Phosphatidylinositol 3-kinase regulatory subunit beta

NamePhosphatidylinositol 3-kinase regulatory subunit beta
Synonyms
  • Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta
  • PI3-kinase regulatory subunit beta
  • PI3-kinase subunit p85-beta
  • PtdIns-3-kinase regulatory subunit p85-beta
Gene NamePIK3R2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019276|Phosphatidylinositol 3-kinase regulatory subunit beta
MAGPEGFQYRALYPFRRERPEDLELLPGDVLVVSRAALQALGVAEGGERCPQSVGWMPGL
NERTRQRGDFPGTYVEFLGPVALARPGPRPRGPRPLPARPRDGAPEPGLTLPDLPEQFSP
PDVAPPLLVKLVEAIERTGLDSESHYRPELPAPRTDWSLSDVDQWDTAALADGIKSFLLA
LPAPLVTPEASAEARRALREAAGPVGPALEPPTLPLHRALTLRFLLQHLGRVASRAPALG
PAVRALGATFGPLLLRAPPPPSSPPPGGAPDGSEPSPDFPALLVEKLLQEHLEEQEVAPP
ALPPKPPKAKPASTVLANGGSPPSLQDAEWYWGDISREEVNEKLRDTPDGTFLVRDASSK
IQGEYTLTLRKGGNNKLIKVFHRDGHYGFSEPLTFCSVVDLINHYRHESLAQYNAKLDTR
LLYPVSKYQQDQIVKEDSVEAVGAQLKVYHQQYQDKSREYDQLYEEYTRTSQELQMKRTA
IEAFNETIKIFEEQGQTQEKCSKEYLERFRREGNEKEMQRILLNSERLKSRIAEIHESRT
KLEQQLRAQASDNREIDKRMNSLKPDLMQLRKIRDQYLVWLTQKGARQKKINEWLGIKNE
TEDQYALMEDEDDLPHHEERTWYVGKINRTQAEEMLSGKRDGTFLIRESSQRGCYACSVV
VDGDTKHCVIYRTATGFGFAEPYNLYGSLKELVLHYQHASLVQHNDALTVTLAHPVRAPG
PGPPPAAR
Number of residues728
Molecular Weight81544.505
Theoretical pI6.48
GO Classification
Functions
  • 1-phosphatidylinositol-3-kinase regulator activity
  • protein heterodimerization activity
  • receptor tyrosine kinase binding
  • protein phosphatase binding
Processes
  • phosphatidylinositol-3-phosphate biosynthetic process
  • neurotrophin TRK receptor signaling pathway
  • positive regulation of transcription from RNA polymerase II promoter
  • blood coagulation
  • regulation of phosphatidylinositol 3-kinase activity
  • vascular endothelial growth factor receptor signaling pathway
  • regulation of small GTPase mediated signal transduction
  • cellular response to insulin stimulus
  • protein transport
  • positive regulation of transcription factor import into nucleus
  • phosphatidylinositol-mediated signaling
  • small GTPase mediated signal transduction
  • phospholipid metabolic process
  • small molecule metabolic process
  • T cell receptor signaling pathway
  • response to endoplasmic reticulum stress
  • epidermal growth factor receptor signaling pathway
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • phosphatidylinositol 3-kinase signaling
  • innate immune response
  • cellular glucose homeostasis
  • regulation of autophagy
  • positive regulation of glucose import in response to insulin stimulus
  • Fc-epsilon receptor signaling pathway
  • phosphatidylinositol phosphorylation
  • leukocyte migration
  • phosphatidylinositol biosynthetic process
  • fibroblast growth factor receptor signaling pathway
  • insulin receptor signaling pathway
Components
  • nucleus
  • cytosol
  • phosphatidylinositol 3-kinase complex
General FunctionReceptor tyrosine kinase binding
Specific FunctionRegulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates 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. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (PubMed:23604317). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO00459
UniProtKB Entry NameP85B_HUMAN
Cellular LocationNot Available
Gene sequence
>lcl|BSEQ0019277|Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2)
ATGGCGGGCCCTGAGGGCTTCCAGTACCGCGCTCTGTACCCGTTCCGCCGGGAGCGGCCG
GAGGACCTGGAGCTGCTGCCCGGCGACGTGCTGGTAGTGAGCCGGGCGGCCTTGCAGGCG
CTGGGCGTGGCCGAGGGTGGCGAGCGCTGCCCACAGAGCGTGGGCTGGATGCCCGGCCTC
AACGAGCGCACACGGCAGCGAGGTGACTTCCCTGGCACCTATGTGGAGTTCCTGGGGCCC
GTGGCCCTGGCCCGGCCCGGCCCTCGCCCACGGGGCCCCCGCCCACTGCCCGCCAGGCCC
CGTGATGGGGCCCCTGAGCCAGGCCTCACACTCCCCGACTTGCCCGAGCAGTTCTCCCCA
CCTGATGTGGCTCCCCCTCTTCTGGTGAAGCTTGTGGAGGCCATTGAAAGGACAGGGCTG
GACAGCGAATCTCACTACCGCCCGGAGCTGCCCGCACCGCGTACAGACTGGTCCCTGAGC
GACGTGGATCAGTGGGACACGGCAGCCCTGGCTGACGGCATTAAGAGCTTCCTGCTGGCA
CTGCCCGCGCCGCTCGTGACCCCCGAGGCCTCGGCCGAGGCGCGCCGGGCCCTGCGGGAG
GCCGCGGGGCCCGTGGGGCCGGCGCTGGAGCCACCGACGCTGCCGCTGCACCGCGCGCTC
ACGCTGCGCTTCCTGCTCCAGCACCTGGGCCGCGTGGCCCGCCGCGCCCCGGCCCTGGGT
CCCGCGGTCCGGGCCCTGGGCGCCACCTTTGGGCCGCTGCTGCTGCGCGCGCCGCCGCCG
CCGTCCTCGCCGCCGCCAGGGGGCGCTCCCGACGGGAGTGAGCCCAGCCCTGACTTCCCG
GCGCTGCTGGTGGAGAAGCTGCTTCAGGAACACTTGGAAGAGCAGGAGGTTGCGCCCCCA
GCGCTGCCGCCTAAACCCCCCAAGGCAAAGCCGGCCCCCACAGTCCTGGCCAATGGAGGG
AGCCCACCCTCCCTGCAGGATGCTGAGTGGTACTGGGGGGACATTTCAAGGGAGGAGGTG
AACGAGAAACTCCGGGACACTCCCGATGGCACCTTCCTAGTCCGAGATGCTTCTAGCAAG
ATCCAGGGCGAGTACACGCTGACCCTCAGGAAAGGCGGGAACAATAAGCTGATCAAGGTC
TTCCACCGAGATGGGCACTATGGCTTCTCAGAGCCACTCACCTTCTGCTCCGTTGTGGAC
CTCATCAATCACTACCGCCACGAGTCTCTGGCCCAGTACAATGCCAAGCTGGACACACGG
CTCCTCTACCCTGTGTCCAAATACCAGCAGGACCAGATTGTCAAGGAGGACAGCGTGGAG
GCAGTGGGCGCCCAGCTTAAGGTCTATCACCAGCAGTACCAGGACAAGAGCCGCGAGTAT
GACCAGCTTTATGAAGAGTACACACGGACCTCCCAGGAGCTGCAGATGAAGCGTACTGCA
ATTGAGGCCTTCAATGAGACTATCAAGATCTTTGAAGAGCAGGGCCAGACTCAAGAGAAA
TGCAGCAAGGAATACCTGGAGCGCTTCCGGCGTGAGGGCAACGAGAAAGAGATGCAAAGG
ATCCTGCTGAACTCCGAGCGGCTCAAGTCCCGCATTGCCGAGATCCATGAGAGCCGCACG
AAGCTGGAGCAGCAGCTGCGGGCCCAGGCCTCGGACAACAGAGAGATCGACAAGCGCATG
AACAGCCTCAAGCCGGACCTCATGCAGCTGCGCAAGATCCGAGACCAGTACCTCGTGTGG
CTCACCCAGAAAGGCGCCCGGCAGAAGAAAATCAACGAGTGGCTGGGGATTAAAAATGAG
ACTGAGGACCAGTACGCACTCATGGAGGACGAGGACGATCTCCCGCACCACGAGGAACGC
ACTTGGTACGTGGGCAAGATCAACCGCACGCAGGCAGAGGAGATGCTGAGTGGCAAGCGG
GATGGCACCTTCCTCATCCGCGAGAGCAGCCAGCGGGGCTGCTACGCCTGCTCCGTGGTA
GTGGACGGCGACACCAAGCACTGCGTCATCTACCGCACGGCCACCGGCTTCGGCTTCGCG
GAGCCCTACAACCTGTACGGGTCGCTGAAGGAGCTGGTGCTGCACTACCAGCACGCCTCG
CTGGTGCAGCACAACGACGCGCTCACCGTCACCCTGGCGCACCCAGTGCGCGCCCCGGGC
CCCGGCCCGCCGCCTGCCGCCCGCTGA
GenBank Gene IDX80907
GeneCard IDNot Available
GenAtlas IDPIK3R2
HGNC IDHGNC:8980
Chromosome Location19
Locus19q13.2-q13.4
References
  1. Volinia S, Patracchini P, Otsu M, Hiles I, Gout I, Calzolari E, Bernardi F, Rooke L, Waterfield MD: Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta. Oncogene. 1992 Apr;7(4):789-93. 1314371
  2. Janssen JW, Schleithoff L, Bartram CR, Schulz AS: An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme. Oncogene. 1998 Apr 2;16(13):1767-72. 9582025
  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  4. 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. 15489334
  5. Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR, Janssen JW: Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene. 1997 Jun 5;14(22):2619-31. 9178760
  6. Igarashi K, Isohara T, Kato T, Shigeta K, Yamano T, Uno I: Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2. Biochem Biophys Res Commun. 1998 May 8;246(1):95-9. 9600074
  7. Wang JF, Zhang X, Groopman JE: Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress. J Biol Chem. 2004 Jun 25;279(26):27088-97. Epub 2004 Apr 21. 15102829
  8. Tsuboi N, Utsunomiya T, Roberts RL, Ito H, Takahashi K, Noda M, Takahashi T: The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. Biochem J. 2008 Jul 1;413(1):193-200. doi: 10.1042/BJ20071317. 18348712
  9. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  10. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  11. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  12. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  13. 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. 21269460
  14. Kuchay S, Duan S, Schenkein E, Peschiaroli A, Saraf A, Florens L, Washburn MP, Pagano M: FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade. Nat Cell Biol. 2013 May;15(5):472-80. doi: 10.1038/ncb2731. Epub 2013 Apr 21. 23604317
  15. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  16. Riviere JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL, Majewski J, Bulman DE, O'Driscoll M, Shendure J, Graham JM Jr, Boycott KM, Dobyns WB: De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012 Jun 24;44(8):934-40. doi: 10.1038/ng.2331. 22729224