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Protein

Phosphatidylinositol 3-kinase regulatory subunit beta

Gene

PIK3R2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Promotes nuclear translocation of XBP1 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Protein transport, Stress response, Transport

Enzyme and pathway databases

ReactomeiR-BTA-109704. PI3K Cascade.
R-BTA-1257604. PIP3 activates AKT signaling.
R-BTA-1660499. Synthesis of PIPs at the plasma membrane.
R-BTA-186763. Downstream signal transduction.
R-BTA-194840. Rho GTPase cycle.
R-BTA-198203. PI3K/AKT activation.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2029485. Role of phospholipids in phagocytosis.
R-BTA-210993. Tie2 Signaling.
R-BTA-2424491. DAP12 signaling.
R-BTA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-BTA-4420097. VEGFA-VEGFR2 Pathway.
R-BTA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 7

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 724724Phosphatidylinositol 3-kinase regulatory subunit betaPRO_0000080762Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei460 – 4601PhosphotyrosineBy similarity
Modified residuei601 – 6011PhosphotyrosineBy similarity
Modified residuei651 – 6511PhosphotyrosineBy similarity

Post-translational modificationi

Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at Tyr-651 by PTPN13. Phosphorylation of Tyr-651 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

PaxDbiP23726.
PRIDEiP23726.

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). Interacts with NYAP1, NYAP2 and MYO16. Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with PTPN13; dephosphorylates PIK3R2. Interacts with XBP1; the interaction is direct and induces translocation of XBP1 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner. Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PIK3CAP328713EBI-1555978,EBI-1373130

Protein-protein interaction databases

DIPiDIP-39878N.
IntActiP23726. 1 interaction.
MINTiMINT-1348098.
STRINGi9913.ENSBTAP00000003033.

Structurei

Secondary structure

1
724
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi432 – 49463Combined sources
Beta strandi495 – 4973Combined sources
Helixi500 – 5023Combined sources
Beta strandi503 – 5075Combined sources
Beta strandi511 – 5133Combined sources
Turni514 – 5185Combined sources
Helixi519 – 57961Combined sources
Helixi584 – 5918Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3L4QX-ray2.30C/D424-593[»]
ProteinModelPortaliP23726.
SMRiP23726. Positions 4-86, 320-592, 608-714.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23726.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 8077SH3PROSITE-ProRule annotationAdd
BLAST
Domaini109 – 291183Rho-GAPPROSITE-ProRule annotationAdd
BLAST
Domaini326 – 42196SH2 1PROSITE-ProRule annotationAdd
BLAST
Domaini618 – 71295SH2 2PROSITE-ProRule annotationAdd
BLAST

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
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation
Contains 2 SH2 domains.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP23726.
KOiK02649.
OMAiHYKHTSL.
OrthoDBiEOG7BP831.
TreeFamiTF102033.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23726-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGNERC
60 70 80 90 100
PQSVGWMPGL NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP
110 120 130 140 150
RDGPPEPGLT LPDLPEQFSP PDVAPPILVK LVEAIERTGL DSYRPEPPAV
160 170 180 190 200
RTDWSLSDVE QWDAAALSDG VKGFLLALPA PLVTPEAAAE AHRALREAAG
210 220 230 240 250
PVGPALEPPT LPLHHALTLR FLLQHLGRVA GRAPAPGPAV RALGATFGPL
260 270 280 290 300
LLRAPPPPSP PPGGAPDGTE PTPDFPALLV EKLLQEHLEE QEVAPPALPP
310 320 330 340 350
KPPKTKPAPT GLANGGSPPS LQDAEWYWGD ISREEVNEKL RDTPDGTFLV
360 370 380 390 400
RDASSKIQGE YTLTLRKGGN NKLIKVFHRD GHYGFSEPLT FCSVVDLITH
410 420 430 440 450
YRHESLAQYN AKLDTRLLYP VSKYQQDQIV KEDSVEAVGA QLKVYHQQYQ
460 470 480 490 500
DKSREYDQLY EEYTRTSQEL QMKRTAIEAF NETIKIFEEQ GQTQEKCSKE
510 520 530 540 550
YLERFRREGN EKEMQRILLN SERLKSRIAE IHESRTKLEQ ELRAQASDNR
560 570 580 590 600
EIDKRMNSLK PDLMQLRKIR DQYLVWLTQK GARQKKINEW LGIKNETEDQ
610 620 630 640 650
YSLMEDEDDL PHHEERTWYV GKINRTQAEE MLSGKRDGTF LIRESSQRGC
660 670 680 690 700
YACSVVVDGD TKHCVIYRTA TGFGFAEPYN LYGSLKELVL HYQHASLVQH
710 720
NDALTVTLAH PVRAPGPGPP PAAR
Length:724
Mass (Da):81,060
Last modified:November 1, 1991 - v1
Checksum:i9D2BA8B6DB087098
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61746 mRNA. Translation: AAA79510.1.
BC118113 mRNA. Translation: AAI18114.1.
PIRiB38749.
RefSeqiNP_777001.1. NM_174576.2.
UniGeneiBt.515.

Genome annotation databases

EnsembliENSBTAT00000003033; ENSBTAP00000003033; ENSBTAG00000002350.
GeneIDi282308.
KEGGibta:282308.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61746 mRNA. Translation: AAA79510.1.
BC118113 mRNA. Translation: AAI18114.1.
PIRiB38749.
RefSeqiNP_777001.1. NM_174576.2.
UniGeneiBt.515.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3L4QX-ray2.30C/D424-593[»]
ProteinModelPortaliP23726.
SMRiP23726. Positions 4-86, 320-592, 608-714.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-39878N.
IntActiP23726. 1 interaction.
MINTiMINT-1348098.
STRINGi9913.ENSBTAP00000003033.

Proteomic databases

PaxDbiP23726.
PRIDEiP23726.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000003033; ENSBTAP00000003033; ENSBTAG00000002350.
GeneIDi282308.
KEGGibta:282308.

Organism-specific databases

CTDi5296.

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP23726.
KOiK02649.
OMAiHYKHTSL.
OrthoDBiEOG7BP831.
TreeFamiTF102033.

Enzyme and pathway databases

ReactomeiR-BTA-109704. PI3K Cascade.
R-BTA-1257604. PIP3 activates AKT signaling.
R-BTA-1660499. Synthesis of PIPs at the plasma membrane.
R-BTA-186763. Downstream signal transduction.
R-BTA-194840. Rho GTPase cycle.
R-BTA-198203. PI3K/AKT activation.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2029485. Role of phospholipids in phagocytosis.
R-BTA-210993. Tie2 Signaling.
R-BTA-2424491. DAP12 signaling.
R-BTA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-BTA-4420097. VEGFA-VEGFR2 Pathway.
R-BTA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Miscellaneous databases

EvolutionaryTraceiP23726.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase."
    Otsu M., Hiles I.D., Goot I., Fry M.J., Ruiz-Larrea F., Panayotou G., Thompson A., Dhand R., Hsuan J., Totty N., Smith A.D., Morgan S.J., Courtneidge S.A., Parker P.J., Waterfield M.D.
    Cell 65:91-104(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Uterus.
  3. "Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes."
    Panayotou G., Bax B., Gout I., Federwisch M., Wroblowski B., Dhand R., Fry M.J., Blundell T.L., Wollmer A., Waterfield M.D.
    EMBO J. 11:4261-4272(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: CIRCULAR DICHROISM ANALYSIS, FLUORESCENCE SPECTROSCOPY.

Entry informationi

Entry nameiP85B_BOVIN
AccessioniPrimary (citable) accession number: P23726
Secondary accession number(s): Q17QY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 8, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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.