PI51C_MOUSE
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 03-AUG-2022, entry version 165.
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 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-
CC glycero-3-phospho-1D-myo-inositol 4-phosphate
CC {ECO:0000269|PubMed:22942276};
CC KM=15 uM for 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-
CC 1D-myo-inositol 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 ---------------------------------------------------------------------------
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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.ENSMUSP00000100964; -.
DR iPTMnet; O70161; -.
DR PhosphoSitePlus; O70161; -.
DR jPOST; O70161; -.
DR MaxQB; O70161; -.
DR PaxDb; O70161; -.
DR PeptideAtlas; O70161; -.
DR PRIDE; O70161; -.
DR ProteomicsDB; 301821; -. [O70161-1]
DR ProteomicsDB; 301822; -. [O70161-2]
DR ProteomicsDB; 301823; -. [O70161-3]
DR Antibodypedia; 2779; 234 antibodies from 31 providers.
DR DNASU; 18717; -.
DR Ensembl; ENSMUST00000105327; ENSMUSP00000100964; ENSMUSG00000034902. [O70161-1]
DR Ensembl; ENSMUST00000163075; ENSMUSP00000124155; ENSMUSG00000034902. [O70161-3]
DR GeneID; 18717; -.
DR KEGG; mmu:18717; -.
DR UCSC; uc007ghc.3; mouse. [O70161-1]
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; SHEEVHV; -.
DR OrthoDB; 1562683at2759; -.
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 74 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 268 other tissues.
DR ExpressionAtlas; O70161; baseline and differential.
DR Genevisible; O70161; MM.
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:0006897; P:endocytosis; 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 Gene3D; 3.30.800.10; -; 1.
DR IDEAL; IID50194; -.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
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
