human epithelial cells. Exp Cell Res. 2007;313:824-33 pubmed
    ..This localization required the activity of Rac1 and phosphatidylinositol-4-phosphate 5-kinase and involved RhoA. We suggest that localization of ezrin in adherens junctions is regulated by Rac in a manner involving PIPK. ..
  15. Durand N, Bastea L, Long J, Döppler H, Ling K, Storz P. Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l γ. Sci Rep. 2016;6:35963 pubmed publisher
    ..Our data reveal a novel function for PKD1 as a regulator of FA dynamics and by identifying PIP5Klγ as a novel PKD1 substrate provide mechanistic insight into this process. ..
  16. Xiong X, Xu Q, Huang Y, Singh R, Anderson R, Leof E, et al. An association between type I? PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization. Mol Biol Cell. 2012;23:87-98 pubmed publisher
    ..This could be an important mechanism that regulates E-cadherin clustering and AJ maturation, which is essential for the establishment of solid, polarized epithelial structures. ..
  17. Le O, Cho O, Tran M, Kim J, Chang S, Jou I, et al. Phosphorylation of phosphatidylinositol 4-phosphate 5-kinase γ by Akt regulates its interaction with talin and focal adhesion dynamics. Biochim Biophys Acta. 2015;1853:2432-43 pubmed publisher
    ..Taken together, our results suggested that Akt-mediated PIP5Kγ90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility. ..
  18. 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). ..
  19. Krauss M, Haucke V. Functional assay of effectors of ADP ribosylation factor 6 during clathrin/AP-2 coat recruitment to membranes. Methods Enzymol. 2005;404:388-98 pubmed
    ..These methods shall help to mechanistically dissect the role of Arf6 in regulating exo-endocytic vesicle cycling at synapses and in related membrane trafficking events. ..
  20. Geng F, Zhu W, Anderson R, Leber B, Andrews D. Multiple post-translational modifications regulate E-cadherin transport during apoptosis. J Cell Sci. 2012;125:2615-25 pubmed publisher
    ..The modifications of E-cadherin by O-GlcNAcylation and lack of pro-region processing represent novel mechanisms for rapid regulation of cell surface transport of E-cadherin in response to intoxication. ..
  21. Akieda Asai S, Zaima N, Ikegami K, Kahyo T, Yao I, Hatanaka T, et al. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. PLoS ONE. 2010;5:e11755 pubmed publisher
    ..SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown...
  22. Kahlfeldt N, Vahedi Faridi A, Koo S, Schäfer J, Krainer G, Keller S, et al. Molecular basis for association of PIPKI gamma-p90 with clathrin adaptor AP-2. J Biol Chem. 2010;285:2734-49 pubmed publisher
    ..We postulate a model according to which multiple interactions between PIPKI gamma-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated SV endocytosis. ..
  23. Jafari N, Zheng Q, Li L, Li W, Qi L, Xiao J, et al. p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I ? Degradation and Cell Invasion. J Biol Chem. 2016;291:25729-25741 pubmed
    ..These data suggest that S6K1-mediated PIPKI?90 phosphorylation regulates cell migration and invasion by controlling PIPKI?90 degradation. ..
  24. Xue J, Chen C, Qi M, Huang Y, Wang L, Gao Y, et al. Type I? phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-?B. Oncotarget. 2017;8:42414-42427 pubmed publisher
    ..These results demonstrate that PIPKI?-dependent expression of PD-L1 is likely important for the progression of triple negative breast cancer. ..
  25. 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. ..
  26. 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). ..
  27. Thapa N, Choi S, Hedman A, Tan X, Anderson R. Phosphatidylinositol phosphate 5-kinase I?i2 in association with Src controls anchorage-independent growth of tumor cells. J Biol Chem. 2013;288:34707-18 pubmed publisher
    ..This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKI?i2, functions with the proto-oncogene Src, to regulate oncogenic signaling. ..
  28. Xu Q, Zhang Y, Wei Q, Huang Y, Hu J, Ling K. Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis. Nat Commun. 2016;7:10777 pubmed publisher
    ..Our results reveal that PtdIns(4)P homoeostasis, coordinated by PIPKIγ and INPP5E at the centrosome/ciliary base, is vital for ciliogenesis by regulating the CEP164-dependent recruitment of TTBK2. ..
  29. Schramp M, Thapa N, Heck J, Anderson R. PIPKI? regulates ?-catenin transcriptional activity downstream of growth factor receptor signaling. Cancer Res. 2011;71:1282-91 pubmed publisher
    ..These results reveal a novel mechanism in which PIPKI? expression and catalytic activity enhance ?-catenin nuclear translocation and expression of its target genes to promote tumorigenic phenotypes. ..
  30. Li X, Zhou Q, Sunkara M, Kutys M, Wu Z, Rychahou P, et al. Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I ? by HECTD1 regulates focal adhesion dynamics and cell migration. J Cell Sci. 2013;126:2617-28 pubmed publisher
    ..Thus, cycling PIPKI?90 ubiquitylation by HECTD1 and consequent degradation remove PIPKI?90 from talin after on-site PIP2 production, providing an essential regulatory mechanism for FA dynamics and cell migration. ..
  31. Sun Y, Hedman A, Tan X, Schill N, Anderson R. Endosomal type I? PIP 5-kinase controls EGF receptor lysosomal sorting. Dev Cell. 2013;25:144-55 pubmed publisher
    ..These findings reveal that PIPKI?i5 and SNX5 form a signaling nexus that controls EGFR endosomal sorting, degradation, and signaling. ..
  32. Figueiredo J, Söderberg O, Simões Correia J, Grannas K, Suriano G, Seruca R. The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC. Eur J Hum Genet. 2013;21:301-9 pubmed publisher
  33. Schill N, Anderson R. Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. Biochem J. 2009;422:473-82 pubmed publisher
  34. Xu Q, Zhang Y, Xiong X, Huang Y, Salisbury J, Hu J, et al. PIPKI? targets to the centrosome and restrains centriole duplication. J Cell Sci. 2014;127:1293-305 pubmed publisher
    ..Here, we report that phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C, hereafter referred to as PIPKI?) plays an important role in centriole fidelity...
  35. Thapa N, Choi S, Tan X, Wise T, Anderson R. Phosphatidylinositol Phosphate 5-Kinase Iγ and Phosphoinositide 3-Kinase/Akt Signaling Couple to Promote Oncogenic Growth. J Biol Chem. 2015;290:18843-54 pubmed publisher
    ..This pathway may represent a signaling nexus required for the survival and growth of metastasizing and circulating tumor cells in vivo. ..
  36. Choi S, Thapa N, Hedman A, Li Z, Sacks D, Anderson R. IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration. EMBO J. 2013;32:2617-30 pubmed publisher
    ..IQGAP1 mutants that lack PIPKI? or PIP? binding lose the ability to control directional cell migration. Collectively, these data reveal a synergy between PIPKI? and IQGAP1 in the control of cell migration. ..
  37. Wu Z, Li X, Sunkara M, Spearman H, Morris A, Huang C. PIPKI? regulates focal adhesion dynamics and colon cancer cell invasion. PLoS ONE. 2011;6:e24775 pubmed publisher
    ..Taken together, PIPKI? positively regulates focal adhesion dynamics and cancer invasion, most probably through PIP?-mediated vinculin activation...
  38. Yu Y, Chou R, Chen L, Shyu W, Hsieh S, Wu C, et al. EZH2 regulates neuronal differentiation of mesenchymal stem cells through PIP5K1C-dependent calcium signaling. J Biol Chem. 2011;286:9657-67 pubmed publisher
    ..EZH2 bound to the promoter region of PIP5K1C to suppress its transcription in proliferating hMSCs...
  39. Gallicchio M, Bach L. Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma. Biochim Biophys Acta. 2010;1803:919-30 pubmed publisher
    ..Transfection of HK2 cells with PIP5Kgamma siRNA prevented AGE-BSA inhibition of NKA activity...
  40. 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. ..
  41. Nader G, Ezratty E, Gundersen G. FAK, talin and PIPKI? regulate endocytosed integrin activation to polarize focal adhesion assembly. Nat Cell Biol. 2016;18:491-503 pubmed publisher
    ..We propose that the conformational memory of endocytosed integrin enhances polarized reassembly of FAs to enable directional cell migration. ..
  42. Sun M, Cai J, Anderson R, Sun Y. Type I ? Phosphatidylinositol Phosphate 5-Kinase i5 Controls the Ubiquitination and Degradation of the Tumor Suppressor Mitogen-inducible Gene 6. J Biol Chem. 2016;291:21461-21473 pubmed
    ..Thus, loss of NEDD4-1 can rescue Mig6 expression in PIPKI?i5 knockdown cells. In this way, PIPKI?i5, NEDD4-1, and Mig6 form a novel molecular nexus that controls EGFR activation and downstream signaling. ..
  43. Lokuta M, Senetar M, Bennin D, Nuzzi P, Chan K, Ott V, et al. Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell. 2007;18:5069-80 pubmed
    ..Together, our findings identify a previously unknown function for PIPKIgamma661 as a novel component of the backness signal that regulates rear retraction during chemotaxis. ..
  44. Barsukov I, Prescot A, Bate N, Patel B, Floyd D, Bhanji N, et al. Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J Biol Chem. 2003;278:31202-9 pubmed
    ..The results suggest that ternary complex formation with a single talin FERM domain is unlikely, although both integrins and PIP kinase may bind simultaneously to the talin anti-parallel dimer. ..