PK3CB_MOUSE
ID PK3CB_MOUSE Reviewed; 1064 AA.
AC Q8BTI9; Q3U4Q1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform;
DE Short=PI3-kinase subunit beta;
DE Short=PI3K-beta;
DE Short=PI3Kbeta;
DE Short=PtdIns-3-kinase subunit beta;
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:P42338};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta;
DE Short=PtdIns-3-kinase subunit p110-beta;
DE Short=p110beta;
DE AltName: Full=Serine/threonine protein kinase PIK3CB {ECO:0000250|UniProtKB:P42338};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P42338};
GN Name=Pik3cb;
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 [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Embryo;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18594509; DOI=10.1038/nature07091;
RA Jia S., Liu Z., Zhang S., Liu P., Zhang L., Lee S.H., Zhang J.,
RA Signoretti S., Loda M., Roberts T.M., Zhao J.J.;
RT "Essential roles of PI(3)K-p110beta in cell growth, metabolism and
RT tumorigenesis.";
RL Nature 454:776-779(2008).
RN [4]
RP FUNCTION.
RX PubMed=18544649; DOI=10.1073/pnas.0707761105;
RA Guillermet-Guibert J., Bjorklof K., Salpekar A., Gonella C., Ramadani F.,
RA Bilancio A., Meek S., Smith A.J.H., Okkenhaug K., Vanhaesebroeck B.;
RT "The p110beta isoform of phosphoinositide 3-kinase signals downstream of G
RT protein-coupled receptors and is functionally redundant with p110gamma.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:8292-8297(2008).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19515725; DOI=10.1182/blood-2009-03-208074;
RA Canobbio I., Stefanini L., Cipolla L., Ciraolo E., Gruppi C., Balduini C.,
RA Hirsch E., Torti M.;
RT "Genetic evidence for a predominant role of PI3Kbeta catalytic activity in
RT ITAM- and integrin-mediated signaling in platelets.";
RL Blood 114:2193-2196(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20065293; DOI=10.1182/blood-2009-04-217224;
RA Martin V., Guillermet-Guibert J., Chicanne G., Cabou C., Jandrot-Perrus M.,
RA Plantavid M., Vanhaesebroeck B., Payrastre B., Gratacap M.-P.;
RT "Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets
RT reveals its central role in Akt activation and thrombus formation in vitro
RT and in vivo.";
RL Blood 115:2008-2013(2010).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
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 [8]
RP FUNCTION.
RX PubMed=19940148; DOI=10.1074/jbc.m109.029132;
RA Schoenwaelder S.M., Ono A., Nesbitt W.S., Lim J., Jarman K., Jackson S.P.;
RT "Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3
RT avidity and the cellular transmission of contractile forces.";
RL J. Biol. Chem. 285:2886-2896(2010).
RN [9]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH PIK3C3 AND PIK3R4, INTERACTION
RP WITH BECN1; ATG14 AND RAB5A, AND DISRUPTION PHENOTYPE.
RX PubMed=21059846; DOI=10.1083/jcb.201006056;
RA Dou Z., Chattopadhyay M., Pan J.-A., Guerriero J.L., Jiang Y.-P.,
RA Ballou L.M., Yue Z., Lin R.Z., Zong W.-X.;
RT "The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive
RT regulator of autophagy.";
RL J. Cell Biol. 191:827-843(2010).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) IN A COMPLEX WITH PIK3R2 AND
RP GDC-0941, AND DOMAIN.
RX PubMed=21362552; DOI=10.1016/j.molcel.2011.01.026;
RA Zhang X., Vadas O., Perisic O., Anderson K.E., Clark J., Hawkins P.T.,
RA Stephens L.R., Williams R.L.;
RT "Structure of lipid kinase p110beta/p85beta elucidates an unusual SH2-
RT domain-mediated inhibitory mechanism.";
RL Mol. Cell 41:567-578(2011).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol (PI) derivatives at position 3 of the inositol
CC ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2
CC (phosphatidylinositol 4,5-bisphosphate) to generate
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity). PIP3
CC plays a key role by recruiting PH domain-containing proteins to the
CC membrane, including AKT1 and PDPK1, activating signaling cascades
CC involved in cell growth, survival, proliferation, motility and
CC morphology. Involved in the activation of AKT1 upon stimulation by G-
CC protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine
CC 1-phosphate, and lysophosphatidic acid. May also act downstream
CC receptor tyrosine kinases. Required in different signaling pathways for
CC stable platelet adhesion and aggregation. Plays a role in platelet
CC activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins
CC (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation
CC motif)-bearing receptors such as GP6. Regulates the strength of
CC adhesion of ITGA2B/ ITGB3 activated receptors necessary for the
CC cellular transmission of contractile forces. Required for platelet
CC aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a
CC role in cell survival. May have a role in cell migration. Involved in
CC the early stage of autophagosome formation. Modulates the intracellular
CC level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates
CC PIK3C3 kinase activity. May act as a scaffold, independently of its
CC lipid kinase activity to positively regulate autophagy. May have a role
CC in insulin signaling as scaffolding protein in which the lipid kinase
CC activity is not required. May have a kinase-independent function in
CC regulating cell proliferation and in clathrin-mediated endocytosis.
CC Mediator of oncogenic signal in cell lines lacking PTEN. The lipid
CC kinase activity is necessary for its role in oncogenic transformation.
CC Required for the growth of ERBB2 and RAS driven tumors. Has also a
CC protein kinase activity showing autophosphorylation.
CC {ECO:0000250|UniProtKB:P42338, ECO:0000269|PubMed:18544649,
CC ECO:0000269|PubMed:18594509, ECO:0000269|PubMed:19515725,
CC ECO:0000269|PubMed:19940148, ECO:0000269|PubMed:20065293,
CC ECO:0000269|PubMed:21059846}.
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:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137,
CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000250|UniProtKB:P42338}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory
CC subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required
CC for nuclear localization and nuclear export (By similarity). Part of a
CC complex with PIK3R1 and PTEN (By similarity). Binding to PTEN may
CC antagonize the lipid kinase activity under normal growth conditions (By
CC similarity). Part of a complex involved in autophagosome formation
CC composed of PIK3C3 and PIK3R4. Interacts with BECN1, ATG14 and RAB5A.
CC {ECO:0000250, ECO:0000269|PubMed:21059846}.
CC -!- INTERACTION:
CC Q8BTI9; P26450: Pik3r1; NbExp=5; IntAct=EBI-644672, EBI-641764;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Interaction with PIK3R2 is required for nuclear localization and
CC export.
CC -!- DOMAIN: The inhibitory interactions with PIK3R1 are mediated by the
CC PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2)
CC region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and
CC the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of
CC PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2)
CC region of PIK3R1. The inhibitory interaction between the PI3K-ABD
CC domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of
CC PIK3R1 is weak. The nuclear localization signal (NLS) is required for
CC its function in cell survival (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-1064 down-regulates lipid kinase activity.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylation at Ser-1064 negatively regulates the
CC phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
CC {ECO:0000250|UniProtKB:P42338}.
CC -!- DISRUPTION PHENOTYPE: Mice have defects in autophagosome formation.
CC Have normal bleeding time but are resistant to thrombosis after
CC arterial injury. Mice fail to induce tumors in a model of prostate
CC tumor formation induced by Pten loss. {ECO:0000269|PubMed:18594509,
CC ECO:0000269|PubMed:19515725, ECO:0000269|PubMed:20065293,
CC ECO:0000269|PubMed:21059846}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879,
CC ECO:0000255|PROSITE-ProRule:PRU00880}.
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; AK090116; BAC41102.1; -; mRNA.
DR EMBL; AK154106; BAE32380.1; -; mRNA.
DR EMBL; CH466560; EDL20998.1; -; Genomic_DNA.
DR CCDS; CCDS23432.1; -.
DR RefSeq; NP_083370.2; NM_029094.3.
DR RefSeq; XP_011241131.1; XM_011242829.2.
DR RefSeq; XP_011241132.1; XM_011242830.2.
DR PDB; 2Y3A; X-ray; 3.30 A; A=1-1064.
DR PDB; 4BFR; X-ray; 2.80 A; A/B=114-1064.
DR PDBsum; 2Y3A; -.
DR PDBsum; 4BFR; -.
DR AlphaFoldDB; Q8BTI9; -.
DR SMR; Q8BTI9; -.
DR BioGRID; 217006; 6.
DR DIP; DIP-49395N; -.
DR IntAct; Q8BTI9; 11.
DR STRING; 10090.ENSMUSP00000035037; -.
DR BindingDB; Q8BTI9; -.
DR ChEMBL; CHEMBL4739696; -.
DR iPTMnet; Q8BTI9; -.
DR PhosphoSitePlus; Q8BTI9; -.
DR MaxQB; Q8BTI9; -.
DR PaxDb; Q8BTI9; -.
DR PRIDE; Q8BTI9; -.
DR ProteomicsDB; 289436; -.
DR Antibodypedia; 33450; 552 antibodies from 41 providers.
DR DNASU; 74769; -.
DR Ensembl; ENSMUST00000035037; ENSMUSP00000035037; ENSMUSG00000032462.
DR GeneID; 74769; -.
DR KEGG; mmu:74769; -.
DR UCSC; uc009rdv.2; mouse.
DR CTD; 5291; -.
DR MGI; MGI:1922019; Pik3cb.
DR VEuPathDB; HostDB:ENSMUSG00000032462; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000157522; -.
DR HOGENOM; CLU_002191_1_3_1; -.
DR InParanoid; Q8BTI9; -.
DR OMA; CVEWNDH; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; Q8BTI9; -.
DR TreeFam; TF102031; -.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-112399; IRS-mediated signalling.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-198203; PI3K/AKT activation.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 74769; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Pik3cb; mouse.
DR PRO; PR:Q8BTI9; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BTI9; protein.
DR Bgee; ENSMUSG00000032462; Expressed in ectoplacental cone and 202 other tissues.
DR ExpressionAtlas; Q8BTI9; baseline and differential.
DR Genevisible; Q8BTI9; MM.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; ISO:MGI.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IMP:MGI.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
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:0106310; F:protein serine kinase activity; ISS:UniProtKB.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IMP:MGI.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0040016; P:embryonic cleavage; IMP:MGI.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:MGI.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IMP:MGI.
DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:BHF-UCL.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:MGI.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISO:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0030168; P:platelet activation; IMP:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IGI:BHF-UCL.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IMP:MGI.
DR GO; GO:0002931; P:response to ischemia; IMP:BHF-UCL.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IGI:BHF-UCL.
DR CDD; cd05173; PI3Kc_IA_beta; 1.
DR DisProt; DP02790; -.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
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; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR003113; PI3K_ABD.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR037702; PI3Kbeta_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF02192; PI3K_p85B; 1.
DR Pfam; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00143; PI3K_p85B; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 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; PS51544; PI3K_ABD; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Autophagy; Cell adhesion; Cytoplasm;
KW Endocytosis; Kinase; Lipid metabolism; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1064
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit beta isoform"
FT /id="PRO_0000088788"
FT DOMAIN 20..109
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 188..279
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 323..490
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 518..695
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 766..1047
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 772..778
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 910..918
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 929..955
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOTIF 404..412
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1064
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P42338"
FT CONFLICT 123
FT /note="L -> R (in Ref. 1; BAC41102)"
FT /evidence="ECO:0000305"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 72..81
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 137..159
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 164..169
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 261..268
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 274..279
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 280..295
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 325..334
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 347..353
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 377..384
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 393..398
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 433..440
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 502..513
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 529..536
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 546..554
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 556..562
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 564..566
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 567..570
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 579..590
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 597..600
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 601..604
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 611..621
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 626..629
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 633..642
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 649..660
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 662..673
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 675..678
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 679..681
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 682..695
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 697..699
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 700..723
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 724..726
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 729..740
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 743..749
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 750..753
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 758..762
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 767..769
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 780..784
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 787..789
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 795..802
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 805..823
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 835..839
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 842..846
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 849..853
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 854..858
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 859..861
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 867..870
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 874..882
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 886..908
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 918..922
FT /evidence="ECO:0007829|PDB:4BFR"
FT STRAND 927..929
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 942..944
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 956..962
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 963..965
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 970..989
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 991..1000
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 1001..1003
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 1012..1015
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 1016..1021
FT /evidence="ECO:0007829|PDB:4BFR"
FT TURN 1022..1025
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 1028..1044
FT /evidence="ECO:0007829|PDB:4BFR"
FT HELIX 1046..1058
FT /evidence="ECO:0007829|PDB:4BFR"
SQ SEQUENCE 1064 AA; 121711 MW; EBDF0266BF0A2032 CRC64;
MPPAMADNLD IWAVDSQIAS DGAISVDFLL PTGIYIQLEV PREATISYIK QMLWKQVHNY
PMFNLLMDID SYMFACVNQT AVYEELEDET RRLCDVRPFL PVLKLVTRSC DPAEKLDSKI
GVLIGKGLHE FDALKDPEVN EFRRKMRKFS EAKIQSLVGL SWIDWLKHTY PPEHEPSVLE
NLEDKLYGGK LVVAVHFENS QDVFSFQVSP NLNPIKINEL AIQKRLTIRG KEDEASPCDY
VLQVSGRVEY VFGDHPLIQF QYIRNCVMNR TLPHFILVEC CKIKKMYEQE MIAIEAAINR
NSSNLPLPLP PKKTRVISHI WDNNNPFQIT LVKGNKLNTE ETVKVHVRAG LFHGTELLCK
TVVSSEISGK NDHIWNEQLE FDINICDLPR MARLCFAVYA VLDKVKTKKS TKTINPSKYQ
TIRKAGKVHY PVAWVNTMVF DFKGQLRSGD VILHSWSSFP DELEEMLNPM GTVQTNPYAE
NATALHITFP ENKKQPCYYP PFDKIIEKAA ELASGDSANV SSRGGKKFLA VLKEILDRDP
LSQLCENEMD LIWTLRQDCR ENFPQSLPKL LLSIKWNKLE DVAQLQALLQ IWPKLPPREA
LELLDFNYPD QYVREYAVGC LRQMSDEELS QYLLQLVQVL KYEPFLDCAL SRFLLERALD
NRRIGQFLFW HLRSEVHTPA VSVQFGVILE AYCRGSVGHM KVLSKQVEAL NKLKTLNSLI
KLNAVKLSRA KGKEAMHTCL KQSAYREALS DLQSPLNPCV ILSELYVEKC KYMDSKMKPL
WLVYSSRAFG EDSVGVIFKN GDDLRQDMLT LQMLRLMDLL WKEAGLDLRM LPYGCLATGD
RSGLIEVVST SETIADIQLN SSNVAATAAF NKDALLNWLK EYNSGDDLDR AIEEFTLSCA
GYCVASYVLG IGDRHSDNIM VKKTGQLFHI DFGHILGNFK SKFGIKRERV PFILTYDFIH
VIQQGKTGNT EKFGRFRQCC EDAYLILRRH GNLFITLFAL MLTAGLPELT SVKDIQYLKD
SLALGKSEEE ALKQFKQKFD EALRESWTTK VNWMAHTVRK DYRS
