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P23727 (P85A_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 alpha

Short name=PI3-kinase regulatory subunit alpha
Short name=PI3K regulatory subunit alpha
Short name=PtdIns-3-kinase regulatory subunit alpha
Alternative name(s):
Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
Short name=PI3-kinase subunit p85-alpha
Short name=PtdIns-3-kinase regulatory subunit p85-alpha
Gene names
Name:PIK3R1
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length724 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling By similarity.

Subunit structure

Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or BCR activation. Interacts with CBLB. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST. Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated) By similarity. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 By similarity. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Ref.3

Domain

The SH3 domain mediates the binding to CBLB By similarity.

Post-translational modification

Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation By similarity.

Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated by FGR. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Dephosphorylated by PTPRJ By similarity. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear. Ref.8

Sequence similarities

Belongs to the PI3K p85 subunit family.

Contains 1 Rho-GAP domain.

Contains 2 SH2 domains.

Contains 1 SH3 domain.

Ontologies

Keywords
   DomainRepeat
SH2 domain
SH3 domain
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from electronic annotation. Source: Ensembl

NFAT protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

cellular response to UV

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

growth hormone receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

insulin-like growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell-matrix adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype PubMed 8052599. Source: BHF-UCL

positive regulation of glucose import

Inferred from mutant phenotype PubMed 8052599. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of phosphatidylinositol 3-kinase activity

Inferred from direct assay PubMed 1322797. Source: BHF-UCL

   Cellular_component1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase complex

Inferred from direct assay PubMed 1322797. Source: BHF-UCL

   Molecular_functionErbB-3 class receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin binding

Inferred from electronic annotation. Source: Ensembl

insulin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor substrate binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin-like growth factor receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol 3-kinase binding

Inferred from physical interaction PubMed 1322797. Source: BHF-UCL

phosphatidylinositol 3-kinase regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10068665PubMed 10336465PubMed 15377662PubMed 7537265PubMed 7683666PubMed 8313896PubMed 8382774Ref.7. Source: IntAct

transmembrane receptor protein tyrosine kinase adaptor activity

Inferred from direct assay PubMed 1322797. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Inpp5dQ9ES52-12EBI-520244,EBI-1452545From a different organism.
KHDRBS1Q076662EBI-520244,EBI-1364From a different organism.
PDGFRBP096196EBI-520244,EBI-641237From a different organism.
PIK3CAP328714EBI-520244,EBI-1373130
RAB5AP203395EBI-520244,EBI-399437From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 724723Phosphatidylinositol 3-kinase regulatory subunit alpha
PRO_0000080757

Regions

Domain3 – 7977SH3
Domain113 – 301189Rho-GAP
Domain333 – 42896SH2 1
Domain624 – 71895SH2 2

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue4671Phosphotyrosine By similarity
Modified residue5801Phosphotyrosine By similarity
Modified residue6081Phosphoserine Ref.8

Secondary structure

........................................................... 724
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23727 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: EBDF6E754BBF7321

FASTA72483,497
        10         20         30         40         50         60 
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEAKP EEIGWLNGYN 

        70         80         90        100        110        120 
ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG PSKTEADSEQ QASTLPDLAE 

       130        140        150        160        170        180 
QFAPPDVAPP LLIKLVEAIE KKGLECSTLY RTQSSSNPAE LRQLLDCDTA SLDLEMFDVH 

       190        200        210        220        230        240 
VLADAFKRYL LDLPNPVIPV AVSSELISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL 

       250        260        270        280        290        300 
QYLLKHFFKL SQTSSKNLLN ARVLSELFSP LLFRFPAASS ENTEHLIKII EILISTEWNE 

       310        320        330        340        350        360 
RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA 

       370        380        390        400        410        420 
STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS VVELINHYRN ESLAQYNPKL 

       430        440        450        460        470        480 
DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEDY TRTSQEIQMK 

       490        500        510        520        530        540 
RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNETE IQRIMHNYEK LKSRISEIVD 

       550        560        570        580        590        600 
SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 

       610        620        630        640        650        660 
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS 

       670        680        690        700        710        720 
VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA 


QQRR 

« Hide

References

[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]"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.
[3]"GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit."
Kazlauskas A., Kashishian A., Cooper J.A., Valius M.
Mol. Cell. Biol. 12:2534-2544(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDGFRB.
[4]"Solution structure and ligand-binding site of the SH3 domain of the p85 alpha subunit of phosphatidylinositol 3-kinase."
Booker G.W., Gout I., Downing A.K., Driscoll P.C., Boyd J., Waterfield M.D., Campbell I.D.
Cell 73:813-822(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-84.
[5]"Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase."
Booker G.W., Breeze A.L., Downing A.K., Panayotou G., Gout I., Waterfield M.D., Campbell I.D.
Nature 358:684-687(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 314-431.
[6]"NMR analysis of interactions of a phosphatidylinositol 3'-kinase SH2 domain with phosphotyrosine peptides reveals interdependence of major binding sites."
Guenther U.L., Liu Y., Sanford D., Bachovchin W.W., Schaffhausen B.
Biochemistry 35:15570-15581(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 321-434.
[7]"Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory subunit of phosphoinositide 3-kinase."
Siegal G., Davis B., Kristensen S.M., Sankar A., Linacre J., Stein R.C., Panayotou G., Waterfield M.D., Driscoll P.C.
J. Mol. Biol. 276:461-478(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 614-724.
[8]"Regulation of phosphoinositide 3-kinase by its intrinsic serine kinase activity in vivo."
Foukas L.C., Beeton C.A., Jensen J., Phillips W.A., Shepherd P.R.
Mol. Cell. Biol. 24:966-975(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-608.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M61745 mRNA. Translation: AAA79511.1.
PIRA38749.
RefSeqNP_777000.1. NM_174575.1.
XP_005221493.1. XM_005221436.1.
UniGeneBt.109755.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BFINMR-A614-724[»]
1BFJNMR-A614-724[»]
1OO3NMR-A321-431[»]
1OO4NMR-A321-431[»]
1PNJNMR-A1-84[»]
1QADX-ray1.80A614-724[»]
2PNANMR-A328-431[»]
2PNBNMR-A328-431[»]
2PNINMR-A1-84[»]
ProteinModelPortalP23727.
SMRP23727. Positions 1-84, 115-309, 328-600, 614-724.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid159569. 1 interaction.
DIPDIP-34247N.
IntActP23727. 15 interactions.
MINTMINT-139236.
STRING9913.ENSBTAP00000014594.

Proteomic databases

PRIDEP23727.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000014594; ENSBTAP00000014594; ENSBTAG00000010989.
GeneID282307.
KEGGbta:282307.

Organism-specific databases

CTD5295.

Phylogenomic databases

eggNOGNOG263689.
GeneTreeENSGT00390000010431.
HOGENOMHOG000008438.
HOVERGENHBG082100.
InParanoidP23727.
KOK02649.
OMALNGYNET.
OrthoDBEOG7BP831.
TreeFamTF102033.

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.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR10155. PTHR10155. 1 hit.
PfamPF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
PF07653. SH3_2. 1 hit.
[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

EvolutionaryTraceP23727.
NextBio20806106.

Entry information

Entry nameP85A_BOVIN
AccessionPrimary (citable) accession number: P23727
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 11, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references