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Protein

Phosphatidylinositol 3-kinase regulatory subunit beta

Gene

PIK3R2

Organism
Homo sapiens (Human)
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 (PubMed:23604317). 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Stress response, Transport

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000105647-MONOMER
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1266695 Interleukin-7 signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-186763 Downstream signal transduction
R-HSA-194840 Rho GTPase cycle
R-HSA-198203 PI3K/AKT activation
R-HSA-202424 Downstream TCR signaling
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-210993 Tie2 Signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491 DAP12 signaling
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-373753 Nephrin family interactions
R-HSA-388841 Costimulation by the CD28 family
R-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-392451 G beta:gamma signalling through PI3Kgamma
R-HSA-416476 G alpha (q) signalling events
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853659 RET signaling
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
SignaLinkiO00459
SIGNORiO00459

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105647.14
HGNCiHGNC:8980 PIK3R2
MIMi603157 gene
neXtProtiNX_O00459

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

Pathology & Biotechi

Involvement in diseasei

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
See also OMIM:603387
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069262373G → R in MPPH1. 2 PublicationsCorresponds to variant dbSNP:rs587776934EnsemblClinVar.1
Natural variantiVAR_075556376K → E in MPPH1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886041591EnsemblClinVar.1
Natural variantiVAR_075683401L → P in MPPH1. 1 PublicationCorresponds to variant dbSNP:rs587777624EnsemblClinVar.1
Natural variantiVAR_075684557D → H in MPPH1. 1 PublicationCorresponds to variant dbSNP:rs372272045EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi651Q → A: Loss of interaction with FBXL2 and increased half-life; when associated with A-652. 1 Publication1
Mutagenesisi652R → A: Loss of interaction with FBXL2 and increased half-life; when associated with A-651. 1 Publication1
Mutagenesisi655Y → A: Stabilized interaction with FBXL2 and decreased half-life. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5296
MalaCardsiPIK3R2
MIMi603387 phenotype
OpenTargetsiENSG00000105647
ENSG00000268173
Orphaneti83473 Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus
PharmGKBiPA33313

Chemistry databases

ChEMBLiCHEMBL3885615
DrugBankiDB01064 Isoprenaline
DB05210 SF1126

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000807631 – 728Phosphatidylinositol 3-kinase regulatory subunit betaAdd BLAST728

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei464PhosphotyrosineCombined sources1
Modified residuei605PhosphotyrosineCombined sources1
Modified residuei655Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated in response to signaling from activated receptor-type protein kinases (PubMed:19690332, PubMed:20068231). Dephosphorylated by PTPRJ (PubMed:18348712). Dephosphorylated at Tyr-655 by PTPN13. Phosphorylation of Tyr-655 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination (PubMed:23604317).2 Publications
Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO00459
MaxQBiO00459
PaxDbiO00459
PeptideAtlasiO00459
PRIDEiO00459
ProteomicsDBi47910

PTM databases

iPTMnetiO00459
PhosphoSitePlusiO00459

Expressioni

Gene expression databases

BgeeiENSG00000105647
CleanExiHS_PIK3R2
ExpressionAtlasiO00459 baseline and differential
GenevisibleiO00459 HS

Organism-specific databases

HPAiHPA069291

Interactioni

Subunit structurei

Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD) (PubMed:23604317). Interacts with AXL (PubMed:9178760). Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (PubMed:9600074, PubMed:15102829). Interacts with NYAP1, NYAP2 and MYO16 (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex (PubMed:23604317). Interacts with PTPN13; dephosphorylates PIK3R2 (PubMed:23604317). 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 (By similarity). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • phosphotyrosine residue binding Source: CAFA
  • protein heterodimerization activity Source: ParkinsonsUK-UCL
  • protein phosphatase binding Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111314, 125 interactors
ComplexPortaliCPX-1917 Phosphatidylinositol 3-kinase complex class I, variant 1
DIPiDIP-31811N
IntActiO00459, 75 interactors
MINTiO00459
STRINGi9606.ENSP00000471914

Chemistry databases

BindingDBiO00459

Structurei

Secondary structure

1728
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 11Combined sources7
Beta strandi30 – 34Combined sources5
Helixi35 – 40Combined sources6
Helixi47 – 49Combined sources3
Helixi51 – 54Combined sources4
Beta strandi56 – 61Combined sources6
Turni62 – 64Combined sources3
Beta strandi67 – 71Combined sources5
Helixi72 – 74Combined sources3
Beta strandi75 – 81Combined sources7
Helixi114 – 117Combined sources4
Helixi126 – 138Combined sources13
Helixi144 – 146Combined sources3
Helixi162 – 164Combined sources3
Helixi167 – 180Combined sources14
Beta strandi181 – 183Combined sources3
Helixi188 – 199Combined sources12
Helixi206 – 209Combined sources4
Turni211 – 213Combined sources3
Helixi216 – 235Combined sources20
Helixi239 – 255Combined sources17
Helixi279 – 293Combined sources15
Helixi439 – 512Combined sources74
Helixi515 – 583Combined sources69
Helixi588 – 594Combined sources7

3D structure databases

ProteinModelPortaliO00459
SMRiO00459
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00459

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 80SH3PROSITE-ProRule annotationAdd BLAST77
Domaini109 – 295Rho-GAPPROSITE-ProRule annotationAdd BLAST187
Domaini330 – 425SH2 1PROSITE-ProRule annotationAdd BLAST96
Domaini622 – 716SH2 2PROSITE-ProRule annotationAdd BLAST95

Domaini

The SH2 2 domain is required for interaction with FBXL2 and PTPN13.1 Publication

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
InParanoidiO00459
KOiK02649
OMAiHCVIYKT
OrthoDBiEOG091G0C3Z
PhylomeDBiO00459
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

Sequencei

Sequence statusi: Complete.

O00459-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGGERC
60 70 80 90 100
PQSVGWMPGL NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP
110 120 130 140 150
RDGAPEPGLT LPDLPEQFSP PDVAPPLLVK LVEAIERTGL DSESHYRPEL
160 170 180 190 200
PAPRTDWSLS DVDQWDTAAL ADGIKSFLLA LPAPLVTPEA SAEARRALRE
210 220 230 240 250
AAGPVGPALE PPTLPLHRAL TLRFLLQHLG RVASRAPALG PAVRALGATF
260 270 280 290 300
GPLLLRAPPP PSSPPPGGAP DGSEPSPDFP ALLVEKLLQE HLEEQEVAPP
310 320 330 340 350
ALPPKPPKAK PASTVLANGG SPPSLQDAEW YWGDISREEV NEKLRDTPDG
360 370 380 390 400
TFLVRDASSK IQGEYTLTLR KGGNNKLIKV FHRDGHYGFS EPLTFCSVVD
410 420 430 440 450
LINHYRHESL AQYNAKLDTR LLYPVSKYQQ DQIVKEDSVE AVGAQLKVYH
460 470 480 490 500
QQYQDKSREY DQLYEEYTRT SQELQMKRTA IEAFNETIKI FEEQGQTQEK
510 520 530 540 550
CSKEYLERFR REGNEKEMQR ILLNSERLKS RIAEIHESRT KLEQQLRAQA
560 570 580 590 600
SDNREIDKRM NSLKPDLMQL RKIRDQYLVW LTQKGARQKK INEWLGIKNE
610 620 630 640 650
TEDQYALMED EDDLPHHEER TWYVGKINRT QAEEMLSGKR DGTFLIRESS
660 670 680 690 700
QRGCYACSVV VDGDTKHCVI YRTATGFGFA EPYNLYGSLK ELVLHYQHAS
710 720
LVQHNDALTV TLAHPVRAPG PGPPPAAR
Length:728
Mass (Da):81,545
Last modified:January 11, 2011 - v2
Checksum:iADAC3E4B61F3F44A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030679234S → R3 PublicationsCorresponds to variant dbSNP:rs2241088Ensembl.1
Natural variantiVAR_030680313S → P3 PublicationsCorresponds to variant dbSNP:rs1011320Ensembl.1
Natural variantiVAR_069262373G → R in MPPH1. 2 PublicationsCorresponds to variant dbSNP:rs587776934EnsemblClinVar.1
Natural variantiVAR_075556376K → E in MPPH1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886041591EnsemblClinVar.1
Natural variantiVAR_075683401L → P in MPPH1. 1 PublicationCorresponds to variant dbSNP:rs587777624EnsemblClinVar.1
Natural variantiVAR_075684557D → H in MPPH1. 1 PublicationCorresponds to variant dbSNP:rs372272045EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80907 mRNA Translation: CAA56868.1
AC007192 Genomic DNA Translation: AAD22671.1
BC070082 mRNA Translation: AAH70082.1
BC090249 mRNA Translation: AAH90249.1
CCDSiCCDS12371.1
PIRiH59435
RefSeqiNP_005018.1, NM_005027.3
UniGeneiHs.371344

Genome annotation databases

EnsembliENST00000222254; ENSP00000222254; ENSG00000105647
ENST00000617130; ENSP00000477864; ENSG00000105647
GeneIDi5296
KEGGihsa:5296
UCSCiuc002nia.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiP85B_HUMAN
AccessioniPrimary (citable) accession number: O00459
Secondary accession number(s): Q5EAT5, Q9UPH9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 11, 2011
Last modified: July 18, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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