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 02-SEP-2026, entry version 190. 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 CC 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol CC 4-phosphate {ECO:0000269|PubMed:22942276}; CC KM=15 uM for CC 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol CC 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=8; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001195733.2. [O60331-4] DR RefSeq; NP_001287778.1; NM_001300849.2. [O60331-3] DR RefSeq; NP_036530.1; NM_012398.3. [O60331-1] DR RefSeq; XP_047294489.1; XM_047438533.1. [O60331-2] DR RefSeq; XP_054176363.1; XM_054320388.1. [O60331-2] 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 AlphaFoldDB; O60331; -. DR MDRepo; O60331; -. DR SMR; O60331; -. DR BioGRID; 116969; 48. DR DIP; DIP-39809N; -. DR FunCoup; O60331; 1314. DR IntAct; O60331; 23. DR MINT; O60331; -. DR NDEx; IQUERY-CP-PIP5K1C; 12 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000466363; -. DR BindingDB; O60331; -. DR ChEMBL; CHEMBL1908383; -. DR DrugCentral; O60331; -. DR SwissLipids; SLP:000000551; -. [O60331-4] DR GlyGen; O60331; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; O60331; -. DR PhosphoSitePlus; O60331; -. DR SwissPalm; O60331; -. DR BioMuta; PIP5K1C; -. DR jPOST; O60331; -. DR MassIVE; O60331; -. DR PaxDb; 9606-ENSP00000466363; -. DR PeptideAtlas; O60331; -. DR ProteomicsDB; 49349; -. [O60331-1] DR ProteomicsDB; 49350; -. [O60331-2] DR ProteomicsDB; 49351; -. [O60331-3] DR ProteomicsDB; 49352; -. [O60331-4] DR Pumba; O60331; -. DR Antibodypedia; 2779; 244 antibodies from 34 providers. DR DNASU; 23396; -. DR Ensembl; ENST00000335312.8; ENSP00000335333.3; ENSG00000186111.12. [O60331-1] DR Ensembl; ENST00000537021.1; ENSP00000444779.1; ENSG00000186111.12. [O60331-2] DR Ensembl; ENST00000539785.5; ENSP00000445992.1; ENSG00000186111.12. [O60331-4] DR Ensembl; ENST00000589578.5; ENSP00000466363.1; ENSG00000186111.12. [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 AGR; HGNC:8996; -. DR ClinPGx; PA33329; -. DR CTD; 23396; -. DR DisGeNET; 23396; -. DR GeneCards; PIP5K1C; -. DR HGNC; HGNC:8996; PIP5K1C. DR HPA; ENSG00000186111; Tissue enhanced (brain). DR MalaCards; PIP5K1C; -. DR MIM; 606102; gene. DR MIM; 611369; phenotype. DR OpenTargets; ENSG00000186111; -. DR Orphanet; 137783; Lethal congenital contracture syndrome type 3. DR VEuPathDB; HostDB:ENSG00000186111; -. DR eggNOG; KOG0229; Eukaryota. DR GeneTree; ENSGT00940000159258; -. DR HOGENOM; CLU_004312_5_1_1; -. DR InParanoid; O60331; -. DR OMA; DIYFFPD; -. DR OrthoDB; 70770at2759; -. DR PAN-GO; O60331; 3 GO annotations based on evolutionary models. DR PhylomeDB; O60331; -. DR BioCyc; MetaCyc:HS02710-MONOMER; -. 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 Reactome; R-HSA-9768727; Regulation of CDH1 posttranslational processing and trafficking to plasma membrane. DR SignaLink; O60331; -. DR SIGNOR; O60331; -. DR Agora; ENSG00000186111; -. DR BioGRID-ORCS; 23396; 19 hits in 1161 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. 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 196 other cell types or tissues. DR ExpressionAtlas; O60331; baseline and differential. DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0012505; C:endomembrane system; ISS:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. 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; EXP:UniProtKB. DR GO; GO:0052742; F:phosphatidylinositol 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:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; TAS:Reactome. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IEA:Ensembl. DR GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:UniProtKB. DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB. DR CDD; cd17308; PIPKc_PIP5K1C; 1. DR FunFam; 3.30.800.10:FF:000001; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma; 1. DR Gene3D; 3.30.810.10; 2-Layer Sandwich; 1. DR Gene3D; 3.30.800.10; Phosphatidylinositol Phosphate Kinase II Beta; 1. DR IDEAL; IID00359; -. DR InterPro; IPR027483; PInositol-4-P-4/5-kinase_C_sf. DR InterPro; IPR002498; PInositol-4-P-4/5-kinase_core. DR InterPro; IPR027484; PInositol-4-P-5-kinase_N. DR InterPro; IPR023610; PInositol-4/5-P-5/4-kinase. DR PANTHER; PTHR23086:SF26; PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE TYPE-1 GAMMA; 1. DR PANTHER; PTHR23086; PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE; 1. DR Pfam; PF01504; PIP5K; 1. DR SMART; SM00330; PIPKc; 1. DR SUPFAM; SSF56104; SAICAR synthase-like; 1. DR PROSITE; PS51455; PIPK; 1. DR PDBsum; 2G35; -. DR PDBsum; 3H1Z; -. DR PDBsum; 3H85; -. 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; Proteomics identification; KW 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..535 FT /note="Low complexity" 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 //