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Overview

Uniprot IDP42338
Protein NamePhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
Gene NamePIK3CB
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
424 TKTINPSKYQTIRKA

Function

Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). 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 receptor (GPCR) 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. Also has a protein kinase activity showing autophosphorylation (PubMed:12502714)

Protein Sequence

10 MCFSFIMPPA 20 MADILDIWAV 30 DSQIASDGSI 40 PVDFLLPTGI 50 YIQLEVPREA 60 TISYIKQMLW 70 KQVHNYPMFN 80 LLMDIDSYMF 90 ACVNQTAVYE 100 ELEDETRRLC 110 DVRPFLPVLK 120 LVTRSCDPGE 130 KLDSKIGVLI 140 GKGLHEFDSL 150 KDPEVNEFRR 160 KMRKFSEEKI 170 LSLVGLSWMD 180 WLKQTYPPEH 190 EPSIPENLED 200 KLYGGKLIVA 210 VHFENCQDVF 220 SFQVSPNMNP 230 IKVNELAIQK 240 RLTIHGKEDE 250 VSPYDYVLQV 260 SGRVEYVFGD 270 HPLIQFQYIR 280 NCVMNRALPH 290 FILVECCKIK 300 KMYEQEMIAI 310 EAAINRNSSN 320 LPLPLPPKKT 330 RIISHVWENN 340 NPFQIVLVKG 350 NKLNTEETVK 360 VHVRAGLFHG 370 TELLCKTIVS 380 SEVSGKNDHI 390 WNEPLEFDIN 400 ICDLPRMARL 410 CFAVYAVLDK 420 VKTKKSTKTI 430 NPSKYQTIRK 440 AGKVHYPVAW 450 VNTMVFDFKG 460 QLRTGDIILH 470 SWSSFPDELE 480 EMLNPMGTVQ 490 TNPYTENATA 500 LHVKFPENKK 510 QPYYYPPFDK 520 IIEKAAEIAS 530 SDSANVSSRG 540 GKKFLPVLKE 550 ILDRDPLSQL 560 CENEMDLIWT 570 LRQDCREIFP 580 QSLPKLLLSI 590 KWNKLEDVAQ 600 LQALLQIWPK 610 LPPREALELL 620 DFNYPDQYVR 630 EYAVGCLRQM 640 SDEELSQYLL 650 QLVQVLKYEP 660 FLDCALSRFL 670 LERALGNRRI 680 GQFLFWHLRS 690 EVHIPAVSVQ 700 FGVILEAYCR 710 GSVGHMKVLS 720 KQVEALNKLK 730 TLNSLIKLNA 740 VKLNRAKGKE 750 AMHTCLKQSA 760 YREALSDLQS 770 PLNPCVILSE 780 LYVEKCKYMD 790 SKMKPLWLVY 800 NNKVFGEDSV 810 GVIFKNGDDL 820 RQDMLTLQML 830 RLMDLLWKEA 840 GLDLRMLPYG 850 CLATGDRSGL 860 IEVVSTSETI 870 ADIQLNSSNV 880 AAAAAFNKDA 890 LLNWLKEYNS 900 GDDLDRAIEE 910 FTLSCAGYCV 920 ASYVLGIGDR 930 HSDNIMVKKT 940 GQLFHIDFGH 950 ILGNFKSKFG 960 IKRERVPFIL 970 TYDFIHVIQQ 980 GKTGNTEKFG 990 RFRQCCEDAY 1000 LILRRHGNLF 1010 ITLFALMLTA 1020 GLPELTSVKD 1030 IQYLKDSLAL 1040 GKSEEEALKQ 1050 FKQKFDEALR 1060 ESWTTKVNWM 1070 AHTVRKDYRS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005943 phosphatidylinositol 3-kinase complex, class IA
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0016303 1-phosphatidylinositol-3-kinase activity
Molecular Function GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Molecular Function GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0043560 insulin receptor substrate binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Biological Process GO:0006914 autophagy
Biological Process GO:0016477 cell migration
Biological Process GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
Biological Process GO:0006935 chemotaxis
Biological Process GO:0006897 endocytosis
Biological Process GO:0007186 G protein-coupled receptor signaling pathway
Biological Process GO:0042267 natural killer cell mediated cytotoxicity
Biological Process GO:1903298 negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway
Biological Process GO:0043409 negative regulation of MAPK cascade
Biological Process GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:1903671 negative regulation of sprouting angiogenesis
Biological Process GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway
Biological Process GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:0046854 phosphatidylinositol phosphate biosynthetic process
Biological Process GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
Biological Process GO:0048015 phosphatidylinositol-mediated signaling
Biological Process GO:0030168 platelet activation
Biological Process GO:0070527 platelet aggregation
Biological Process GO:0010508 positive regulation of autophagy
Biological Process GO:0010595 positive regulation of endothelial cell migration
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0033031 positive regulation of neutrophil apoptotic process
Biological Process GO:0045429 positive regulation of nitric oxide biosynthetic process
Biological Process GO:0035022 positive regulation of Rac protein signal transduction
Biological Process GO:0001952 regulation of cell-matrix adhesion
Biological Process GO:2000369 regulation of clathrin-dependent endocytosis
Biological Process GO:0002931 response to ischemia
Biological Process GO:0007165 signal transduction
Biological Process GO:0003376 sphingosine-1-phosphate receptor signaling pathway
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005942 phosphatidylinositol 3-kinase complex

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.