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O00459 (P85B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PIK3R2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length728 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.5 Ref.6 Ref.7

Post-translational modification

Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Ref.8

Involvement in disease

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Sequence similarities

Belongs to the PI3K p85 subunit family.

Contains 1 Rho-GAP domain.

Contains 2 SH2 domains.

Contains 1 SH3 domain.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
SH2 domain
SH3 domain
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Fc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

leukocyte migration

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from sequence or structural similarity. Source: GOC

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

phospholipid metabolic process

Traceable author statement. Source: Reactome

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

phosphatidylinositol 3-kinase complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionphosphatidylinositol 3-kinase regulator activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 16273093PubMed 16963558PubMed 17500595PubMed 19380743PubMed 20936779PubMed 21706016PubMed 22402981PubMed 22810585PubMed 24189400PubMed 24728074PubMed 7537096. Source: IntAct

receptor tyrosine kinase binding

Inferred from physical interaction PubMed 10627473. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 728728Phosphatidylinositol 3-kinase regulatory subunit beta
PRO_0000080763

Regions

Domain4 – 8077SH3
Domain109 – 295187Rho-GAP
Domain330 – 42596SH2 1
Domain622 – 71695SH2 2

Amino acid modifications

Modified residue4641Phosphotyrosine Ref.12
Modified residue6051Phosphotyrosine Ref.11

Natural variations

Natural variant2341S → R. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2241088 [ dbSNP | Ensembl ].
VAR_030679
Natural variant3131S → P. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1011320 [ dbSNP | Ensembl ].
VAR_030680
Natural variant3731G → R in MPPH. Ref.14
VAR_069262

Secondary structure

.............................................. 728
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00459 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: ADAC3E4B61F3F44A

FASTA72881,545
        10         20         30         40         50         60 
MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGGERC PQSVGWMPGL 

        70         80         90        100        110        120 
NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP RDGAPEPGLT LPDLPEQFSP 

       130        140        150        160        170        180 
PDVAPPLLVK LVEAIERTGL DSESHYRPEL PAPRTDWSLS DVDQWDTAAL ADGIKSFLLA 

       190        200        210        220        230        240 
LPAPLVTPEA SAEARRALRE AAGPVGPALE PPTLPLHRAL TLRFLLQHLG RVASRAPALG 

       250        260        270        280        290        300 
PAVRALGATF GPLLLRAPPP PSSPPPGGAP DGSEPSPDFP ALLVEKLLQE HLEEQEVAPP 

       310        320        330        340        350        360 
ALPPKPPKAK PASTVLANGG SPPSLQDAEW YWGDISREEV NEKLRDTPDG TFLVRDASSK 

       370        380        390        400        410        420 
IQGEYTLTLR KGGNNKLIKV FHRDGHYGFS EPLTFCSVVD LINHYRHESL AQYNAKLDTR 

       430        440        450        460        470        480 
LLYPVSKYQQ DQIVKEDSVE AVGAQLKVYH QQYQDKSREY DQLYEEYTRT SQELQMKRTA 

       490        500        510        520        530        540 
IEAFNETIKI FEEQGQTQEK CSKEYLERFR REGNEKEMQR ILLNSERLKS RIAEIHESRT 

       550        560        570        580        590        600 
KLEQQLRAQA SDNREIDKRM NSLKPDLMQL RKIRDQYLVW LTQKGARQKK INEWLGIKNE 

       610        620        630        640        650        660 
TEDQYALMED EDDLPHHEER TWYVGKINRT QAEEMLSGKR DGTFLIRESS QRGCYACSVV 

       670        680        690        700        710        720 
VDGDTKHCVI YRTATGFGFA EPYNLYGSLK ELVLHYQHAS LVQHNDALTV TLAHPVRAPG 


PGPPPAAR 

« Hide

References

« Hide 'large scale' references
[1]"Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta."
Volinia S., Patracchini P., Otsu M., Hiles I., Gout I., Calzolari E., Bernardi F., Rooke L., Waterfield M.D.
Oncogene 7:789-793(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-234 AND PRO-313.
[2]"An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme."
Janssen J.W.G., Schleithhoff L., Bartram C.R., Schulz A.S.
Oncogene 16:1767-1772(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-234 AND PRO-313.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-234 AND PRO-313.
Tissue: Brain and Placenta.
[5]"Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site."
Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W.
Oncogene 14:2619-2631(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AXL.
[6]"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2."
Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I.
Biochem. Biophys. Res. Commun. 246:95-99(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLT1.
[7]"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
Wang J.F., Zhang X., Groopman J.E.
J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLT4.
[8]"The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase."
Tsuboi N., Utsunomiya T., Roberts R.L., Ito H., Takahashi K., Noda M., Takahashi T.
Biochem. J. 413:193-200(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-605, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes."
Riviere J.B., Mirzaa G.M., O'Roak B.J., Beddaoui M., Alcantara D., Conway R.L., St-Onge J., Schwartzentruber J.A., Gripp K.W., Nikkel S.M., Worthylake T., Sullivan C.T., Ward T.R., Butler H.E., Kramer N.A., Albrecht B., Armour C.M., Armstrong L. expand/collapse author list , Caluseriu O., Cytrynbaum C., Drolet B.A., Innes A.M., Lauzon J.L., Lin A.E., Mancini G.M., Meschino W.S., Reggin J.D., Saggar A.K., Lerman-Sagie T., Uyanik G., Weksberg R., Zirn B., Beaulieu C.L., Majewski J., Bulman D.E., O'Driscoll M., Shendure J., Graham J.M. Jr., Boycott K.M., Dobyns W.B.
Nat. Genet. 44:934-940(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MPPH ARG-373.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X80907 mRNA. Translation: CAA56868.1.
AC007192 Genomic DNA. Translation: AAD22671.1.
BC070082 mRNA. Translation: AAH70082.1.
BC090249 mRNA. Translation: AAH90249.1.
CCDSCCDS12371.1.
PIRH59435.
RefSeqNP_005018.1. NM_005027.3.
UniGeneHs.371344.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KT1NMR-A1-80[»]
2XS6X-ray2.09A108-298[»]
3MTTX-ray3.30A433-610[»]
3O5ZX-ray2.01A/B1-85[»]
ProteinModelPortalO00459.
SMRO00459. Positions 3-84, 109-294, 324-720.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111314. 87 interactions.
IntActO00459. 47 interactions.
MINTMINT-1210047.
STRING9606.ENSP00000222254.

Chemistry

BindingDBO00459.

PTM databases

PhosphoSiteO00459.

Proteomic databases

MaxQBO00459.
PaxDbO00459.
PRIDEO00459.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222254; ENSP00000222254; ENSG00000105647.
GeneID5296.
KEGGhsa:5296.
UCSCuc002nia.2. human.

Organism-specific databases

CTD5296.
GeneCardsGC19P018263.
HGNCHGNC:8980. PIK3R2.
MIM603157. gene.
603387. phenotype.
neXtProtNX_O00459.
Orphanet83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBPA33313.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263689.
HOGENOMHOG000008438.
HOVERGENHBG082100.
InParanoidO00459.
KOK02649.
OMAHCVIYKT.
PhylomeDBO00459.
TreeFamTF102033.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000105647-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkO00459.

Gene expression databases

BgeeO00459.
CleanExHS_PIK3R2.
GenevestigatorO00459.

Family and domain databases

Gene3D1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProIPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR10155. PTHR10155. 1 hit.
PfamPF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSPR00678. PI3KINASEP85.
PR00401. SH2DOMAIN.
SMARTSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIK3R2. human.
EvolutionaryTraceO00459.
GeneWikiPIK3R2.
GenomeRNAi5296.
NextBio20470.
PROO00459.
SOURCESearch...

Entry information

Entry nameP85B_HUMAN
AccessionPrimary (citable) accession number: O00459
Secondary accession number(s): Q5EAT5, Q9UPH9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM