P42338 · PK3CB_HUMAN
- ProteinPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
- GenePIK3CB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1070 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 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. Has also a protein kinase activity showing autophosphorylation (PubMed:12502714).
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 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. Has also a protein kinase activity showing autophosphorylation (PubMed:12502714).
Catalytic activity
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H+This reaction proceeds in the forward direction.
- 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H+This reaction proceeds in the forward direction.
Pathway
Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
- EC number
- Short namesPI3-kinase subunit beta; PI3K-beta; PI3Kbeta; PtdIns-3-kinase subunit beta
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP42338
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 342 | Enhanced inhibition by PIK3R1 leading to reduced lipid kinase activity and reduced oncogenicity. Does not modify regulation by GPCRs. | ||||
Sequence: K → N | ||||||
Natural variant | VAR_050530 | 672 | in dbSNP:rs2230462 | |||
Sequence: Q → H | ||||||
Mutagenesis | 805 | Loss of lipid kinase activity. May not affect insulin signaling and cell proliferation. Partially affects oncogene-induced transformation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 1070 | Loss of autophosphorylation. No effect on phosphatidylinositol-4,5-bisphosphate 3-kinase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1070 | Loss of autophosphorylation. Decreased basal and stimulated phosphatidylinositol-4,5-bisphosphate 3-kinase activity. | ||||
Sequence: S → D or E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,750 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000088787 | 1-1070 | UniProt | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform | |||
Sequence: MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGEKLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEHEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAIEAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS | |||||||
Modified residue | 324 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 961 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 962 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 1070 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S |
Post-translational modification
Autophosphorylation at Ser-1070 negatively regulates the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed ubiquitously.
Gene expression databases
Organism-specific databases
Interaction
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).
Interacts with BECN1, ATG14 and RAB5A (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P42338 | APP P05067 | 3 | EBI-2609540, EBI-77613 | |
BINARY | P42338 | PIK3R1 P27986 | 6 | EBI-2609540, EBI-79464 | |
BINARY | P42338 | PIK3R1 P27986-2 | 6 | EBI-2609540, EBI-9090282 | |
BINARY | P42338 | PIK3R2 O00459 | 7 | EBI-2609540, EBI-346930 | |
BINARY | P42338 | PIK3R3 Q92569 | 5 | EBI-2609540, EBI-79893 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 26-115 | PI3K-ABD | ||||
Sequence: SDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRS | ||||||
Domain | 194-285 | PI3K-RBD | ||||
Sequence: GGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVE | ||||||
Domain | 327-496 | C2 PI3K-type | ||||
Sequence: WENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTNPYTENATALHVKFP | ||||||
Motif | 410-418 | Nuclear localization signal | ||||
Sequence: KVKTKKSTK | ||||||
Domain | 524-701 | PIK helical | ||||
Sequence: ANVSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRG | ||||||
Domain | 772-1053 | PI3K/PI4K catalytic | ||||
Sequence: YVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESW | ||||||
Region | 778-784 | G-loop | ||||
Sequence: YMDSKMK | ||||||
Region | 916-924 | Catalytic loop | ||||
Sequence: GIGDRHSDN | ||||||
Region | 935-961 | Activation loop | ||||
Sequence: HIDFGHILGNFKSKFGIKRERVPFILT |
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.
Sequence similarities
Belongs to the PI3/PI4-kinase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,070
- Mass (Da)122,762
- Last updated1995-11-01 v1
- Checksum81135FE93452C00E
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S67334 EMBL· GenBank· DDBJ | AAB29081.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ297549 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297550 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297551 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297552 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297553 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297554 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297555 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297556 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297557 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297558 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297559 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ297560 EMBL· GenBank· DDBJ | CAC21449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW79053.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW79055.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC114432 EMBL· GenBank· DDBJ | AAI14433.1 EMBL· GenBank· DDBJ | mRNA |