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Protein

Phosphatidylinositol 3-kinase regulatory subunit beta

Gene

Pik3r2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (By similarity). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348926).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Stress response, Transport

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-112399 IRS-mediated signalling
R-MMU-114604 GPVI-mediated activation cascade
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1266695 Interleukin-7 signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-186763 Downstream signal transduction
R-MMU-194840 Rho GTPase cycle
R-MMU-198203 PI3K/AKT activation
R-MMU-202424 Downstream TCR signaling
R-MMU-2029485 Role of phospholipids in phagocytosis
R-MMU-210993 Tie2 Signaling
R-MMU-2424491 DAP12 signaling
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389357 CD28 dependent PI3K/Akt signaling
R-MMU-416476 G alpha (q) signalling events
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8853659 RET signaling
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3-kinase regulatory subunit beta
Short name:
PI3-kinase regulatory subunit beta
Short name:
PI3K regulatory subunit beta
Short name:
PtdIns-3-kinase regulatory subunit beta
Alternative name(s):
Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta
Short name:
PI3-kinase subunit p85-beta
Short name:
PtdIns-3-kinase regulatory subunit p85-beta
Gene namesi
Name:Pik3r2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1098772 Pik3r2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000807641 – 722Phosphatidylinositol 3-kinase regulatory subunit betaAdd BLAST722

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei458PhosphotyrosineCombined sources1
Modified residuei599PhosphotyrosineBy similarity1
Modified residuei649PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at Tyr-649 by PTPN13. Phosphorylation of Tyr-649 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination.By similarity
Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO08908
MaxQBiO08908
PaxDbiO08908
PeptideAtlasiO08908
PRIDEiO08908

PTM databases

iPTMnetiO08908
PhosphoSitePlusiO08908

Expressioni

Gene expression databases

BgeeiENSMUSG00000031834 Expressed in 262 organ(s), highest expression level in cerebellum
ExpressionAtlasiO08908 baseline and differential
GenevisibleiO08908 MM

Interactioni

Subunit structurei

Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL. Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with PTPN13; dephosphorylates PIK3R2 (By similarity). Interacts with NYAP1, NYAP2 and MYO16 (PubMed:21946561). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202163, 4 interactors
IntActiO08908, 11 interactors
STRINGi10090.ENSMUSP00000034296

Structurei

Secondary structure

1722
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO08908
SMRiO08908
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 80SH3PROSITE-ProRule annotationAdd BLAST77
Domaini112 – 293Rho-GAPPROSITE-ProRule annotationAdd BLAST182
Domaini324 – 419SH2 1PROSITE-ProRule annotationAdd BLAST96
Domaini616 – 710SH2 2PROSITE-ProRule annotationAdd BLAST95

Domaini

The SH2 2 domain is required for interaction with FBXL2 and PTPN13.By similarity

Sequence similaritiesi

Belongs to the PI3K p85 subunit family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4637 Eukaryota
ENOG410XP6R LUCA
GeneTreeiENSGT00390000010431
HOGENOMiHOG000008438
HOVERGENiHBG082100
InParanoidiO08908
KOiK02649
OMAiHCVIYKT
OrthoDBiEOG091G0C3Z
TreeFamiTF102033

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11909 SH3_PI3K_p85beta, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035586 PI3K_p85beta_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O08908-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGAEGFQYR AVYPFRRERP EDLELLPGDL LVVSRVALQA LGVADGGERC
60 70 80 90 100
PHNVGWMPGF NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP
110 120 130 140 150
LDGSSESGHI LPDLAEQFSP PDPAPPILVK LVEAIEQAEL DSECYSKPEL
160 170 180 190 200
PATRTDWSLS DLEQWDRTAL YDAVKGFLLA LPAAVVTPEA AAEAYRALRE
210 220 230 240 250
VAGPVGLVLE PPTLPLHQAL TLRFLLQHLG RVARRAPSPD TAVHALASAF
260 270 280 290 300
GPLLLRIPPS GGEGDGSEPV PDFPVLLLER LVQEHVEEQD AAPPALPPKP
310 320 330 340 350
SKAKPAPTAL ANGGSPPSLQ DAEWYWGDIS REEVNERLRD TPDGTFLVRD
360 370 380 390 400
ASSKIQGEYT LTLRKGGNNK LIKVFHRDGH YGFSEPLTFC SVVELISHYR
410 420 430 440 450
HESLAQYNAK LDTRLLYPVS KYQQDQVVKE DSIEAVGAQL KVYHQQYQDK
460 470 480 490 500
SREYDQLYEE YTRTSQELQM KRTAIEAFNE TIKIFEEQGQ TQEKCSKEYL
510 520 530 540 550
ERFRREGNEK EMQRILLNSE RLKSRIAEIH ESRTKLEQDL RAQASDNREI
560 570 580 590 600
DKRMNSLKPD LMQLRKIRDQ YLVWLTQKGA RQRKINEWLG IKNETEDQYS
610 620 630 640 650
LMEDEDALPH HEERTWYVGK INRTQAEEML SGKRDGTFLI RESSQRGCYA
660 670 680 690 700
CSVVVDGDTK HCVIYRTATG FGFAEPYNLY GSLKELVLHY QHASLVQHND
710 720
ALTVTLAHPV RAPGPGPPSA AR
Length:722
Mass (Da):81,266
Last modified:July 27, 2011 - v2
Checksum:iA999FAF9011455FE
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F7CB91F7CB91_MOUSE
Phosphatidylinositol 3-kinase regul...
Pik3r2
71Annotation score:
F6R2V5F6R2V5_MOUSE
Phosphatidylinositol 3-kinase regul...
Pik3r2
84Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti433I → V in CAA73903 (PubMed:9582025).Curated1
Sequence conflicti433I → V in AAH06796 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13569 mRNA Translation: CAA73903.1
CH466569 Genomic DNA Translation: EDL28873.1
BC006796 mRNA Translation: AAH06796.1
BC085501 mRNA Translation: AAH85501.1
CCDSiCCDS22381.1
RefSeqiNP_032867.2, NM_008841.3
UniGeneiMm.12945

Genome annotation databases

EnsembliENSMUST00000034296; ENSMUSP00000034296; ENSMUSG00000031834
ENSMUST00000214106; ENSMUSP00000151035; ENSMUSG00000111826
GeneIDi18709
KEGGimmu:18709
UCSCiuc009mbn.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13569 mRNA Translation: CAA73903.1
CH466569 Genomic DNA Translation: EDL28873.1
BC006796 mRNA Translation: AAH06796.1
BC085501 mRNA Translation: AAH85501.1
CCDSiCCDS22381.1
RefSeqiNP_032867.2, NM_008841.3
UniGeneiMm.12945

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y3AX-ray3.30B423-722[»]
ProteinModelPortaliO08908
SMRiO08908
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202163, 4 interactors
IntActiO08908, 11 interactors
STRINGi10090.ENSMUSP00000034296

PTM databases

iPTMnetiO08908
PhosphoSitePlusiO08908

Proteomic databases

EPDiO08908
MaxQBiO08908
PaxDbiO08908
PeptideAtlasiO08908
PRIDEiO08908

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034296; ENSMUSP00000034296; ENSMUSG00000031834
ENSMUST00000214106; ENSMUSP00000151035; ENSMUSG00000111826
GeneIDi18709
KEGGimmu:18709
UCSCiuc009mbn.2 mouse

Organism-specific databases

CTDi5296
MGIiMGI:1098772 Pik3r2

Phylogenomic databases

eggNOGiKOG4637 Eukaryota
ENOG410XP6R LUCA
GeneTreeiENSGT00390000010431
HOGENOMiHOG000008438
HOVERGENiHBG082100
InParanoidiO08908
KOiK02649
OMAiHCVIYKT
OrthoDBiEOG091G0C3Z
TreeFamiTF102033

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-112399 IRS-mediated signalling
R-MMU-114604 GPVI-mediated activation cascade
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1266695 Interleukin-7 signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-186763 Downstream signal transduction
R-MMU-194840 Rho GTPase cycle
R-MMU-198203 PI3K/AKT activation
R-MMU-202424 Downstream TCR signaling
R-MMU-2029485 Role of phospholipids in phagocytosis
R-MMU-210993 Tie2 Signaling
R-MMU-2424491 DAP12 signaling
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389357 CD28 dependent PI3K/Akt signaling
R-MMU-416476 G alpha (q) signalling events
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8853659 RET signaling
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL

Miscellaneous databases

PROiPR:O08908
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031834 Expressed in 262 organ(s), highest expression level in cerebellum
ExpressionAtlasiO08908 baseline and differential
GenevisibleiO08908 MM

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11909 SH3_PI3K_p85beta, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035586 PI3K_p85beta_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP85B_MOUSE
AccessioniPrimary (citable) accession number: O08908
Secondary accession number(s): Q5U3K7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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