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Identification
HMDB Protein ID HMDBP03978
Secondary Accession Numbers
  • 9566
Name Phosphatidylinositol 3-kinase regulatory subunit alpha
Synonyms
  1. PI3-kinase regulatory subunit alpha
  2. PI3-kinase subunit p85-alpha
  3. PI3K regulatory subunit alpha
  4. Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
  5. PtdIns-3-kinase regulatory subunit alpha
  6. PtdIns-3-kinase regulatory subunit p85-alpha
Gene Name PIK3R1
Protein Type Enzyme
Biological Properties
General Function Involved in phosphoinositide 3-kinase regulator activity
Specific Function Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues
Pathways
  • Bafetinib Inhibition of BCR-ABL
  • BCR-ABL Action in CML Pathogenesis
  • Bosutinib Inhibition of BCR-ABL
  • Dasatinib Inhibition of BCR-ABL
  • Fc Epsilon Receptor I Signaling in Mast Cells
  • Imatinib Inhibition of BCR-ABL
  • Joubert syndrome
  • Nilotinib Inhibition of BCR-ABL
  • Phosphatidylinositol Phosphate Metabolism
  • Ponatinib Inhibition of BCR-ABL
Reactions Not Available
GO Classification
Component
cell part
macromolecular complex
protein complex
intracellular
phosphoinositide 3-kinase complex
Function
binding
phosphoinositide 3-kinase regulator activity
enzyme regulator activity
protein binding
kinase regulator activity
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:5
Locus 5q13.1
SNPs PIK3R1
Gene Sequence
>2175 bp
ATGAGTGCTGAGGGGTACCAGTACAGAGCGCTGTATGATTATAAAAAGGAAAGAGAAGAA
GATATTGACTTGCACTTGGGTGACATATTGACTGTGAATAAAGGGTCCTTAGTAGCTCTT
GGATTCAGTGATGGACAGGAAGCCAGGCCTGAAGAAATTGGCTGGTTAAATGGCTATAAT
GAAACCACAGGGGAAAGGGGGGACTTTCCGGGAACTTACGTAGAATATATTGGAAGGAAA
AAAATCTCGCCTCCCACACCAAAGCCCCGGCCACCTCGGCCTCTTCCTGTTGCACCAGGT
TCTTCGAAAACTGAAGCAGATGTTGAACAACAAGCTTTGACTCTCCCGGATCTTGCAGAG
CAGTTTGCCCCTCCTGACATTGCCCCGCCTCTTCTTATCAAGCTCGTGGAAGCCATTGAA
AAGAAAGGTCTGGAATGTTCAACTCTATACAGAACACAGAGCTCCAGCAACCTGGCAGAA
TTACGACAGCTTCTTGATTGTGATACACCCTCCGTGGACTTGGAAATGATCGATGTGCAC
GTTTTGGCTGACGCTTTCAAACGCTATCTCCTGGACTTACCAAATCCTGTCATTCCAGCA
GCCGTTTACAGTGAAATGATTTCTTTAGCTCCAGAAGTACAAAGCTCCGAAGAATATATT
CAGCTATTGAAGAAGCTTATTAGGTCGCCTAGCATACCTCATCAGTATTGGCTTACGCTT
CAGTATTTGTTAAAACATTTCTTCAAGCTCTCTCAAACCTCCAGCAAAAATCTGTTGAAT
GCAAGAGTACTCTCTGAAATTTTCAGCCCTATGCTTTTCAGATTCTCAGCAGCCAGCTCT
GATAATACTGAAAACCTCATAAAAGTTATAGAAATTTTAATCTCAACTGAATGGAATGAA
CGACAGCCTGCACCAGCACTGCCTCCTAAACCACCAAAACCTACTACTGTAGCCAACAAC
GGTATGAATAACAATATGTCCTTACAAGATGCTGAATGGTACTGGGGAGATATCTCGAGG
GAAGAAGTGAATGAAAAACTTCGAGATACAGCAGACGGGACCTTTTTGGTACGAGATGCG
TCTACTAAAATGCATGGTGATTATACTCTTACACTAAGGAAAGGGGGAAATAACAAATTA
ATCAAAATATTTCATCGAGATGGGAAATATGGCTTCTCTGACCCATTAACCTTCAGTTCT
GTGGTTGAATTAATAAACCACTACCGGAATGAATCTCTAGCTCAGTATAATCCCAAATTG
GATGTGAAATTACTTTATCCAGTATCCAAATACCAACAGGATCAAGTTGTCAAAGAAGAT
AATATTGAAGCTGTAGGGAAAAAATTACATGAATATAACACTCAGTTTCAAGAAAAAAGT
CGAGAATATGATAGATTATATGAAGAATATACCCGCACATCCCAGGAAATCCAAATGAAA
AGGACAGCTATTGAAGCATTTAATGAAACCATAAAAATATTTGAAGAACAGTGCCAGACC
CAAGAGCGGTACAGCAAAGAATACATAGAAAAGTTTAAACGTGAAGGCAATGAGAAAGAA
ATACAAAGGATTATGCATAATTATGATAAGTTGAAGTCTCGAATCAGTGAAATTATTGAC
AGTAGAAGAAGATTGGAAGAAGACTTGAAGAAGCAGGCAGCTGAGTATCGAGAAATTGAC
AAACGTATGAACAGCATTAAACCAGACCTTATCCAGCTGAGAAAGACGAGAGACCAATAC
TTGATGTGGTTGACTCAAAAAGGTGTTCGGCAAAAGAAGTTGAACGAGTGGTTGGGCAAT
GAAAACACTGAAGACCAATATTCACTGGTGGAAGATGATGAAGATTTGCCCCATCATGAT
GAGAAGACATGGAATGTTGGAAGCAGCAACCGAAACAAAGCTGAAAACCTGTTGCGAGGG
AAGCGAGATGGCACTTTTCTTGTCCGGGAGAGCAGTAAACAGGGCTGCTATGCCTGCTCT
GTAGTGGTGGACGGCGAAGTAAAGCATTGTGTCATAAACAAAACAGCAACTGGCTATGGC
TTTGCCGAGCCCTATAACTTGTACAGCTCTCTGAAAGAACTGGTGCTACATTACCAACAC
ACCTCCCTTGTGCAGCACAACGACTCCCTCAATGTCACACTAGCCTACCCAGTATATGCA
CAGCAGAGGCGATGA
Protein Properties
Number of Residues 724
Molecular Weight 83597.7
Theoretical pI 6.06
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Phosphatidylinositol 3-kinase regulatory subunit alpha
MSAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYN
ETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGSSKTEADVEQQALTLPDLAE
QFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVH
VLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTL
QYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILISTEWNE
RQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDA
STKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKL
DVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMK
RTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIID
SRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGN
ENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACS
VVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYA
QQRR
GenBank ID Protein 32455248
UniProtKB/Swiss-Prot ID P27986
UniProtKB/Swiss-Prot Entry Name P85A_HUMAN
PDB IDs
GenBank Gene ID NM_181523.1
GeneCard ID PIK3R1
GenAtlas ID PIK3R1
HGNC ID HGNC:8979
References
General References
  1. 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 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. 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. [PubMed:19369195 ]
  4. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  5. Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM: Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Mol Cell Proteomics. 2005 Sep;4(9):1240-50. Epub 2005 Jun 11. [PubMed:15951569 ]
  6. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  7. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998 Jan 9;92(1):83-92. [PubMed:9489702 ]
  8. Wolf-Yadlin A, Hautaniemi S, Lauffenburger DA, White FM: Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5860-5. Epub 2007 Mar 26. [PubMed:17389395 ]
  9. Craparo A, O'Neill TJ, Gustafson TA: Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995 Jun 30;270(26):15639-43. [PubMed:7541045 ]
  10. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE: Insulin receptor substrate 4 associates with the protein IRAS. J Biol Chem. 2002 May 31;277(22):19439-47. Epub 2002 Mar 23. [PubMed:11912194 ]
  11. Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE: Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry. 1996 Dec 10;35(49):15646-53. [PubMed:8961927 ]
  12. Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN: NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1397-404. Epub 2001 Sep 21. [PubMed:11567151 ]
  13. Van Horn DJ, Myers MG Jr, Backer JM: Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor. J Biol Chem. 1994 Jan 7;269(1):29-32. [PubMed:8276809 ]
  14. Gustafson TA, He W, Craparo A, Schaub CD, O'Neill TJ: Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol. 1995 May;15(5):2500-8. [PubMed:7537849 ]
  15. Skolnik EY, Margolis B, Mohammadi M, Lowenstein E, Fischer R, Drepps A, Ullrich A, Schlessinger J: Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83-90. [PubMed:1849461 ]
  16. Antonetti DA, Algenstaedt P, Kahn CR: Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol. 1996 May;16(5):2195-203. [PubMed:8628286 ]
  17. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE: Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells. J Biol Chem. 1998 Apr 24;273(17):10726-32. [PubMed:9553137 ]
  18. Bruyns E, Marie-Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, Autschbach F, Bensussan A, Meuer S, Schraven B: T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane. J Exp Med. 1998 Aug 3;188(3):561-75. [PubMed:9687533 ]
  19. Chang C, Dietrich J, Harpur AG, Lindquist JA, Haude A, Loke YW, King A, Colonna M, Trowsdale J, Wilson MJ: Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. J Immunol. 1999 Nov 1;163(9):4651-4. [PubMed:10528161 ]
  20. Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S: cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. [PubMed:10086340 ]
  21. Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC: Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001 Feb 16;276(7):4872-8. Epub 2000 Nov 21. [PubMed:11087752 ]
  22. Fang D, Liu YC: Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001 Sep;2(9):870-5. [PubMed:11526404 ]
  23. Zhu M, Janssen E, Leung K, Zhang W: Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. J Biol Chem. 2002 Nov 29;277(48):46151-8. Epub 2002 Sep 30. [PubMed:12359715 ]
  24. Linnemann T, Zheng YH, Mandic R, Peterlin BM: Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV. Virology. 2002 Mar 15;294(2):246-55. [PubMed:12009866 ]
  25. He Y, Nakao H, Tan SL, Polyak SJ, Neddermann P, Vijaysri S, Jacobs BL, Katze MG: Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase. J Virol. 2002 Sep;76(18):9207-17. [PubMed:12186904 ]
  26. Liang J, Chen JK, Schreiber ST, Clardy J: Crystal structure of P13K SH3 domain at 20 angstroms resolution. J Mol Biol. 1996 Apr 5;257(3):632-43. [PubMed:8648629 ]
  27. Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC: Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat Struct Biol. 1996 Apr;3(4):364-74. [PubMed:8599763 ]
  28. Musacchio A, Cantley LC, Harrison SC: Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14373-8. [PubMed:8962058 ]
  29. Koyama S, Yu H, Dalgarno DC, Shin TB, Zydowsky LD, Schreiber SL: Structure of the PI3K SH3 domain and analysis of the SH3 family. Cell. 1993 Mar 26;72(6):945-52. [PubMed:7681364 ]
  30. Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA: Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase. EMBO J. 1996 Jul 15;15(14):3579-89. [PubMed:8670861 ]
  31. Hansen T, Andersen CB, Echwald SM, Urhammer SA, Clausen JO, Vestergaard H, Owens D, Hansen L, Pedersen O: Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. Diabetes. 1997 Mar;46(3):494-501. [PubMed:9032108 ]
  32. Baynes KC, Beeton CA, Panayotou G, Stein R, Soos M, Hansen T, Simpson H, O'Rahilly S, Shepherd PR, Whitehead JP: Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity. Diabetologia. 2000 Mar;43(3):321-31. [PubMed:10768093 ]