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Q63787 (P85A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. 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·Alt products·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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 activation. Interacts with phosphorylated TOM1L1. 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 NISCH, SOCS7 and HCST By similarity. Interacts with IRS1 and phosphorylated IRS4. Interacts with RUFY3. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) Probable. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR By similarity. Interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity By similarity. Interacts with NTRK1 (phosphorylated upon ligand-binding) By similarity. Interacts with PTK2/FAK1. Ref.5 Ref.6

Tissue specificity

The P85-alpha isoform iswidely expressed. Expression of the P55-alpha isoform ishighest in brain and skeletal muscle. The P50-alpha isoform isabundant in liver with lower levels in brain and muscle.

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 by CSF1R. Phosphorylated on tyrosine residues by TEK/TIE2. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR and ERBB4 By similarity.

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 diversityAlternative splicing
   DomainRepeat
SH2 domain
SH3 domain
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from expression pattern PubMed 16123202. Source: RGD

cellular response to fatty acid

Inferred from expression pattern PubMed 17593346. Source: RGD

cellular response to insulin stimulus

Inferred from expression pattern PubMed 18922131. Source: RGD

glucose metabolic process

Inferred from mutant phenotype PubMed 9440811. Source: RGD

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

negative regulation of blood pressure

Inferred from mutant phenotype PubMed 19015400. Source: RGD

negative regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 15530849. Source: RGD

negative regulation of heart rate

Inferred from mutant phenotype PubMed 19015400. Source: RGD

negative regulation of muscle cell apoptotic process

Inferred from mutant phenotype PubMed 15089039. Source: RGD

negative regulation of proteolysis

Inferred from mutant phenotype PubMed 15161606. Source: RGD

negative regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 19783773. Source: RGD

phosphatidylinositol phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from direct assay PubMed 20236230. Source: GOC

positive regulation of cell migration

Inferred from mutant phenotype PubMed 15530849. Source: RGD

positive regulation of gene expression

Inferred from mutant phenotype PubMed 20333648. Source: RGD

positive regulation of myoblast differentiation

Inferred from mutant phenotype PubMed 9440811. Source: RGD

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 19723872. Source: RGD

regulation of phosphatidylinositol 3-kinase activity

Inferred from direct assay PubMed 12882977. Source: RGD

response to amino acid

Inferred from expression pattern PubMed 19106217. Source: RGD

response to cAMP

Inferred from direct assay PubMed 10875243. Source: RGD

response to dexamethasone

Inferred from expression pattern PubMed 20032058. Source: RGD

response to drug

Inferred from expression pattern PubMed 20519555. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 19462258. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 17622585. Source: RGD

response to fatty acid

Inferred from expression pattern PubMed 19369057. Source: RGD

response to fructose

Inferred from expression pattern PubMed 17976658. Source: RGD

response to glucocorticoid

Inferred from direct assay PubMed 15187100. Source: RGD

response to growth factor

Inferred from expression pattern PubMed 18421086. Source: RGD

response to insulin

Inferred from direct assay PubMed 16150536. Source: RGD

response to iron(II) ion

Inferred from expression pattern PubMed 17600839. Source: RGD

response to nutrient

Inferred from expression pattern PubMed 19657097PubMed 19880292. Source: RGD

response to progesterone

Inferred from expression pattern PubMed 18752305. Source: RGD

response to testosterone

Inferred from expression pattern PubMed 20032058. Source: RGD

response to yeast

Inferred from expression pattern PubMed 19958054. Source: RGD

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

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

membrane

Inferred from direct assay PubMed 20519555. Source: RGD

neuron projection

Inferred from direct assay PubMed 17600839. Source: RGD

nucleus

Inferred from direct assay PubMed 17918740. Source: RGD

phosphatidylinositol 3-kinase complex

Inferred from direct assay PubMed 12882977PubMed 20236230. Source: RGD

plasma membrane

Inferred from direct assay PubMed 11826414. Source: RGD

protein complex

Inferred from direct assay PubMed 10973965. Source: RGD

   Molecular_function1-phosphatidylinositol-3-kinase activity

Traceable author statement Ref.1. Source: RGD

1-phosphatidylinositol-3-kinase regulator activity

Inferred from direct assay PubMed 12882977. Source: RGD

ATPase binding

Inferred from physical interaction PubMed 17728397. Source: RGD

ErbB-3 class receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

calmodulin binding

Inferred from physical interaction PubMed 17492691. Source: RGD

estrogen receptor binding

Inferred from physical interaction PubMed 16971528. Source: RGD

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 18773943. Source: RGD

phosphatidylinositol 3-kinase regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphoprotein binding

Inferred from physical interaction PubMed 12882964. Source: RGD

platelet-derived growth factor receptor binding

Inferred from physical interaction PubMed 18421086. Source: RGD

protein C-terminus binding

Inferred from direct assay PubMed 12692262. Source: RGD

protein domain specific binding

Inferred from physical interaction PubMed 10973965. Source: RGD

protein kinase binding

Inferred from physical interaction PubMed 15530849PubMed 18854312. Source: RGD

receptor binding

Inferred from physical interaction PubMed 14962484. Source: RGD

receptor tyrosine kinase binding

Inferred from physical interaction PubMed 18292389. Source: RGD

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 18773943. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform p85-alpha (identifier: Q63787-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform p55-alpha (identifier: Q63787-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2-270: Missing.
     271-304: VLFRFPAASSDNTEHLIKAVELLISAEWSERQPA → MYTTVWTMEDLDLECAKTDINCGTDLMFYIEMDP
Isoform p50-alpha (identifier: Q63787-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2-300: Missing.
     301-306: RQPAPA → MHNLQT

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 724723Phosphatidylinositol 3-kinase regulatory subunit alpha
PRO_0000080760

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 By similarity

Natural variations

Alternative sequence2 – 300299Missing in isoform p50-alpha.
VSP_004711
Alternative sequence2 – 270269Missing in isoform p55-alpha.
VSP_004709
Alternative sequence271 – 30434VLFRF…ERQPA → MYTTVWTMEDLDLECAKTDI NCGTDLMFYIEMDP in isoform p55-alpha.
VSP_004710
Alternative sequence301 – 3066RQPAPA → MHNLQT in isoform p50-alpha.
VSP_004712

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform p85-alpha [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 95C65CF612873B84

FASTA72483,531
        10         20         30         40         50         60 
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EDIGWLNGYN 

        70         80         90        100        110        120 
ETTGERGDFP GTYVEYIGRK RISPPTPKPR PPRPLPVAPG SSKTEADTEQ PVLTLPDLAE 

       130        140        150        160        170        180 
QFAPPDVAPP LLIKLLEAIE KKGLECSTLY RTQSSSNPAE LRQLLDCDPP SVDLDVFDEH 

       190        200        210        220        230        240 
VLADAFKRYL ADLPNPVIPV AVYNEMMSLA QEVPSSEDYI QLLKKLIRSP NIPHQYWLTL 

       250        260        270        280        290        300 
QYLLKHFFKL SQASSKNLLN ARALSEIFSH VLFRFPAASS DNTEHLIKAV ELLISAEWSE 

       310        320        330        340        350        360 
RQPAPALPPK PPKPTSIANN SMNNNMSLQD 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 REYDRLYEEY TRTSQEIQMK 

       490        500        510        520        530        540 
RTAIEAFNDT IKIFEEQCHP QERYSKDYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID 

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

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

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


QQRR 

« Hide

Isoform p55-alpha [UniParc].

Checksum: F28B7DCFCB94F170
Show »

FASTA45553,525
Isoform p50-alpha [UniParc].

Checksum: 5C77A94F4E24A11D
Show »

FASTA42550,090

References

[1]"A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK is generated by alternative splicing of the p85alpha gene."
Inukai K., Anai M., van Breda E., Hosaka T., Katagiri H., Funaki M., Fukushima Y., Ogihara T., Yazaki Y., Kikuchi M., Oka Y., Asano T.
J. Biol. Chem. 271:5317-5320(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P85-ALPHA AND P55-ALPHA).
Strain: Wistar.
Tissue: Brain.
[2]"p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin."
Inukai K., Funaki M., Ogihara T., Katagiri H., Kanda A., Anai M., Fukushima Y., Hosaka T., Suzuki M., Shin B., Takata K., Yazaki Y., Kikuchi M., Oka Y., Asano T.
J. Biol. Chem. 272:7873-7882(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P50-ALPHA).
Tissue: Liver.
[3]"Structural organization and alternative splicing of the murine phosphoinositide 3-kinase p85 alpha gene."
Fruman D.A., Cantley L.C., Carpenter C.L.
Genomics 37:113-121(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P50-ALPHA).
Tissue: Liver.
[4]"Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1."
Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K.
J. Biol. Chem. 269:18320-18326(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY FGFR4.
[5]"Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase."
Chen H.C., Appeddu P.A., Isoda H., Guan J.L.
J. Biol. Chem. 271:26329-26334(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTK2/FAK1.
[6]"Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain."
Antonetti D.A., Algenstaedt P., Kahn C.R.
Mol. Cell. Biol. 16:2195-2203(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IRS1.
[7]"Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins."
Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., Lax I.
Proc. Natl. Acad. Sci. U.S.A. 98:6074-6079(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY FGFR1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D64045 mRNA. Translation: BAA18932.1.
D64048 mRNA. Translation: BAA18933.1.
U50412 mRNA. Translation: AAC52846.1.
D78486 mRNA. Translation: BAA24426.1.
RefSeqNP_037137.1. NM_013005.1.
UniGeneRn.10599.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FU5NMR-A322-431[»]
1FU6NMR-A322-431[»]
ProteinModelPortalQ63787.
SMRQ63787. Positions 1-84, 115-309, 328-600, 614-724.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247545. 7 interactions.
IntActQ63787. 18 interactions.
MINTMINT-2880471.

PTM databases

PhosphoSiteQ63787.

Proteomic databases

PaxDbQ63787.
PRIDEQ63787.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25513.
KEGGrno:25513.
UCSCRGD:3329. rat. [Q63787-1]

Organism-specific databases

CTD5295.
RGD3329. Pik3r1.

Phylogenomic databases

eggNOGNOG263689.
HOGENOMHOG000008438.
HOVERGENHBG082100.
KOK02649.
PhylomeDBQ63787.

Gene expression databases

GenevestigatorQ63787.

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

EvolutionaryTraceQ63787.
NextBio606957.
PROQ63787.

Entry information

Entry nameP85A_RAT
AccessionPrimary (citable) accession number: Q63787
Secondary accession number(s): O55085, P70544, Q63790
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 133 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