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   24-JAN-2024, entry version 214.
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};
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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   EMDB; EMD-22647; -.
DR   SMR; Q9Y2I7; -.
DR   BioGRID; 128336; 54.
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; 9606-ENSP00000264380; -.
DR   PeptideAtlas; Q9Y2I7; -.
DR   ProteomicsDB; 85801; -. [Q9Y2I7-1]
DR   ProteomicsDB; 85802; -. [Q9Y2I7-2]
DR   ProteomicsDB; 85803; -. [Q9Y2I7-3]
DR   ProteomicsDB; 85804; -. [Q9Y2I7-4]
DR   Pumba; Q9Y2I7; -.
DR   ABCD; Q9Y2I7; 1 sequenced antibody.
DR   Antibodypedia; 34200; 428 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-MONOMER; -.
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 203 other cell types or 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
//