P85B_BOVIN
ID P85B_BOVIN Reviewed; 724 AA.
AC P23726; Q17QY7;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 176.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1707345; DOI=10.1016/0092-8674(91)90411-q;
RA Otsu M., Hiles I.D., Goot I., Fry M.J., Ruiz-Larrea F., Panayotou G.,
RA Thompson A., Dhand R., Hsuan J., Totty N., Smith A.D., Morgan S.J.,
RA Courtneidge S.A., Parker P.J., Waterfield M.D.;
RT "Characterization of two 85 kd proteins that associate with receptor
RT tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase.";
RL Cell 65:91-104(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP CIRCULAR DICHROISM ANALYSIS, AND FLUORESCENCE SPECTROSCOPY.
RX PubMed=1330535; DOI=10.1002/j.1460-2075.1992.tb05524.x;
RA Panayotou G., Bax B., Gout I., Federwisch M., Wroblowski B., Dhand R.,
RA Fry M.J., Blundell T.L., Wollmer A., Waterfield M.D.;
RT "Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2
RT domain with a PDGF receptor phosphorylation site: structural features and
RT analysis of conformational changes.";
RL EMBO J. 11:4261-4272(1992).
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 -!- INTERACTION:
CC P23726; P32871: PIK3CA; NbExp=3; IntAct=EBI-1555978, EBI-1373130;
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-651 by PTPN13. Phosphorylation of Tyr-651 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; M61746; AAA79510.1; -; mRNA.
DR EMBL; BC118113; AAI18114.1; -; mRNA.
DR PIR; B38749; B38749.
DR RefSeq; NP_777001.1; NM_174576.2.
DR PDB; 3L4Q; X-ray; 2.30 A; C/D=424-593.
DR PDBsum; 3L4Q; -.
DR AlphaFoldDB; P23726; -.
DR BMRB; P23726; -.
DR SMR; P23726; -.
DR CORUM; P23726; -.
DR DIP; DIP-39878N; -.
DR IntAct; P23726; 3.
DR MINT; P23726; -.
DR STRING; 9913.ENSBTAP00000003033; -.
DR PaxDb; P23726; -.
DR PRIDE; P23726; -.
DR Ensembl; ENSBTAT00000003033; ENSBTAP00000003033; ENSBTAG00000002350.
DR GeneID; 282308; -.
DR KEGG; bta:282308; -.
DR CTD; 5296; -.
DR VEuPathDB; HostDB:ENSBTAG00000002350; -.
DR VGNC; VGNC:52862; PIK3R2.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000157050; -.
DR HOGENOM; CLU_007031_1_0_1; -.
DR InParanoid; P23726; -.
DR OMA; CIYPQLQ; -.
DR OrthoDB; 737926at2759; -.
DR TreeFam; TF102033; -.
DR Reactome; R-BTA-109704; PI3K Cascade.
DR Reactome; R-BTA-112399; IRS-mediated signalling.
DR Reactome; R-BTA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-BTA-1433557; Signaling by SCF-KIT.
DR Reactome; R-BTA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-BTA-198203; PI3K/AKT activation.
DR Reactome; R-BTA-201556; Signaling by ALK.
DR Reactome; R-BTA-202424; Downstream TCR signaling.
DR Reactome; R-BTA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-BTA-2424491; DAP12 signaling.
DR Reactome; R-BTA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-BTA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-BTA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-BTA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-BTA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-BTA-8980692; RHOA GTPase cycle.
DR Reactome; R-BTA-9013404; RAC2 GTPase cycle.
DR Reactome; R-BTA-9013405; RHOD GTPase cycle.
DR Reactome; R-BTA-9013409; RHOJ GTPase cycle.
DR Reactome; R-BTA-9013420; RHOU GTPase cycle.
DR Reactome; R-BTA-9013423; RAC3 GTPase cycle.
DR Reactome; R-BTA-9035034; RHOF GTPase cycle.
DR Reactome; R-BTA-9696264; RND3 GTPase cycle.
DR Reactome; R-BTA-9696270; RND2 GTPase cycle.
DR EvolutionaryTrace; P23726; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000002350; Expressed in Ammon's horn and 105 other tissues.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IEA:Ensembl.
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 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..724
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT beta"
FT /id="PRO_0000080762"
FT DOMAIN 4..80
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 109..291
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 326..421
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 618..712
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 81..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..111
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..269
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 460
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
FT MOD_RES 601
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
FT MOD_RES 651
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00459"
FT HELIX 432..494
FT /evidence="ECO:0007829|PDB:3L4Q"
FT STRAND 495..497
FT /evidence="ECO:0007829|PDB:3L4Q"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:3L4Q"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:3L4Q"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:3L4Q"
FT TURN 514..518
FT /evidence="ECO:0007829|PDB:3L4Q"
FT HELIX 519..579
FT /evidence="ECO:0007829|PDB:3L4Q"
FT HELIX 584..591
FT /evidence="ECO:0007829|PDB:3L4Q"
SQ SEQUENCE 724 AA; 81060 MW; 9D2BA8B6DB087098 CRC64;
MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGNERC PQSVGWMPGL
NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP RDGPPEPGLT LPDLPEQFSP
PDVAPPILVK LVEAIERTGL DSYRPEPPAV RTDWSLSDVE QWDAAALSDG VKGFLLALPA
PLVTPEAAAE AHRALREAAG PVGPALEPPT LPLHHALTLR FLLQHLGRVA GRAPAPGPAV
RALGATFGPL LLRAPPPPSP PPGGAPDGTE PTPDFPALLV EKLLQEHLEE QEVAPPALPP
KPPKTKPAPT GLANGGSPPS LQDAEWYWGD ISREEVNEKL RDTPDGTFLV RDASSKIQGE
YTLTLRKGGN NKLIKVFHRD GHYGFSEPLT FCSVVDLITH YRHESLAQYN AKLDTRLLYP
VSKYQQDQIV KEDSVEAVGA QLKVYHQQYQ DKSREYDQLY EEYTRTSQEL QMKRTAIEAF
NETIKIFEEQ GQTQEKCSKE YLERFRREGN EKEMQRILLN SERLKSRIAE IHESRTKLEQ
ELRAQASDNR EIDKRMNSLK PDLMQLRKIR DQYLVWLTQK GARQKKINEW LGIKNETEDQ
YSLMEDEDDL PHHEERTWYV GKINRTQAEE MLSGKRDGTF LIRESSQRGC YACSVVVDGD
TKHCVIYRTA TGFGFAEPYN LYGSLKELVL HYQHASLVQH NDALTVTLAH PVRAPGPGPP
PAAR
