ID FYV1_HUMAN Reviewed; 2098 AA.
AC Q9Y2I7; Q08AR7; Q08AR8; Q53ST3; Q53T36; Q8N5H0; Q8NB67;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 28-JUN-2023, entry version 211.
DE RecName: Full=1-phosphatidylinositol 3-phosphate 5-kinase {ECO:0000305};
DE Short=Phosphatidylinositol 3-phosphate 5-kinase;
DE EC=2.7.1.150 {ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:33098764};
DE AltName: Full=FYVE finger-containing phosphoinositide kinase;
DE AltName: Full=PIKfyve;
DE AltName: Full=Phosphatidylinositol 3-phosphate 5-kinase type III;
DE Short=PIPkin-III;
DE Short=Type III PIP kinase;
DE AltName: Full=Serine-protein kinase PIKFYVE;
DE EC=2.7.11.1 {ECO:0000269|PubMed:33098764};
GN Name=PIKFYVE {ECO:0000312|HGNC:HGNC:23785}; Synonyms=KIAA0981, PIP5K3;
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] (ISOFORM 1), AND VARIANTS ASN-696; SER-932;
RP LEU-995; SER-998 AND LYS-1183.
RC TISSUE=Brain;
RA Cabezas A., Pattni K., Stenmark H.;
RT "Human PIKfyve, a PI3P 5-kinase that regulates endocytic trafficking.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ASN-696;
RP SER-932; LEU-995; SER-998 AND LYS-1183.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1037-2098 (ISOFORM 1), AND
RP VARIANT LYS-1183.
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1521-2098 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11706043; DOI=10.1074/jbc.m110194200;
RA Sbrissa D., Ikonomov O.C., Shisheva A.;
RT "Phosphatidylinositol 3-phosphate-interacting domains in PIKfyve. Binding
RT specificity and role in PIKfyve endomembrane localization.";
RL J. Biol. Chem. 277:6073-6079(2002).
RN [8]
RP INTERACTION WITH RABEPK.
RX PubMed=14530284; DOI=10.1074/jbc.m307260200;
RA Ikonomov O.C., Sbrissa D., Mlak K., Deeb R., Fligger J., Soans A.,
RA Finley R.L. Jr., Shisheva A.;
RT "Active PIKfyve associates with and promotes the membrane attachment of the
RT late endosome-to-trans-Golgi network transport factor Rab9 effector p40.";
RL J. Biol. Chem. 278:50863-50871(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP FUNCTION, AND INTERACTION WITH EGFR.
RX PubMed=17909029; DOI=10.1158/0008-5472.can-07-1333;
RA Kim J., Jahng W.J., Di Vizio D., Lee J.S., Jhaveri R., Rubin M.A.,
RA Shisheva A., Freeman M.R.;
RT "The phosphoinositide kinase PIKfyve mediates epidermal growth factor
RT receptor trafficking to the nucleus.";
RL Cancer Res. 67:9229-9237(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE PI(3,5)P2
RP REGULATORY COMPLEX.
RX PubMed=17556371; DOI=10.1074/jbc.m611678200;
RA Sbrissa D., Ikonomov O.C., Fu Z., Ijuin T., Gruenberg J., Takenawa T.,
RA Shisheva A.;
RT "Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate
RT synthesis and turnover that regulates the progression of endosomal
RT transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex.";
RL J. Biol. Chem. 282:23878-23891(2007).
RN [13]
RP IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX.
RX PubMed=18950639; DOI=10.1016/j.jmb.2008.10.009;
RA Sbrissa D., Ikonomov O.C., Fenner H., Shisheva A.;
RT "ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3
RT in a complex to promote PIKfyve activity and functionality.";
RL J. Mol. Biol. 384:766-779(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-1544, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-299; SER-1544; SER-1549 AND SER-1754, CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION AT SER-318.
RX PubMed=20513353; DOI=10.1016/j.bbrc.2010.05.134;
RA Hill E.V., Hudson C.A., Vertommen D., Rider M.H., Tavare J.M.;
RT "Regulation of PIKfyve phosphorylation by insulin and osmotic stress.";
RL Biochem. Biophys. Res. Commun. 397:650-655(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22621786; DOI=10.1152/ajpcell.00105.2012;
RA Sbrissa D., Ikonomov O.C., Filios C., Delvecchio K., Shisheva A.;
RT "Functional dissociation between PIKfyve-synthesized PtdIns5P and
RT PtdIns(3,5)P2 by means of the PIKfyve inhibitor YM201636.";
RL Am. J. Physiol. 303:C436-C446(2012).
RN [20]
RP REVIEW.
RX PubMed=23086417; DOI=10.1007/978-94-007-5025-8_7;
RA Shisheva A.;
RT "PIKfyve and its Lipid products in health and in sickness.";
RL Curr. Top. Microbiol. Immunol. 362:127-162(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-88; SER-299; SER-307;
RP SER-1544 AND SER-1549, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [23]
RP FUNCTION.
RX PubMed=27623384; DOI=10.1016/j.devcel.2016.08.001;
RA Krishna S., Palm W., Lee Y., Yang W., Bandyopadhyay U., Xu H., Florey O.,
RA Thompson C.B., Overholtzer M.;
RT "PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following
RT Engulfment.";
RL Dev. Cell 38:536-547(2016).
RN [24]
RP FUNCTION.
RX PubMed=28779020; DOI=10.4049/jimmunol.1601466;
RA Dayam R.M., Sun C.X., Choy C.H., Mancuso G., Glogauer M., Botelho R.J.;
RT "The Lipid Kinase PIKfyve Coordinates the Neutrophil Immune Response
RT through the Activation of the Rac GTPase.";
RL J. Immunol. 199:2096-2105(2017).
RN [25]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=29584722; DOI=10.1371/journal.pgen.1007290;
RA Liggins M.C., Flesher J.L., Jahid S., Vasudeva P., Eby V., Takasuga S.,
RA Sasaki J., Sasaki T., Boissy R.E., Ganesan A.K.;
RT "PIKfyve regulates melanosome biogenesis.";
RL PLoS Genet. 14:e1007290-e1007290(2018).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=30612035; DOI=10.1016/j.isci.2018.12.015;
RA Baranov M.V., Bianchi F., Schirmacher A., van Aart M.A.C., Maassen S.,
RA Muntjewerff E.M., Dingjan I., Ter Beest M., Verdoes M., Keyser S.G.L.,
RA Bertozzi C.R., Diederichsen U., van den Bogaart G.;
RT "The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major
RT Histocompatibility Complex Class II Antigen Presentation.";
RL IScience 11:160-177(2019).
RN [27]
RP FUNCTION (MICROBIAL INFECTION), AND ACTIVITY REGULATION.
RX PubMed=32221306; DOI=10.1038/s41467-020-15562-9;
RA Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T.,
RA Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z.;
RT "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and
RT its immune cross-reactivity with SARS-CoV.";
RL Nat. Commun. 11:1620-1620(2020).
RN [28] {ECO:0007744|PDB:7K2V}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.60 ANGSTROMS) OF 547-983 AND 1822-2085,
RP IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, CATALYTIC
RP ACTIVITY, PHOSPHORYLATION AT SER-23; SER-48; SER-1522; SER-1669; SER-1969
RP AND SER-2053, AND MUTAGENESIS OF LYS-1877 AND SER-2053.
RX PubMed=33098764; DOI=10.1016/j.molcel.2020.10.003;
RA Lees J.A., Li P., Kumar N., Weisman L.S., Reinisch K.M.;
RT "Insights into Lysosomal PI(3,5)P2 Homeostasis from a Structural-
RT Biochemical Analysis of the PIKfyve Lipid Kinase Complex.";
RL Mol. Cell 80:736-743.e4(2020).
RN [29]
RP VARIANTS CFD 988-GLN--CYS-2098 DEL AND ARG-1103.
RX PubMed=15902656; DOI=10.1086/431346;
RA Li S., Tiab L., Jiao X., Munier F.L., Zografos L., Frueh B.E., Sergeev Y.,
RA Smith J., Rubin B., Meallet M.A., Forster R.K., Hejtmancik J.F.,
RA Schorderet D.F.;
RT "Mutations in PIP5K3 are associated with Francois-Neetens mouchetee fleck
RT corneal dystrophy.";
RL Am. J. Hum. Genet. 77:54-63(2005).
CC -!- FUNCTION: Dual specificity kinase implicated in myriad essential
CC cellular processes such as maintenance of endomembrane homeostasis, and
CC endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport,
CC stress- or hormone-induced signaling and cell cycle progression
CC (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the
CC synthesis and turnover of phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of
CC phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-
CC inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also
CC catalyzes the phosphorylation of phosphatidylinositol on the fifth
CC hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-
CC phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase
CC activity and is able to autophosphorylate and transphosphorylate.
CC Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate
CC 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-
CC regulates lipid product formation (PubMed:33098764). Involved in key
CC endosome operations such as fission and fusion in the course of
CC endosomal cargo transport (PubMed:22621786). Required for the
CC maturation of early into late endosomes, phagosomes and lysosomes
CC (PubMed:30612035). Regulates vacuole maturation and nutrient recovery
CC following engulfment of macromolecules, initiates the redistribution of
CC accumulated lysosomal contents back into the endosome network
CC (PubMed:27623384). Critical regulator of the morphology, degradative
CC activity, and protein turnover of the endolysosomal system in
CC macrophages and platelets (By similarity). In neutrophils, critical to
CC perform chemotaxis, generate ROS, and undertake phagosome fusion with
CC lysosomes (PubMed:28779020). Plays a key role in the processing and
CC presentation of antigens by major histocompatibility complex class II
CC (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome
CC biogenesis by controlling the delivery of proteins from the endosomal
CC compartment to the melanosome (PubMed:29584722). Essential for systemic
CC glucose homeostasis, mediates insulin-induced signals for
CC endosome/actin remodeling in the course of GLUT4 translocation/glucose
CC uptake activation (By similarity). Supports microtubule-based endosome-
CC to-trans-Golgi network cargo transport, through association with SPAG9
CC and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus
CC (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6,
CC ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:17909029,
CC ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:27623384,
CC ECO:0000269|PubMed:28779020, ECO:0000269|PubMed:29584722,
CC ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:33098764,
CC ECO:0000303|PubMed:23086417}.
CC -!- FUNCTION: (Microbial infection) Required for cell entry of
CC coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC
CC (HCoV-EMC) by endocytosis. {ECO:0000269|PubMed:32221306}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:13609,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57923,
CC ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.150;
CC Evidence={ECO:0000269|PubMed:33098764, ECO:0000305|PubMed:17556371};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13610;
CC Evidence={ECO:0000305|PubMed:33098764};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:44680, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57795, ChEBI:CHEBI:57880, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:22621786};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44681;
CC Evidence={ECO:0000305|PubMed:22621786};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:33098764};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:33098764};
CC -!- ACTIVITY REGULATION: Inhibited by apilimod and YM201636.
CC {ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:29584722,
CC ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:32221306}.
CC -!- SUBUNIT: Component of the PI(3,5)P2 regulatory complex/PAS complex, at
CC least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly
CC of the complex and serves as a scaffold by pentamerizing into a star-
CC shaped structure, which can bind a single copy each of PIKFYVE and FIG4
CC and coordinates their activities (PubMed:17556371, PubMed:18950639,
CC PubMed:33098764). Interacts (via chaperonin-like domain) with RABEPK;
CC the interaction recruits RABEPK to the endosomal membrane
CC (PubMed:14530284). Interacts with SPAG9 (By similarity). Interacts with
CC EGFR (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6,
CC ECO:0000269|PubMed:14530284, ECO:0000269|PubMed:17556371,
CC ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:18950639,
CC ECO:0000269|PubMed:33098764}.
CC -!- INTERACTION:
CC Q9Y2I7; Q08AM6: VAC14; NbExp=5; IntAct=EBI-6138650, EBI-2107455;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:11706043,
CC ECO:0000269|PubMed:17556371}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9Z1T6}. Early endosome membrane
CC {ECO:0000269|PubMed:30612035}; Peripheral membrane protein. Cytoplasmic
CC vesicle, phagosome membrane {ECO:0000269|PubMed:30612035}; Peripheral
CC membrane protein {ECO:0000305}. Late endosome membrane
CC {ECO:0000269|PubMed:11706043}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9Z1T6}. Note=Mainly associated with membranes
CC of the late endocytic pathway. {ECO:0000269|PubMed:11706043}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9Y2I7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2I7-2; Sequence=VSP_040108, VSP_040110, VSP_040111;
CC Name=3;
CC IsoId=Q9Y2I7-3; Sequence=VSP_040109, VSP_040110, VSP_040111;
CC Name=4;
CC IsoId=Q9Y2I7-4; Sequence=VSP_040110, VSP_040111;
CC -!- DOMAIN: Interaction of FYVE-type domain with phosphatidylinositol 3-
CC phosphate (PtdIns(3)P) is necessary for targeting to the membranes of
CC the late endocytic pathway. {ECO:0000269|PubMed:11706043}.
CC -!- PTM: Autophosphorylates which inhibits its own phosphatidylinositol 3-
CC phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity
CC and down-regulates lipid product formation (PubMed:33098764).
CC Dephosphorylated by FIG4 in the PI(3,5)P2 regulatory complex, at Ser-
CC 48, Ser-1669 and Ser-2053 (PubMed:33098764). Phosphorylated in response
CC to insulin at Ser-318 in a protein kinase B (PKB)-dependent manner
CC (PubMed:20513353). {ECO:0000269|PubMed:20513353,
CC ECO:0000269|PubMed:33098764}.
CC -!- DISEASE: Corneal dystrophy, fleck (CFD) [MIM:121850]: A form of stromal
CC corneal dystrophy characterized by numerous small white flecks
CC scattered in all levels of the stroma, with configurations varying from
CC semicircular to wreath-like, curvilinear, or punctate. Although CFD may
CC occasionally cause mild photophobia, patients are typically
CC asymptomatic and have normal vision. {ECO:0000269|PubMed:15902656}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC03674.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AY457063; AAR19397.1; -; mRNA.
DR EMBL; AC012362; AAY14870.1; -; Genomic_DNA.
DR EMBL; AC016697; AAX93222.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70444.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70445.1; -; Genomic_DNA.
DR EMBL; BC032389; AAH32389.1; -; mRNA.
DR EMBL; BC125052; AAI25053.1; -; mRNA.
DR EMBL; BC125053; AAI25054.1; -; mRNA.
DR EMBL; AK091482; BAC03674.1; ALT_INIT; mRNA.
DR EMBL; AB023198; BAA76825.1; -; mRNA.
DR CCDS; CCDS2382.1; -. [Q9Y2I7-1]
DR CCDS; CCDS33368.1; -. [Q9Y2I7-2]
DR CCDS; CCDS54431.1; -. [Q9Y2I7-4]
DR RefSeq; NP_001171471.1; NM_001178000.1. [Q9Y2I7-4]
DR RefSeq; NP_055855.2; NM_015040.3. [Q9Y2I7-1]
DR RefSeq; NP_689884.1; NM_152671.3. [Q9Y2I7-2]
DR PDB; 7K2V; EM; 6.60 A; P=1822-2085.
DR PDBsum; 7K2V; -.
DR AlphaFoldDB; Q9Y2I7; -.
DR SMR; Q9Y2I7; -.
DR BioGRID; 128336; 53.
DR CORUM; Q9Y2I7; -.
DR IntAct; Q9Y2I7; 8.
DR MINT; Q9Y2I7; -.
DR STRING; 9606.ENSP00000264380; -.
DR BindingDB; Q9Y2I7; -.
DR ChEMBL; CHEMBL1938222; -.
DR GuidetoPHARMACOLOGY; 2857; -.
DR GlyCosmos; Q9Y2I7; 4 sites, 1 glycan.
DR GlyGen; Q9Y2I7; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9Y2I7; -.
DR MetOSite; Q9Y2I7; -.
DR PhosphoSitePlus; Q9Y2I7; -.
DR BioMuta; PIKFYVE; -.
DR DMDM; 300669693; -.
DR EPD; Q9Y2I7; -.
DR jPOST; Q9Y2I7; -.
DR MassIVE; Q9Y2I7; -.
DR MaxQB; Q9Y2I7; -.
DR PaxDb; Q9Y2I7; -.
DR PeptideAtlas; Q9Y2I7; -.
DR ProteomicsDB; 85801; -. [Q9Y2I7-1]
DR ProteomicsDB; 85802; -. [Q9Y2I7-2]
DR ProteomicsDB; 85803; -. [Q9Y2I7-3]
DR ProteomicsDB; 85804; -. [Q9Y2I7-4]
DR ABCD; Q9Y2I7; 1 sequenced antibody.
DR Antibodypedia; 34200; 422 antibodies from 34 providers.
DR DNASU; 200576; -.
DR Ensembl; ENST00000264380.9; ENSP00000264380.4; ENSG00000115020.17. [Q9Y2I7-1]
DR Ensembl; ENST00000308862.10; ENSP00000308715.6; ENSG00000115020.17. [Q9Y2I7-3]
DR Ensembl; ENST00000392202.7; ENSP00000376038.3; ENSG00000115020.17. [Q9Y2I7-2]
DR Ensembl; ENST00000407449.5; ENSP00000384356.1; ENSG00000115020.17. [Q9Y2I7-4]
DR GeneID; 200576; -.
DR KEGG; hsa:200576; -.
DR MANE-Select; ENST00000264380.9; ENSP00000264380.4; NM_015040.4; NP_055855.2.
DR UCSC; uc002vcv.4; human. [Q9Y2I7-1]
DR AGR; HGNC:23785; -.
DR CTD; 200576; -.
DR DisGeNET; 200576; -.
DR GeneCards; PIKFYVE; -.
DR HGNC; HGNC:23785; PIKFYVE.
DR HPA; ENSG00000115020; Low tissue specificity.
DR MalaCards; PIKFYVE; -.
DR MIM; 121850; phenotype.
DR MIM; 609414; gene.
DR neXtProt; NX_Q9Y2I7; -.
DR OpenTargets; ENSG00000115020; -.
DR Orphanet; 98970; Fleck corneal dystrophy.
DR PharmGKB; PA165697116; -.
DR VEuPathDB; HostDB:ENSG00000115020; -.
DR eggNOG; KOG0230; Eukaryota.
DR GeneTree; ENSGT00940000156307; -.
DR HOGENOM; CLU_000480_2_1_1; -.
DR InParanoid; Q9Y2I7; -.
DR OMA; QEKVVEW; -.
DR OrthoDB; 5481504at2759; -.
DR PhylomeDB; Q9Y2I7; -.
DR TreeFam; TF321717; -.
DR BioCyc; MetaCyc:HS03825-MON; -.
DR BRENDA; 2.7.1.150; 2681.
DR BRENDA; 2.7.1.68; 2681.
DR PathwayCommons; Q9Y2I7; -.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane.
DR SignaLink; Q9Y2I7; -.
DR SIGNOR; Q9Y2I7; -.
DR BioGRID-ORCS; 200576; 12 hits in 1158 CRISPR screens.
DR ChiTaRS; PIKFYVE; human.
DR GeneWiki; PIKFYVE; -.
DR GenomeRNAi; 200576; -.
DR Pharos; Q9Y2I7; Tchem.
DR PRO; PR:Q9Y2I7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y2I7; protein.
DR Bgee; ENSG00000115020; Expressed in secondary oocyte and 201 other tissues.
DR ExpressionAtlas; Q9Y2I7; baseline and differential.
DR Genevisible; Q9Y2I7; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IDA:HGNC-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; IBA:GO_Central.
DR GO; GO:0000285; F:1-phosphatidylinositol-3-phosphate 5-kinase activity; IDA:UniProtKB.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; TAS:HGNC-UCL.
DR GO; GO:0052810; F:1-phosphatidylinositol-5-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043813; F:phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; TAS:Reactome.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:1903100; P:1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0032438; P:melanosome organization; IDA:UniProtKB.
DR GO; GO:0032288; P:myelin assembly; IEA:Ensembl.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0090382; P:phagosome maturation; IDA:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; IDA:UniProtKB.
DR GO; GO:1904562; P:phosphatidylinositol 5-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; IDA:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IDA:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR CDD; cd04448; DEP_PIKfyve; 1.
DR CDD; cd03334; Fab1_TCP; 1.
DR CDD; cd15725; FYVE_PIKfyve_Fab1; 1.
DR CDD; cd17300; PIPKc_PIKfyve; 1.
DR Gene3D; 3.30.810.10; 2-Layer Sandwich; 1.
DR Gene3D; 3.50.7.10; GroEL; 1.
DR Gene3D; 3.30.800.10; Phosphatidylinositol Phosphate Kinase II Beta; 1.
DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR002423; Cpn60/GroEL/TCP-1.
DR InterPro; IPR000591; DEP_dom.
DR InterPro; IPR027409; GroEL-like_apical_dom_sf.
DR InterPro; IPR043548; PIKfyve.
DR InterPro; IPR037378; PIKfyve_DEP.
DR InterPro; IPR044769; PIKfyve_PIPKc.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR InterPro; IPR027410; TCP-1-like_intermed_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR46715; 1-PHOSPHATIDYLINOSITOL 3-PHOSPHATE 5-KINASE; 1.
DR PANTHER; PTHR46715:SF1; 1-PHOSPHATIDYLINOSITOL 3-PHOSPHATE 5-KINASE; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR Pfam; PF00610; DEP; 1.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF01504; PIP5K; 2.
DR SMART; SM00049; DEP; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00330; PIPKc; 1.
DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR SUPFAM; SSF52029; GroEL apical domain-like; 1.
DR SUPFAM; SSF54849; GroEL-intermediate domain like; 1.
DR SUPFAM; SSF56104; SAICAR synthase-like; 1.
DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR PROSITE; PS50186; DEP; 1.
DR PROSITE; PS51455; PIPK; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Corneal dystrophy; Cytoplasmic vesicle; Disease variant; Endosome;
KW Host-virus interaction; Kinase; Lipid metabolism; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..2098
FT /note="1-phosphatidylinositol 3-phosphate 5-kinase"
FT /id="PRO_0000185452"
FT DOMAIN 365..440
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT DOMAIN 1758..2084
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT ZN_FING 158..218
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 616..868
FT /note="Chaperonin-like domain"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1T6"
FT REGION 1161..1191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1512..1616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1692..1799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1842..2098
FT /note="Catalytic"
FT COMPBIAS 1..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..118
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1170..1186
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1559..1584
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1692..1739
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 213
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 23
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764"
FT MOD_RES 48
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1T6"
FT MOD_RES 318
FT /note="Phosphoserine; by PKB/AKT1 or PKB/AKT2"
FT /evidence="ECO:0000269|PubMed:20513353"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1T6"
FT MOD_RES 1522
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764"
FT MOD_RES 1544
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 1549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1669
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764"
FT MOD_RES 1754
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 1969
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764"
FT MOD_RES 2053
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:33098764"
FT VAR_SEQ 108..204
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040108"
FT VAR_SEQ 109..203
FT /note="TRRKAEPTFGGHDPRTAVQLRSLSTVLKRLKEIMEGKSQDSDLKQYWMPDSQ
FT CKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGY -> NSLQHPQEN
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040109"
FT VAR_SEQ 546..548
FT /note="EYL -> GRR (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040110"
FT VAR_SEQ 549..2098
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040111"
FT VARIANT 617
FT /note="M -> V (in dbSNP:rs16840913)"
FT /id="VAR_057097"
FT VARIANT 696
FT /note="S -> N (in dbSNP:rs10932258)"
FT /evidence="ECO:0000269|Ref.1, ECO:0000269|Ref.3"
FT /id="VAR_063406"
FT VARIANT 932
FT /note="L -> S (in dbSNP:rs2363468)"
FT /evidence="ECO:0000269|Ref.1, ECO:0000269|Ref.3"
FT /id="VAR_063407"
FT VARIANT 988..2098
FT /note="Missing (in CFD)"
FT /evidence="ECO:0000269|PubMed:15902656"
FT /id="VAR_083736"
FT VARIANT 995
FT /note="Q -> L (in dbSNP:rs893254)"
FT /evidence="ECO:0000269|Ref.1, ECO:0000269|Ref.3"
FT /id="VAR_063408"
FT VARIANT 998
FT /note="T -> S (in dbSNP:rs893253)"
FT /evidence="ECO:0000269|Ref.1, ECO:0000269|Ref.3"
FT /id="VAR_063409"
FT VARIANT 1033
FT /note="S -> A (in dbSNP:rs999890)"
FT /id="VAR_057098"
FT VARIANT 1103
FT /note="K -> R (in CFD; dbSNP:rs121918336)"
FT /evidence="ECO:0000269|PubMed:15902656"
FT /id="VAR_025309"
FT VARIANT 1183
FT /note="Q -> K (in dbSNP:rs1529979)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.3"
FT /id="VAR_063410"
FT VARIANT 1858
FT /note="R -> Q (in dbSNP:rs2289170)"
FT /id="VAR_057099"
FT MUTAGEN 1877
FT /note="K->E: Loss of autophosphorylation. Loss of
FT phosphatidylinositol 3-phosphate 5-kinase activity."
FT /evidence="ECO:0000269|PubMed:33098764"
FT MUTAGEN 2053
FT /note="S->A: No effect on phosphatidylinositol 3-phosphate
FT 5-kinase activity."
FT /evidence="ECO:0000269|PubMed:33098764"
FT MUTAGEN 2053
FT /note="S->E: Reduces 2-folds phosphatidylinositol 3-
FT phosphate 5-kinase activity."
FT /evidence="ECO:0000269|PubMed:33098764"
FT CONFLICT 1335
FT /note="M -> I (in Ref. 5; BAC03674)"
FT /evidence="ECO:0000305"
FT CONFLICT 2019
FT /note="L -> S (in Ref. 5; BAC03674)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2098 AA; 237136 MW; 390C43530D3B1E81 CRC64;
MATDDKTSPT LDSANDLPRS PTSPSHLTHF KPLTPDQDEP PFKSAYSSFV NLFRFNKERA
EGGQGEQQPL SGSWTSPQLP SRTQSVRSPT PYKKQLNEEL QRRSSALDTR RKAEPTFGGH
DPRTAVQLRS LSTVLKRLKE IMEGKSQDSD LKQYWMPDSQ CKECYDCSEK FTTFRRRHHC
RLCGQIFCSR CCNQEIPGKF MGYTGDLRAC TYCRKIALSY AHSTDSNSIG EDLNALSDSA
CSVSVLDPSE PRTPVGSRKA SRNIFLEDDL AWQSLIHPDS SNTPLSTRLV SVQEDAGKSP
ARNRSASITN LSLDRSGSPM VPSYETSVSP QANRTYVRTE TTEDERKILL DSVQLKDLWK
KICHHSSGME FQDHRYWLRT HPNCIVGKEL VNWLIRNGHI ATRAQAIAIG QAMVDGRWLD
CVSHHDQLFR DEYALYRPLQ STEFSETPSP DSDSVNSVEG HSEPSWFKDI KFDDSDTEQI
AEEGDDNLAN SASPSKRTSV SSFQSTVDSD SAASISLNVE LDNVNFHIKK PSKYPHVPPH
PADQKEYLIS DTGGQQLSIS DAFIKESLFN RRVEEKSKEL PFTPLGWHHN NLELLREENG
EKQAMERLLS ANHNHMMALL QQLLHSDSLS SSWRDIIVSL VCQVVQTVRP DVKNQDDDMD
IRQFVHIKKI PGGKKFDSVV VNGFVCTKNI AHKKMSSCIK NPKILLLKCS IEYLYREETK
FTCIDPIVLQ EREFLKNYVQ RIVDVRPTLV LVEKTVSRIA QDMLLEHGIT LVINVKSQVL
ERISRMTQGD LVMSMDQLLT KPHLGTCHKF YMQIFQLPNE QTKTLMFFEG CPQHLGCTIK
LRGGSDYELA RVKEILIFMI CVAYHSQLEI SFLMDEFAMP PTLMQNPSFH SLIEGRGHEG
AVQEQYGGGS IPWDPDIPPE SLPCDDSSLL ELRIVFEKGE QENKNLPQAV ASVKHQEHST
TACPAGLPCA FFAPVPESLL PLPVDDQQDA LGSEQPETLQ QTVVLQDPKS QIRAFRDPLQ
DDTGLYVTEE VTSSEDKRKT YSLAFKQELK DVILCISPVI TFREPFLLTE KGMRCSTRDY
FAEQVYWSPL LNKEFKEMEN RRKKQLLRDL SGLQGMNGSI QAKSIQVLPS HELVSTRIAE
HLGDSQSLGR MLADYRARGG RIQPKNSDPF AHSKDASSTS SGQSGSKNEG DEERGLILSD
AVWSTKVDCL NPINHQRLCV LFSSSSAQSS NAPSACVSPW IVTMEFYGKN DLTLGIFLER
YCFRPSYQCP SMFCDTPMVH HIRRFVHGQG CVQIILKELD SPVPGYQHTI LTYSWCRICK
QVTPVVALSN ESWSMSFAKY LELRFYGHQY TRRANAEPCG HSIHHDYHQY FSYNQMVASF
SYSPIRLLEV CVPLPKIFIK RQAPLKVSLL QDLKDFFQKV SQVYVAIDER LASLKTDTFS
KTREEKMEDI FAQKEMEEGE FKNWIEKMQA RLMSSSVDTP QQLQSVFESL IAKKQSLCEV
LQAWNNRLQD LFQQEKGRKR PSVPPSPGRL RQGEESKISA MDASPRNISP GLQNGEKEDR
FLTTLSSQSS TSSTHLQLPT PPEVMSEQSV GGPPELDTAS SSEDVFDGHL LGSTDSQVKE
KSTMKAIFAN LLPGNSYNPI PFPFDPDKHY LMYEHERVPI AVCEKEPSSI IAFALSCKEY
RNALEELSKA TQWNSAEEGL PTNSTSDSRP KSSSPIRLPE MSGGQTNRTT ETEPQPTKKA
SGMLSFFRGT AGKSPDLSSQ KRETLRGADS AYYQVGQTGK EGTENQGVEP QDEVDGGDTQ
KKQLINPHVE LQFSDANAKF YCRLYYAGEF HKMREVILDS SEEDFIRSLS HSSPWQARGG
KSGAAFYATE DDRFILKQMP RLEVQSFLDF APHYFNYITN AVQQKRPTAL AKILGVYRIG
YKNSQNNTEK KLDLLVMENL FYGRKMAQVF DLKGSLRNRN VKTDTGKESC DVVLLDENLL
KMVRDNPLYI RSHSKAVLRT SIHSDSHFLS SHLIIDYSLL VGRDDTSNEL VVGIIDYIRT
FTWDKKLEMV VKSTGILGGQ GKMPTVVSPE LYRTRFCEAM DKYFLMVPDH WTGLGLNC
//