CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007558
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 
Protein Synonyms/Alias
 PI3-kinase subunit beta; PI3K-beta; PI3Kbeta; PtdIns-3-kinase subunit beta; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta; PtdIns-3-kinase subunit p110-beta; p110beta 
Gene Name
 PIK3CB 
Gene Synonyms/Alias
 PIK3C1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
230VNELAIQKRLTIHGKubiquitination[1]
514PFDKIIEKAAEIASSubiquitination[1]
711GHMKVLSKQVEALNKubiquitination[2]
732LIKLNAVKLNRAKGKubiquitination[2]
828RLMDLLWKEAGLDLRubiquitination[1]
886DALLNWLKEYNSGDDubiquitination[1]
1025VKDIQYLKDSLALGKubiquitination[1]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. 
Sequence Annotation
 DOMAIN 26 115 PI3K-ABD.
 DOMAIN 194 285 PI3K-RBD.
 DOMAIN 327 496 C2 PI3K-type.
 DOMAIN 524 701 PIK helical.
 DOMAIN 800 1067 PI3K/PI4K.
 MOTIF 410 418 Nuclear localization signal.
 MOD_RES 1070 1070 Phosphoserine; by autocatalysis.  
Keyword
 ATP-binding; Autophagy; Cell adhesion; Complete proteome; Cytoplasm; Endocytosis; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1070 AA 
Protein Sequence
MCFSFIMPPA MADILDIWAV DSQIASDGSI PVDFLLPTGI YIQLEVPREA TISYIKQMLW 60
KQVHNYPMFN LLMDIDSYMF ACVNQTAVYE ELEDETRRLC DVRPFLPVLK LVTRSCDPGE 120
KLDSKIGVLI GKGLHEFDSL KDPEVNEFRR KMRKFSEEKI LSLVGLSWMD WLKQTYPPEH 180
EPSIPENLED KLYGGKLIVA VHFENCQDVF SFQVSPNMNP IKVNELAIQK RLTIHGKEDE 240
VSPYDYVLQV SGRVEYVFGD HPLIQFQYIR NCVMNRALPH FILVECCKIK KMYEQEMIAI 300
EAAINRNSSN LPLPLPPKKT RIISHVWENN NPFQIVLVKG NKLNTEETVK VHVRAGLFHG 360
TELLCKTIVS SEVSGKNDHI WNEPLEFDIN ICDLPRMARL CFAVYAVLDK VKTKKSTKTI 420
NPSKYQTIRK AGKVHYPVAW VNTMVFDFKG QLRTGDIILH SWSSFPDELE EMLNPMGTVQ 480
TNPYTENATA LHVKFPENKK QPYYYPPFDK IIEKAAEIAS SDSANVSSRG GKKFLPVLKE 540
ILDRDPLSQL CENEMDLIWT LRQDCREIFP QSLPKLLLSI KWNKLEDVAQ LQALLQIWPK 600
LPPREALELL DFNYPDQYVR EYAVGCLRQM SDEELSQYLL QLVQVLKYEP FLDCALSRFL 660
LERALGNRRI GQFLFWHLRS EVHIPAVSVQ FGVILEAYCR GSVGHMKVLS KQVEALNKLK 720
TLNSLIKLNA VKLNRAKGKE AMHTCLKQSA YREALSDLQS PLNPCVILSE LYVEKCKYMD 780
SKMKPLWLVY NNKVFGEDSV GVIFKNGDDL RQDMLTLQML RLMDLLWKEA GLDLRMLPYG 840
CLATGDRSGL IEVVSTSETI ADIQLNSSNV AAAAAFNKDA LLNWLKEYNS GDDLDRAIEE 900
FTLSCAGYCV ASYVLGIGDR HSDNIMVKKT GQLFHIDFGH ILGNFKSKFG IKRERVPFIL 960
TYDFIHVIQQ GKTGNTEKFG RFRQCCEDAY LILRRHGNLF ITLFALMLTA GLPELTSVKD 1020
IQYLKDSLAL GKSEEEALKQ FKQKFDEALR ESWTTKVNWM AHTVRKDYRS 1070 
Gene Ontology
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:RefGenome.
 GO:0005886; C:plasma membrane; IBA:RefGenome.
 GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:RefGenome.
 GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
 GO:0000187; P:activation of MAPK activity; TAS:ProtInc.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0006874; P:cellular calcium ion homeostasis; IEA:Compara.
 GO:0006935; P:chemotaxis; TAS:ProtInc.
 GO:0040016; P:embryonic cleavage; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:UniProtKB.
 GO:0007156; P:homophilic cell adhesion; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; TAS:UniProtKB.
 GO:0070527; P:platelet aggregation; TAS:UniProtKB.
 GO:0010508; P:positive regulation of autophagy; TAS:UniProtKB.
 GO:0001952; P:regulation of cell-matrix adhesion; IEA:Compara.
 GO:2000369; P:regulation of clathrin-mediated endocytosis; TAS:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR016024; ARM-type_fold.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR011009; Kinase-like_dom.
 IPR000403; PI3/4_kinase_cat_dom.
 IPR018936; PI3/4_kinase_CS.
 IPR003113; PI3K_adapt-bd_dom.
 IPR002420; PI3K_C2_dom.
 IPR000341; PI3K_Ras-bd_dom.
 IPR015433; PI_Kinase.
 IPR001263; PInositide-3_kin_accessory_dom. 
Pfam
 PF00454; PI3_PI4_kinase
 PF00792; PI3K_C2
 PF02192; PI3K_p85B
 PF00794; PI3K_rbd
 PF00613; PI3Ka 
SMART
 SM00142; PI3K_C2
 SM00143; PI3K_p85B
 SM00144; PI3K_rbd
 SM00145; PI3Ka
 SM00146; PI3Kc 
PROSITE
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3
 PS51544; PI3K_ABD
 PS51547; PI3K_C2
 PS51546; PI3K_RBD
 PS51545; PIK_HELICAL 
PRINTS