PI51A_HUMAN
ID PI51A_HUMAN Reviewed; 562 AA.
AC Q99755; A8K4Q0; B4DIN0; Q99754; Q99756;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha {ECO:0000305|PubMed:19158393};
DE Short=PIP5K1-alpha {ECO:0000303|PubMed:19158393, ECO:0000303|PubMed:8955136};
DE Short=PtdIns(4)P-5-kinase 1 alpha {ECO:0000305|PubMed:19158393};
DE EC=2.7.1.68 {ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:8955136};
DE AltName: Full=68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha {ECO:0000303|PubMed:8955136};
DE AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I alpha {ECO:0000305|PubMed:19158393};
DE Short=PIP5KIalpha {ECO:0000303|PubMed:19158393, ECO:0000303|PubMed:8955136};
GN Name=PIP5K1A {ECO:0000312|HGNC:HGNC:8994};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=8955136; DOI=10.1074/jbc.271.51.32937;
RA Loijens J.C., Anderson R.A.;
RT "Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of
RT this novel lipid kinase family.";
RL J. Biol. Chem. 271:32937-32943(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
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 INTERACTION WITH DGKZ, AND SUBCELLULAR LOCATION.
RX PubMed=15157668; DOI=10.1016/j.cellsig.2004.01.010;
RA Luo B., Prescott S.M., Topham M.K.;
RT "Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-
RT kinase Ialpha by a novel mechanism.";
RL Cell. Signal. 16:891-897(2004).
RN [7]
RP FUNCTION, AND INTERACTION WITH TUT1.
RX PubMed=18288197; DOI=10.1038/nature06666;
RA Mellman D.L., Gonzales M.L., Song C., Barlow C.A., Wang P., Kendziorski C.,
RA Anderson R.A.;
RT "A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of
RT select mRNAs.";
RL Nature 451:1013-1017(2008).
RN [8]
RP FUNCTION IN KERATINOCYTE DIFFERENTIATION, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN A COMPLEX WITH CDH1; CTNNB1 AND CTNND1.
RX PubMed=19158393; DOI=10.1091/mbc.e08-07-0756;
RA Xie Z., Chang S.M., Pennypacker S.D., Liao E.-Y., Bikle D.D.;
RT "Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular
RT calcium-induced keratinocyte differentiation.";
RL Mol. Biol. Cell 20:1695-1704(2009).
RN [9]
RP FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-322 AND ARG-440.
RX PubMed=20660631; DOI=10.1083/jcb.200911110;
RA Chao W.-T., Daquinag A.C., Ashcroft F., Kunz J.;
RT "Type I PIPK-alpha regulates directed cell migration by modulating Rac1
RT plasma membrane targeting and activation.";
RL J. Cell Biol. 190:247-262(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND MUTAGENESIS OF LEU-215.
RX PubMed=21477596; DOI=10.1016/j.jmb.2011.03.071;
RA Shulga Y.V., Topham M.K., Epand R.M.;
RT "Study of arachidonoyl specificity in two enzymes of the PI cycle.";
RL J. Mol. Biol. 409:101-112(2011).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF LEU-215; LEU-223 AND ASP-322.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH PIP4K2C, AND CATALYTIC ACTIVITY.
RX PubMed=31091439; DOI=10.1016/j.celrep.2019.04.070;
RA Wang D.G., Paddock M.N., Lundquist M.R., Sun J.Y., Mashadova O.,
RA Amadiume S., Bumpus T.W., Hodakoski C., Hopkins B.D., Fine M., Hill A.,
RA Yang T.J., Baskin J.M., Dow L.E., Cantley L.C.;
RT "PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent
RT Mechanism.";
RL Cell Rep. 27:1991.e5-2001.e5(2019).
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:8955136, PubMed:21477596, PubMed:22942276).
CC PtdIns(4,5)P2 can directly act as a second messenger or can be utilized
CC as a precursor to generate other second messengers: inositol 1,4,5-
CC trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-
CC 3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (PubMed:19158393,
CC PubMed:20660631). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the
CC predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can
CC also use phosphatidylinositol (PtdIns) as substrate in vitro
CC (PubMed:22942276). Together with PIP5K1C, is required for phagocytosis,
CC both enzymes regulating different types of actin remodeling at
CC sequential steps (By similarity). Promotes particle ingestion by
CC activating the WAS GTPase-binding protein that induces Arp2/3 dependent
CC actin polymerization at the nascent phagocytic cup (By similarity).
CC Together with PIP5K1B, is required, after stimulation by G-protein
CC coupled receptors, for the synthesis of IP3 that will induce stable
CC platelet adhesion (By similarity). Recruited to the plasma membrane by
CC the E-cadherin/beta-catenin complex where it provides the substrate
CC PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that
CC will mobilize internal calcium and drive keratinocyte differentiation
CC (PubMed:19158393). Positively regulates insulin-induced translocation
CC of SLC2A4 to the cell membrane in adipocytes (By similarity). Together
CC with PIP5K1C has a role during embryogenesis (By similarity).
CC Independently of its catalytic activity, is required for membrane
CC ruffling formation, actin organization and focal adhesion formation
CC during directional cell migration by controlling integrin-induced
CC translocation of the small GTPase RAC1 to the plasma membrane
CC (PubMed:20660631). Also functions in the nucleus where it acts as an
CC activator of TUT1 adenylyltransferase activity in nuclear speckles,
CC thereby regulating mRNA polyadenylation of a select set of mRNAs
CC (PubMed:18288197). {ECO:0000250|UniProtKB:P70182,
CC ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393,
CC ECO:0000269|PubMed:20660631, ECO:0000269|PubMed:21477596,
CC ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:8955136}.
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:21477596, ECO:0000269|PubMed:22942276,
CC ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:8955136};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14426;
CC Evidence={ECO:0000305|PubMed:21477596, ECO:0000305|PubMed:22942276,
CC ECO:0000305|PubMed:31091439, ECO:0000305|PubMed:8955136};
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:0000269|PubMed:21477596, ECO:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40364;
CC Evidence={ECO:0000305|PubMed:21477596, ECO:0000305|PubMed:22942276};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4-
CC phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:65356,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83423,
CC ChEBI:CHEBI:83436, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:21477596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65357;
CC Evidence={ECO:0000305|PubMed:21477596};
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:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40368;
CC Evidence={ECO:0000305|PubMed:22942276};
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:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40380;
CC Evidence={ECO:0000305|PubMed:22942276};
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:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40384;
CC Evidence={ECO:0000305|PubMed:22942276};
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:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40376;
CC Evidence={ECO:0000305|PubMed:22942276};
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:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40388;
CC Evidence={ECO:0000305|PubMed:22942276};
CC -!- ACTIVITY REGULATION: Activated by diarachidonoyl phosphatidic acid
CC (DAPA), when 1,2-dipalmitoyl-PI4P is used as a substrate.
CC {ECO:0000269|PubMed:22942276}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 uM for 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-
CC glycero-3-phospho-1D-myo-inositol 4-phosphate
CC {ECO:0000269|PubMed:21477596};
CC KM=2.8 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=16 uM for 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-
CC 1D-myo-inositol 4-phosphate {ECO:0000269|PubMed:22942276};
CC -!- SUBUNIT: Interacts with RAC1 (By similarity). Interacts with TUT1
CC (PubMed:18288197). Forms a complex with CDH1/E-cadherin, CTNNB1/beta-
CC catenin and CTNND1 at the plasma membrane upon calcium stimulation
CC (PubMed:18288197). Found in a ternary complex with IRS1 and DGKZ in the
CC absence of insulin stimulation (By similarity). Interacts with DGKZ
CC (PubMed:15157668). Interacts with PIP4K2C; the interaction inhibits
CC PIP5K1A kinase activity (PubMed:31091439).
CC {ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:15157668,
CC ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:31091439}.
CC -!- INTERACTION:
CC Q99755; P01116: KRAS; NbExp=9; IntAct=EBI-726414, EBI-367415;
CC Q99755; Q9H6E5: TUT1; NbExp=3; IntAct=EBI-726414, EBI-2511680;
CC Q99755-1; Q9H6E5: TUT1; NbExp=2; IntAct=EBI-15687389, EBI-2511680;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P70182}.
CC Cytoplasm {ECO:0000250|UniProtKB:P70182}. Nucleus
CC {ECO:0000269|PubMed:15157668}. Nucleus speckle
CC {ECO:0000269|PubMed:18288197}. Cell projection, ruffle
CC {ECO:0000269|PubMed:20660631}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:15157668}. Note=Colocalizes with RAC1 at actin-rich
CC membrane ruffles (PubMed:20660631). Localizes to nuclear speckles and
CC associates with TUT1 to regulate polyadenylation of selected mRNAs
CC (PubMed:18288197). {ECO:0000269|PubMed:18288197,
CC ECO:0000269|PubMed:20660631}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PIP5KIalpha2 {ECO:0000303|PubMed:8955136};
CC IsoId=Q99755-1; Sequence=Displayed;
CC Name=2; Synonyms=PIP5KIalpha3 {ECO:0000303|PubMed:8955136};
CC IsoId=Q99755-2; Sequence=VSP_016007, VSP_016008;
CC Name=3; Synonyms=PIP5KIalpha1 {ECO:0000303|PubMed:8955136};
CC IsoId=Q99755-3; Sequence=VSP_016007;
CC Name=4;
CC IsoId=Q99755-4; Sequence=VSP_041912, VSP_041913;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal
CC muscle, kidney and pancreas. Detected at lower levels in brain, lung
CC and liver. {ECO:0000269|PubMed:8955136}.
CC -!- CAUTION: There is confusion in the literature with phosphatidylinositol
CC 4-phosphate 5-kinase type I nomenclature due to the fact that
CC frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5-
CC kinase type I alpha. {ECO:0000305}.
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DR EMBL; U78575; AAC50910.1; -; mRNA.
DR EMBL; U78576; AAC50911.1; -; mRNA.
DR EMBL; U78577; AAC50912.1; -; mRNA.
DR EMBL; AK291015; BAF83704.1; -; mRNA.
DR EMBL; AK295691; BAG58542.1; -; mRNA.
DR EMBL; AL592424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53461.1; -; Genomic_DNA.
DR EMBL; BC007833; AAH07833.1; -; mRNA.
DR CCDS; CCDS44219.1; -. [Q99755-1]
DR CCDS; CCDS44220.1; -. [Q99755-4]
DR CCDS; CCDS44221.1; -. [Q99755-2]
DR CCDS; CCDS990.1; -. [Q99755-3]
DR RefSeq; NP_001129108.1; NM_001135636.1. [Q99755-4]
DR RefSeq; NP_001129109.1; NM_001135637.1. [Q99755-2]
DR RefSeq; NP_001129110.1; NM_001135638.1. [Q99755-1]
DR RefSeq; NP_001317618.1; NM_001330689.1.
DR RefSeq; NP_003548.1; NM_003557.2. [Q99755-3]
DR AlphaFoldDB; Q99755; -.
DR SMR; Q99755; -.
DR BioGRID; 113983; 141.
DR DIP; DIP-60649N; -.
DR IntAct; Q99755; 42.
DR MINT; Q99755; -.
DR STRING; 9606.ENSP00000357883; -.
DR BindingDB; Q99755; -.
DR ChEMBL; CHEMBL5969; -.
DR DrugCentral; Q99755; -.
DR SwissLipids; SLP:000000553; -. [Q99755-3]
DR SwissLipids; SLP:000000554; -.
DR iPTMnet; Q99755; -.
DR PhosphoSitePlus; Q99755; -.
DR SwissPalm; Q99755; -.
DR BioMuta; PIP5K1A; -.
DR DMDM; 74752158; -.
DR EPD; Q99755; -.
DR jPOST; Q99755; -.
DR MassIVE; Q99755; -.
DR MaxQB; Q99755; -.
DR PaxDb; Q99755; -.
DR PeptideAtlas; Q99755; -.
DR PRIDE; Q99755; -.
DR ProteomicsDB; 78458; -. [Q99755-1]
DR ProteomicsDB; 78459; -. [Q99755-2]
DR ProteomicsDB; 78460; -. [Q99755-3]
DR ProteomicsDB; 78461; -. [Q99755-4]
DR Antibodypedia; 34058; 197 antibodies from 29 providers.
DR DNASU; 8394; -.
DR Ensembl; ENST00000349792.9; ENSP00000271663.7; ENSG00000143398.20. [Q99755-3]
DR Ensembl; ENST00000368888.9; ENSP00000357883.4; ENSG00000143398.20. [Q99755-1]
DR Ensembl; ENST00000368890.8; ENSP00000357885.4; ENSG00000143398.20. [Q99755-2]
DR Ensembl; ENST00000441902.6; ENSP00000415648.2; ENSG00000143398.20. [Q99755-4]
DR GeneID; 8394; -.
DR KEGG; hsa:8394; -.
DR MANE-Select; ENST00000368888.9; ENSP00000357883.4; NM_001135638.2; NP_001129110.1.
DR UCSC; uc001exi.4; human. [Q99755-1]
DR CTD; 8394; -.
DR DisGeNET; 8394; -.
DR GeneCards; PIP5K1A; -.
DR HGNC; HGNC:8994; PIP5K1A.
DR HPA; ENSG00000143398; Low tissue specificity.
DR MIM; 603275; gene.
DR neXtProt; NX_Q99755; -.
DR OpenTargets; ENSG00000143398; -.
DR PharmGKB; PA33327; -.
DR VEuPathDB; HostDB:ENSG00000143398; -.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000154703; -.
DR HOGENOM; CLU_004312_5_1_1; -.
DR InParanoid; Q99755; -.
DR OMA; NIRLVAM; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; Q99755; -.
DR TreeFam; TF319618; -.
DR BioCyc; MetaCyc:HS07047-MON; -.
DR BRENDA; 2.7.1.68; 2681.
DR PathwayCommons; Q99755; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; Q99755; -.
DR SIGNOR; Q99755; -.
DR BioGRID-ORCS; 8394; 108 hits in 1085 CRISPR screens.
DR ChiTaRS; PIP5K1A; human.
DR GeneWiki; PIP5K1A; -.
DR GenomeRNAi; 8394; -.
DR Pharos; Q99755; Tbio.
DR PRO; PR:Q99755; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q99755; protein.
DR Bgee; ENSG00000143398; Expressed in right testis and 186 other tissues.
DR ExpressionAtlas; Q99755; baseline and differential.
DR Genevisible; Q99755; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0000285; F:1-phosphatidylinositol-3-phosphate 5-kinase activity; TAS:Reactome.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:UniProtKB.
DR GO; GO:0052810; F:1-phosphatidylinositol-5-kinase activity; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; IDA:UniProtKB.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; TAS:Reactome.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; NAS:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0006650; P:glycerophospholipid metabolic process; TAS:ProtInc.
DR GO; GO:0030216; P:keratinocyte differentiation; TAS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; TAS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
DR GO; GO:0097178; P:ruffle assembly; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 3.30.800.10; -; 1.
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 Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasm; Isopeptide bond; Kinase; Lipid metabolism; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation.
FT CHAIN 1..562
FT /note="Phosphatidylinositol 4-phosphate 5-kinase type-1
FT alpha"
FT /id="PRO_0000185456"
FT DOMAIN 81..449
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 506..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 103
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VAR_SEQ 30..52
FT /note="ASGIKRPMASEVLEARQDSYISL -> SGIKRPMASE (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8955136"
FT /id="VSP_016007"
FT VAR_SEQ 41..52
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041912"
FT VAR_SEQ 382..410
FT /note="HMGGIPARNSKGERLLLYIGIIDILQSYR -> Q (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041913"
FT VAR_SEQ 455..504
FT /note="LKPSPSKKFRSGSSFSRRAGSSGNSCITYQPSVSGEHKAQVTTKAEVEPG
FT -> C (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8955136"
FT /id="VSP_016008"
FT MUTAGEN 215
FT /note="L->I: Decreased 1-phosphatidylinositol-4-phosphate
FT 5-kinase activity with 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-
FT eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-
FT phosphate (arachidonate-PtdIns4P) as substrate. Increased
FT enzyme activation by diarachidonoyl phosphatidic acid
FT (DAPA). No change in enzyme activation by 1-stearoyl-2-
FT oleoyl phosphatidic acid (SOPA) or 1-stearoyl-2-
FT arachidonoyl phosphatidic acid (SAPA)."
FT /evidence="ECO:0000269|PubMed:21477596,
FT ECO:0000269|PubMed:22942276"
FT MUTAGEN 223
FT /note="L->I: Decreased 1-phosphatidylinositol-4-phosphate
FT 5-kinase activity with 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-
FT eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-
FT phosphate (arachidonate-PtdIns4P) as substrate. Increased
FT enzyme activation by diarachidonoyl phosphatidic acid
FT (DAPA). No change in enzyme activation by 1-stearoyl-2-
FT oleoyl phosphatidic acid (SOPA) or 1-stearoyl-2-
FT arachidonoyl phosphatidic acid (SAPA)."
FT /evidence="ECO:0000269|PubMed:22942276"
FT MUTAGEN 322
FT /note="D->A: Increased enzyme activation by diarachidonoyl
FT phosphatidic acid (DAPA)."
FT /evidence="ECO:0000269|PubMed:22942276"
FT MUTAGEN 322
FT /note="D->N: Does not affect targeting of RAC1 to the
FT plasma membrane; when associated with Q-440."
FT /evidence="ECO:0000269|PubMed:20660631"
FT MUTAGEN 440
FT /note="R->Q: Does not affect targeting of RAC1 to the
FT plasma membrane; when associated with N-322."
FT /evidence="ECO:0000269|PubMed:20660631"
FT CONFLICT 257
FT /note="K -> E (in Ref. 2; BAG58542)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 562 AA; 62633 MW; A8F7988EB73506A0 CRC64;
MASASSGPSS SVGFSSFDPA VPSCTLSSAA SGIKRPMASE VLEARQDSYI SLVPYASGMP
IKKIGHRSVD SSGETTYKKT TSSALKGAIQ LGITHTVGSL STKPERDVLM QDFYVVESIF
FPSEGSNLTP AHHYNDFRFK TYAPVAFRYF RELFGIRPDD YLYSLCSEPL IELCSSGASG
SLFYVSSDDE FIIKTVQHKE AEFLQKLLPG YYMNLNQNPR TLLPKFYGLY CVQAGGKNIR
IVVMNNLLPR SVKMHIKYDL KGSTYKRRAS QKEREKPLPT FKDLDFLQDI PDGLFLDADM
YNALCKTLQR DCLVLQSFKI MDYSLLMSIH NIDHAQREPL SSETQYSVDT RRPAPQKALY
STAMESIQGE ARRGGTMETD DHMGGIPARN SKGERLLLYI GIIDILQSYR FVKKLEHSWK
ALVHDGDTVS VHRPGFYAER FQRFMCNTVF KKIPLKPSPS KKFRSGSSFS RRAGSSGNSC
ITYQPSVSGE HKAQVTTKAE VEPGVHLGRP DVLPQTPPLE EISEGSPIPD PSFSPLVGET
LQMLTTSTTL EKLEVAESEF TH
