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Protein

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform

Gene

PIK3CB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.

Pathwayi: phosphatidylinositol phosphate biosynthesis

This protein is involved in the pathway phosphatidylinositol phosphate biosynthesis, which is part of Phospholipid metabolism.
View all proteins of this organism that are known to be involved in the pathway phosphatidylinositol phosphate biosynthesis and in Phospholipid metabolism.

GO - Molecular functioni

GO - Biological processi

  • activation of MAPK activity Source: ProtInc
  • adaptive immune response Source: GO_Central
  • angiogenesis involved in wound healing Source: Ensembl
  • autophagy Source: UniProtKB-KW
  • axon guidance Source: Reactome
  • cell chemotaxis Source: GO_Central
  • cell migration Source: UniProtKB
  • cellular calcium ion homeostasis Source: Ensembl
  • chemotaxis Source: ProtInc
  • cytokine-mediated signaling pathway Source: Reactome
  • embryonic cleavage Source: Ensembl
  • endothelial cell proliferation Source: Ensembl
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: Ensembl
  • inflammatory response Source: GO_Central
  • innate immune response Source: GO_Central
  • leukocyte migration Source: Reactome
  • phosphatidylinositol 3-kinase signaling Source: CAFA
  • phosphatidylinositol-mediated signaling Source: Reactome
  • phosphorylation Source: MGI
  • platelet activation Source: UniProtKB
  • platelet aggregation Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of gene expression Source: MGI
  • positive regulation of neutrophil apoptotic process Source: CAFA
  • positive regulation of protein kinase B signaling Source: Reactome
  • regulation of cell-matrix adhesion Source: MGI
  • regulation of clathrin-dependent endocytosis Source: UniProtKB
  • signal transduction Source: ProtInc
  • T cell receptor signaling pathway Source: Reactome
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome

Keywordsi

Molecular functionKinase, Transferase
Biological processAutophagy, Cell adhesion, Endocytosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00644-MONOMER
BRENDAi2.7.1.137 2681
2.7.1.153 2681
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-186763 Downstream signal transduction
R-HSA-198203 PI3K/AKT activation
R-HSA-202424 Downstream TCR signaling
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-210993 Tie2 Signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491 DAP12 signaling
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-373753 Nephrin family interactions
R-HSA-392451 G beta:gamma signalling through PI3Kgamma
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853659 RET signaling
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
SignaLinkiP42338
SIGNORiP42338
UniPathwayiUPA00220

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (EC:2.7.1.153)
Short name:
PI3-kinase subunit beta
Short name:
PI3K-beta
Short name:
PI3Kbeta
Short name:
PtdIns-3-kinase subunit beta
Alternative name(s):
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta
Short name:
PtdIns-3-kinase subunit p110-beta
Short name:
p110beta
Gene namesi
Name:PIK3CB
Synonyms:PIK3C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000051382.8
HGNCiHGNC:8976 PIK3CB
MIMi602925 gene
neXtProtiNX_P42338

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi342K → N: Enhanced inhibition by PIK3R1 leading to reduced lipid kinase activity and reduced oncogenicity. Does not modify regulation by GPCRs. 1 Publication1
Mutagenesisi805K → R: Loss of lipid kinase activity. May not affect insulin signaling and cell proliferation. Partially affects oncogene-induced trasformation. 1 Publication1

Organism-specific databases

DisGeNETi5291
OpenTargetsiENSG00000051382
PharmGKBiPA33309

Chemistry databases

ChEMBLiCHEMBL3145
DrugBankiDB00201 Caffeine
DB05241 XL765
GuidetoPHARMACOLOGYi2154

Polymorphism and mutation databases

BioMutaiPIK3CB
DMDMi1171955

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000887871 – 1070Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoformAdd BLAST1070

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei324PhosphoserineBy similarity1
Modified residuei1070Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylation at Ser-1070 down-regulates lipid kinase activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP42338
MaxQBiP42338
PaxDbiP42338
PeptideAtlasiP42338
PRIDEiP42338
ProteomicsDBi55510

PTM databases

CarbonylDBiP42338
iPTMnetiP42338
PhosphoSitePlusiP42338

Expressioni

Tissue specificityi

Expressed ubiquitously.

Gene expression databases

BgeeiENSG00000051382
CleanExiHS_PIK3CB
ExpressionAtlasiP42338 baseline and differential
GenevisibleiP42338 HS

Organism-specific databases

HPAiCAB031938
HPA064207

Interactioni

Subunit structurei

Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required for nuclear localization and nuclear export. Part of a complex with PIK3R1 and PTEN. Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions. Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4 (By similarity). Interacts with BECN1, ATG14 and RAB5A (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111309, 46 interactors
DIPiDIP-44775N
IntActiP42338, 22 interactors
MINTiP42338
STRINGi9606.ENSP00000289153

Chemistry databases

BindingDBiP42338

Structurei

3D structure databases

ProteinModelPortaliP42338
SMRiP42338
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 115PI3K-ABDPROSITE-ProRule annotationAdd BLAST90
Domaini194 – 285PI3K-RBDPROSITE-ProRule annotationAdd BLAST92
Domaini327 – 496C2 PI3K-typePROSITE-ProRule annotationAdd BLAST170
Domaini524 – 701PIK helicalPROSITE-ProRule annotationAdd BLAST178
Domaini800 – 1067PI3K/PI4KPROSITE-ProRule annotationAdd BLAST268

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi410 – 418Nuclear localization signal9

Domaini

The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival.

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0904 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00760000119110
HOGENOMiHOG000252911
HOVERGENiHBG052721
InParanoidiP42338
KOiK00922
OMAiSLNWASH
OrthoDBiEOG091G027R
PhylomeDBiP42338
TreeFamiTF102031

Family and domain databases

CDDicd05173 PI3Kc_IA_beta, 1 hit
Gene3Di1.10.1070.11, 1 hit
2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035892 C2_domain_sf
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003113 PI3K_adapt-bd_dom
IPR002420 PI3K_C2_dom
IPR000341 PI3K_Ras-bd_dom
IPR008290 PI3K_Vps34
IPR037702 PI3Kbeta_dom
IPR015433 PI_Kinase
IPR001263 PInositide-3_kin_accessory_dom
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR10048 PTHR10048, 1 hit
PfamiView protein in Pfam
PF00454 PI3_PI4_kinase, 1 hit
PF00792 PI3K_C2, 1 hit
PF02192 PI3K_p85B, 1 hit
PF00794 PI3K_rbd, 1 hit
PF00613 PI3Ka, 1 hit
PIRSFiPIRSF000587 PI3K_Vps34, 1 hit
SMARTiView protein in SMART
SM00142 PI3K_C2, 1 hit
SM00143 PI3K_p85B, 1 hit
SM00144 PI3K_rbd, 1 hit
SM00145 PI3Ka, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00915 PI3_4_KINASE_1, 1 hit
PS00916 PI3_4_KINASE_2, 1 hit
PS50290 PI3_4_KINASE_3, 1 hit
PS51544 PI3K_ABD, 1 hit
PS51547 PI3K_C2, 1 hit
PS51546 PI3K_RBD, 1 hit
PS51545 PIK_HELICAL, 1 hit

Sequencei

Sequence statusi: Complete.

P42338-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCFSFIMPPA MADILDIWAV DSQIASDGSI PVDFLLPTGI YIQLEVPREA
60 70 80 90 100
TISYIKQMLW KQVHNYPMFN LLMDIDSYMF ACVNQTAVYE ELEDETRRLC
110 120 130 140 150
DVRPFLPVLK LVTRSCDPGE KLDSKIGVLI GKGLHEFDSL KDPEVNEFRR
160 170 180 190 200
KMRKFSEEKI LSLVGLSWMD WLKQTYPPEH EPSIPENLED KLYGGKLIVA
210 220 230 240 250
VHFENCQDVF SFQVSPNMNP IKVNELAIQK RLTIHGKEDE VSPYDYVLQV
260 270 280 290 300
SGRVEYVFGD HPLIQFQYIR NCVMNRALPH FILVECCKIK KMYEQEMIAI
310 320 330 340 350
EAAINRNSSN LPLPLPPKKT RIISHVWENN NPFQIVLVKG NKLNTEETVK
360 370 380 390 400
VHVRAGLFHG TELLCKTIVS SEVSGKNDHI WNEPLEFDIN ICDLPRMARL
410 420 430 440 450
CFAVYAVLDK VKTKKSTKTI NPSKYQTIRK AGKVHYPVAW VNTMVFDFKG
460 470 480 490 500
QLRTGDIILH SWSSFPDELE EMLNPMGTVQ TNPYTENATA LHVKFPENKK
510 520 530 540 550
QPYYYPPFDK IIEKAAEIAS SDSANVSSRG GKKFLPVLKE ILDRDPLSQL
560 570 580 590 600
CENEMDLIWT LRQDCREIFP QSLPKLLLSI KWNKLEDVAQ LQALLQIWPK
610 620 630 640 650
LPPREALELL DFNYPDQYVR EYAVGCLRQM SDEELSQYLL QLVQVLKYEP
660 670 680 690 700
FLDCALSRFL LERALGNRRI GQFLFWHLRS EVHIPAVSVQ FGVILEAYCR
710 720 730 740 750
GSVGHMKVLS KQVEALNKLK TLNSLIKLNA VKLNRAKGKE AMHTCLKQSA
760 770 780 790 800
YREALSDLQS PLNPCVILSE LYVEKCKYMD SKMKPLWLVY NNKVFGEDSV
810 820 830 840 850
GVIFKNGDDL RQDMLTLQML RLMDLLWKEA GLDLRMLPYG CLATGDRSGL
860 870 880 890 900
IEVVSTSETI ADIQLNSSNV AAAAAFNKDA LLNWLKEYNS GDDLDRAIEE
910 920 930 940 950
FTLSCAGYCV ASYVLGIGDR HSDNIMVKKT GQLFHIDFGH ILGNFKSKFG
960 970 980 990 1000
IKRERVPFIL TYDFIHVIQQ GKTGNTEKFG RFRQCCEDAY LILRRHGNLF
1010 1020 1030 1040 1050
ITLFALMLTA GLPELTSVKD IQYLKDSLAL GKSEEEALKQ FKQKFDEALR
1060 1070
ESWTTKVNWM AHTVRKDYRS
Length:1,070
Mass (Da):122,762
Last modified:November 1, 1995 - v1
Checksum:i81135FE93452C00E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050530672Q → H. Corresponds to variant dbSNP:rs2230462Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S67334 mRNA Translation: AAB29081.1
AJ297549
, AJ297550, AJ297551, AJ297552, AJ297553, AJ297554, AJ297555, AJ297556, AJ297557, AJ297558, AJ297559, AJ297560 Genomic DNA Translation: CAC21449.1
CH471052 Genomic DNA Translation: EAW79053.1
CH471052 Genomic DNA Translation: EAW79055.1
BC114432 mRNA Translation: AAI14433.1
CCDSiCCDS3104.1
PIRiA54600
RefSeqiNP_006210.1, NM_006219.2
XP_005247587.1, XM_005247530.2
XP_006713722.1, XM_006713659.3
XP_011511197.1, XM_011512895.2
XP_016862108.1, XM_017006619.1
UniGeneiHs.239818

Genome annotation databases

EnsembliENST00000289153; ENSP00000289153; ENSG00000051382
ENST00000477593; ENSP00000418143; ENSG00000051382
GeneIDi5291
KEGGihsa:5291
UCSCiuc011bmq.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPK3CB_HUMAN
AccessioniPrimary (citable) accession number: P42338
Secondary accession number(s): D3DNF0, Q24JU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 20, 2018
This is version 178 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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