PK3CB_HUMAN
ID PK3CB_HUMAN Reviewed; 1070 AA.
AC P42338; D3DNF0; Q24JU2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 204.
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:0000269|PubMed:12502714, ECO:0000269|PubMed:15135396};
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 {ECO:0000303|PubMed:15135396};
DE AltName: Full=Serine/threonine protein kinase PIK3CB {ECO:0000305|PubMed:12502714};
DE EC=2.7.11.1 {ECO:0000269|PubMed:12502714};
GN Name=PIK3CB; Synonyms=PIK3C1;
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].
RX PubMed=8246984; DOI=10.1128/mcb.13.12.7677-7688.1993;
RA Hu P., Mondino A., Skolnik E.Y., Schlessinger J.;
RT "Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-
RT kinase and identification of its binding site on p85.";
RL Mol. Cell. Biol. 13:7677-7688(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11016459; DOI=10.2337/diabetes.49.10.1740;
RA Kossila M., Sinkovic M., Karkkainen P., Laukkanen M.O., Miettinen R.,
RA Rissanen J., Kekalainen P., Kuusisto J., Yla-Herttuala S., Laakso M.;
RT "Gene encoding the catalytic subunit p110beta of human phosphatidylinositol
RT 3-kinase: cloning, genomic structure, and screening for variants in
RT patients with type 2 diabetes.";
RL Diabetes 49:1740-1743(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-1070, AND MUTAGENESIS OF
RP SER-1070.
RX PubMed=12502714; DOI=10.1074/jbc.m210351200;
RA Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K.,
RA Krause E., Nurnberg B.;
RT "Identification and characterization of the autophosphorylation sites of
RT phosphoinositide 3-kinase isoforms beta and gamma.";
RL J. Biol. Chem. 278:11536-11545(2003).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15135396; DOI=10.1016/j.pep.2003.12.010;
RA Meier T.I., Cook J.A., Thomas J.E., Radding J.A., Horn C., Lingaraj T.,
RA Smith M.C.;
RT "Cloning, expression, purification, and characterization of the human Class
RT Ia phosphoinositide 3-kinase isoforms.";
RL Protein Expr. Purif. 35:218-224(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF LYS-805.
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 [8]
RP FUNCTION IN ONCOGENIC SIGNALING.
RX PubMed=18755892; DOI=10.1073/pnas.0802655105;
RA Wee S., Wiederschain D., Maira S.-M., Loo A., Miller C., deBeaumont R.,
RA Stegmeier F., Yao Y.-M., Lengauer C.;
RT "PTEN-deficient cancers depend on PIK3CB.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:13057-13062(2008).
RN [9]
RP IDENTIFICATION IN A COMPLEX WITH PIK3R1 AND PTEN.
RX PubMed=19635806; DOI=10.1128/mcb.01649-08;
RA Rabinovsky R., Pochanard P., McNear C., Brachmann S.M., Duke-Cohan J.S.,
RA Garraway L.A., Sellers W.R.;
RT "p85 Associates with unphosphorylated PTEN and the PTEN-associated
RT complex.";
RL Mol. Cell. Biol. 29:5377-5388(2009).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF LYS-342.
RX PubMed=21030680; DOI=10.1073/pnas.1008739107;
RA Dbouk H.A., Pang H., Fiser A., Backer J.M.;
RT "A biochemical mechanism for the oncogenic potential of the p110beta
RT catalytic subunit of phosphoinositide 3-kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:19897-19902(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, INTERACTION WITH PIK3R2, SUBCELLULAR LOCATION, AND MOTIF NUCLEAR
RP LOCALIZATION SIGNAL.
RX PubMed=21383062; DOI=10.1128/mcb.01313-10;
RA Kumar A., Redondo-Munoz J., Perez-Garcia V., Cortes I., Chagoyen M.,
RA Carrera A.C.;
RT "Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential
RT function in cell survival.";
RL Mol. Cell. Biol. 31:2122-2133(2011).
RN [13]
RP REVIEW ON FUNCTION.
RX PubMed=21321382; DOI=10.18632/oncotarget.101205;
RA Dbouk H.A., Backer J.M.;
RT "A beta version of life: p110beta takes center stage.";
RL Oncotarget 1:729-733(2010).
RN [14]
RP REVIEW ON FUNCTION.
RX PubMed=21035500; DOI=10.1016/j.advenzreg.2010.09.011;
RA Gratacap M.-P., Guillermet-Guibert J., Martin V., Chicanne G.,
RA Tronchere H., Gaits-Iacovoni F., Payrastre B.;
RT "Regulation and roles of PI3Kbeta, a major actor in platelet signaling and
RT functions.";
RL Adv. Enzyme Regul. 51:106-116(2011).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol derivatives at position 3 of the inositol ring to
CC produce 3-phosphoinositides (PubMed:15135396). Uses ATP and
CC PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). 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 (PubMed:12502714).
CC {ECO:0000269|PubMed:12502714, ECO:0000269|PubMed:15135396,
CC ECO:0000269|PubMed:18594509, ECO:0000269|PubMed:18755892,
CC ECO:0000269|PubMed:21030680, ECO:0000269|PubMed:21383062}.
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:0000269|PubMed:12502714, ECO:0000269|PubMed:15135396};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000305|PubMed:15135396};
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:0000305|PubMed:15135396};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000305|PubMed:15135396};
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:0000269|PubMed:12502714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000305|PubMed:12502714};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000305|PubMed:15135396}.
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. Part of a complex with
CC PIK3R1 and PTEN. Binding to PTEN may antagonize the lipid kinase
CC activity under normal growth conditions. Part of a complex involved in
CC autophagosome formation composed of PIK3C3 and PIK3R4 (By similarity).
CC Interacts with BECN1, ATG14 and RAB5A (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P42338; P05067: APP; NbExp=3; IntAct=EBI-2609540, EBI-77613;
CC P42338; P27986: PIK3R1; NbExp=4; IntAct=EBI-2609540, EBI-79464;
CC P42338; P27986-2: PIK3R1; NbExp=6; IntAct=EBI-2609540, EBI-9090282;
CC P42338; O00459: PIK3R2; NbExp=5; IntAct=EBI-2609540, EBI-346930;
CC P42338; Q92569: PIK3R3; NbExp=3; IntAct=EBI-2609540, EBI-79893;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21383062}. Nucleus
CC {ECO:0000269|PubMed:21383062}. Note=Interaction with PIK3R2 is required
CC for nuclear localization and export.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
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.
CC -!- PTM: Autophosphorylation at Ser-1070 negatively regulates the
CC phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
CC {ECO:0000269|PubMed:12502714}.
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}.
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DR EMBL; S67334; AAB29081.1; -; mRNA.
DR EMBL; AJ297549; CAC21449.1; -; Genomic_DNA.
DR EMBL; AJ297550; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297551; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297552; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297553; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297554; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297555; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297556; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297557; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297558; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297559; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; AJ297560; CAC21449.1; JOINED; Genomic_DNA.
DR EMBL; CH471052; EAW79053.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79055.1; -; Genomic_DNA.
DR EMBL; BC114432; AAI14433.1; -; mRNA.
DR CCDS; CCDS3104.1; -.
DR PIR; A54600; A54600.
DR RefSeq; NP_006210.1; NM_006219.2.
DR RefSeq; XP_005247587.1; XM_005247530.2.
DR RefSeq; XP_006713722.1; XM_006713659.3.
DR RefSeq; XP_011511197.1; XM_011512895.2.
DR RefSeq; XP_016862108.1; XM_017006619.1.
DR AlphaFoldDB; P42338; -.
DR SMR; P42338; -.
DR BioGRID; 111309; 78.
DR ComplexPortal; CPX-5972; Phosphatidylinositol 3-kinase complex class IA, p110beta/p50alpha.
DR ComplexPortal; CPX-5974; Phosphatidylinositol 3-kinase complex class IA, p110beta/p55alpha.
DR ComplexPortal; CPX-5975; Phosphatidylinositol 3-kinase complex class IA, p110beta/p85alpha.
DR ComplexPortal; CPX-5976; Phosphatidylinositol 3-kinase complex class IA, p110beta/p85beta.
DR ComplexPortal; CPX-5977; Phosphatidylinositol 3-kinase complex class IA, p110beta/p55gamma.
DR DIP; DIP-44775N; -.
DR IntAct; P42338; 50.
DR MINT; P42338; -.
DR STRING; 9606.ENSP00000289153; -.
DR BindingDB; P42338; -.
DR ChEMBL; CHEMBL3145; -.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB05241; XL765.
DR DrugCentral; P42338; -.
DR GuidetoPHARMACOLOGY; 2154; -.
DR CarbonylDB; P42338; -.
DR iPTMnet; P42338; -.
DR PhosphoSitePlus; P42338; -.
DR BioMuta; PIK3CB; -.
DR DMDM; 1171955; -.
DR EPD; P42338; -.
DR jPOST; P42338; -.
DR MassIVE; P42338; -.
DR MaxQB; P42338; -.
DR PaxDb; P42338; -.
DR PeptideAtlas; P42338; -.
DR PRIDE; P42338; -.
DR ProteomicsDB; 55510; -.
DR Antibodypedia; 33450; 552 antibodies from 41 providers.
DR DNASU; 5291; -.
DR Ensembl; ENST00000289153.6; ENSP00000289153.2; ENSG00000051382.9.
DR Ensembl; ENST00000477593.5; ENSP00000418143.1; ENSG00000051382.9.
DR Ensembl; ENST00000674063.1; ENSP00000501150.1; ENSG00000051382.9.
DR GeneID; 5291; -.
DR KEGG; hsa:5291; -.
DR MANE-Select; ENST00000674063.1; ENSP00000501150.1; NM_006219.3; NP_006210.1.
DR UCSC; uc011bmq.4; human.
DR CTD; 5291; -.
DR DisGeNET; 5291; -.
DR GeneCards; PIK3CB; -.
DR HGNC; HGNC:8976; PIK3CB.
DR HPA; ENSG00000051382; Low tissue specificity.
DR MIM; 602925; gene.
DR neXtProt; NX_P42338; -.
DR OpenTargets; ENSG00000051382; -.
DR PharmGKB; PA33309; -.
DR VEuPathDB; HostDB:ENSG00000051382; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000157522; -.
DR HOGENOM; CLU_002191_1_3_1; -.
DR InParanoid; P42338; -.
DR OMA; CVEWNDH; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; P42338; -.
DR TreeFam; TF102031; -.
DR BioCyc; MetaCyc:HS00644-MON; -.
DR BRENDA; 2.7.1.137; 2681.
DR BRENDA; 2.7.1.153; 2681.
DR PathwayCommons; P42338; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-112399; IRS-mediated signalling.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-198203; PI3K/AKT activation.
DR Reactome; R-HSA-201556; Signaling by ALK.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-2424491; DAP12 signaling.
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants.
DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants.
DR SignaLink; P42338; -.
DR SIGNOR; P42338; -.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 5291; 64 hits in 1092 CRISPR screens.
DR ChiTaRS; PIK3CB; human.
DR GeneWiki; PIK3CB; -.
DR GenomeRNAi; 5291; -.
DR Pharos; P42338; Tchem.
DR PRO; PR:P42338; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P42338; protein.
DR Bgee; ENSG00000051382; Expressed in tendon of biceps brachii and 204 other tissues.
DR ExpressionAtlas; P42338; baseline and differential.
DR Genevisible; P42338; HS.
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; IDA:HPA.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IDA:UniProtKB.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0040016; P:embryonic cleavage; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:Ensembl.
DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:BHF-UCL.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IGI:BHF-UCL.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IGI:BHF-UCL.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA: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; IDA:MGI.
DR GO; GO:0030168; P:platelet activation; TAS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; TAS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; TAS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IMP:CAFA.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL.
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:2000369; P:regulation of clathrin-dependent endocytosis; TAS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:UniProtKB.
DR CDD; cd05173; PI3Kc_IA_beta; 1.
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 ATP-binding; Autophagy; Cell adhesion; Cytoplasm; Endocytosis; Kinase;
KW Lipid metabolism; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..1070
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit beta isoform"
FT /id="PRO_0000088787"
FT DOMAIN 26..115
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 194..285
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 327..496
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 524..701
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 772..1053
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 778..784
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 916..924
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 935..961
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOTIF 410..418
FT /note="Nuclear localization signal"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BTI9"
FT MOD_RES 1070
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12502714"
FT VARIANT 672
FT /note="Q -> H (in dbSNP:rs2230462)"
FT /id="VAR_050530"
FT MUTAGEN 342
FT /note="K->N: Enhanced inhibition by PIK3R1 leading to
FT reduced lipid kinase activity and reduced oncogenicity.
FT Does not modify regulation by GPCRs."
FT /evidence="ECO:0000269|PubMed:21030680"
FT MUTAGEN 805
FT /note="K->R: Loss of lipid kinase activity. May not affect
FT insulin signaling and cell proliferation. Partially affects
FT oncogene-induced transformation."
FT /evidence="ECO:0000269|PubMed:18594509"
FT MUTAGEN 1070
FT /note="S->A: Loss of autophosphorylation. No effect on
FT phosphatidylinositol-4,5-bisphosphate 3-kinase activity."
FT /evidence="ECO:0000269|PubMed:12502714"
FT MUTAGEN 1070
FT /note="S->D,E: Loss of autophosphorylation. Decreased basal
FT and stimulated phosphatidylinositol-4,5-bisphosphate 3-
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:12502714"
SQ SEQUENCE 1070 AA; 122762 MW; 81135FE93452C00E CRC64;
MCFSFIMPPA MADILDIWAV DSQIASDGSI PVDFLLPTGI YIQLEVPREA TISYIKQMLW
KQVHNYPMFN LLMDIDSYMF ACVNQTAVYE ELEDETRRLC DVRPFLPVLK LVTRSCDPGE
KLDSKIGVLI GKGLHEFDSL KDPEVNEFRR KMRKFSEEKI LSLVGLSWMD WLKQTYPPEH
EPSIPENLED KLYGGKLIVA VHFENCQDVF SFQVSPNMNP IKVNELAIQK RLTIHGKEDE
VSPYDYVLQV SGRVEYVFGD HPLIQFQYIR NCVMNRALPH FILVECCKIK KMYEQEMIAI
EAAINRNSSN LPLPLPPKKT RIISHVWENN NPFQIVLVKG NKLNTEETVK VHVRAGLFHG
TELLCKTIVS SEVSGKNDHI WNEPLEFDIN ICDLPRMARL CFAVYAVLDK VKTKKSTKTI
NPSKYQTIRK AGKVHYPVAW VNTMVFDFKG QLRTGDIILH SWSSFPDELE EMLNPMGTVQ
TNPYTENATA LHVKFPENKK QPYYYPPFDK IIEKAAEIAS SDSANVSSRG GKKFLPVLKE
ILDRDPLSQL CENEMDLIWT LRQDCREIFP QSLPKLLLSI KWNKLEDVAQ LQALLQIWPK
LPPREALELL DFNYPDQYVR EYAVGCLRQM SDEELSQYLL QLVQVLKYEP FLDCALSRFL
LERALGNRRI GQFLFWHLRS EVHIPAVSVQ FGVILEAYCR GSVGHMKVLS KQVEALNKLK
TLNSLIKLNA VKLNRAKGKE AMHTCLKQSA YREALSDLQS PLNPCVILSE LYVEKCKYMD
SKMKPLWLVY NNKVFGEDSV GVIFKNGDDL RQDMLTLQML RLMDLLWKEA GLDLRMLPYG
CLATGDRSGL IEVVSTSETI ADIQLNSSNV AAAAAFNKDA LLNWLKEYNS GDDLDRAIEE
FTLSCAGYCV ASYVLGIGDR HSDNIMVKKT GQLFHIDFGH ILGNFKSKFG IKRERVPFIL
TYDFIHVIQQ GKTGNTEKFG RFRQCCEDAY LILRRHGNLF ITLFALMLTA GLPELTSVKD
IQYLKDSLAL GKSEEEALKQ FKQKFDEALR ESWTTKVNWM AHTVRKDYRS
