P85B_MOUSE
ID P85B_MOUSE Reviewed; 722 AA.
AC O08908; Q5U3K7;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit beta;
DE Short=PI3-kinase regulatory subunit beta;
DE Short=PI3K regulatory subunit beta;
DE Short=PtdIns-3-kinase regulatory subunit beta;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta;
DE Short=PI3-kinase subunit p85-beta;
DE Short=PtdIns-3-kinase regulatory subunit p85-beta;
GN Name=Pik3r2;
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].
RC STRAIN=NIH Swiss;
RX PubMed=9582025; DOI=10.1038/sj.onc.1201695;
RA Janssen J.W.G., Schleithhoff L., Bartram C.R., Schulz A.S.;
RT "An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta
RT subunit and HUMORF8, a putative deubiquitinating enzyme.";
RL Oncogene 16:1767-1772(1998).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary gland;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-458, AND IDENTIFICATION BY
RP 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-458, 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-458, 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, 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 [9]
RP FUNCTION, AND INTERACTION WITH PIK3R1 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 [10]
RP INTERACTION WITH NYAP1; NYAP2 AND MYO16.
RX PubMed=21946561; DOI=10.1038/emboj.2011.348;
RA Yokoyama K., Tezuka T., Kotani M., Nakazawa T., Hoshina N., Shimoda Y.,
RA Kakuta S., Sudo K., Watanabe K., Iwakura Y., Yamamoto T.;
RT "NYAP: a phosphoprotein family that links PI3K to WAVE1 signalling in
RT neurons.";
RL EMBO J. 30:4739-4754(2011).
CC -!- FUNCTION: Regulatory subunit of phosphoinositide-3-kinase (PI3K), a
CC kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-
CC bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate
CC (PIP3). PIP3 plays a key role by recruiting PH domain-containing
CC proteins to the membrane, including AKT1 and PDPK1, activating
CC signaling cascades involved in cell growth, survival, proliferation,
CC motility and morphology. Binds to activated (phosphorylated) protein-
CC tyrosine kinases, through its SH2 domain, and acts as an adapter,
CC mediating the association of the p110 catalytic unit to the plasma
CC membrane. Indirectly regulates autophagy (By similarity). Promotes
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|UniProtKB:O00459, ECO:0000269|PubMed:20348926}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R2 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL.
CC Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-
CC phosphorylated) (By similarity). Interacts with FBXL2; PIK3R2 is a
CC substrate of the SCF(FBXL2) complex. Interacts with PTPN13;
CC dephosphorylates PIK3R2 (By similarity). Interacts with NYAP1, NYAP2
CC and MYO16 (PubMed:21946561). Interacts with XBP1 isoform 2; the
CC interaction is direct and induces translocation of XBP1 isoform 2 into
CC the nucleus in a ER stress- and/or insulin-dependent but PI3K-
CC independent manner (PubMed:20348926). Interacts with PIK3R1; the
CC interaction is dissociated in an insulin-dependent manner
CC (PubMed:20348926). Interacts with SRC (By similarity).
CC {ECO:0000250|UniProtKB:O00459, ECO:0000269|PubMed:20348926,
CC ECO:0000269|PubMed:21946561}.
CC -!- INTERACTION:
CC O08908; O88665: Brd7; NbExp=4; IntAct=EBI-643570, EBI-643930;
CC O08908; Q9JK42: Pdk2; NbExp=3; IntAct=EBI-643570, EBI-643530;
CC -!- DOMAIN: The SH2 2 domain is required for interaction with FBXL2 and
CC PTPN13. {ECO:0000250|UniProtKB:O00459}.
CC -!- PTM: Phosphorylated in response to signaling from activated receptor-
CC type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at
CC Tyr-649 by PTPN13. Phosphorylation of Tyr-649 impairs while its
CC dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-
CC mediated polyubiquitination. {ECO:0000250|UniProtKB:O00459}.
CC -!- PTM: Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex
CC probably promotes proteasomal degradation of PIK3R2.
CC {ECO:0000250|UniProtKB:O00459}.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
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DR EMBL; Y13569; CAA73903.1; -; mRNA.
DR EMBL; CH466569; EDL28873.1; -; Genomic_DNA.
DR EMBL; BC006796; AAH06796.1; -; mRNA.
DR EMBL; BC085501; AAH85501.1; -; mRNA.
DR CCDS; CCDS22381.1; -.
DR RefSeq; NP_032867.2; NM_008841.3.
DR PDB; 2Y3A; X-ray; 3.30 A; B=423-722.
DR PDBsum; 2Y3A; -.
DR AlphaFoldDB; O08908; -.
DR SMR; O08908; -.
DR BioGRID; 202163; 34.
DR IntAct; O08908; 27.
DR STRING; 10090.ENSMUSP00000034296; -.
DR ChEMBL; CHEMBL4106167; -.
DR iPTMnet; O08908; -.
DR PhosphoSitePlus; O08908; -.
DR EPD; O08908; -.
DR MaxQB; O08908; -.
DR PaxDb; O08908; -.
DR PeptideAtlas; O08908; -.
DR PRIDE; O08908; -.
DR ProteomicsDB; 294423; -.
DR DNASU; 18709; -.
DR Ensembl; ENSMUST00000034296; ENSMUSP00000034296; ENSMUSG00000031834.
DR GeneID; 18709; -.
DR KEGG; mmu:18709; -.
DR UCSC; uc009mbn.2; mouse.
DR CTD; 5296; -.
DR MGI; MGI:1098772; Pik3r2.
DR VEuPathDB; HostDB:ENSMUSG00000031834; -.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000157050; -.
DR HOGENOM; CLU_007031_1_0_1; -.
DR InParanoid; O08908; -.
DR OMA; CIYPQLQ; -.
DR OrthoDB; 737926at2759; -.
DR PhylomeDB; O08908; -.
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-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-186763; Downstream signal transduction.
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-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
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-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-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-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
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-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 18709; 5 hits in 77 CRISPR screens.
DR ChiTaRS; Pik3r2; mouse.
DR PRO; PR:O08908; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O08908; protein.
DR Bgee; ENSMUSG00000031834; Expressed in embryonic brain and 62 other tissues.
DR ExpressionAtlas; O08908; baseline and differential.
DR Genevisible; O08908; MM.
DR GO; GO:0005925; C:focal adhesion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISO:MGI.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO: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:0008286; P:insulin receptor signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; IBA:GO_Central.
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:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11909; SH3_PI3K_p85beta; 1.
DR DisProt; DP02791; -.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035586; PI3K_p85beta_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 3D-structure; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; SH2 domain; SH3 domain; Stress response; Transport;
KW Ubl conjugation.
FT CHAIN 1..722
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT beta"
FT /id="PRO_0000080764"
FT DOMAIN 4..80
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 112..293
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 324..419
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 616..710
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 84..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 458
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:17947660, ECO:0007744|PubMed:18034455"
FT MOD_RES 599
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
FT MOD_RES 649
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
FT CONFLICT 433
FT /note="I -> V (in Ref. 1; CAA73903 and 3; AAH06796)"
FT /evidence="ECO:0000305"
FT HELIX 448..451
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 455..496
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 508..510
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 511..557
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 559..568
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 609..611
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 614..616
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 623..630
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 637..640
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 649..654
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 656..667
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 670..674
FT /evidence="ECO:0007829|PDB:2Y3A"
FT HELIX 683..688
FT /evidence="ECO:0007829|PDB:2Y3A"
FT STRAND 691..693
FT /evidence="ECO:0007829|PDB:2Y3A"
FT TURN 696..698
FT /evidence="ECO:0007829|PDB:2Y3A"
SQ SEQUENCE 722 AA; 81266 MW; A999FAF9011455FE CRC64;
MAGAEGFQYR AVYPFRRERP EDLELLPGDL LVVSRVALQA LGVADGGERC PHNVGWMPGF
NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP LDGSSESGHI LPDLAEQFSP
PDPAPPILVK LVEAIEQAEL DSECYSKPEL PATRTDWSLS DLEQWDRTAL YDAVKGFLLA
LPAAVVTPEA AAEAYRALRE VAGPVGLVLE PPTLPLHQAL TLRFLLQHLG RVARRAPSPD
TAVHALASAF GPLLLRIPPS GGEGDGSEPV PDFPVLLLER LVQEHVEEQD AAPPALPPKP
SKAKPAPTAL ANGGSPPSLQ DAEWYWGDIS REEVNERLRD TPDGTFLVRD ASSKIQGEYT
LTLRKGGNNK LIKVFHRDGH YGFSEPLTFC SVVELISHYR HESLAQYNAK LDTRLLYPVS
KYQQDQVVKE DSIEAVGAQL KVYHQQYQDK SREYDQLYEE YTRTSQELQM KRTAIEAFNE
TIKIFEEQGQ TQEKCSKEYL ERFRREGNEK EMQRILLNSE RLKSRIAEIH ESRTKLEQDL
RAQASDNREI DKRMNSLKPD LMQLRKIRDQ YLVWLTQKGA RQRKINEWLG IKNETEDQYS
LMEDEDALPH HEERTWYVGK INRTQAEEML SGKRDGTFLI RESSQRGCYA CSVVVDGDTK
HCVIYRTATG FGFAEPYNLY GSLKELVLHY QHASLVQHND ALTVTLAHPV RAPGPGPPSA
AR
