P85B_RAT
ID P85B_RAT Reviewed; 722 AA.
AC Q63788;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 154.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=8621382; DOI=10.1074/jbc.271.10.5317;
RA Inukai K., Anai M., van Breda E., Hosaka T., Katagiri H., Funaki M.,
RA Fukushima Y., Ogihara T., Yazaki Y., Kikuchi M., Oka Y., Asano T.;
RT "A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase
RT structurally similar to p55PIK is generated by alternative splicing of the
RT p85alpha gene.";
RL J. Biol. Chem. 271:5317-5320(1996).
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. Promotes nuclear
CC translocation of XBP1 in a ER stress- and/or insulin-dependent manner
CC during metabolic overloading in the liver and hence plays a role in
CC glucose tolerance improvement (By similarity).
CC {ECO:0000250|UniProtKB:O00459, ECO:0000250|UniProtKB:O08908}.
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). Interacts with NYAP1, NYAP2 and MYO16. Interacts with
CC FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with
CC PTPN13; dephosphorylates PIK3R2. Interacts with XBP1; the interaction
CC is direct and induces translocation of XBP1 into the nucleus in a ER
CC stress- and/or insulin-dependent but PI3K-independent manner. Interacts
CC with PIK3R1; the interaction is dissociated in an insulin-dependent
CC manner (By similarity). Interacts with SRC (By similarity).
CC {ECO:0000250|UniProtKB:O00459, ECO:0000250|UniProtKB:O08908}.
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; D64046; BAA10926.1; -; mRNA.
DR AlphaFoldDB; Q63788; -.
DR SMR; Q63788; -.
DR IntAct; Q63788; 3.
DR STRING; 10116.ENSRNOP00000026210; -.
DR iPTMnet; Q63788; -.
DR PhosphoSitePlus; Q63788; -.
DR PaxDb; Q63788; -.
DR PRIDE; Q63788; -.
DR RGD; 68341; Pik3r2.
DR eggNOG; KOG4637; Eukaryota.
DR InParanoid; Q63788; -.
DR PhylomeDB; Q63788; -.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-112399; IRS-mediated signalling.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1266695; Interleukin-7 signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-388841; Costimulation by the CD28 family.
DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR Reactome; R-RNO-912631; Regulation of signaling by CBL.
DR Reactome; R-RNO-9696264; RND3 GTPase cycle.
DR Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR PRO; PR:Q63788; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS: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:RGD.
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; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030833; P:regulation of actin filament polymerization; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0051492; P:regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS: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 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 2: Evidence at transcript level;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; SH2 domain;
KW SH3 domain; Stress response; Transport; Ubl conjugation.
FT CHAIN 1..722
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT beta"
FT /id="PRO_0000080765"
FT DOMAIN 4..80
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 112..289
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 83..109
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 COMPBIAS 86..100
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 458
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
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"
SQ SEQUENCE 722 AA; 81329 MW; 1208368B9F6F0C95 CRC64;
MAGAEGFQYR AVYPFRRERP EDLELLPGDL LVVSRVALQA LGVADGGERC PHNVGWMPGF
NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP LDGPSESGHT LASLAEQFSP
PESAPPILVK LIEAIEQAEL DSEFYSRPEL PAPRTDWSLS DLEQWDRTTL YDAVKGFLLA
LPAAVVTPEA ASEAYRAMRE VTGPVGLVLE PPTLPLHQAL TLRFLLQHLG RVARRAPSPA
TAVHALASAF GPLLLRAPPP GGEGDGSEPA PDFPVLLLER LVQEHVDEQD TAPPALPPKP
SKVKPAPTAL ANGGSTPSLQ DAEWYWGDIS REEVNERLRD TPDGTFLVRD ASSKIQGEYT
LTLRKGGNNK LIKVFHRDGH YGFSEPLTFC SVVELISHYR HESLAQYNAK LDTRLLYPVS
KYQQDQVVKE DSVEAVGAQL KVYHQQYQDK SREYDQLYEE YTRTSQELQM KRTAIEAFNE
TILIFEEQGQ TQEKCSKEYL ERFRREGNEK EMQRILLNSE RLKSRIAEIH ESRTKLEQDL
RAQASDNREI DKRMNSLKPD LMQLRKIRDQ YLVWLTQKGA RQRKINEWLG IKNETEDQYS
LMEDEDALPH HEERTWYVGK INRTQAEEML SAKRDGTFLI RESSQRGCYA CSVVVDGDTK
HCVIYRTATG FGFAEPYNLY GSLKELVLHY QHASLVQHND ALTVTLAHPV RAPGPGPPPA
AR
