PI51C_HUMAN
ID PI51C_HUMAN Reviewed; 668 AA.
AC O60331; B7Z9E7; C6GIJ7; C6GIJ8; Q7LE07;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma {ECO:0000305|PubMed:12422219};
DE Short=PIP5K1gamma {ECO:0000305|PubMed:12422219};
DE Short=PtdIns(4)P-5-kinase 1 gamma {ECO:0000305|PubMed:12422219};
DE EC=2.7.1.68 {ECO:0000269|PubMed:12422219, ECO:0000269|PubMed:22942276};
DE AltName: Full=Type I phosphatidylinositol 4-phosphate 5-kinase gamma {ECO:0000250|UniProtKB:O70161};
GN Name=PIP5K1C {ECO:0000312|HGNC:HGNC:8996}; Synonyms=KIAA0589;
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 2 AND 3), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY (ISOFORMS 1; 2 AND 3).
RX PubMed=19548880; DOI=10.1042/bj20090638;
RA Schill N.J., Anderson R.A.;
RT "Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice
RT variants expressed in human cells display distinctive cellular targeting.";
RL Biochem. J. 422:473-482(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP FUNCTION, INTERACTION WITH TLN2, SUBCELLULAR LOCATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=12422219; DOI=10.1038/nature01147;
RA Di Paolo G., Pellegrini L., Letinic K., Cestra G., Zoncu R., Voronov S.,
RA Chang S., Guo J., Wenk M.R., De Camilli P.;
RT "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1
RT gamma by the FERM domain of talin.";
RL Nature 420:85-89(2002).
RN [6]
RP FUNCTION, INTERACTION WITH ARF6, AND SUBCELLULAR LOCATION.
RX PubMed=12847086; DOI=10.1083/jcb.200301006;
RA Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V.;
RT "ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by
RT activating phosphatidylinositol phosphate kinase type Igamma.";
RL J. Cell Biol. 162:113-124(2003).
RN [7]
RP PHOSPHORYLATION AT TYR-649 AND SER-650, AND MUTAGENESIS OF SER-650.
RX PubMed=15738269; DOI=10.1083/jcb.200409028;
RA Lee S.Y., Voronov S., Letinic K., Nairn A.C., Di Paolo G., De Camilli P.;
RT "Regulation of the interaction between PIPKI gamma and talin by proline-
RT directed protein kinases.";
RL J. Cell Biol. 168:789-799(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDH1.
RX PubMed=17261850; DOI=10.1083/jcb.200606023;
RA Ling K., Bairstow S.F., Carbonara C., Turbin D.A., Huntsman D.G.,
RA Anderson R.A.;
RT "Type I gamma phosphatidylinositol phosphate kinase modulates adherens
RT junction and E-cadherin trafficking via a direct interaction with mu 1B
RT adaptin.";
RL J. Cell Biol. 176:343-353(2007).
RN [9]
RP FUNCTION IN CELL MIGRATION AND ADHESION.
RX PubMed=17635937; DOI=10.1083/jcb.200701078;
RA Sun Y., Ling K., Wagoner M.P., Anderson R.A.;
RT "Type I gamma phosphatidylinositol phosphate kinase is required for EGF-
RT stimulated directional cell migration.";
RL J. Cell Biol. 178:297-308(2007).
RN [10]
RP ACETYLATION AT LYS-265 AND LYS-268, AND DEACETYLATION BY SIRT1.
RX PubMed=20668706; DOI=10.1371/journal.pone.0011755;
RA Akieda-Asai S., Zaima N., Ikegami K., Kahyo T., Yao I., Hatanaka T.,
RA Iemura S., Sugiyama R., Yokozeki T., Eishi Y., Koike M., Ikeda K.,
RA Chiba T., Yamaza H., Shimokawa I., Song S.Y., Matsuno A., Mizutani A.,
RA Sawabe M., Chao M.V., Tanaka M., Kanaho Y., Natsume T., Sugimura H.,
RA Date Y., McBurney M.W., Guarente L., Setou M.;
RT "SIRT1 regulates thyroid-stimulating hormone release by enhancing
RT PIP5Kgamma activity through deacetylation of specific lysine residues in
RT mammals.";
RL PLoS ONE 5:E11755-E11755(2010).
RN [11]
RP REVIEW ON FUNCTION.
RX PubMed=19889969; DOI=10.1242/jcs.056127;
RA van den Bout I., Divecha N.;
RT "PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions.";
RL J. Cell Sci. 122:3837-3850(2009).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22942276; DOI=10.1074/jbc.m112.370155;
RA Shulga Y.V., Anderson R.A., Topham M.K., Epand R.M.;
RT "Phosphatidylinositol-4-phosphate 5-kinase isoforms exhibit acyl chain
RT selectivity for both substrate and lipid activator.";
RL J. Biol. Chem. 287:35953-35963(2012).
RN [13]
RP INTERACTION WITH LAPTM4B.
RX PubMed=25588945; DOI=10.15252/embj.201489425;
RA Tan X., Sun Y., Thapa N., Liao Y., Hedman A.C., Anderson R.A.;
RT "LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling,
RT lysosomal sorting, and degradation.";
RL EMBO J. 34:475-490(2015).
RN [14]
RP VARIANT LCCS3 ASN-253, AND CHARACTERIZATION OF VARIANT LCCS3 ASN-253.
RX PubMed=17701898; DOI=10.1086/520771;
RA Narkis G., Ofir R., Landau D., Manor E., Volokita M., Hershkowitz R.,
RA Elbedour K., Birk O.S.;
RT "Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in
RT PIP5K1C, which encodes PIPKI gamma of the phophatidylinositol pathway.";
RL Am. J. Hum. Genet. 81:530-539(2007).
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:12422219, PubMed:22942276). PtdIns(4,5)P2 can
CC directly act as a second messenger or can be utilized as a precursor to
CC generate other second messengers: inositol 1,4,5-trisphosphate (IP3),
CC diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate
CC (PtdIns(3,4,5)P3/PIP3) (Probable). PIP5K1A-mediated phosphorylation of
CC PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By
CC similarity). Together with PIP5K1A, is required for phagocytosis, both
CC enzymes regulating different types of actin remodeling at sequential
CC steps (By similarity). Promotes particle attachment by generating the
CC pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to
CC facilitate Fc-gamma-R clustering. Mediates RAC1-dependent
CC reorganization of actin filaments. Required for synaptic vesicle
CC transport (By similarity). Controls the plasma membrane pool of
CC PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis
CC (PubMed:12847086). Plays a role in endocytosis mediated by clathrin and
CC AP-2 (adaptor protein complex 2) (PubMed:12847086). Required for
CC clathrin-coated pits assembly at the synapse (PubMed:17261850).
CC Participates in cell junction assembly (PubMed:17261850). Modulates
CC adherens junctions formation by facilitating CDH1/cadherin trafficking
CC (PubMed:17261850). Required for focal adhesion dynamics. Modulates the
CC targeting of talins (TLN1 and TLN2) to the plasma membrane and their
CC efficient assembly into focal adhesions (PubMed:12422219). Regulates
CC the interaction between talins (TLN1 and TLN2) and beta-integrins
CC (PubMed:12422219). Required for uropodium formation and retraction of
CC the cell rear during directed migration (By similarity). Has a role in
CC growth factor-stimulated directional cell migration and adhesion (By
CC similarity). Required for talin assembly into nascent adhesions forming
CC at the leading edge toward the direction of the growth factor
CC (PubMed:17635937). Negative regulator of T-cell activation and adhesion
CC (By similarity). Negatively regulates integrin alpha-L/beta-2 (LFA-1)
CC polarization and adhesion induced by T-cell receptor (By similarity).
CC Together with PIP5K1A has a role during embryogenesis and together with
CC PIP5K1B may have a role immediately after birth (By similarity).
CC {ECO:0000250|UniProtKB:O70161, ECO:0000250|UniProtKB:P70182,
CC ECO:0000269|PubMed:12422219, ECO:0000269|PubMed:12847086,
CC ECO:0000269|PubMed:17261850, ECO:0000269|PubMed:17635937,
CC ECO:0000269|PubMed:22942276, ECO:0000305|PubMed:19889969}.
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:12422219, ECO:0000269|PubMed:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14426;
CC Evidence={ECO:0000305|PubMed:12422219, 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 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:22942276};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40364;
CC Evidence={ECO:0000305|PubMed:22942276};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.6 uM for 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-
CC glycero-3-phospho-1D-myo-inositol 4-phosphate
CC {ECO:0000269|PubMed:22942276};
CC KM=15 uM for 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-
CC 1D-myo-inositol 4-phosphate {ECO:0000269|PubMed:22942276};
CC -!- SUBUNIT: Interacts with TLN1 (By similarity). Interacts with TLN2;
CC interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase
CC activity (PubMed:12422219). May compete with beta-integrins for the
CC same binding site on TLN1 and TLN2. Interacts with ARF6; interaction
CC stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity.
CC Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C
CC by CSK disrupts the interaction; clathrin competes with PIP5K1C (By
CC similarity). Interacts with CDH1. Interacts with CSK (By similarity).
CC Interacts with PLCG1; interaction is abolished upon EGF stimulation (By
CC similarity). Interacts with LAPTM4B; promotes SNX5 association with
CC LAPTM4B; kinase activity of PIP5K1C is required; interaction is
CC regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C
CC (PubMed:25588945). {ECO:0000250|UniProtKB:O70161,
CC ECO:0000250|UniProtKB:Q5I6B8, ECO:0000269|PubMed:12422219,
CC ECO:0000269|PubMed:25588945}.
CC -!- INTERACTION:
CC O60331; Q9Y490: TLN1; NbExp=3; IntAct=EBI-8869029, EBI-2462036;
CC O60331-4; P46940: IQGAP1; NbExp=7; IntAct=EBI-8838062, EBI-297509;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side {ECO:0000250|UniProtKB:Q5I6B8}. Endomembrane system
CC {ECO:0000250|UniProtKB:Q5I6B8}. Cytoplasm
CC {ECO:0000250|UniProtKB:O70161}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:12422219}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:17261850}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q5I6B8}. Cell projection, phagocytic cup
CC {ECO:0000250|UniProtKB:O70161}. Cell projection, uropodium
CC {ECO:0000250|UniProtKB:O70161}. Note=Detected in plasma membrane
CC invaginations. Isoform 3 is detected in intracellular vesicle-like
CC structures.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PIPKIgamma-90, PIPKIgamma-668, PIPkinIgamma-a,
CC PIPKIgamma_i2;
CC IsoId=O60331-1; Sequence=Displayed;
CC Name=2; Synonyms=variant 700, PIPKIgamma-700, PIPKIgamma_i4;
CC IsoId=O60331-2; Sequence=VSP_042078;
CC Name=3; Synonyms=variant 707, PIPKIgamma-707, PIPKIgamma_i5;
CC IsoId=O60331-3; Sequence=VSP_042080;
CC Name=4; Synonyms=PIPKIgamma-87, PIPKIgamma-640, PIPkinIgamma-b,
CC PIPKIgamma_i1;
CC IsoId=O60331-4; Sequence=VSP_042079;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Isoform 1 is strongly expressed in
CC brain and also detected in heart and lung.
CC {ECO:0000269|PubMed:19548880}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Isoform 2 is strongly expressed in
CC pancreas and liver and in lesser quantities in brain, heart, lung and
CC kidney. {ECO:0000269|PubMed:19548880}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Isoform 3 is detected in large amounts
CC in heart and large intestine, is also present in lung, pancreas and
CC thyroid, and to a lesser extent in brain, stomach and kidney.
CC {ECO:0000269|PubMed:19548880}.
CC -!- PTM: Phosphorylation on Ser-650 negatively regulates binding to TLN2
CC and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is
CC necessary for targeting to focal adhesions. Phosphorylation on Ser-650
CC and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK (By
CC similarity). Tyrosine phosphorylation is enhanced by PTK2 signaling.
CC Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest
CC that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and
CC TLN2). According to PubMed:15738269 phosphorylation at Tyr-649 does not
CC directly enhance binding to tailins (TLN1 and TLN2) but may act
CC indirectly by inhibiting phosphorylation at Ser-650. {ECO:0000250,
CC ECO:0000269|PubMed:15738269}.
CC -!- PTM: Acetylation at Lys-265 and Lys-268 seems to decrease lipid 1-
CC phosphatidylinositol-4-phosphate 5-kinase activity. Deacetylation of
CC these sites by SIRT1 positively regulates the exocytosis of TSH-
CC containing granules from pituitary cells.
CC {ECO:0000269|PubMed:20668706}.
CC -!- DISEASE: Lethal congenital contracture syndrome 3 (LCCS3) [MIM:611369]:
CC A form of lethal congenital contracture syndrome, an autosomal
CC recessive disorder characterized by degeneration of anterior horn
CC neurons, extreme skeletal muscle atrophy, and congenital non-
CC progressive joint contractures (arthrogryposis). The contractures can
CC involve the upper or lower limbs and/or the vertebral column, leading
CC to various degrees of flexion or extension limitations evident at
CC birth. LCCS3 patients present at birth with severe multiple joint
CC contractures and severe muscle wasting and atrophy, mainly in the legs.
CC Death occurs minutes to hours after birth due to respiratory
CC insufficiency. The phenotype can be distinguished from that of LCCS1 by
CC the absence of hydrops, fractures and multiple pterygia, and from LCCS2
CC by the absence of neurogenic bladder defect.
CC {ECO:0000269|PubMed:17701898}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25515.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; FJ965536; ACS73483.1; -; mRNA.
DR EMBL; FJ965537; ACS73484.1; -; mRNA.
DR EMBL; AB011161; BAA25515.1; ALT_INIT; mRNA.
DR EMBL; AK315912; BAH14283.1; -; mRNA.
DR EMBL; AC005542; AAC32904.1; -; Genomic_DNA.
DR EMBL; AC093071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32872.1; -. [O60331-1]
DR CCDS; CCDS56074.1; -. [O60331-4]
DR CCDS; CCDS74257.1; -. [O60331-3]
DR RefSeq; NP_001182662.1; NM_001195733.1. [O60331-4]
DR RefSeq; NP_001287778.1; NM_001300849.1. [O60331-3]
DR RefSeq; NP_036530.1; NM_012398.2. [O60331-1]
DR PDB; 2G35; NMR; -; B=646-653.
DR PDB; 3H1Z; X-ray; 1.83 A; P=639-653.
DR PDB; 3H85; X-ray; 2.60 A; P=646-653.
DR PDBsum; 2G35; -.
DR PDBsum; 3H1Z; -.
DR PDBsum; 3H85; -.
DR AlphaFoldDB; O60331; -.
DR SMR; O60331; -.
DR BioGRID; 116969; 37.
DR DIP; DIP-39809N; -.
DR IntAct; O60331; 12.
DR MINT; O60331; -.
DR STRING; 9606.ENSP00000466363; -.
DR BindingDB; O60331; -.
DR ChEMBL; CHEMBL1908383; -.
DR DrugCentral; O60331; -.
DR SwissLipids; SLP:000000551; -. [O60331-4]
DR GlyGen; O60331; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60331; -.
DR PhosphoSitePlus; O60331; -.
DR SwissPalm; O60331; -.
DR BioMuta; PIP5K1C; -.
DR EPD; O60331; -.
DR jPOST; O60331; -.
DR MassIVE; O60331; -.
DR MaxQB; O60331; -.
DR PaxDb; O60331; -.
DR PeptideAtlas; O60331; -.
DR PRIDE; O60331; -.
DR ProteomicsDB; 49349; -. [O60331-1]
DR ProteomicsDB; 49350; -. [O60331-2]
DR ProteomicsDB; 49351; -. [O60331-3]
DR ProteomicsDB; 49352; -. [O60331-4]
DR Antibodypedia; 2779; 234 antibodies from 31 providers.
DR DNASU; 23396; -.
DR Ensembl; ENST00000335312.8; ENSP00000335333.3; ENSG00000186111.11. [O60331-1]
DR Ensembl; ENST00000537021.1; ENSP00000444779.1; ENSG00000186111.11. [O60331-2]
DR Ensembl; ENST00000539785.5; ENSP00000445992.1; ENSG00000186111.11. [O60331-4]
DR Ensembl; ENST00000589578.5; ENSP00000466363.1; ENSG00000186111.11. [O60331-3]
DR GeneID; 23396; -.
DR KEGG; hsa:23396; -.
DR MANE-Select; ENST00000335312.8; ENSP00000335333.3; NM_012398.3; NP_036530.1.
DR UCSC; uc002lyj.3; human. [O60331-1]
DR CTD; 23396; -.
DR DisGeNET; 23396; -.
DR GeneCards; PIP5K1C; -.
DR HGNC; HGNC:8996; PIP5K1C.
DR HPA; ENSG00000186111; Low tissue specificity.
DR MalaCards; PIP5K1C; -.
DR MIM; 606102; gene.
DR MIM; 611369; phenotype.
DR neXtProt; NX_O60331; -.
DR OpenTargets; ENSG00000186111; -.
DR Orphanet; 137783; Lethal congenital contracture syndrome type 3.
DR PharmGKB; PA33329; -.
DR VEuPathDB; HostDB:ENSG00000186111; -.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000159258; -.
DR HOGENOM; CLU_004312_5_1_1; -.
DR InParanoid; O60331; -.
DR OMA; SHEEVHV; -.
DR OrthoDB; 296899at2759; -.
DR PhylomeDB; O60331; -.
DR TreeFam; TF319618; -.
DR BioCyc; MetaCyc:HS02710-MON; -.
DR BRENDA; 2.7.1.68; 2681.
DR PathwayCommons; O60331; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; O60331; -.
DR SIGNOR; O60331; -.
DR BioGRID-ORCS; 23396; 18 hits in 1081 CRISPR screens.
DR ChiTaRS; PIP5K1C; human.
DR EvolutionaryTrace; O60331; -.
DR GeneWiki; PIP5K1C; -.
DR GenomeRNAi; 23396; -.
DR Pharos; O60331; Tchem.
DR PRO; PR:O60331; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O60331; protein.
DR Bgee; ENSG00000186111; Expressed in right hemisphere of cerebellum and 194 other tissues.
DR Genevisible; O60331; HS.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; TAS:UniProtKB.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; TAS:Reactome.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0034333; P:adherens junction assembly; TAS:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; TAS:UniProtKB.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; TAS:UniProtKB.
DR GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR GO; GO:0030593; P:neutrophil chemotaxis; 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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:UniProtKB.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB.
DR Gene3D; 3.30.800.10; -; 1.
DR IDEAL; IID00359; -.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell adhesion; Cell junction; Cell membrane; Cell projection; Chemotaxis;
KW Cytoplasm; Disease variant; Endocytosis; Exocytosis; Kinase;
KW Lipid metabolism; Membrane; Methylation; Nucleotide-binding; Nucleus;
KW Phagocytosis; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..668
FT /note="Phosphatidylinositol 4-phosphate 5-kinase type-1
FT gamma"
FT /id="PRO_0000185462"
FT DOMAIN 75..443
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 45..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 593..642
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 641..668
FT /note="Mediates interaction with TLN2"
FT /evidence="ECO:0000269|PubMed:12422219"
FT COMPBIAS 526..542
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..568
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 265
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20668706"
FT MOD_RES 268
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20668706"
FT MOD_RES 459
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 459
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5I6B8"
FT MOD_RES 639
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 649
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:15738269"
FT MOD_RES 650
FT /note="Phosphoserine; by CDK5, MAPK1 and CDK1"
FT /evidence="ECO:0000269|PubMed:15738269"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70161"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5I6B8"
FT MOD_RES 668
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5I6B8"
FT VAR_SEQ 640..668
FT /note="FPTDERSWVYSPLHYSAQAPPASDGESDT -> FWRLWGPHAPTWPWRREGR
FT AACLCPYPPHVVTPFPGTGLCASWSPDGTGGLGAMSCCVSVS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19548880"
FT /id="VSP_042078"
FT VAR_SEQ 641..668
FT /note="PTDERSWVYSPLHYSAQAPPASDGESDT -> FTDGRYWIYSPRHRRLRAVT
FT LSASGTVSDRSRPPWGEGAVPLGQQGAAGPRPEAQCLTSVVFQKGFG (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:19548880"
FT /id="VSP_042080"
FT VAR_SEQ 641..668
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042079"
FT VARIANT 253
FT /note="D -> N (in LCCS3; loss of activity;
FT dbSNP:rs121908315)"
FT /evidence="ECO:0000269|PubMed:17701898"
FT /id="VAR_036996"
FT MUTAGEN 650
FT /note="S->D: Abolishes binding to TLN2. Affects
FT localization to focal adhesions."
FT /evidence="ECO:0000269|PubMed:15738269"
FT MUTAGEN 650
FT /note="S->N: Does not affect binding to TLN2 and
FT localization to focal adhesions."
FT /evidence="ECO:0000269|PubMed:15738269"
FT CONFLICT 236
FT /note="V -> M (in Ref. 3; BAH14283)"
FT /evidence="ECO:0000305"
FT HELIX 644..646
FT /evidence="ECO:0007829|PDB:3H1Z"
SQ SEQUENCE 668 AA; 73260 MW; 45A9FB32B4E43083 CRC64;
MELEVPDEAE SAEAGAVPSE AAWAAESGAA AGLAQKKAAP TEVLSMTAQP GPGHGKKLGH
RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGHLSSKPER DVLMQDFYVV ESIFFPSEGS
NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSLFYVT
SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN
ILPRVVKMHL KFDLKGSTYK RRASKKEKEK SFPTYKDLDF MQDMPEGLLL DADTFSALVK
TLQRDCLVLE SFKIMDYSLL LGVHNIDQHE RERQAQGAQS TSDEKRPVGQ KALYSTAMES
IQGGAARGEA IESDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG
DTVSVHRPSF YAERFFKFMS NTVFRKNSSL KSSPSKKGRG GALLAVKPLG PTAAFSASQI
PSEREEAQYD LRGARSYPTL EDEGRPDLLP CTPPSFEEAT TASIATTLSS TSLSIPERSP
SETSEQPRYR RRTQSSGQDG RPQEEPPAEE DLQQITVQVE PACSVEIVVP KEEDAGVEAS
PAGASAAVEV ETASQASDEE GAPASQASDE EDAPATDIYF PTDERSWVYS PLHYSAQAPP
ASDGESDT
