P85A_MOUSE
ID P85A_MOUSE Reviewed; 724 AA.
AC P26450; Q8K3B3;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit alpha;
DE Short=PI3-kinase regulatory subunit alpha;
DE Short=PI3K regulatory subunit alpha;
DE Short=PtdIns-3-kinase regulatory subunit alpha;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha;
DE Short=PI3-kinase subunit p85-alpha;
DE Short=PtdIns-3-kinase regulatory subunit p85-alpha;
GN Name=Pik3r1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=BALB/cJ;
RX PubMed=1849460; DOI=10.1016/0092-8674(91)90409-r;
RA Escobedo J.A., Navankasattusas S., Kavanaugh W.M., Milfay D., Fried V.A.,
RA Williams L.T.;
RT "cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates
RT binding of PI3-kinase to the PDGF beta-receptor.";
RL Cell 65:75-82(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH PDGFRA, AND ACTIVATION BY PDGFRA.
RX PubMed=1646396; DOI=10.1128/mcb.11.7.3780-3785.1991;
RA Yu J.C., Heidaran M.A., Pierce J.H., Gutkind J.S., Lombardi D.,
RA Ruggiero M., Aaronson S.A.;
RT "Tyrosine mutations within the alpha platelet-derived growth factor
RT receptor kinase insert domain abrogate receptor-associated
RT phosphatidylinositol-3 kinase activity without affecting mitogenic or
RT chemotactic signal transduction.";
RL Mol. Cell. Biol. 11:3780-3785(1991).
RN [5]
RP INTERACTION WITH LYN.
RX PubMed=8128248; DOI=10.1126/science.8128248;
RA Pleiman C.M., Hertz W.M., Cambier J.C.;
RT "Activation of phosphatidylinositol-3' kinase by Src-family kinase SH3
RT binding to the p85 subunit.";
RL Science 263:1609-1612(1994).
RN [6]
RP INTERACTION WITH PDGFRA.
RX PubMed=8943348; DOI=10.1128/mcb.16.12.6926;
RA Bazenet C.E., Gelderloos J.A., Kazlauskas A.;
RT "Phosphorylation of tyrosine 720 in the platelet-derived growth factor
RT alpha receptor is required for binding of Grb2 and SHP-2 but not for
RT activation of Ras or cell proliferation.";
RL Mol. Cell. Biol. 16:6926-6936(1996).
RN [7]
RP PHOSPHORYLATION, AND INTERACTION WITH CSF1R.
RX PubMed=9312046; DOI=10.1093/emboj/16.19.5880;
RA Bourette R.P., Myles G.M., Choi J.L., Rohrschneider L.R.;
RT "Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-
RT gamma2 by the M-CSF receptor is necessary for differentiation signaling.";
RL EMBO J. 16:5880-5893(1997).
RN [8]
RP INTERACTION WITH TEK/TIE2, AND PHOSPHORYLATION.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [9]
RP INTERACTION WITH HCST.
RX PubMed=10528161;
RA Chang C., Dietrich J., Harpur A.G., Lindquist J.A., Haude A., Loke Y.W.,
RA King A., Colonna M., Trowsdale J., Wilson M.J.;
RT "KAP10, a novel transmembrane adapter protein genetically linked to DAP12
RT but with unique signaling properties.";
RL J. Immunol. 163:4651-4654(1999).
RN [10]
RP INTERACTION WITH ERBB4, PHOSPHORYLATION, AND CATALYTIC ACTIVITY.
RX PubMed=10353604; DOI=10.1038/sj.onc.1202612;
RA Elenius K., Choi C.J., Paul S., Santiestevan E., Nishi E., Klagsbrun M.;
RT "Characterization of a naturally occurring ErbB4 isoform that does not bind
RT or activate phosphatidyl inositol 3-kinase.";
RL Oncogene 18:2607-2615(1999).
RN [11]
RP INTERACTION WITH FER.
RX PubMed=11006284; DOI=10.1074/jbc.m006665200;
RA Iwanishi M., Czech M.P., Cherniack A.D.;
RT "The protein-tyrosine kinase fer associates with signaling complexes
RT containing insulin receptor substrate-1 and phosphatidylinositol 3-
RT kinase.";
RL J. Biol. Chem. 275:38995-39000(2000).
RN [12]
RP INTERACTION WITH CBLB.
RX PubMed=10646608; DOI=10.1038/35003228;
RA Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T.,
RA Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A.,
RA Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M.;
RT "Negative regulation of lymphocyte activation and autoimmunity by the
RT molecular adaptor Cbl-b.";
RL Nature 403:211-216(2000).
RN [13]
RP FUNCTION, ACTIVATION BY FGFR3, INTERACTION WITH FGFR3, AND PHOSPHORYLATION.
RX PubMed=11294897; DOI=10.1091/mbc.12.4.931;
RA Hart K.C., Robertson S.C., Donoghue D.J.;
RT "Identification of tyrosine residues in constitutively activated fibroblast
RT growth factor receptor 3 involved in mitogenesis, Stat activation, and
RT phosphatidylinositol 3-kinase activation.";
RL Mol. Biol. Cell 12:931-942(2001).
RN [14]
RP INTERACTION WITH IRS4.
RX PubMed=11113178; DOI=10.1128/mcb.21.1.26-38.2001;
RA Tsuruzoe K., Emkey R., Kriauciunas K.M., Ueki K., Kahn C.R.;
RT "Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-
RT mediated signaling.";
RL Mol. Cell. Biol. 21:26-38(2001).
RN [15]
RP INTERACTION WITH CD3Z AND CD28, AND UBIQUITINATION.
RX PubMed=11526404; DOI=10.1038/ni0901-870;
RA Fang D., Liu Y.-C.;
RT "Proteolysis-independent regulation of PI3K by Cbl-b-mediated
RT ubiquitination in T cells.";
RL Nat. Immunol. 2:870-875(2001).
RN [16]
RP INTERACTION WITH TOM1L1.
RX PubMed=11711534; DOI=10.1074/jbc.m106813200;
RA Seykora J.T., Mei L., Dotto G.P., Stein P.L.;
RT "'Srcasm: a novel Src activating and signaling molecule.";
RL J. Biol. Chem. 277:2812-2822(2002).
RN [17]
RP INTERACTION WITH SOCS7.
RX PubMed=12052866; DOI=10.1128/mcb.22.13.4567-4578.2002;
RA Krebs D.L., Uren R.T., Metcalf D., Rakar S., Zhang J.-G., Starr R.,
RA De Souza D.P., Hanzinikolas K., Eyles J., Connolly L.M., Simpson R.J.,
RA Nicola N.A., Nicholson S.E., Baca M., Hilton D.J., Alexander W.S.;
RT "SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6
RT gene exhibit mild growth retardation.";
RL Mol. Cell. Biol. 22:4567-4578(2002).
RN [18]
RP INTERACTION WITH LIME1.
RX PubMed=14610044; DOI=10.1084/jem.20030232;
RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT "LIME, a novel transmembrane adaptor protein, associates with p56lck and
RT mediates T cell activation.";
RL J. Exp. Med. 198:1463-1473(2003).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [20]
RP INTERACTION WITH LIME1.
RX PubMed=16249387; DOI=10.1182/blood-2005-05-1859;
RA Ahn E., Lee H., Yun Y.;
RT "LIME acts as a transmembrane adapter mediating BCR-dependent B-cell
RT activation.";
RL Blood 107:1521-1527(2006).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-580, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [24]
RP FUNCTION, AND INTERACTION WITH PIK3R2 AND XBP1.
RX PubMed=20348926; DOI=10.1038/nm.2099;
RA Park S.W., Zhou Y., Lee J., Lu A., Sun C., Chung J., Ueki K., Ozcan U.;
RT "The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1
RT and increase its nuclear translocation.";
RL Nat. Med. 16:429-437(2010).
RN [25]
RP INTERACTION WITH APPL2 AND APPL1.
RX PubMed=25328665; DOI=10.1186/2045-3701-4-60;
RA Mao L., Lin W., Nie T., Hui X., Gao X., Li K., Ding M., Tang X., Li P.,
RA Wang Y., Xu A., Liu P., Wu D.;
RT "Absence of Appl2 sensitizes endotoxin shock through activation of PI3K/Akt
RT pathway.";
RL Cell Biosci. 4:60-60(2014).
CC -!- FUNCTION: Binds to activated (phosphorylated) protein-Tyr kinases,
CC through its SH2 domain, and acts as an adapter, mediating the
CC association of the p110 catalytic unit to the plasma membrane.
CC Necessary for the insulin-stimulated increase in glucose uptake and
CC glycogen synthesis in insulin-sensitive tissues. Plays an important
CC role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF,
CC KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By
CC similarity). Modulates the cellular response to ER stress by promoting
CC nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-
CC dependent manner during metabolic overloading in the liver and hence
CC plays a role in glucose tolerance improvement (PubMed:20348926).
CC {ECO:0000250, ECO:0000269|PubMed:20348926}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R1 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2
CC domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the
CC interaction enables recruitment of PIK3R1 to the EGFR receptor,
CC enhancing PI3K activity and cell migration (By similarity). Interacts
CC with XBP1 isoform 2; the interaction is direct and induces
CC translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or
CC insulin-dependent but PI3K-independent manner (PubMed:20348926).
CC Interacts with PIK3R2; the interaction is dissociated in an insulin-
CC dependent manner (PubMed:20348926). Interacts with phosphorylated LAT,
CC LAX1 and TRAT1 upon TCR activation. The SH2 domains interact with the
CC YTHM motif of phosphorylated INSR in vitro. Also interacts with
CC tyrosine-phosphorylated IGF1R in vitro. Interacts with IRS1 and
CC phosphorylated IRS4. Interacts with NISCH and RUFY3 (By similarity).
CC Interacts with phosphorylated TOM1L1. Interacts with phosphorylated
CC LIME1 upon TCR or BCR activation. Interacts with CBLB. Interacts with
CC CD28 and CD3Z upon T-cell activation. Interacts with SOCS7 and HCST.
CC Interacts with AXL, FASLG, FGR, HCK, KIT and BCR. Interacts with
CC PTK2/FAK1 (By similarity). Interacts with PDGFRB (tyrosine
CC phosphorylated) (By similarity). Interacts with NTRK1 (phosphorylated
CC upon ligand-binding) (By similarity). Interacts (via SH2 domain) with
CC CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with FER.
CC Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated)
CC (Probable). Interacts with PDGFRA (tyrosine phosphorylated). Interacts
CC with LYN (via SH3 domain); this enhances enzyme activity. Interacts
CC with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine
CC phosphorylated). Interacts with FAM83B; activates the PI3K/AKT
CC signaling cascade (By similarity). Interacts with APPL1 and APPL2
CC (PubMed:25328665). Interacts with SRC (By similarity). Interacts with
CC ALOX5; this interaction bridges ALOX5 with CD40 after CD40 ligation in
CC B cells and leads to the production of reactive oxygen species (ROS)
CC (By similarity). Interacts with TYK2 (By similarity).
CC {ECO:0000250|UniProtKB:P23727, ECO:0000250|UniProtKB:P27986,
CC ECO:0000250|UniProtKB:Q63787, ECO:0000269|PubMed:10353604,
CC ECO:0000269|PubMed:10521483, ECO:0000269|PubMed:10528161,
CC ECO:0000269|PubMed:10646608, ECO:0000269|PubMed:11006284,
CC ECO:0000269|PubMed:11113178, ECO:0000269|PubMed:11294897,
CC ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:11711534,
CC ECO:0000269|PubMed:12052866, ECO:0000269|PubMed:14610044,
CC ECO:0000269|PubMed:16249387, ECO:0000269|PubMed:1646396,
CC ECO:0000269|PubMed:20348926, ECO:0000269|PubMed:25328665,
CC ECO:0000269|PubMed:8128248, ECO:0000269|PubMed:8943348,
CC ECO:0000269|PubMed:9312046, ECO:0000305}.
CC -!- INTERACTION:
CC P26450; O88665: Brd7; NbExp=11; IntAct=EBI-641764, EBI-643930;
CC P26450; Q62448: Eif4g2; NbExp=3; IntAct=EBI-641764, EBI-296494;
CC P26450; Q9WVS0: Icos; NbExp=2; IntAct=EBI-641764, EBI-16721736;
CC P26450; P35569: Irs1; NbExp=3; IntAct=EBI-641764, EBI-400825;
CC P26450; P42337: Pik3ca; NbExp=7; IntAct=EBI-641764, EBI-641748;
CC P26450; Q8BTI9: Pik3cb; NbExp=5; IntAct=EBI-641764, EBI-644672;
CC P26450; O35904-2: Pik3cd; NbExp=2; IntAct=EBI-641764, EBI-6470774;
CC P26450; Q8R5H6: Wasf1; NbExp=2; IntAct=EBI-641764, EBI-774719;
CC P26450; Q8IZP0: ABI1; Xeno; NbExp=3; IntAct=EBI-641764, EBI-375446;
CC -!- DOMAIN: The SH3 domain mediates the binding to CBLB. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated in T-cells by CBLB; which does not promote
CC proteasomal degradation but impairs association with CD28 and CD3Z upon
CC T-cell activation. {ECO:0000269|PubMed:11526404}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylated in response to signaling
CC by FGFR1, FGFR2, FGFR3 and FGFR4. Dephosphorylated by PTPRJ.
CC Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by
CC insulin and PDGF. The relevance of phosphorylation by PIK3CA is however
CC unclear. Phosphorylated in response to KIT and KITLG/SCF.
CC Phosphorylated by FGR (By similarity). Phosphorylated by CSF1R.
CC Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by
CC TEK/TIE2. {ECO:0000250, ECO:0000269|PubMed:10353604,
CC ECO:0000269|PubMed:10521483, ECO:0000269|PubMed:11294897,
CC ECO:0000269|PubMed:9312046}.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
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DR EMBL; M60651; AAA39886.1; -; mRNA.
DR EMBL; CH466567; EDL00772.1; -; Genomic_DNA.
DR EMBL; BC026146; AAH26146.1; -; mRNA.
DR CCDS; CCDS36769.1; -.
DR RefSeq; NP_001070963.1; NM_001077495.2.
DR AlphaFoldDB; P26450; -.
DR BMRB; P26450; -.
DR SMR; P26450; -.
DR BioGRID; 202162; 64.
DR CORUM; P26450; -.
DR DIP; DIP-39593N; -.
DR IntAct; P26450; 46.
DR MINT; P26450; -.
DR STRING; 10090.ENSMUSP00000056774; -.
DR ChEMBL; CHEMBL4106132; -.
DR ChEMBL; CHEMBL4106142; -.
DR ChEMBL; CHEMBL4106168; -.
DR iPTMnet; P26450; -.
DR PhosphoSitePlus; P26450; -.
DR SwissPalm; P26450; -.
DR EPD; P26450; -.
DR MaxQB; P26450; -.
DR PaxDb; P26450; -.
DR PeptideAtlas; P26450; -.
DR PRIDE; P26450; -.
DR ProteomicsDB; 287757; -.
DR Antibodypedia; 717; 1140 antibodies from 46 providers.
DR DNASU; 18708; -.
DR Ensembl; ENSMUST00000055518; ENSMUSP00000056774; ENSMUSG00000041417.
DR GeneID; 18708; -.
DR KEGG; mmu:18708; -.
DR UCSC; uc007rrt.3; mouse.
DR CTD; 5295; -.
DR MGI; MGI:97583; Pik3r1.
DR VEuPathDB; HostDB:ENSMUSG00000041417; -.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000155553; -.
DR HOGENOM; CLU_007031_1_0_1; -.
DR InParanoid; P26450; -.
DR OMA; VIPVQWY; -.
DR OrthoDB; 737926at2759; -.
DR PhylomeDB; P26450; -.
DR TreeFam; TF102033; -.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-112399; IRS-mediated signalling.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1266695; Interleukin-7 signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-180292; GAB1 signalosome.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-MMU-198203; PI3K/AKT activation.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-430116; GP1b-IX-V activation signalling.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-9035034; RHOF GTPase cycle.
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 18708; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Pik3r1; mouse.
DR PRO; PR:P26450; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P26450; protein.
DR Bgee; ENSMUSG00000041417; Expressed in lacrimal gland and 262 other tissues.
DR ExpressionAtlas; P26450; baseline and differential.
DR Genevisible; P26450; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005801; C:cis-Golgi network; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990578; C:perinuclear endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; ISO:MGI.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISO:MGI.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISS:UniProtKB.
DR GO; GO:0043559; F:insulin binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; ISS:UniProtKB.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:UniProtKB.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISS:UniProtKB.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0001678; P:cellular glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IMP:MGI.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:MGI.
DR GO; GO:0006006; P:glucose metabolic process; ISO:MGI.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0097529; P:myeloid leukocyte migration; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:MGI.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISO:MGI.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IGI:MGI.
DR GO; GO:0010459; P:negative regulation of heart rate; ISO:MGI.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IGI:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:BHF-UCL.
DR GO; GO:0030316; P:osteoclast differentiation; IGI:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:BHF-UCL.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IDA:BHF-UCL.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IGI:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IGI:MGI.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; ISO:MGI.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IDA:MGI.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IMP:MGI.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0032868; P:response to insulin; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR CDD; cd12924; iSH2_PIK3R1; 1.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11910; SH3_PI3K_p85alpha; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR044124; ISH2_PIK3R1.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035591; PI3K_p85alpha_SH3.
DR InterPro; IPR035020; PI3kinase_P85_cSH2.
DR InterPro; IPR035022; PI3kinase_P85_nSH2.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF16454; PI3K_P85_iSH2; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00017; SH2; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Stress response;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT CHAIN 2..724
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT alpha"
FT /id="PRO_0000080759"
FT DOMAIN 3..79
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 113..301
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 333..428
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 624..718
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 80..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..98
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 467
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23727"
FT CONFLICT 46
FT /note="Q -> P (in Ref. 1; AAA39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="E -> G (in Ref. 1; AAA39886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 724 AA; 83517 MW; 9975D7AD8BABBA9C CRC64;
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EDIGWLNGYN
ETTGERGDFP GTYVEYIGRK RISPPTPKPR PPRPLPVAPG SSKTEADTEQ QALPLPDLAE
QFAPPDVAPP LLIKLLEAIE KKGLECSTLY RTQSSSNPAE LRQLLDCDAA SVDLEMIDVH
VLADAFKRYL ADLPNPVIPV AVYNEMMSLA QELQSPEDCI QLLKKLIRLP NIPHQCWLTL
QYLLKHFFKL SQASSKNLLN ARVLSEIFSP VLFRFPAASS DNTEHLIKAI EILISTEWNE
RQPAPALPPK PPKPTTVANN SMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA
STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS VVELINHYRN ESLAQYNPKL
DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK
RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID
SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS
VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA
QQRR
