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 27-MAR-2024, entry version 187. 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 INSULIN 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}; 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; 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 PDB; 7Z74; X-ray; 2.50 A; A=375-532, A=545-549, A=666-1400. DR PDB; 7Z75; X-ray; 2.59 A; A=375-532, A=545-549, A=666-1400. DR PDB; 8A9I; X-ray; 2.87 A; A=375-532, A=545-549, A=666-1400. DR PDBsum; 2B3R; -. DR PDBsum; 7BI2; -. DR PDBsum; 7BI4; -. DR PDBsum; 7BI6; -. DR PDBsum; 7BI9; -. DR PDBsum; 7Z74; -. DR PDBsum; 7Z75; -. DR PDBsum; 8A9I; -. DR AlphaFoldDB; Q61194; -. DR SMR; Q61194; -. DR BioGRID; 202158; 17. DR IntAct; Q61194; 1. DR STRING; 10090.ENSMUSP00000126092; -. DR GlyGen; Q61194; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q61194; -. DR PhosphoSitePlus; Q61194; -. DR EPD; Q61194; -. DR jPOST; Q61194; -. DR MaxQB; Q61194; -. DR PaxDb; 10090-ENSMUSP00000126092; -. DR PeptideAtlas; Q61194; -. DR ProteomicsDB; 294359; -. [Q61194-1] DR ProteomicsDB; 294360; -. [Q61194-2] DR Pumba; Q61194; -. DR DNASU; 18704; -. DR GeneID; 18704; -. DR KEGG; mmu:18704; -. DR AGR; MGI:1203729; -. DR CTD; 5286; -. DR MGI; MGI:1203729; Pik3c2a. DR eggNOG; KOG0905; Eukaryota. DR InParanoid; Q61194; -. DR OrthoDB; 10350at2759; -. 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 76 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: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:0046934; F:1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity; ISS: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:1905037; P:autophagosome organization; IGI:MGI. 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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IGI:MGI. 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; cd04012; C2A_PI3K_class_II; 1. DR CDD; cd08381; C2B_PI3K_class_II; 1. DR CDD; cd00869; PI3Ka_II; 1. DR CDD; cd05176; PI3Kc_C2_alpha; 1. DR CDD; cd07289; PX_PI3K_C2_alpha; 1. DR Gene3D; 2.60.40.150; C2 domain; 2. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 1. DR Gene3D; 3.30.1520.10; Phox-like domain; 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:SF28; PHOSPHATIDYLINOSITOL 4-PHOSPHATE 3-KINASE C2 DOMAIN-CONTAINING SUBUNIT ALPHA; 1. DR PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 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; ARM repeat; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 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 HELIX 379..393 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 401..403 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 406..409 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 424..430 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 438..443 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 448..459 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:7Z74" FT HELIX 468..470 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 471..475 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 478..481 FT /evidence="ECO:0007829|PDB:7BI9" FT STRAND 484..487 FT /evidence="ECO:0007829|PDB:7Z74" FT HELIX 488..490 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 492..500 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 504..510 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 511..513 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 517..519 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 522..526 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 552..565 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 568..570 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 571..588 FT /evidence="ECO:0007829|PDB:7BI2" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 595..609 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 640..660 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 675..678 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 679..681 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 685..694 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 698..703 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 704..715 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 718..721 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 735..750 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 751..753 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 759..768 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 786..796 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 800..802 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 805..812 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 833..840 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 844..848 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 870..879 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 884..886 FT /evidence="ECO:0007829|PDB:7BI6" FT HELIX 889..897 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 899..902 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 906..908 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 909..914 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 921..923 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 924..932 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 939..942 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 943..946 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 948..950 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 953..963 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 968..972 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 975..981 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 982..984 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 987..989 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 991..1001 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1004..1017 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 1021..1023 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1024..1038 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1040..1065 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 1068..1070 FT /evidence="ECO:0007829|PDB:7BI9" FT HELIX 1072..1078 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1080..1088 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1091..1093 FT /evidence="ECO:0007829|PDB:7Z75" FT STRAND 1094..1096 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1100..1104 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 1106..1108 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1114..1116 FT /evidence="ECO:0007829|PDB:7Z74" FT STRAND 1119..1127 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1133..1141 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1144..1162 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1174..1176 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1181..1185 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1188..1192 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1193..1201 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1207..1209 FT /evidence="ECO:0007829|PDB:7BI9" FT HELIX 1210..1218 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1222..1245 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 1253..1255 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1256..1259 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1264..1266 FT /evidence="ECO:0007829|PDB:7BI4" FT TURN 1270..1273 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1275..1280 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1293..1300 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1301..1304 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1307..1324 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1327..1335 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1336..1340 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1345..1347 FT /evidence="ECO:0007829|PDB:7BI9" FT HELIX 1348..1358 FT /evidence="ECO:0007829|PDB:7BI4" FT STRAND 1360..1362 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1364..1379 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1380..1385 FT /evidence="ECO:0007829|PDB:7BI4" FT HELIX 1418..1421 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 1424..1435 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 1437..1452 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 1457..1462 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1463..1473 FT /evidence="ECO:0007829|PDB:7BI2" FT TURN 1474..1476 FT /evidence="ECO:0007829|PDB:7BI2" FT TURN 1479..1481 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1496..1514 FT /evidence="ECO:0007829|PDB:7BI2" FT STRAND 1515..1517 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1519..1522 FT /evidence="ECO:0007829|PDB:7BI2" FT HELIX 1525..1530 FT /evidence="ECO:0007829|PDB:7BI2" FT TURN 1535..1537 FT /evidence="ECO:0007829|PDB:7BI2" 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 //