P3C2A_MOUSE
ID P3C2A_MOUSE Reviewed; 1686 AA.
AC Q61194; Q61182;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha;
DE Short=PI3K-C2-alpha;
DE Short=PtdIns-3-kinase C2 subunit alpha;
DE EC=2.7.1.137 {ECO:0000269|PubMed:10329640, ECO:0000269|PubMed:8663140};
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:O00443};
DE EC=2.7.1.154 {ECO:0000250|UniProtKB:O00443};
DE AltName: Full=Cpk-m;
DE AltName: Full=Phosphoinositide 3-kinase-C2-alpha;
DE AltName: Full=p170;
GN Name=Pik3c2a; Synonyms=Cpk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ;
RX PubMed=8662856; DOI=10.1074/jbc.271.23.13892;
RA Molz L., Chen Y.-W., Hirano M., Williams L.T.;
RT "Cpk is a novel class of Drosophila PtdIns 3-kinase containing a C2
RT domain.";
RL J. Biol. Chem. 271:13892-13899(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-356 (ISOFORM 1).
RC TISSUE=Embryonic spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 157-1686 (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Adipocyte;
RX PubMed=8663140; DOI=10.1074/jbc.271.23.13304;
RA Virbasius J.V., Guilherme A., Czech M.P.;
RT "Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2
RT domain.";
RL J. Biol. Chem. 271:13304-13307(1996).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION.
RX PubMed=10329640; DOI=10.1074/jbc.274.21.14529;
RA Brown R.A., Domin J., Arcaro A., Waterfield M.D., Shepherd P.R.;
RT "Insulin activates the alpha isoform of class II phosphoinositide 3-
RT kinase.";
RL J. Biol. Chem. 274:14529-14532(1999).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION IN ISULIN SECRETION.
RX PubMed=20061534; DOI=10.1096/fj.09-148072;
RA Leibiger B., Moede T., Uhles S., Barker C.J., Creveaux M., Domin J.,
RA Berggren P.-O., Leibiger I.B.;
RT "Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for
RT glucose-stimulated insulin secretion.";
RL FASEB J. 24:1824-1837(2010).
RN [8]
RP FUNCTION IN KIDNEY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20974805; DOI=10.1128/mcb.00468-10;
RA Harris D.P., Vogel P., Wims M., Moberg K., Humphries J., Jhaver K.G.,
RA DaCosta C.M., Shadoan M.K., Xu N., Hansen G.M., Balakrishnan S., Domin J.,
RA Powell D.R., Oravecz T.;
RT "Requirement for class II phosphoinositide 3-kinase C2alpha in maintenance
RT of glomerular structure and function.";
RL Mol. Cell. Biol. 31:63-80(2011).
RN [9]
RP INTERACTION WITH SBF2, AND TISSUE SPECIFICITY.
RX PubMed=22648168; DOI=10.1091/mbc.e12-05-0375;
RA Jean S., Cox S., Schmidt E.J., Robinson F.L., Kiger A.;
RT "Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of
RT cellular remodeling.";
RL Mol. Biol. Cell 23:2723-2740(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1561-1686, AND INTERACTION WITH
RP PHOSPHATIDYLINOSITIDE-CONTAINING MEMBRANES.
RX PubMed=16338929; DOI=10.1074/jbc.m510791200;
RA Liu L., Song X., He D., Komma C., Kita A., Virbasius J.V., Huang G.,
RA Bellamy H.D., Miki K., Czech M.P., Zhou G.W.;
RT "Crystal structure of the C2 domain of class II phosphatidylinositide 3-
RT kinase C2alpha.";
RL J. Biol. Chem. 281:4254-4260(2006).
CC -!- FUNCTION: Generates phosphatidylinositol 3-phosphate (PtdIns3P) and
CC phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as
CC second messengers. Has a role in several intracellular trafficking
CC events. Functions in insulin signaling and secretion. Required for
CC translocation of the glucose transporter SLC2A4/GLUT4 to the plasma
CC membrane and glucose uptake in response to insulin-mediated RHOQ
CC activation. Regulates insulin secretion through two different
CC mechanisms: involved in glucose-induced insulin secretion downstream of
CC insulin receptor in a pathway that involves AKT1 activation and
CC TBC1D4/AS160 phosphorylation, and participates in the late step of
CC insulin granule exocytosis probably in insulin granule fusion.
CC Synthesizes PtdIns3P in response to insulin signaling. Functions in
CC clathrin-coated endocytic vesicle formation and distribution. Regulates
CC dynamin-independent endocytosis, probably by recruiting EEA1 to
CC internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on
CC large dense core vesicles. Participates in calcium induced contraction
CC of vascular smooth muscle by regulating myosin light chain (MLC)
CC phosphorylation through a mechanism involving Rho kinase-dependent
CC phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role
CC in the EGF signaling cascade. May be involved in mitosis and UV-induced
CC damage response. Required for maintenance of normal renal structure and
CC function by supporting normal podocyte function. Involved in the
CC regulation of ciliogenesis and trafficking of ciliary components (By
CC similarity). {ECO:0000250|UniProtKB:O00443,
CC ECO:0000269|PubMed:10329640, ECO:0000269|PubMed:20061534,
CC ECO:0000269|PubMed:20974805, ECO:0000269|PubMed:8663140}.
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-3,4-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:18373,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:58178, ChEBI:CHEBI:456216; EC=2.7.1.154;
CC Evidence={ECO:0000250|UniProtKB:O00443};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18374;
CC Evidence={ECO:0000250|UniProtKB:O00443};
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-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000269|PubMed:10329640,
CC ECO:0000269|PubMed:8663140};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:10329640};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153;
CC Evidence={ECO:0000250|UniProtKB:O00443};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:O00443};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:O00443};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O00443};
CC Note=Ca(2+) or Mg(2+). Mn(2+) cannot be used.
CC {ECO:0000250|UniProtKB:O00443};
CC -!- ACTIVITY REGULATION: Activated by clathrin (By similarity). Only
CC slightly inhibited by wortmannin and LY294002. Activated by insulin.
CC {ECO:0000250|UniProtKB:O00443, ECO:0000269|PubMed:10329640,
CC ECO:0000269|PubMed:8663140}.
CC -!- SUBUNIT: Interacts with ERBB2 and EGFR (By similarity). Interacts with
CC clathrin trimers (By similarity). Interacts with SBF2/MTMR13
CC (PubMed:22648168). {ECO:0000250|UniProtKB:O00443,
CC ECO:0000269|PubMed:22648168}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O00443}.
CC Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:O00443}. Nucleus {ECO:0000250|UniProtKB:O00443}.
CC Cytoplasm {ECO:0000250|UniProtKB:O00443}. Golgi apparatus, trans-Golgi
CC network {ECO:0000250|UniProtKB:O00443}. Note=Inserts preferentially
CC into membranes containing PtdIns(4,5)P2. Associated with RNA-containing
CC structures. {ECO:0000250|UniProtKB:O00443}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q61194-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q61194-2; Sequence=VSP_015254;
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level)
CC (PubMed:22648168). Detected in podocytes (PubMed:20974805).
CC {ECO:0000269|PubMed:20974805, ECO:0000269|PubMed:22648168}.
CC -!- PTM: Phosphorylated on Ser-261 during mitosis and upon UV irradiation;
CC which does not change enzymatic activity but leads to proteasomal
CC degradation (By similarity). Phosphorylated upon insulin stimulation;
CC which may lead to enzyme activation. {ECO:0000250|UniProtKB:O00443,
CC ECO:0000269|PubMed:10329640}.
CC -!- DISRUPTION PHENOTYPE: Chronic renal failure and kidney lesions. Affects
CC podocyte morphology and function. {ECO:0000269|PubMed:20974805}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB07682.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U52193; AAC52604.1; -; mRNA.
DR EMBL; AK049609; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U55772; AAB07682.1; ALT_INIT; mRNA.
DR CCDS; CCDS52371.1; -. [Q61194-1]
DR PIR; T42642; T42642.
DR RefSeq; NP_035213.2; NM_011083.2.
DR PDB; 2B3R; X-ray; 2.30 A; A/B=1561-1686.
DR PDB; 7BI2; X-ray; 3.25 A; A=377-532, A=545-1539.
DR PDB; 7BI4; X-ray; 2.42 A; A=377-532, A=666-1400.
DR PDB; 7BI6; X-ray; 2.75 A; A=377-532, A=666-1400.
DR PDB; 7BI9; X-ray; 2.65 A; A=377-532, A=666-1400.
DR PDBsum; 2B3R; -.
DR PDBsum; 7BI2; -.
DR PDBsum; 7BI4; -.
DR PDBsum; 7BI6; -.
DR PDBsum; 7BI9; -.
DR AlphaFoldDB; Q61194; -.
DR SMR; Q61194; -.
DR BioGRID; 202158; 15.
DR IntAct; Q61194; 1.
DR STRING; 10090.ENSMUSP00000126092; -.
DR iPTMnet; Q61194; -.
DR PhosphoSitePlus; Q61194; -.
DR EPD; Q61194; -.
DR jPOST; Q61194; -.
DR MaxQB; Q61194; -.
DR PaxDb; Q61194; -.
DR PeptideAtlas; Q61194; -.
DR PRIDE; Q61194; -.
DR ProteomicsDB; 294359; -. [Q61194-1]
DR ProteomicsDB; 294360; -. [Q61194-2]
DR DNASU; 18704; -.
DR GeneID; 18704; -.
DR KEGG; mmu:18704; -.
DR CTD; 5286; -.
DR MGI; MGI:1203729; Pik3c2a.
DR eggNOG; KOG0905; Eukaryota.
DR InParanoid; Q61194; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; Q61194; -.
DR BRENDA; 2.7.1.154; 3474.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-MMU-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 18704; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Pik3c2a; mouse.
DR EvolutionaryTrace; Q61194; -.
DR PRO; PR:Q61194; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61194; protein.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:UniProtKB.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030276; F:clathrin binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; ISS:UniProtKB.
DR GO; GO:1905037; P:autophagosome organization; IGI:MGI.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IGI:MGI.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0016236; P:macroautophagy; IGI:MGI.
DR GO; GO:0071583; P:negative regulation of zinc ion transmembrane transport; IMP:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IGI:MGI.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR CDD; cd05176; PI3Kc_C2_alpha; 1.
DR CDD; cd07289; PX_PI3K_C2_alpha; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR037705; PI3K-C2-alpha_dom.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR042133; PX_PI3K_C2_alpha.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell membrane; Cytoplasm; Cytoplasmic vesicle; Endocytosis; Exocytosis;
KW Golgi apparatus; Kinase; Lipid metabolism; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT CHAIN 2..1686
FT /note="Phosphatidylinositol 4-phosphate 3-kinase C2 domain-
FT containing subunit alpha"
FT /id="PRO_0000088796"
FT DOMAIN 422..510
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 682..841
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 861..1037
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 1105..1383
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 1420..1536
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 1559..1678
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..142
FT /note="Interaction with clathrin; sufficient to induce
FT clathrin assembly"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT REGION 41..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 615..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1111..1117
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1247..1255
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1266..1292
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1488..1493
FT /note="Interaction with PtdIns(4,5)P2-containing membranes"
FT /evidence="ECO:0000269|PubMed:16338929"
FT MOTIF 1606..1617
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT COMPBIAS 1..20
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 1281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT MOD_RES 1553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00443"
FT VAR_SEQ 276..303
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8662856"
FT /id="VSP_015254"
FT CONFLICT 140
FT /note="G -> V (in Ref. 2; AK049609)"
FT /evidence="ECO:0000305"
FT CONFLICT 668
FT /note="A -> G (in Ref. 1; AAC52604)"
FT /evidence="ECO:0000305"
FT CONFLICT 954
FT /note="E -> G (in Ref. 1; AAC52604)"
FT /evidence="ECO:0000305"
FT CONFLICT 1206..1208
FT /note="FKD -> LR (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1211..1212
FT /note="LA -> TS (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1218
FT /note="Y -> N (in Ref. 3; AAB07682)"
FT /evidence="ECO:0000305"
FT CONFLICT 1325..1326
FT /note="KQ -> T (in Ref. 3; AAB07682)"
FT /evidence="ECO:0000305"
FT STRAND 1562..1570
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1573..1582
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1594..1602
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1604..1606
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1622..1631
FT /evidence="ECO:0007829|PDB:2B3R"
FT HELIX 1634..1637
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1641..1648
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1651..1653
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1656..1664
FT /evidence="ECO:0007829|PDB:2B3R"
FT HELIX 1665..1667
FT /evidence="ECO:0007829|PDB:2B3R"
FT STRAND 1674..1679
FT /evidence="ECO:0007829|PDB:2B3R"
SQ SEQUENCE 1686 AA; 190758 MW; E390BA7D730F4F87 CRC64;
MAQISNNSEF KQCSSSHPEP IRTKDVNKAE ALQMEAEALA KLQKDRQMTD SPRGFELSSS
TRQRTQGFNK QDYDLMVFPE LDSQKRAVDI DVEKLTQAEL EKILLDDNFE TRKPPALPVT
PVLSPSFSTQ LYLRPSGQRG QWPPGLCGPS TYTLPSTYPS AYSKQATFQN GFSPRMPTFP
STESVYLRLP GQSPYFSYPL TPATPFHPQG SLPVYRPLVS PDMAKLFEKI ASTSEFLKNG
KARTDLEIAN SKASVCNLQI SPKSEDINKF DWLDLDPLSK PKVDYVEVLE HEEEKKDPVL
LAEDPWDAVL LEERSPSCHL ERKVNGKSLS GATVTRSQSL IIRTAQFTKA QGQVSQKDPN
GTSSLPTGSS LLQEFEVQND EVAAFCQSIM KLKTKFPYTD HCTNPGYLLS PVTVQRNMCG
ENASVKVSIE IEGLQLPVTF TCDVSSTVEI IIMQALCWVH DDLNQVDVGS YILKVCGQEE
VLQNNHCLGS HEHIQNCRKW DTEIKLQLLT LSAMCQNLAR TAEDDEAPVD LNKYLYQIEK
PYKEVMTRHP VEELLDSYHY QVELALQTEN QHRAVDQVIK AVRKICSALD GVETPSVTEA
VKKLKRAVNL PRNKSADVTS LSGSDTRKNS TKGSLNPENP VQVSMDHLTT AIYDLLRLHA
NSSRCSTACP RGSRNIKEAW TATEQLQFTV YAAHGISSNW VSNYEKYYLI CSLSHNGKDL
FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ ISQLPLESVL HLTLFGVLNQ SSGSSPDSNK
QRKGPEALGK VSLTLFDFKR FLTCGTKLLY LWTSSHTNSI PGAIPKKSYV MERIVLQVDF
PSPAFDIIYT SPQIDRNIIQ QDKLETLESD IKGKLLDIIH RDSSFGLSKE DKVFLWENRY
YCLKHPNCLP KILASAPNWK WANLAKTYSL LHQWPPLCPL AALELLDAKF ADQEVRSLAV
SWMEAISDDE LADLLPQFVQ ALKYEIYLNS SLVRFLLSRA LGNIQIAHSL YWLLKDALHD
THFGSRYEHV LGALLSVGGK GLREELSKQM KLVQLLGGVA EKVRQASGST RQVVLQKSME
RVQSFFLRNK CRLPLKPSLV AKELNIKSCS FFSSNAMPLK VTMVNADPLG EEINVMFKVG
EDLRQDMLAL QMIKIMDKIW LKEGLDLRMV IFRCLSTGRD RGMVELVPAS DTLRKIQVEY
GVTGSFKDKP LAEWLRKYNP SEEEYEKASE NFIYSCAGCC VATYVLGICD RHNDNIMLRS
TGHMFHIDFG KFLGHAQMFG SFKRDRAPFV LTSDMAYVIN GGEKPTIRFQ LFVDLCCQAY
NLIRKQTNLF LNLLSLMIPS GLPELTSIQD LKYVRDALQP QTTDAEATIF FTRLIESSLG
SIATKFNFFI HNLAQLRFSG LPSNDEPILS FSPKTYSFRQ DGRIKEVSVF TYHKKYNPDK
HYIYVVRILR EGHLEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA
AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSAGAV PFSPTLGQIG
GAVKLSVSYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL LPDTHKTSKR KTKISRKTRN
PTFNEMLVYS GYSKETLRQR ELQLSVLSAE SLRENFFLGG ITLPLKDFNL SKETVKWYQL
TAATYL
