Phosphatidylinositol 3-kinase regulatory subunit alpha

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P26450 (P85A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 134. History...

Clusters with 100%, 90%, 50% identity |

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.13
Subunit structure	Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH and RUFY3 By similarity. Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR or BCR activation. Interacts with CBLB. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7 and HCST. Interacts with AXL, FASLG, FGR, HCK, KIT and BCR. Interacts with PTK2/FAK1 By similarity. Interacts with PDGFRB (tyrosine phosphorylated) By similarity. Interacts with NTRK1 (phosphorylated upon ligand-binding) By similarity. Interacts with FER. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) Probable. Interacts with PDGFRA (tyrosine phosphorylated). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
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. Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. 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 By similarity. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by TEK/TIE2. Ref.7 Ref.8 Ref.13
Sequence similarities	Belongs to the PI3K p85 subunit family. Contains 1 Rho-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

Ontologies

Keywords
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from mutant phenotype PubMed 9988280. Source: MGI NFAT protein import into nucleus Inferred from mutant phenotype PubMed 17242187. Source: MGI cellular response to UV Inferred from mutant phenotype PubMed 17242187. Source: MGI growth hormone receptor signaling pathway Inferred from electronic annotation. Source: Compara 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 apoptotic process Inferred from direct assay PubMed 15192701. Source: MGI negative regulation of cell-matrix adhesion Inferred from genetic interaction PubMed 17053831. Source: MGI negative regulation of osteoclast differentiation Inferred from genetic interaction PubMed 17053831. Source: MGI phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from mutant phenotype PubMed 17242187. Source: MGI positive regulation of cell migration Inferred from genetic interaction PubMed 17053831. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 17242187. Source: MGI protein phosphorylation Inferred from direct assay PubMed 15192701. Source: MGI
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from sequence or structural similarity. Source: UniProtKB membrane Inferred from direct assay PubMed 16043515. Source: UniProtKB
Molecular_function	1-phosphatidylinositol-3-kinase activity Traceable author statement PubMed 9988280. Source: MGI ErbB-3 class receptor binding Inferred from sequence or structural similarity. Source: UniProtKB insulin binding Inferred from electronic annotation. Source: Compara insulin receptor 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 regulator activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
Brd7	O88665	11	EBI-641764,EBI-643930
Eif4g2	Q62448	3	EBI-641764,EBI-296494
Pik3ca	P42337	6	EBI-641764,EBI-641748
Pik3cb	Q8BTI9	4	EBI-641764,EBI-644672
Pik3cd	O35904-2	2	EBI-641764,EBI-6470774

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 724

724

Phosphatidylinositol 3-kinase regulatory subunit alpha

PRO_0000080759

Regions

Domain

3 – 79

SH3

Domain

113 – 301

189

Rho-GAP

Domain

333 – 428

SH2 1

Domain

624 – 718

SH2 2

Amino acid modifications

Modified residue

467

Phosphotyrosine Ref.20 Ref.21

Modified residue

580

Phosphotyrosine By similarity

Modified residue

607

Phosphotyrosine Ref.20

Modified residue

608

Phosphoserine By similarity

Experimental info

Sequence conflict

Q → P in AAA39886. Ref.1

Sequence conflict

510

E → G in AAA39886. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P26450 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 9975D7AD8BABBA9C
Show »

FASTA

724

83,517

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

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

       130        140        150        160        170        180 
QFAPPDVAPP LLIKLLEAIE KKGLECSTLY RTQSSSNPAE LRQLLDCDAA SVDLEMIDVH 

       190        200        210        220        230        240 
VLADAFKRYL ADLPNPVIPV AVYNEMMSLA QELQSPEDCI QLLKKLIRLP NIPHQCWLTL 

       250        260        270        280        290        300 
QYLLKHFFKL SQASSKNLLN ARVLSEIFSP VLFRFPAASS DNTEHLIKAI EILISTEWNE 

       310        320        330        340        350        360 
RQPAPALPPK PPKPTTVANN 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 
RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID 

       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

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor." Escobedo J.A., Navankasattusas S., Kavanaugh W.M., Milfay D., Fried V.A., Williams L.T. Cell 65:75-82(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Strain: BALB/c.
[2]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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]. Strain: FVB/N. Tissue: Mammary tumor.
[4]	"Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction." Yu J.C., Heidaran M.A., Pierce J.H., Gutkind J.S., Lombardi D., Ruggiero M., Aaronson S.A. Mol. Cell. Biol. 11:3780-3785(1991) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDGFRA, ACTIVATION BY PDGFRA.
[5]	"Activation of phosphatidylinositol-3' kinase by Src-family kinase SH3 binding to the p85 subunit." Pleiman C.M., Hertz W.M., Cambier J.C. Science 263:1609-1612(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LYN.
[6]	"Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation." Bazenet C.E., Gelderloos J.A., Kazlauskas A. Mol. Cell. Biol. 16:6926-6936(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDGFRA.
[7]	"Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-gamma2 by the M-CSF receptor is necessary for differentiation signaling." Bourette R.P., Myles G.M., Choi J.L., Rohrschneider L.R. EMBO J. 16:5880-5893(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CSF1R.
[8]	"Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration." Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R., Alitalo K., Dumont D.J. J. Biol. Chem. 274:30896-30905(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TEK/TIE2, PHOSPHORYLATION.
[9]	"KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties." Chang C., Dietrich J., Harpur A.G., Lindquist J.A., Haude A., Loke Y.W., King A., Colonna M., Trowsdale J., Wilson M.J. J. Immunol. 163:4651-4654(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCST.
[10]	"Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase." Elenius K., Choi C.J., Paul S., Santiestevan E., Nishi E., Klagsbrun M. Oncogene 18:2607-2615(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ERBB4, PHOSPHORYLTION, CATALYTIC ACTIVITY.
[11]	"The protein-tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate-1 and phosphatidylinositol 3-kinase." Iwanishi M., Czech M.P., Cherniack A.D. J. Biol. Chem. 275:38995-39000(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FER.
[12]	"Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b." Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T., Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A., Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M. Nature 403:211-216(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBLB.
[13]	"Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation." Hart K.C., Robertson S.C., Donoghue D.J. Mol. Biol. Cell 12:931-942(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ACTIVATION BY FGFR3, INTERACTION WITH FGFR3, PHOSPHORYLATION.
[14]	"Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling." Tsuruzoe K., Emkey R., Kriauciunas K.M., Ueki K., Kahn C.R. Mol. Cell. Biol. 21:26-38(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IRS4.
[15]	"Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells." Fang D., Liu Y.-C. Nat. Immunol. 2:870-875(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD3Z AND CD28, UBIQUITINATION.
[16]	"'Srcasm: a novel Src activating and signaling molecule." Seykora J.T., Mei L., Dotto G.P., Stein P.L. J. Biol. Chem. 277:2812-2822(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TOM1L1.
[17]	"SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation." Krebs D.L., Uren R.T., Metcalf D., Rakar S., Zhang J.-G., Starr R., De Souza D.P., Hanzinikolas K., Eyles J., Connolly L.M., Simpson R.J., Nicola N.A., Nicholson S.E., Baca M., Hilton D.J., Alexander W.S. Mol. Cell. Biol. 22:4567-4578(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SOCS7.
[18]	"LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation." Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y. J. Exp. Med. 198:1463-1473(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LIME1.
[19]	"LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation." Ahn E., Lee H., Yun Y. Blood 107:1521-1527(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LIME1.
[20]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467 AND TYR-607, MASS SPECTROMETRY.
[21]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467, MASS SPECTROMETRY. Tissue: Mast cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M60651 mRNA. Translation: AAA39886.1. CH466567 Genomic DNA. Translation: EDL00772.1. BC026146 mRNA. Translation: AAH26146.1.
IPI	IPI00263878.
RefSeq	NP_001070963.1. NM_001077495.1.
UniGene	Mm.259333.
3D structure databases
ProteinModelPortal	P26450.
SMR	P26450. Positions 4-80, 115-309, 326-724.
ModBase	Search...
Protein-protein interaction databases
IntAct	P26450. 17 interactions.
MINT	MINT-103410.
PTM databases
PhosphoSite	P26450.
Proteomic databases
PaxDb	P26450.
PRIDE	P26450.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000055518; ENSMUSP00000056774; ENSMUSG00000041417.
GeneID	18708.
KEGG	mmu:18708.
Organism-specific databases
CTD	5295.
MGI	MGI:97583. Pik3r1.
Phylogenomic databases
eggNOG	NOG263689.
GeneTree	ENSGT00390000010431.
HOGENOM	HOG000008438.
HOVERGEN	HBG082100.
InParanoid	Q8K3B3.
KO	K02649.
OMA	RPEEIGW.
OrthoDB	EOG4GXFM8.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
ArrayExpress	P26450.
Bgee	P26450.
Genevestigator	P26450.
GermOnline	ENSMUSG00000041417. Mus musculus.
Family and domain databases
Gene3D	1.10.555.10. 1 hit. 3.30.505.10. 2 hits.
InterPro	IPR001720. PI3kinase_P85. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. IPR000980. SH2. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
PANTHER	PTHR10155. PTHR10155. 1 hit.
Pfam	PF00620. RhoGAP. 1 hit. PF00017. SH2. 2 hits. PF07653. SH3_2. 1 hit. [Graphical view]
PRINTS	PR00678. PI3KINASEP85. PR00401. SH2DOMAIN.
SMART	SM00324. RhoGAP. 1 hit. SM00252. SH2. 2 hits. SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF48350. Rho_GAP. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS50238. RHOGAP. 1 hit. PS50001. SH2. 2 hits. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P26450.
ChEMBL	CHEMBL4392.
ChiTaRS	PIK3R1. mouse.
NextBio	294779.
SOURCE	Search...

Entry information

Entry name

P85A_MOUSE

Accession

Primary (citable) accession number: P26450
Secondary accession number(s): Q8K3B3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents