Gene/Proteome Database (LMPD)

LMPD ID
LMP001333
Gene ID
Species
Homo sapiens (Human)
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Gene Symbol
Synonyms
P110BETA; PI3K; PI3KBETA; PIK3C1
Chromosome
3
Map Location
3q22.3
EC Number
2.7.1.153
Summary
This gene encodes an isoform of the catalytic subunit of phosphoinositide 3-kinase (PI3K). These kinases are important in signaling pathways involving receptors on the outer membrane of eukaryotic cells and are named for their catalytic subunit. The encoded protein is the catalytic subunit for PI3Kbeta (PI3KB). PI3KB has been shown to be part of the activation pathway in neutrophils which have bound immune complexes at sites of injury or infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
Orthologs

Proteins

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1
Refseq ID NP_006210
Protein GI 5453894
UniProt ID P42338
mRNA ID NM_006219
Length 1070
RefSeq Status VALIDATED
MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGEKLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEHEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAIEAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS
phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 2
Refseq ID NP_001242974
Protein GI 365777411
UniProt ID B4DER4
mRNA ID NM_001256045
Length 582
RefSeq Status VALIDATED
MLNPMGTVQTNPYTENATALHVKFPENKKQPYYYPPFDKSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS

Gene Information

Entrez Gene ID
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Gene Symbol
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005829 TAS:Reactome C cytosol
GO:0005634 IEA:UniProtKB-KW C nucleus
GO:0005942 IBA:RefGenome C phosphatidylinositol 3-kinase complex
GO:0005886 IBA:RefGenome C plasma membrane
GO:0016303 IBA:RefGenome F 1-phosphatidylinositol-3-kinase activity
GO:0035005 IBA:RefGenome F 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0035004 TAS:UniProtKB F phosphatidylinositol 3-kinase activity
GO:0046934 IBA:RefGenome F phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0038095 TAS:Reactome P Fc-epsilon receptor signaling pathway
GO:0038096 TAS:Reactome P Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0007186 TAS:UniProtKB P G-protein coupled receptor signaling pathway
GO:0050852 TAS:Reactome P T cell receptor signaling pathway
GO:0000187 TAS:ProtInc P activation of MAPK activity
GO:0006914 IEA:UniProtKB-KW P autophagy
GO:0007596 TAS:Reactome P blood coagulation
GO:0016477 TAS:UniProtKB P cell migration
GO:0006874 IEA:Ensembl P cellular calcium ion homeostasis
GO:0006935 TAS:ProtInc P chemotaxis
GO:0040016 IEA:Ensembl P embryonic cleavage
GO:0007173 TAS:Reactome P epidermal growth factor receptor signaling pathway
GO:0008543 TAS:Reactome P fibroblast growth factor receptor signaling pathway
GO:0007156 IEA:Ensembl P homophilic cell adhesion via plasma membrane adhesion molecules
GO:0045087 TAS:Reactome P innate immune response
GO:0008286 TAS:Reactome P insulin receptor signaling pathway
GO:0050900 TAS:Reactome P leukocyte migration
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0014065 TAS:UniProtKB P phosphatidylinositol 3-kinase signaling
GO:0006661 TAS:Reactome P phosphatidylinositol biosynthetic process
GO:0048015 TAS:Reactome P phosphatidylinositol-mediated signaling
GO:0006644 TAS:Reactome P phospholipid metabolic process
GO:0030168 TAS:UniProtKB P platelet activation
GO:0070527 TAS:UniProtKB P platelet aggregation
GO:0010508 TAS:UniProtKB P positive regulation of autophagy
GO:0001952 IEA:Ensembl P regulation of cell-matrix adhesion
GO:2000369 TAS:UniProtKB P regulation of clathrin-mediated endocytosis
GO:0007165 NAS:ProtInc P signal transduction
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0007169 TAS:UniProtKB P transmembrane receptor protein tyrosine kinase signaling pathway

KEGG Pathway Links

KEGG Pathway ID Description
hsa04152 AMPK signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04024 cAMP signaling pathway
hsa04022 cGMP-PKG signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR016024 Armadillo-type fold
IPR000008 C2 domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR018936 Phosphatidylinositol 3/4-kinase, conserved site
IPR015433 Phosphatidylinositol Kinase
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR011009 Protein kinase-like domain
IPR029071 Ubiquitin-related domain

UniProt Annotations

Entry Information

Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Protein Entry
PK3CB_HUMAN
UniProt ID
Species
Human

Comments

Comment Type Description
Catalytic Activity ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
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.
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. {ECO
Interaction P08631:HCK; NbExp=2; IntAct=EBI-2609540, EBI-346340; O00459:PIK3R2; NbExp=3; IntAct=EBI-2609540, EBI-346930;
Pathway Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
Ptm Phosphorylation at Ser-1070 down-regulates lipid kinase activity.
Similarity Belongs to the PI3/PI4-kinase family. {ECO
Similarity Contains 1 C2 PI3K-type domain. {ECO
Similarity Contains 1 PI3K-ABD domain. {ECO
Similarity Contains 1 PI3K-RBD domain. {ECO
Similarity Contains 1 PI3K/PI4K domain. {ECO
Similarity Contains 1 PIK helical domain. {ECO
Subcellular Location Cytoplasm . Nucleus . Note=Interaction with PIK3R2 is required for nuclear localization and export.
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).
Tissue Specificity Expressed ubiquitously.

Identical and Related Proteins

Unique RefSeq proteins for LMP001333 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
5453894 RefSeq NP_006210 1070 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1
365777411 RefSeq NP_001242974 582 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 2

Identical Sequences to LMP001333 proteins

Reference Database Accession Length Protein Name
GI:5453894 GenBank AHD73883.1 1070 Sequence 12341 from patent US 8586006
GI:5453894 GenBank AHL55942.1 1070 Sequence 6 from patent US 8642604
GI:5453894 GenBank AIC49395.1 1070 PIK3CB, partial [synthetic construct]
GI:5453894 RefSeq XP_005247587.1 1070 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [Homo sapiens]
GI:5453894 RefSeq XP_005247588.1 1070 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [Homo sapiens]
GI:5453894 RefSeq XP_006713722.1 1070 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X4 [Homo sapiens]

Related Sequences to LMP001333 proteins

Reference Database Accession Length Protein Name
GI:365777411 DBBJ BAG57175.1 582 unnamed protein product [Homo sapiens]
GI:365777411 DBBJ BAG64095.1 657 unnamed protein product [Homo sapiens]
GI:5453894 GenBank AAQ02515.1 1071 phosphoinositide-3-kinase, catalytic, beta polypeptide, partial [synthetic construct]
GI:5453894 GenBank AFL58920.1 1070 Sequence 4 from patent US 8105796
GI:5453894 GenBank AFQ71137.1 1194 Sequence 12 from patent US 8227462
GI:5453894 GenBank AFX12677.1 1194 Sequence 12 from patent US 8293753
GI:5453894 GenBank AGD78810.1 1194 Sequence 12 from patent US 8357707
GI:5453894 GenBank AGU04801.1 1194 Sequence 12 from patent US 8476268
GI:365777411 RefSeq XP_005247589.1 1053 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X3 [Homo sapiens]
GI:365777411 RefSeq XP_008007132.1 1053 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [Chlorocebus sabaeus]
GI:365777411 RefSeq XP_008982004.1 1053 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [Callithrix jacchus]
GI:365777411 RefSeq XP_008950193.1 1053 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [Pan paniscus]