UniProtKB - O08908 (P85B_MOUSE)
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Protein
Phosphatidylinositol 3-kinase regulatory subunit beta
Gene
Pik3r2
Organism
Mus musculus (Mouse)
Status
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
- 1-phosphatidylinositol-3-kinase regulator activity Source: GO_Central
- phosphatidylinositol 3-kinase regulatory subunit binding Source: ParkinsonsUK-UCL
- phosphotyrosine binding Source: MGI
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein phosphatase binding Source: MGI
- receptor tyrosine kinase binding Source: MGI
- transcription factor binding Source: UniProtKB
GO - Biological processi
- cellular glucose homeostasis Source: UniProtKB
- cellular response to insulin stimulus Source: UniProtKB
- insulin receptor signaling pathway Source: GO_Central
- phosphatidylinositol 3-kinase signaling Source: UniProtKB
- phosphatidylinositol-3-phosphate biosynthetic process Source: GOC
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of cell adhesion Source: MGI
- positive regulation of transcription factor import into nucleus Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
- protein transport Source: UniProtKB-KW
- regulation of actin filament polymerization Source: MGI
- regulation of autophagy Source: UniProtKB
- regulation of establishment of protein localization to plasma membrane Source: MGI
- regulation of phosphatidylinositol 3-kinase activity Source: GO_Central
- regulation of phosphorylation Source: UniProtKB
- regulation of stress fiber assembly Source: MGI
- response to endoplasmic reticulum stress Source: UniProtKB
Keywordsi
| Biological process | Protein transport, Stress response, Transport |
Enzyme and pathway databases
| Reactomei | R-MMU-109704. PI3K Cascade. R-MMU-1257604. PIP3 activates AKT signaling. R-MMU-1266695. Interleukin-7 signaling. 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-4420097. VEGFA-VEGFR2 Pathway. R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. |
Names & Taxonomyi
| Protein namesi | Recommended name: Phosphatidylinositol 3-kinase regulatory subunit betaShort 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 |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI:1098772. Pik3r2. |
Subcellular locationi
GO - Cellular componenti
- focal adhesion Source: MGI
- nucleus Source: UniProtKB
- phosphatidylinositol 3-kinase complex Source: GO_Central
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000080764 | 1 – 722 | Phosphatidylinositol 3-kinase regulatory subunit betaAdd BLAST | 722 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 458 | PhosphotyrosineCombined sources | 1 | |
| Modified residuei | 599 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 649 | PhosphotyrosineBy similarity | 1 |
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 conjugationProteomic databases
| EPDi | O08908. |
| MaxQBi | O08908. |
| PaxDbi | O08908. |
| PeptideAtlasi | O08908. |
| PRIDEi | O08908. |
PTM databases
| iPTMneti | O08908. |
| PhosphoSitePlusi | O08908. |
Expressioni
Gene expression databases
| Bgeei | ENSMUSG00000031834. |
| ExpressionAtlasi | O08908. baseline and differential. |
| Genevisiblei | O08908. 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
- phosphatidylinositol 3-kinase regulatory subunit binding Source: ParkinsonsUK-UCL
- phosphotyrosine binding Source: MGI
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein phosphatase binding Source: MGI
- receptor tyrosine kinase binding Source: MGI
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 202163. 4 interactors. |
| IntActi | O08908. 11 interactors. |
| MINTi | MINT-1723872. |
| STRINGi | 10090.ENSMUSP00000034296. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 448 – 451 | Combined sources | 4 | |
| Turni | 452 – 454 | Combined sources | 3 | |
| Helixi | 455 – 496 | Combined sources | 42 | |
| Turni | 508 – 510 | Combined sources | 3 | |
| Helixi | 511 – 557 | Combined sources | 47 | |
| Helixi | 559 – 568 | Combined sources | 10 | |
| Helixi | 609 – 611 | Combined sources | 3 | |
| Turni | 614 – 616 | Combined sources | 3 | |
| Helixi | 623 – 630 | Combined sources | 8 | |
| Beta strandi | 637 – 640 | Combined sources | 4 | |
| Beta strandi | 649 – 654 | Combined sources | 6 | |
| Beta strandi | 656 – 667 | Combined sources | 12 | |
| Beta strandi | 670 – 674 | Combined sources | 5 | |
| Helixi | 683 – 688 | Combined sources | 6 | |
| Beta strandi | 691 – 693 | Combined sources | 3 | |
| Turni | 696 – 698 | Combined sources | 3 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 2Y3A | X-ray | 3.30 | B | 423-722 | [»] | |
| ProteinModelPortali | O08908. | |||||
| SMRi | O08908. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 4 – 80 | SH3PROSITE-ProRule annotationAdd BLAST | 77 | |
| Domaini | 112 – 293 | Rho-GAPPROSITE-ProRule annotationAdd BLAST | 182 | |
| Domaini | 324 – 419 | SH2 1PROSITE-ProRule annotationAdd BLAST | 96 | |
| Domaini | 616 – 710 | SH2 2PROSITE-ProRule annotationAdd BLAST | 95 |
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 domainPhylogenomic databases
| eggNOGi | KOG4637. Eukaryota. ENOG410XP6R. LUCA. |
| GeneTreei | ENSGT00390000010431. |
| HOGENOMi | HOG000008438. |
| HOVERGENi | HBG082100. |
| InParanoidi | O08908. |
| KOi | K02649. |
| OMAi | HCVIYKT. |
| OrthoDBi | EOG091G0C3Z. |
| TreeFami | TF102033. |
Family and domain databases
| CDDi | cd09930. SH2_cSH2_p85_like. 1 hit. cd09942. SH2_nSH2_p85_like. 1 hit. |
| Gene3Di | 3.30.505.10. 2 hits. |
| InterProi | View protein in InterPro IPR032498. PI3K_P85_iSH2. IPR001720. PI3kinase_P85. IPR035020. PI3kinase_P85_cSH2. IPR035022. PI3kinase_P85_nSH2. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. IPR000980. SH2. IPR001452. SH3_domain. |
| PANTHERi | PTHR10155. PTHR10155. 1 hit. |
| Pfami | View protein in Pfam PF16454. PI3K_P85_iSH2. 1 hit. PF00620. RhoGAP. 1 hit. PF00017. SH2. 2 hits. |
| PRINTSi | PR00401. SH2DOMAIN. |
| SMARTi | View protein in SMART SM00324. RhoGAP. 1 hit. SM00252. SH2. 2 hits. SM00326. SH3. 1 hit. |
| SUPFAMi | SSF48350. SSF48350. 1 hit. SSF50044. SSF50044. 1 hit. SSF55550. SSF55550. 2 hits. |
| PROSITEi | View protein in PROSITE PS50238. RHOGAP. 1 hit. PS50001. SH2. 2 hits. PS50002. SH3. 1 hit. |
Sequencei
Sequence statusi: Complete.
O08908-1 [UniParc]FASTAAdd to basket
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
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 433 | I → V in CAA73903 (PubMed:9582025).Curated | 1 | |
| Sequence conflicti | 433 | I → V in AAH06796 (PubMed:15489334).Curated | 1 |
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. |
| CCDSi | CCDS22381.1. |
| RefSeqi | NP_032867.2. NM_008841.3. |
| UniGenei | Mm.12945. |
Genome annotation databases
| Ensembli | ENSMUST00000034296; ENSMUSP00000034296; ENSMUSG00000031834. ENSMUST00000214106; ENSMUSP00000151035; ENSMUSG00000111826. |
| GeneIDi | 18709. |
| KEGGi | mmu:18709. |
| UCSCi | uc009mbn.2. mouse. |
Similar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | P85B_MOUSE | |
| Accessioni | O08908Primary (citable) accession number: O08908 Secondary accession number(s): Q5U3K7 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
| Last sequence update: | July 27, 2011 | |
| Last modified: | June 7, 2017 | |
| This is version 157 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
