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

Details

Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
Synonyms
  • 2.7.1.153
  • p110beta
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta
  • PI3-kinase subunit beta
  • PIK3C1
  • PtdIns-3-kinase subunit p110-beta
Gene Name
PIK3CB
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011722|Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLW
KQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGE
KLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEH
EPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDE
VSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAI
EAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHG
TELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTI
NPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQ
TNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKE
ILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPK
LPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFL
LERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLK
TLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMD
SKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG
CLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEE
FTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFIL
TYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD
IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS
Number of residues
1070
Molecular Weight
122761.225
Theoretical pI
7.09
GO Classification
Functions
1-phosphatidylinositol-3-kinase activity / 1-phosphatidylinositol-4-phosphate 3-kinase activity / ATP binding / phosphatidylinositol 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Processes
activation of MAPK activity / angiogenesis involved in wound healing / autophagy / blood coagulation / cell migration / cellular calcium ion homeostasis / chemotaxis / embryonic cleavage / endothelial cell proliferation / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / Fc-gamma receptor signaling pathway involved in phagocytosis / fibroblast growth factor receptor signaling pathway / G-protein coupled receptor signaling pathway / homophilic cell adhesion via plasma membrane adhesion molecules / innate immune response / insulin receptor signaling pathway / leukocyte migration / neurotrophin TRK receptor signaling pathway / phosphatidylinositol 3-kinase signaling / phosphatidylinositol biosynthetic process / phosphatidylinositol-mediated signaling / phospholipid metabolic process / platelet activation / platelet aggregation / positive regulation of autophagy / positive regulation of gene expression / regulation of cell-matrix adhesion / regulation of clathrin-mediated endocytosis / signal transduction / small molecule metabolic process / T cell receptor signaling pathway / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor receptor signaling pathway
Components
cytosol / intercellular bridge / nucleolus / nucleus / phosphatidylinositol 3-kinase complex / plasma membrane
General Function
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0004727|3213 bp
ATGTGCTTCAGTTTCATAATGCCTCCTGCTATGGCAGACATCCTTGACATCTGGGCGGTG
GATTCACAGATAGCATCTGATGGCTCCATACCTGTGGATTTCCTTTTGCCCACTGGGATT
TATATCCAGTTGGAGGTACCTCGGGAAGCTACCATTTCTTATATTAAGCAGATGTTATGG
AAGCAAGTTCACAATTACCCAATGTTCAACCTCCTTATGGATATTGACTCCTATATGTTT
GCATGTGTGAATCAGACTGCTGTATATGAGGAGCTTGAAGATGAAACACGAAGACTCTGT
GATGTCAGACCTTTTCTTCCAGTTCTCAAATTAGTGACAAGAAGTTGTGACCCAGGGGAA
AAATTAGACTCAAAAATTGGAGTCCTTATAGGAAAAGGTCTGCATGAATTTGATTCCTTG
AAGGATCCTGAAGTAAATGAATTTCGAAGAAAAATGCGCAAATTCAGCGAGGAAAAAATC
CTGTCACTTGTGGGATTGTCTTGGATGGACTGGCTAAAACAAACATATCCACCAGAGCAT
GAACCATCCATCCCTGAAAACTTAGAAGATAAACTTTATGGGGGAAAGCTCATCGTAGCT
GTTCATTTTGAAAACTGCCAGGACGTGTTTAGCTTTCAAGTGTCTCCTAATATGAATCCT
ATCAAAGTAAATGAATTGGCAATCCAAAAACGTTTGACTATTCATGGGAAGGAAGATGAA
GTTAGCCCCTATGATTATGTGTTGCAAGTCAGCGGGAGAGTAGAATATGTTTTTGGTGAT
CATCCACTAATTCAGTTCCAGTATATCCGGAACTGTGTGATGAACAGAGCCCTGCCCCAT
TTTATACTTGTGGAATGCTGCAAGATCAAGAAAATGTATGAACAAGAAATGATTGCCATA
GAGGCTGCCATAAATCGAAATTCATCTAATCTTCCTCTTCCATTACCACCAAAGAAAACA
CGAATTATTTCTCATGTTTGGGAAAATAACAACCCTTTCCAAATTGTCTTGGTTAAGGGA
AATAAACTTAACACAGAGGAAACTGTAAAAGTTCATGTCAGGGCTGGTCTTTTTCATGGT
ACTGAGCTCCTGTGTAAAACCATCGTAAGCTCAGAGGTATCAGGGAAAAATGATCATATT
TGGAATGAACCACTGGAATTTGATATTAATATTTGTGACTTACCAAGAATGGCTCGATTA
TGTTTTGCTGTTTATGCAGTTTTGGATAAAGTAAAAACGAAGAAATCAACGAAAACTATT
AATCCCTCTAAATATCAGACCATCAGGAAAGCTGGAAAAGTGCATTATCCTGTAGCGTGG
GTAAATACGATGGTTTTTGACTTTAAAGGACAATTGAGAACTGGAGACATAATATTACAC
AGCTGGTCTTCATTTCCTGATGAACTCGAAGAAATGTTGAATCCAATGGGAACTGTTCAA
ACAAATCCATATACTGAAAATGCAACAGCTTTGCATGTTAAATTTCCAGAGAATAAAAAA
CAACCTTATTATTACCCTCCCTTCGATAAGATTATTGAAAAGGCAGCTGAGATTGCAAGC
AGTGATAGTGCTAATGTGTCAAGTCGAGGTGGAAAAAAGTTTCTTCCTGTATTGAAAGAA
ATCTTGGACAGGGATCCCTTGTCTCAACTGTGTGAAAATGAAATGGATCTTATTTGGACT
TTGCGACAAGACTGCCGAGAGATTTTCCCACAATCACTGCCAAAATTACTGCTGTCAATC
AAGTGGAATAAACTTGAGGATGTTGCTCAGCTTCAGGCGCTGCTTCAGATTTGGCCTAAA
CTGCCCCCCCGGGAGGCCCTAGAGCTTCTGGATTTCAACTATCCAGACCAGTACGTTCGA
GAATATGCTGTAGGCTGCCTGCGACAGATGAGTGATGAAGAACTTTCTCAATATCTTTTA
CAACTGGTGCAAGTGTTAAAATATGAGCCTTTTCTTGATTGTGCCCTCTCTAGATTCCTA
TTAGAAAGAGCACTTGGTAATCGGAGGATAGGGCAGTTTCTATTTTGGCATCTTAGGTCA
GAAGTGCACATTCCTGCTGTCTCAGTACAATTTGGTGTCATCCTTGAAGCATACTGCCGG
GGAAGTGTGGGGCACATGAAAGTGCTTTCTAAGCAGGTTGAAGCACTCAATAAGTTAAAA
ACTTTAAATAGTTTAATCAAACTGAATGCCGTGAAGTTAAACAGAGCCAAAGGGAAGGAG
GCCATGCATACCTGTTTAAAACAGAGTGCTTACCGGGAAGCCCTCTCTGACCTGCAGTCA
CCCCTGAACCCATGTGTTATCCTCTCAGAACTCTATGTTGAAAAGTGCAAATACATGGAT
TCCAAAATGAAGCCTTTGTGGCTGGTATACAATAACAAGGTATTTGGTGAGGATTCAGTT
GGAGTGATTTTTAAAAATGGTGATGATTTACGACAGGATATGTTGACACTCCAAATGTTG
CGCTTGATGGATTTACTCTGGAAAGAAGCTGGTTTGGATCTTCGGATGTTGCCTTATGGC
TGTTTAGCAACAGGAGATCGCTCTGGCCTCATTGAAGTTGTGAGCACCTCTGAAACAATT
GCTGACATTCAGCTGAACAGTAGCAATGTGGCTGCTGCAGCAGCCTTCAACAAAGATGCC
CTTCTGAACTGGCTTAAAGAATACAACTCTGGGGATGACCTGGACCGAGCCATTGAGGAA
TTTACACTGTCCTGTGCTGGCTACTGTGTAGCTTCTTATGTCCTTGGGATTGGTGACAGA
CATAGTGACAACATCATGGTCAAAAAAACTGGCCAGCTCTTCCACATTGACTTTGGACAT
ATTCTTGGAAATTTCAAATCTAAGTTTGGCATTAAAAGGGAGCGAGTGCCTTTTATTCTT
ACCTATGATTTCATCCATGTCATTCAACAAGGAAAAACAGGAAATACAGAAAAGTTTGGC
CGGTTCCGCCAGTGTTGTGAGGATGCATATCTGATTTTACGACGGCATGGGAATCTCTTC
ATCACTCTCTTTGCGCTGATGTTGACTGCAGGGCTTCCTGAACTCACATCAGTCAAAGAT
ATACAGTATCTTAAGGACTCTCTTGCATTAGGGAAGAGTGAAGAAGAAGCACTCAAACAG
TTTAAGCAAAAATTTGATGAGGCGCTCAGGGAAAGCTGGACTACTAAAGTGAACTGGATG
GCCCACACAGTTCGGAAAGACTACAGATCTTAA
Chromosome Location
Not Available
Locus
3q22.3
External Identifiers
ResourceLink
UniProtKB IDP42338
UniProtKB Entry NamePK3CB_HUMAN
GenBank Gene IDS67334
GenAtlas IDPIK3CB
HGNC IDHGNC:8976
General References
  1. Hu P, Mondino A, Skolnik EY, Schlessinger J: Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. Mol Cell Biol. 1993 Dec;13(12):7677-88. [PubMed:8246984]
  2. Kossila M, Sinkovic M, Karkkainen P, Laukkanen MO, Miettinen R, Rissanen J, Kekalainen P, Kuusisto J, Yla-Herttuala S, Laakso M: Gene encoding the catalytic subunit p110beta of human phosphatidylinositol 3-kinase: cloning, genomic structure, and screening for variants in patients with type 2 diabetes. Diabetes. 2000 Oct;49(10):1740-3. [PubMed:11016459]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Czupalla C, Culo M, Muller EC, Brock C, Reusch HP, Spicher K, Krause E, Nurnberg B: Identification and characterization of the autophosphorylation sites of phosphoinositide 3-kinase isoforms beta and gamma. J Biol Chem. 2003 Mar 28;278(13):11536-45. Epub 2002 Dec 26. [PubMed:12502714]
  5. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, Zhao JJ: Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature. 2008 Aug 7;454(7205):776-9. doi: 10.1038/nature07091. Epub 2008 Jun 25. [PubMed:18594509]
  6. Wee S, Wiederschain D, Maira SM, Loo A, Miller C, deBeaumont R, Stegmeier F, Yao YM, Lengauer C: PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13057-62. doi: 10.1073/pnas.0802655105. Epub 2008 Aug 28. [PubMed:18755892]
  7. Rabinovsky R, Pochanard P, McNear C, Brachmann SM, Duke-Cohan JS, Garraway LA, Sellers WR: p85 Associates with unphosphorylated PTEN and the PTEN-associated complex. Mol Cell Biol. 2009 Oct;29(19):5377-88. doi: 10.1128/MCB.01649-08. Epub 2009 Jul 27. [PubMed:19635806]
  8. Dbouk HA, Pang H, Fiser A, Backer JM: A biochemical mechanism for the oncogenic potential of the p110beta catalytic subunit of phosphoinositide 3-kinase. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19897-902. doi: 10.1073/pnas.1008739107. Epub 2010 Oct 28. [PubMed:21030680]
  9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  10. Kumar A, Redondo-Munoz J, Perez-Garcia V, Cortes I, Chagoyen M, Carrera AC: Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival. Mol Cell Biol. 2011 May;31(10):2122-33. doi: 10.1128/MCB.01313-10. Epub 2011 Mar 7. [PubMed:21383062]
  11. Dbouk HA, Backer JM: A beta version of life: p110beta takes center stage. Oncotarget. 2010 Dec;1(8):729-33. [PubMed:21321382]
  12. Gratacap MP, Guillermet-Guibert J, Martin V, Chicanne G, Tronchere H, Gaits-Iacovoni F, Payrastre B: Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions. Adv Enzyme Regul. 2011;51(1):106-16. doi: 10.1016/j.advenzreg.2010.09.011. Epub 2010 Oct 28. [PubMed:21035500]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05241XL765investigationalunknownDetails
DB00201CaffeineapprovedunknowninhibitorDetails