Human Gene PIK3CB (ENST00000674063.1_5) from GENCODE V47lift37
  Description: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, transcript variant 1 (from RefSeq NM_006219.3)
Gencode Transcript: ENST00000674063.1_5
Gencode Gene: ENSG00000051382.10_15
Transcript (Including UTRs)
   Position: hg19 chr3:138,371,540-138,553,770 Size: 182,231 Total Exon Count: 24 Strand: -
Coding Region
   Position: hg19 chr3:138,374,231-138,478,185 Size: 103,955 Coding Exon Count: 22 

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Gene AllelesMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:138,371,540-138,553,770)mRNA (may differ from genome)Protein (1070 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PK3CB_HUMAN
DESCRIPTION: RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Short=PI3-kinase subunit beta; Short=PI3K-beta; Short=PI3Kbeta; Short=PtdIns-3-kinase subunit beta; EC=2.7.1.153; AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta; Short=PtdIns-3-kinase subunit p110-beta; Short=p110beta;
FUNCTION: 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.
CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
SUBUNIT: 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).
INTERACTION: O00459:PIK3R2; NbExp=3; IntAct=EBI-2609540, EBI-346930;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Interaction with PIK3R2 is required for nuclear localization and export.
TISSUE SPECIFICITY: Expressed ubiquitously.
DOMAIN: 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.
PTM: Phosphorylation at Ser-1070 down-regulates lipid kinase activity.
SIMILARITY: Belongs to the PI3/PI4-kinase family.
SIMILARITY: Contains 1 C2 PI3K-type domain.
SIMILARITY: Contains 1 PI3K-ABD domain.
SIMILARITY: Contains 1 PI3K-RBD domain.
SIMILARITY: Contains 1 PI3K/PI4K domain.
SIMILARITY: Contains 1 PIK helical domain.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PIK3CB
Diseases sorted by gene-association score: breast cancer (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -148.50355-0.418 Picture PostScript Text
3' UTR -710.602691-0.264 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
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 Domains:
PF00454 - Phosphatidylinositol 3- and 4-kinase
PF00613 - Phosphoinositide 3-kinase family, accessory domain (PIK domain)
PF00792 - Phosphoinositide 3-kinase C2
PF00794 - PI3-kinase family, ras-binding domain
PF02192 - PI3-kinase family, p85-binding domain

SCOP Domains:
48371 - ARM repeat
49562 - C2 domain (Calcium/lipid-binding domain, CaLB)
56112 - Protein kinase-like (PK-like)
54236 - Ubiquitin-like

ModBase Predicted Comparative 3D Structure on P42338
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016303 1-phosphatidylinositol-3-kinase activity
GO:0016740 transferase activity
GO:0035004 phosphatidylinositol 3-kinase activity
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0043560 insulin receptor substrate binding
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process:
GO:0000187 activation of MAPK activity
GO:0001935 endothelial cell proliferation
GO:0001952 regulation of cell-matrix adhesion
GO:0002250 adaptive immune response
GO:0006874 cellular calcium ion homeostasis
GO:0006897 endocytosis
GO:0006914 autophagy
GO:0006935 chemotaxis
GO:0006954 inflammatory response
GO:0007155 cell adhesion
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007411 axon guidance
GO:0009611 response to wounding
GO:0010508 positive regulation of autophagy
GO:0010628 positive regulation of gene expression
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0019221 cytokine-mediated signaling pathway
GO:0030168 platelet activation
GO:0033031 positive regulation of neutrophil apoptotic process
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0040016 embryonic cleavage
GO:0045087 innate immune response
GO:0046854 phosphatidylinositol phosphorylation
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0050852 T cell receptor signaling pathway
GO:0050900 leukocyte migration
GO:0051897 positive regulation of protein kinase B signaling
GO:0060055 angiogenesis involved in wound healing
GO:0060326 cell chemotaxis
GO:0070527 platelet aggregation
GO:2000369 regulation of clathrin-dependent endocytosis

Cellular Component:
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005942 phosphatidylinositol 3-kinase complex
GO:0030496 midbody


-  Descriptions from all associated GenBank mRNAs
  CR749357 - Homo sapiens mRNA; cDNA DKFZp779K1237 (from clone DKFZp779K1237).
AK293754 - Homo sapiens cDNA FLJ57102 complete cds, highly similar to Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform (EC 2.7.1.153).
AK302937 - Homo sapiens cDNA FLJ51708 complete cds, highly similar to Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform (EC 2.7.1.153).
BC114432 - Homo sapiens phosphoinositide-3-kinase, catalytic, beta polypeptide, mRNA (cDNA clone MGC:133043 IMAGE:40008544), complete cds.
LF384587 - JP 2014500723-A/192090: Polycomb-Associated Non-Coding RNAs.
S67334 - phosphatidylinositol 3-kinase p110 beta isoform=110 kda catalytic subunit [human, mRNA Partial, 3213 nt].
KJ891808 - Synthetic construct Homo sapiens clone ccsbBroadEn_01202 PIK3CB gene, encodes complete protein.
AB384841 - Synthetic construct DNA, clone: pF1KB3705, Homo sapiens PIK3CB gene for phosphoinositide-3-kinase, catalytic, beta polypeptide, complete cds, without stop codon, in Flexi system.
MA620164 - JP 2018138019-A/192090: Polycomb-Associated Non-Coding RNAs.
BC035432 - Homo sapiens cDNA clone IMAGE:4152092.
BC033948 - Homo sapiens cDNA clone IMAGE:5285846.
BC045790 - Homo sapiens cDNA clone IMAGE:4796653.
BC003393 - Homo sapiens, clone IMAGE:3447173, mRNA, partial cds.
BC022049 - Homo sapiens phosphoinositide-3-kinase, catalytic, beta polypeptide, mRNA (cDNA clone IMAGE:4291567), partial cds.
LF378270 - JP 2014500723-A/185773: Polycomb-Associated Non-Coding RNAs.
LF378275 - JP 2014500723-A/185778: Polycomb-Associated Non-Coding RNAs.
MA613847 - JP 2018138019-A/185773: Polycomb-Associated Non-Coding RNAs.
MA613852 - JP 2018138019-A/185778: Polycomb-Associated Non-Coding RNAs.
MP330164 - Sequence 129 from Patent WO2019180153.
LF378278 - JP 2014500723-A/185781: Polycomb-Associated Non-Coding RNAs.
LF378279 - JP 2014500723-A/185782: Polycomb-Associated Non-Coding RNAs.
LF378280 - JP 2014500723-A/185783: Polycomb-Associated Non-Coding RNAs.
LF378281 - JP 2014500723-A/185784: Polycomb-Associated Non-Coding RNAs.
LF378283 - JP 2014500723-A/185786: Polycomb-Associated Non-Coding RNAs.
LF378284 - JP 2014500723-A/185787: Polycomb-Associated Non-Coding RNAs.
LF378286 - JP 2014500723-A/185789: Polycomb-Associated Non-Coding RNAs.
LF378288 - JP 2014500723-A/185791: Polycomb-Associated Non-Coding RNAs.
LF378289 - JP 2014500723-A/185792: Polycomb-Associated Non-Coding RNAs.
MA613855 - JP 2018138019-A/185781: Polycomb-Associated Non-Coding RNAs.
MA613856 - JP 2018138019-A/185782: Polycomb-Associated Non-Coding RNAs.
MA613857 - JP 2018138019-A/185783: Polycomb-Associated Non-Coding RNAs.
MA613858 - JP 2018138019-A/185784: Polycomb-Associated Non-Coding RNAs.
MA613860 - JP 2018138019-A/185786: Polycomb-Associated Non-Coding RNAs.
MA613861 - JP 2018138019-A/185787: Polycomb-Associated Non-Coding RNAs.
MA613863 - JP 2018138019-A/185789: Polycomb-Associated Non-Coding RNAs.
MA613865 - JP 2018138019-A/185791: Polycomb-Associated Non-Coding RNAs.
MA613866 - JP 2018138019-A/185792: Polycomb-Associated Non-Coding RNAs.
LF378294 - JP 2014500723-A/185797: Polycomb-Associated Non-Coding RNAs.
MA613871 - JP 2018138019-A/185797: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-6352 - 3-phosphoinositide biosynthesis
PWY-6371 - superpathway of inositol phosphate compounds

Reactome (by CSHL, EBI, and GO)

Protein P42338 (Reactome details) participates in the following event(s):

R-HSA-508247 Gab2 binds the p85 subunit of Class 1A PI3 kinases
R-HSA-879917 CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated
R-HSA-914182 14-3-3 zeta binding allows recruitment of PI3K
R-HSA-74737 p-Y-IRS1,p-Y-IRS2 bind PI3K
R-HSA-186780 PI3-kinase binds to the active receptor
R-HSA-198315 Active IRS recruits PI3K to the plasma membrane and activates it
R-HSA-202203 Recruitment of PI3K to plasma membrane
R-HSA-204798 Interaction of Tie2 and p85 of PI3K
R-HSA-451758 p85 associates with both p-Nephrin and CD2AP
R-HSA-2029273 PI3K binds to p-6Y-SYK
R-HSA-2424482 p85 regulatory unit of PI3K binds p-6Y-SYK
R-HSA-2730842 PI3K associates with phosphorylated GAB2
R-HSA-5218852 p-6Y-VEGFR2 binds PI3K
R-HSA-5357479 p-AXL binds PI3K
R-HSA-437162 PI3K alpha, beta, gamma convert PIP2 to PIP3
R-HSA-912629 CBL is tyrosine phosphorylated
R-HSA-1676109 PI4P is phosphorylated to PI(3,4)P2 by PI3K3C[2] at the plasma membrane
R-HSA-1676048 PI(4,5)P2 is phosphorylated to PI(3,4,5)P3 by PIK3C[1] at the plasma membrane
R-HSA-186800 PI3K catalyses the phosphorylation of PIP2 to PIP3
R-HSA-198266 PI3K produces PIP3 and other phosphatidyl inositides
R-HSA-202365 PI3K bound to TRAT1 phosphorylates PIP2 to PIP3
R-HSA-2029271 PI3K phosphorylates PIP2 to PIP3
R-HSA-2424480 PI3K phosphorylates PIP2 to PIP3
R-HSA-2730870 Phosphorylation of PIP2 to PIP3 by PI3K
R-HSA-109699 PI3K-containing complexes phosphorylate PIP2 to PIP3
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-5218819 VEGFA dimer:p-6Y-VEGFR2 dimer:PI3K phosphorylates PIP2 to PIP3
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-8853659 RET signaling
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-109704 PI3K Cascade
R-HSA-186763 Downstream signal transduction
R-HSA-198203 PI3K/AKT activation
R-HSA-202424 Downstream TCR signaling
R-HSA-210993 Tie2 Signaling
R-HSA-373753 Nephrin family interactions
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2424491 DAP12 signaling
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-451927 Interleukin-2 family signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-422475 Axon guidance
R-HSA-109582 Hemostasis
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-112399 IRS-mediated signalling
R-HSA-186797 Signaling by PDGF
R-HSA-187037 Signaling by NTRK1 (TRKA)
R-HSA-202403 TCR signaling
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-1500931 Cell-Cell communication
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2172127 DAP12 interactions
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-194138 Signaling by VEGF
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-1266738 Developmental Biology
R-HSA-1483255 PI Metabolism
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-166520 Signaling by NTRKs
R-HSA-1280218 Adaptive Immune System
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System
R-HSA-1483257 Phospholipid metabolism
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74752 Signaling by Insulin receptor
R-HSA-2428924 IGF1R signaling cascade
R-HSA-162582 Signal Transduction
R-HSA-556833 Metabolism of lipids
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-1430728 Metabolism
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: D3DNF0, NM_006219, P42338, PIK3C1, PK3CB_HUMAN, Q24JU2, uc329xtk.1, uc329xtk.2
UCSC ID: ENST00000674063.1_5
RefSeq Accession: NM_006219.3
Protein: P42338 (aka PK3CB_HUMAN or P11B_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.