Phosphatidylinositol 3-kinase regulatory subunit alpha

Contribute

Send feedback

Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P26450 (P85A_MOUSE)

Last modified February 9, 2010. Version 102. History...

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

Documents (2) |

Third-party data |

Customize display

text xml rdf/xml gff fasta

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein names

Recommended name:
    Phosphatidylinositol 3-kinase regulatory subunit alpha
      Short name=PtdIns-3-kinase regulatory subunit alpha
      Short name=PI3-kinase regulatory subunit alpha
      Short name=PI3K regulatory subunit alpha
Alternative name(s):
    Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
      Short name=PtdIns-3-kinase regulatory subunit p85-alpha
      Short name=PI3-kinase subunit p85-alpha

Gene names

Name:

Pik3r1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Hide | Top

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

Hide | Top

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.
Subunit structure	Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits. 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. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
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.
Sequence similarities	Belongs to the PI3K p85 subunit family. Contains 1 Rho-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

Hide | Top

Ontologies

Keywords
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	B cell differentiation Inferred from mutant phenotype. Source: MGI 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 apoptosis Inferred from direct assay. Source: MGI negative regulation of cell-matrix adhesion Inferred from genetic interaction. Source: MGI negative regulation of osteoclast differentiation Inferred from genetic interaction. Source: MGI phosphoinositide phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from genetic interaction. Source: MGI protein amino acid phosphorylation Inferred from direct assay. Source: MGI
Cellular component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	1-phosphatidylinositol-3-kinase activity Traceable author statement. Source: MGI ErbB-3 class receptor binding Inferred from sequence or structural similarity. Source: UniProtKB insulin receptor binding Inferred from sequence or structural similarity. Source: UniProtKB insulin receptor substrate binding Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB phosphoinositide 3-kinase regulator activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Hide | Top

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Brd7	O88665	2	EBI-641764,EBI-643930
Ctnnb1	Q02248	2	EBI-641764,EBI-397872
Hras1	Q61411	1	EBI-641764,EBI-400273
IRS1	P35568	1	EBI-641764,EBI-517592	From a different organism.
Nme2	Q01768	2	EBI-641764,EBI-642573
Pdgfrb	P05622	1	EBI-641764,EBI-1554855
Pik3ca	P42337	4	EBI-641764,EBI-641748
PTPN6	P29350	1	EBI-641764,EBI-78260	From a different organism.

Hide | Top

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

152

Phosphothreonine By similarity

Modified residue

154

Phosphoserine By similarity

Modified residue

452

Phosphotyrosine By similarity

Modified residue

467

Phosphotyrosine Ref.10 Ref.11 Ref.12

Modified residue

508

Phosphotyrosine By similarity

Modified residue

530

N6-acetyllysine By similarity

Modified residue

556

Phosphotyrosine By similarity

Modified residue

580

Phosphotyrosine By similarity

Modified residue

607

Phosphotyrosine Ref.10 Ref.12

Modified residue

679

Phosphotyrosine By similarity

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

P26450-1 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: DEAAE6EE297CF07A
Show »

FASTA

724

83,414

        10         20         30         40         50         60 
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGPEARP 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 QERYSKEYIG 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

Hide | Top

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: 1849460] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Strain: BALB/c.
[2]	"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: 10528161] [Abstract] Cited for: INTERACTION WITH HCST.
[3]	"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: 10646608] [Abstract] Cited for: INTERACTION WITH CBLB.
[4]	"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: 11113178] [Abstract] Cited for: INTERACTION WITH IRS4.
[5]	"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: 11526404] [Abstract] Cited for: INTERACTION WITH CD3Z AND CD28, UBIQUITINATION.
[6]	"'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: 11711534] [Abstract] Cited for: INTERACTION WITH TOM1L1.
[7]	"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: 12052866] [Abstract] Cited for: INTERACTION WITH SOCS7.
[8]	"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: 14610044] [Abstract] Cited for: INTERACTION WITH LIME1.
[9]	"LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation." Ahn E., Lee H., Yun Y. Blood 107:1521-1527(2006) [PubMed: 16249387] [Abstract] Cited for: INTERACTION WITH LIME1.
[10]	"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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467 AND TYR-607, MASS SPECTROMETRY.
[11]	"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: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467, MASS SPECTROMETRY. Tissue: Mast cell.
[12]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-467 AND TYR-607, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases
EMBL GenBank DDBJ	M60651 mRNA. Translation: AAA39886.1.
IPI	IPI00263878.
UniGene	Mm.259333
3D structure databases
SMR	P26450. Positions 1-84, 89-294, 115-309, 328-431, 431-600, 614-724.
ModBase	Search...
Protein-protein interaction databases
IntAct	P26450. 16 interactions.
STRING	P26450.
PTM databases
PhosphoSite	P26450.
Proteomic databases
PRIDE	P26450.
Genome annotation databases
Ensembl	ENSMUST00000055518; ENSMUSP00000056774; ENSMUSG00000041417; Mus musculus. [Genome view]
Organism-specific databases
MGI	MGI:97583. Pik3r1.
Phylogenomic databases
eggNOG	roNOG06718.
HOGENOM	HBG506175.
HOVERGEN	P26450.
InParanoid	P26450.
Gene expression databases
ArrayExpress	P26450.
Bgee	P26450.
Genevestigator	P26450.
GermOnline	ENSMUSG00000041417. Mus musculus.
Family and domain databases
InterPro	IPR001720. PI3kinase_P85. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP. IPR000980. SH2. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
Gene3D	G3DSA:1.10.555.10. RhoGAP. 1 hit. G3DSA:3.30.505.10. SH2. 2 hits.
PANTHER	PTHR10155. PI3kinase_P85. 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]
PROSITE	PS50238. RHOGAP. 1 hit. PS50001. SH2. 2 hits. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Hide | Top

Entry information

Entry name

P85A_MOUSE

Accession

Primary (citable) accession number: P26450

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	February 9, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

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

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents