ID PI51C_MOUSE Reviewed; 661 AA. AC O70161; Q505A1; Q80TW9; Q8VCU5; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2005, sequence version 2. DT 27-MAR-2024, entry version 174. DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma {ECO:0000305|PubMed:9535851}; DE Short=PIP5K1-gamma {ECO:0000305|PubMed:9535851}; DE Short=PtdIns(4)P-5-kinase 1 gamma {ECO:0000305|PubMed:9535851}; DE EC=2.7.1.68 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:20622009, ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:9535851}; DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I gamma {ECO:0000305|PubMed:9535851}; DE Short=PIP5KIgamma {ECO:0000305|PubMed:9535851}; GN Name=Pip5k1c {ECO:0000312|MGI:MGI:1298224}; Synonyms=Kiaa0589; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, ALTERNATIVE SPLICING, RP AND TISSUE SPECIFICITY. RX PubMed=9535851; DOI=10.1074/jbc.273.15.8741; RA Ishihara H., Shibasaki Y., Kizuki N., Wada T., Yazaki Y., Asano T., Oka Y.; RT "Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third RT isoform and deletion/substitution analysis of members of this novel lipid RT kinase family."; RL J. Biol. Chem. 273:8741-8748(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Fetal brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). RN [3] RP SEQUENCE REVISION. RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC STRAIN=C57BL/6J, and NOD; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC STRAIN=FVB/N; TISSUE=Brain, and Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION IN FOCAL ADHESION DYNAMIC, SUBCELLULAR LOCATION, PHOSPHORYLATION RP AT TYROSINE RESIDUES, INTERACTION WITH TLN1, AND MUTAGENESIS OF ASP-253. RX PubMed=12422220; DOI=10.1038/nature01082; RA Ling K., Doughman R.L., Firestone A.J., Bunce M.W., Anderson R.A.; RT "Type I gamma phosphatidylinositol phosphate kinase targets and regulates RT focal adhesions."; RL Nature 420:89-93(2002). RN [7] RP INTERACTION WITH TLN1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-644, RP AND MUTAGENESIS OF TYR-644. RX PubMed=14691141; DOI=10.1083/jcb.200310067; RA Ling K., Doughman R.L., Iyer V.V., Firestone A.J., Bairstow S.F., RA Mosher D.F., Schaller M.D., Anderson R.A.; RT "Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate RT kinase by Src regulates an integrin-talin switch."; RL J. Cell Biol. 163:1339-1349(2003). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=14741049; DOI=10.1042/bj20031394; RA Giudici M.-L., Emson P.C., Irvine R.F.; RT "A novel neuronal-specific splice variant of Type I phosphatidylinositol 4- RT phosphate 5-kinase isoform gamma."; RL Biochem. J. 379:489-496(2004). RN [9] RP FUNCTION IN SYNAPTIC VESICLE TRAFFICKING, AND DISRUPTION PHENOTYPE. RX PubMed=15386003; DOI=10.1038/nature02896; RA Di Paolo G., Moskowitz H.S., Gipson K., Wenk M.R., Voronov S., Obayashi M., RA Flavell R., Fitzsimonds R.M., Ryan T.A., De Camilli P.; RT "Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in RT synaptic vesicle trafficking."; RL Nature 431:415-422(2004). RN [10] RP FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS, INTERACTION WITH AP2M1 AND TLN1, RP PHOSPHORYLATION, AND MUTAGENESIS OF TYR-644; PRO-646 AND LEU-647. RX PubMed=16707488; DOI=10.1074/jbc.m601465200; RA Bairstow S.F., Ling K., Su X., Firestone A.J., Carbonara C., Anderson R.A.; RT "Type Igamma661 phosphatidylinositol phosphate kinase directly interacts RT with AP2 and regulates endocytosis."; RL J. Biol. Chem. 281:20632-20642(2006). RN [11] RP FUNCTION IN CELL MIGRATION AND ADHESION, INTERACTION WITH PLCG1, RP PHOSPHORYLATION AT TYR-634, AND MUTAGENESIS OF TYR-634; TYR-644 AND RP SER-645. RX PubMed=17635937; DOI=10.1083/jcb.200701078; RA Sun Y., Ling K., Wagoner M.P., Anderson R.A.; RT "Type I gamma phosphatidylinositol phosphate kinase is required for EGF- RT stimulated directional cell migration."; RL J. Cell Biol. 178:297-308(2007). RN [12] RP FUNCTION IN NEUTROPHIL CHEMOTAXIS, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-253. RX PubMed=17928408; DOI=10.1091/mbc.e07-05-0428; RA Lokuta M.A., Senetar M.A., Bennin D.A., Nuzzi P.A., Chan K.T., Ott V.L., RA Huttenlocher A.; RT "Type Igamma PIP kinase is a novel uropod component that regulates rear RT retraction during neutrophil chemotaxis."; RL Mol. Biol. Cell 18:5069-5080(2007). RN [13] RP FUNCTION IN EMBRYOGENESIS, AND DISRUPTION PHENOTYPE. RX PubMed=17609388; DOI=10.1073/pnas.0700019104; RA Wang Y., Lian L., Golden J.A., Morrisey E.E., Abrams C.S.; RT "PIP5KI gamma is required for cardiovascular and neuronal development."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11748-11753(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [15] RP INTERACTION WITH AP2B1, AND MUTAGENESIS OF PHE-635; TRP-642 AND TYR-644. RX PubMed=19287005; DOI=10.1074/jbc.m901017200; RA Thieman J.R., Mishra S.K., Ling K., Doray B., Anderson R.A., Traub L.M.; RT "Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor RT beta2 appendage."; RL J. Biol. Chem. 284:13924-13939(2009). RN [16] RP FUNCTION IN PHAGOCYTOSIS, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND RP DISRUPTION PHENOTYPE. RX PubMed=19153220; DOI=10.1083/jcb.200806121; RA Mao Y.S., Yamaga M., Zhu X., Wei Y., Sun H.-Q., Wang J., Yun M., Wang Y., RA Di Paolo G., Bennett M., Mellman I., Abrams C.S., De Camilli P., Lu C.Y., RA Yin H.L.; RT "Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor- RT mediated phagocytosis."; RL J. Cell Biol. 184:281-296(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-655, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [18] RP FUNCTION IN EMBRYOGENESIS, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=20622009; DOI=10.1074/jbc.m110.132191; RA Volpicelli-Daley L.A., Lucast L., Gong L.-W., Liu L., Sasaki J., Sasaki T., RA Abrams C.S., Kanaho Y., De Camilli P.; RT "Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5- RT bisphosphate synthesis in the brain."; RL J. Biol. Chem. 285:28708-28714(2010). RN [19] RP FUNCTION IN CELL ADHESION, AND DISRUPTION PHENOTYPE. RX PubMed=20855869; DOI=10.4049/jimmunol.1001445; RA Wernimont S.A., Legate K.R., Simonson W.T.N., Fassler R., Huttenlocher A.; RT "PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation RT in antigen-induced CD4+ T cells."; RL J. Immunol. 185:4714-4723(2010). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22942276; DOI=10.1074/jbc.m112.370155; RA Shulga Y.V., Anderson R.A., Topham M.K., Epand R.M.; RT "Phosphatidylinositol-4-phosphate 5-kinase isoforms exhibit acyl chain RT selectivity for both substrate and lipid activator."; RL J. Biol. Chem. 287:35953-35963(2012). RN [21] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-459, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 636-652 IN COMPLEX WITH TLN1. RX PubMed=15623515; DOI=10.1074/jbc.m413180200; RA de Pereda J.M., Wegener K.L., Santelli E., Bate N., Ginsberg M.H., RA Critchley D.R., Campbell I.D., Liddington R.C.; RT "Structural basis for phosphatidylinositol phosphate kinase type Igamma RT binding to talin at focal adhesions."; RL J. Biol. Chem. 280:8381-8386(2005). CC -!- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 4- CC phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5- CC bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that CC regulates several cellular processes such as signal transduction, CC vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and CC cell motility (PubMed:9535851, PubMed:14741049, PubMed:20622009, CC PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger CC or can be utilized as a precursor to generate other second messengers: CC inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or CC phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (By CC similarity). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the CC predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). CC Together with PIP5K1A, is required for phagocytosis, both enzymes CC regulating different types of actin remodeling at sequential steps CC (PubMed:19153220). Promotes particle attachment by generating the pool CC of PtdIns(4,5)P2 that induces controlled actin depolymerization to CC facilitate Fc-gamma-R clustering. Mediates RAC1-dependent CC reorganization of actin filaments. Required for synaptic vesicle CC transport (PubMed:15386003). Controls the plasma membrane pool of CC PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis CC (By similarity). Plays a role in endocytosis mediated by clathrin and CC AP-2 (adaptor protein complex 2) (PubMed:16707488). Required for CC clathrin-coated pits assembly at the synapse (By similarity). CC Participates in cell junction assembly (By similarity). Modulates CC adherens junctions formation by facilitating CDH1/cadherin trafficking CC (By similarity). Required for focal adhesion dynamics CC (PubMed:12422220). Modulates the targeting of talins (TLN1 and TLN2) to CC the plasma membrane and their efficient assembly into focal adhesions CC (By similarity). Regulates the interaction between talins (TLN1 and CC TLN2) and beta-integrins (By similarity). Required for uropodium CC formation and retraction of the cell rear during directed migration CC (PubMed:17928408). Has a role in growth factor-stimulated directional CC cell migration and adhesion (PubMed:17635937). Required for talin CC assembly into nascent adhesions forming at the leading edge toward the CC direction of the growth factor (PubMed:17635937). Negative regulator of CC T-cell activation and adhesion (PubMed:20855869). Negatively regulates CC integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T- CC cell receptor (PubMed:20855869). Together with PIP5K1A has a role CC during embryogenesis and together with PIP5K1B may have a role CC immediately after birth (PubMed:17609388, PubMed:20622009). CC {ECO:0000250|UniProtKB:O60331, ECO:0000269|PubMed:12422220, CC ECO:0000269|PubMed:14741049, ECO:0000269|PubMed:15386003, CC ECO:0000269|PubMed:16707488, ECO:0000269|PubMed:17609388, CC ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:17928408, CC ECO:0000269|PubMed:19153220, ECO:0000269|PubMed:20622009, CC ECO:0000269|PubMed:20855869, ECO:0000269|PubMed:22942276, CC ECO:0000269|PubMed:9535851}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4- CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:14425, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:58178, CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.68; CC Evidence={ECO:0000269|PubMed:14741049, ECO:0000269|PubMed:20622009, CC ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:9535851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14426; CC Evidence={ECO:0000305|PubMed:15489334, ECO:0000305|PubMed:20622009, CC ECO:0000305|PubMed:22942276, ECO:0000305|PubMed:9535851}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero- CC 3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2- CC (5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol CC 4,5-bisphosphate + ADP + H(+); Xref=Rhea:RHEA:40363, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77136, CC ChEBI:CHEBI:77137, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40364; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D- CC myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl- CC sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+); CC Xref=Rhea:RHEA:40367, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:77139, ChEBI:CHEBI:77140, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40368; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D- CC myo-inositol + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3- CC phospho-1D-myo-inositol 5-phosphate + ADP + H(+); CC Xref=Rhea:RHEA:40379, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:77163, ChEBI:CHEBI:77164, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40380; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3- CC phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z,12Z)- CC octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + CC ADP + H(+); Xref=Rhea:RHEA:40383, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77158, ChEBI:CHEBI:77159, CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40384; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero- CC 3-phospho-(1D-myo-inositol) + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)- CC eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + CC ADP + H(+); Xref=Rhea:RHEA:40375, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77160, ChEBI:CHEBI:133606, CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40376; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo- CC inositol + ATP = 1,2-di(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho- CC 1D-myo-inositol 5-phosphate + ADP + H(+); Xref=Rhea:RHEA:40387, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77165, CC ChEBI:CHEBI:77167, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40388; CC Evidence={ECO:0000250|UniProtKB:O60331}; CC -!- ACTIVITY REGULATION: Activated by phosphatidic acid. CC {ECO:0000269|PubMed:9535851}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=37 uM for phosphatidylinositol-4-phosphate/PtdIns(4)P CC {ECO:0000269|PubMed:9535851}; CC KM=39 uM for ATP {ECO:0000269|PubMed:9535851}; CC KM=1.6 uM for CC 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol CC 4-phosphate {ECO:0000269|PubMed:22942276}; CC KM=15 uM for CC 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol CC 4-phosphate {ECO:0000269|PubMed:22942276}; CC -!- SUBUNIT: Isoform 1 interacts with TLN1 (PubMed:12422220, CC PubMed:14691141, PubMed:16707488). Interacts with TLN2; interaction CC stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity (By CC similarity). May compete with beta-integrins for the same binding site CC on TLN1 and TLN2. Interacts with ARF6 (By similarity). Interacts with CC AP2B1 (PubMed:19287005). Isoform 1 interacts with AP2M1; CC phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin CC competes with PIP5K1C (PubMed:16707488). Interacts with CDH1 (By CC similarity). Interacts with CSK. Interacts with PLCG1; interaction is CC abolished upon EGF stimulation (PubMed:17635937). Interacts with CC LAPTM4B; promotes SNX5 association with LAPTM4B; kinase activity of CC PIP5K1C is required; interaction is regulated by phosphatidylinositol CC 4,5-bisphosphate generated by PIP5K1C (By similarity). CC {ECO:0000250|UniProtKB:O60331, ECO:0000250|UniProtKB:Q5I6B8, CC ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:14691141, CC ECO:0000269|PubMed:15623515, ECO:0000269|PubMed:16707488, CC ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:19287005}. CC -!- INTERACTION: CC O70161; Q9DBG3-1: Ap2b1; NbExp=3; IntAct=EBI-773657, EBI-775239; CC O70161; Q9DBG3-2: Ap2b1; NbExp=8; IntAct=EBI-773657, EBI-7257021; CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; CC Cytoplasmic side {ECO:0000250|UniProtKB:Q5I6B8}. Endomembrane system CC {ECO:0000250|UniProtKB:Q5I6B8}. Cytoplasm {ECO:0000269|PubMed:19153220, CC ECO:0000269|PubMed:20622009}. Cell junction, focal adhesion CC {ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:14691141}. Cell CC junction, adherens junction {ECO:0000250|UniProtKB:O60331}. Cell CC projection, ruffle membrane {ECO:0000250|UniProtKB:Q5I6B8}. Cell CC projection, phagocytic cup {ECO:0000269|PubMed:19153220}. Cell CC projection, uropodium {ECO:0000269|PubMed:17928408}. Note=During CC directional migration isoform 1 localized at the uropodium, and isoform CC 3 localized all along cell membrane including the uropodium and the CC leading edge. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=PIPKIgamma661; CC IsoId=O70161-1; Sequence=Displayed; CC Name=2; Synonyms=PIPKIgamma627; CC IsoId=O70161-2; Sequence=VSP_016013, VSP_016014; CC Name=3; Synonyms=PIPKIgamma635; CC IsoId=O70161-3; Sequence=VSP_016015; CC -!- TISSUE SPECIFICITY: High expression in brain. Also detected in lung, CC thymus, heart, testicle, kidney and embryo. Highly expressed in CC forebrain, in particular in cerebellum, hippocampus and cerebral CC cortex. {ECO:0000269|PubMed:14741049, ECO:0000269|PubMed:20622009, CC ECO:0000269|PubMed:9535851}. CC -!- DEVELOPMENTAL STAGE: Expression increases during embryonic development CC and continued to steadily increase postnatally. CC {ECO:0000269|PubMed:20622009}. CC -!- PTM: Phosphorylation on Ser-645 negatively regulates binding to TLN2 CC and is strongly stimulated in mitosis. Phosphorylation on Tyr-644 is CC necessary for targeting to focal adhesions. Phosphorylation on Ser-645 CC and Tyr-644 are mutually exclusive. Phosphorylated by SYK and CSK. CC Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated CC at Tyr-634 upon EGF stimulation. Some studies suggest that CC phosphorylation on Tyr-644 enhances binding to tailins (TLN1 and TLN2); CC others that phosphorylation at Tyr-644 does not directly enhance CC binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting CC phosphorylation at Ser-645. {ECO:0000269|PubMed:12422220, CC ECO:0000269|PubMed:14691141, ECO:0000269|PubMed:16707488, CC ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:19153220}. CC -!- PTM: Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase CC activity. Deacetylation of these sites by SIRT1 positively regulates CC the exocytosis of TSH-containing granules from pituitary cells (By CC similarity). {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: According to some authors, mutants die within CC hours after birth and are unable to feed after birth (PubMed:15386003). CC According to another report, mutants are embryonically lethal at CC organogenesis stage, and display cardiovascular and neuronal defects CC (PubMed:15386003). PIP5K1C and PIP5K1B double mutant mice die within CC minutes after birth. PIP5K1C and PIP5K1A double mutant mice are CC embryonic lethal. Bone marrow-derived macrophages are defective in CC phagocytosis, attachment to IgG-opsonized particles and Fc-gamma-R CC clustering, and display highly polymerized actin cytoskeleton. Neurons CC display defects in synaptic transmission due to defects in synaptic CC vesicle trafficking at different levels. T-cells mutant for isoform 1 CC display increase adhesion and polarization. CC {ECO:0000269|PubMed:15386003, ECO:0000269|PubMed:17609388, CC ECO:0000269|PubMed:19153220, ECO:0000269|PubMed:20622009, CC ECO:0000269|PubMed:20855869}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC65601.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB006916; BAA25664.1; -; mRNA. DR EMBL; AK122319; BAC65601.2; ALT_INIT; mRNA. DR EMBL; AK154816; BAE32849.1; -; mRNA. DR EMBL; AK171576; BAE42536.1; -; mRNA. DR EMBL; BC019138; AAH19138.1; -; mRNA. DR EMBL; BC094665; AAH94665.1; -; mRNA. DR CCDS; CCDS35994.1; -. [O70161-1] DR CCDS; CCDS48643.1; -. [O70161-3] DR RefSeq; NP_001140159.1; NM_001146687.2. [O70161-3] DR RefSeq; NP_001280575.1; NM_001293646.1. DR RefSeq; NP_001280576.1; NM_001293647.1. DR RefSeq; NP_032870.2; NM_008844.3. [O70161-1] DR PDB; 1Y19; X-ray; 2.60 A; A/C/E/G/I/K=638-651. DR PDB; 2H7D; NMR; -; B=643-652. DR PDB; 2H7E; NMR; -; B=643-652. DR PDBsum; 1Y19; -. DR PDBsum; 2H7D; -. DR PDBsum; 2H7E; -. DR AlphaFoldDB; O70161; -. DR SMR; O70161; -. DR BioGRID; 202169; 12. DR IntAct; O70161; 7. DR MINT; O70161; -. DR STRING; 10090.ENSMUSP00000038225; -. DR GlyGen; O70161; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; O70161; -. DR PhosphoSitePlus; O70161; -. DR SwissPalm; O70161; -. DR jPOST; O70161; -. DR MaxQB; O70161; -. DR PaxDb; 10090-ENSMUSP00000100964; -. DR PeptideAtlas; O70161; -. DR ProteomicsDB; 301821; -. [O70161-1] DR ProteomicsDB; 301822; -. [O70161-2] DR ProteomicsDB; 301823; -. [O70161-3] DR Pumba; O70161; -. DR Antibodypedia; 2779; 254 antibodies from 31 providers. DR DNASU; 18717; -. DR Ensembl; ENSMUST00000105327.10; ENSMUSP00000100964.4; ENSMUSG00000034902.18. [O70161-1] DR Ensembl; ENSMUST00000163075.8; ENSMUSP00000124155.2; ENSMUSG00000034902.18. [O70161-3] DR GeneID; 18717; -. DR KEGG; mmu:18717; -. DR UCSC; uc007ghc.3; mouse. [O70161-1] DR AGR; MGI:1298224; -. DR CTD; 23396; -. DR MGI; MGI:1298224; Pip5k1c. DR VEuPathDB; HostDB:ENSMUSG00000034902; -. DR eggNOG; KOG0229; Eukaryota. DR GeneTree; ENSGT00940000159258; -. DR HOGENOM; CLU_004312_5_1_1; -. DR InParanoid; O70161; -. DR OMA; YKFMSNT; -. DR OrthoDB; 5481504at2759; -. DR PhylomeDB; O70161; -. DR TreeFam; TF319618; -. DR BRENDA; 2.7.1.68; 3474. DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-MMU-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion. DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis. DR SABIO-RK; O70161; -. DR BioGRID-ORCS; 18717; 2 hits in 79 CRISPR screens. DR ChiTaRS; Pip5k1c; mouse. DR EvolutionaryTrace; O70161; -. DR PRO; PR:O70161; -. DR Proteomes; UP000000589; Chromosome 10. DR RNAct; O70161; Protein. DR Bgee; ENSMUSG00000034902; Expressed in superior frontal gyrus and 271 other cell types or tissues. DR ExpressionAtlas; O70161; baseline and differential. DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO. DR GO; GO:0098835; C:presynaptic endocytic zone membrane; ISO:MGI. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0001931; C:uropod; IEA:UniProtKB-SubCell. DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0007409; P:axonogenesis; IDA:MGI. DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW. DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW. DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IDA:MGI. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:MGI. DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0070527; P:platelet aggregation; IMP:MGI. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IDA:SynGO. DR CDD; cd17308; PIPKc_PIP5K1C; 1. DR Gene3D; 3.30.810.10; 2-Layer Sandwich; 1. DR Gene3D; 3.30.800.10; Phosphatidylinositol Phosphate Kinase II Beta; 1. DR IDEAL; IID50194; -. DR InterPro; IPR027483; PInositol-4-P-4/5-kinase_C_sf. DR InterPro; IPR002498; PInositol-4-P-4/5-kinase_core. DR InterPro; IPR027484; PInositol-4-P-5-kinase_N. DR InterPro; IPR023610; PInositol-4/5-P-5/4-kinase. DR PANTHER; PTHR23086:SF26; PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE TYPE-1 GAMMA; 1. DR PANTHER; PTHR23086; PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE; 1. DR Pfam; PF01504; PIP5K; 1. DR SMART; SM00330; PIPKc; 1. DR SUPFAM; SSF56104; SAICAR synthase-like; 1. DR PROSITE; PS51455; PIPK; 1. DR Genevisible; O70161; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell adhesion; Cell junction; Cell membrane; Cell projection; Chemotaxis; KW Cytoplasm; Endocytosis; Exocytosis; Kinase; Lipid metabolism; Membrane; KW Methylation; Nucleotide-binding; Phagocytosis; Phosphoprotein; KW Reference proteome; Transferase. FT CHAIN 1..661 FT /note="Phosphatidylinositol 4-phosphate 5-kinase type-1 FT gamma" FT /id="PRO_0000185463" FT DOMAIN 75..443 FT /note="PIPK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781" FT REGION 44..69 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 525..572 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 605..661 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 636..661 FT /note="Mediates interaction with TLN2" FT COMPBIAS 525..541 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 542..571 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 613..627 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 265 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O60331" FT MOD_RES 268 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O60331" FT MOD_RES 459 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 459 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 554 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5I6B8" FT MOD_RES 634 FT /note="Phosphotyrosine; by EGFR" FT /evidence="ECO:0000269|PubMed:17635937" FT MOD_RES 644 FT /note="Phosphotyrosine; by CSK" FT /evidence="ECO:0000269|PubMed:14691141" FT MOD_RES 645 FT /note="Phosphoserine; by CDK5, MAPK1 and CDK1" FT /evidence="ECO:0000250|UniProtKB:O60331" FT MOD_RES 655 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5I6B8" FT MOD_RES 661 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5I6B8" FT VAR_SEQ 343..402 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12693553" FT /id="VSP_016013" FT VAR_SEQ 635 FT /note="F -> FFAHGRYWLFSPRRRQLRAVTPNHTGT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12693553" FT /id="VSP_016014" FT VAR_SEQ 636..661 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072" FT /id="VSP_016015" FT MUTAGEN 253 FT /note="D->A: Abolishes lipid kinase activity. Does not FT affect targeting of TLN1 to plasma membrane. Affects FT assembly of TLN1 into focal adhesions. Affects uropodium FT formation and retraction of the cell rear." FT /evidence="ECO:0000269|PubMed:12422220, FT ECO:0000269|PubMed:17928408" FT MUTAGEN 634 FT /note="Y->F: Cannot rescue the effect PIP5K1C knockdown on FT EGF-stimulated cell migration. Does not affect lipid kinase FT activity. Does not alter binding to tailin. Decreased FT tailin assembly into focal adhesions. Increased interaction FT with PLCG1." FT /evidence="ECO:0000269|PubMed:17635937" FT MUTAGEN 635 FT /note="F->A: Abolishes interaction with AP2B1." FT /evidence="ECO:0000269|PubMed:19287005" FT MUTAGEN 642 FT /note="W->A: Abolishes interaction with AP2B1." FT /evidence="ECO:0000269|PubMed:19287005" FT MUTAGEN 644 FT /note="Y->F: Loss of phosphorylation by CSK. Abolishes FT interaction with AP-2 complex. Cannot rescue the effect FT PIP5K1C knockdown on EGF-stimulated cell migration." FT /evidence="ECO:0000269|PubMed:14691141, FT ECO:0000269|PubMed:16707488, ECO:0000269|PubMed:17635937, FT ECO:0000269|PubMed:19287005" FT MUTAGEN 645 FT /note="S->F: Cannot rescue the effect PIP5K1C knockdown on FT EGF-stimulated cell migration. Decreased tailin assembly FT into focal adhesions." FT /evidence="ECO:0000269|PubMed:17635937" FT MUTAGEN 646 FT /note="P->F: Abolishes interaction with AP-2 complex." FT /evidence="ECO:0000269|PubMed:16707488" FT MUTAGEN 647 FT /note="L->V: Abolishes interaction with AP-2 complex." FT /evidence="ECO:0000269|PubMed:16707488" FT CONFLICT 110 FT /note="V -> M (in Ref. 1; BAA25664)" FT /evidence="ECO:0000305" FT CONFLICT 122 FT /note="L -> F (in Ref. 1; BAA25664)" FT /evidence="ECO:0000305" FT STRAND 642..644 FT /evidence="ECO:0007829|PDB:1Y19" FT HELIX 646..648 FT /evidence="ECO:0007829|PDB:1Y19" SQ SEQUENCE 661 AA; 72408 MW; 4A3B71E4465B83C3 CRC64; MELEVPDEAE SAEAGAVTAE AAWSAESGAA AGMTQKKAGL AEAPLVTGQP GPGHGKKLGH RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGNLSSKPER DVLMQDFYVV ESIFFPSEGS NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSVFYVT SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN VLPRVVKMHL KFDLKGSTYK RRASKKEKEK SLPTYKDLDF MQDMPEGLLL DSDTFGALVK TLQRDCLVLE SFKIMDYSLL LGVHNIDQQE RERQAEGAQS KADEKRPVAQ KALYSTAMES IQGGAARGEA IETDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG DTVSVHRPSF YAERFFKFMS STVFRKSSSL KSSPSKKGRG ALLAVKPLGP TAAFSASQIP SEREDVQYDL RGARSYPTLE DEGRPDLLPC TPPSFEEATT ASIATTLSST SLSIPERSPS DTSEQPRYRR RTQSSGQDGR PQEEPHAEDL QKITVQVEPV CGVGVVPKEE GAGVEVPPCG ASAAASVEID AASQASEPAS QASDEEDAPS TDIYFPTDER SWVYSPLHYS ARPASDGESD T //