Phosphatidylinositol 3-kinase regulatory subunit alpha

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Q63787 (P85A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 125. History...

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

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Names·Attributes·General annotation·Ontologies·Interactions·Alt products·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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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.
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 is widely expressed. Expression of the P55-alpha isoform is highest in brain and skeletal muscle. The P50-alpha isoform is abundant 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 diversity	Alternative splicing
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 16123202. Source: RGD cellular response to fatty acid Inferred from expression pattern PubMed 17593346. 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 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 response to amino acid stimulus Inferred from expression pattern PubMed 19106217. Source: RGD response to cAMP Inferred from direct assay PubMed 10875243. Source: RGD response to dexamethasone stimulus Inferred from expression pattern PubMed 20032058. Source: RGD response to drug Inferred from expression pattern PubMed 20519555. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 19462258. Source: RGD response to ethanol Inferred from expression pattern PubMed 17622585. Source: RGD response to fructose stimulus Inferred from expression pattern PubMed 17976658. Source: RGD response to growth factor stimulus Inferred from expression pattern PubMed 18421086. Source: RGD response to iron(II) ion Inferred from expression pattern PubMed 17600839. Source: RGD response to nutrient Inferred from expression pattern PubMed 19657097 PubMed 19880292. Source: RGD response to progesterone stimulus Inferred from expression pattern PubMed 18752305. Source: RGD response to testosterone stimulus Inferred from expression pattern PubMed 20032058. Source: RGD response to yeast Inferred from expression pattern PubMed 19958054. Source: RGD
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from sequence or structural similarity. Source: UniProtKB neuron projection Inferred from direct assay PubMed 17600839. Source: RGD nucleus Inferred from direct assay PubMed 17918740. Source: RGD plasma membrane Inferred from direct assay PubMed 11826414. Source: RGD
Molecular_function	1-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 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 sequence or structural similarity. Source: UniProtKB insulin-like growth factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB protein C-terminus binding Inferred from direct assay PubMed 12692262. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	A0MZ67	2	EBI-518443,EBI-1392040
Khdrbs1	Q91V33	2	EBI-518443,EBI-518436

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: 1-270: Missing. 271-304: VLFRFPAASSDNTEHLIKAVELLISAEWSERQPA → MYTTVWTMEDLDLECAKTDINCGTDLMFYIEMDP

Isoform p50-alpha (identifier: Q63787-3) The sequence of this isoform differs from the canonical sequence as follows: 1-300: Missing. 301-306: RQPAPA → MHNLQT

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_0000080760

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 By similarity

Modified residue

580

Phosphotyrosine By similarity

Modified residue

607

Phosphotyrosine By similarity

Modified residue

608

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 300

300

Missing in isoform p50-alpha.

VSP_004711

Alternative sequence

1 – 270

270

Missing in isoform p55-alpha.

VSP_004709

Alternative sequence

271 – 304

VLFRF…ERQPA → MYTTVWTMEDLDLECAKTDI NCGTDLMFYIEMDP in isoform p55-alpha.

VSP_004710

Alternative sequence

301 – 306

RQPAPA → MHNLQT in isoform p50-alpha.

VSP_004712

Secondary structure

724

Helix Strand Turn

Details...

Sequences

Sequence		Length	Mass (Da)
Isoform p85-alpha [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 95C65CF612873B84 Show »	FASTA	724	83,531
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: 6F578AB47105FC38 Show »	FASTA	454	53,394
10 20 30 40 50 60 MYTTVWTMED LDLECAKTDI NCGTDLMFYI EMDPPALPPK PPKPTSIANN SMNNNMSLQD 70 80 90 100 110 120 AEWYWGDISR EEVNEKLRDT ADGTFLVRDA STKMHGDYTL TLRKGGNNKL IKIFHRDGKY 130 140 150 160 170 180 GFSDPLTFNS VVELINHYRN ESLAQYNPKL DVKLLYPVSK YQQDQVVKED NIEAVGKKLH 190 200 210 220 230 240 EYNTQFQEKS REYDRLYEEY TRTSQEIQMK RTAIEAFNDT IKIFEEQCHP QERYSKDYIE 250 260 270 280 290 300 KFKREGNEKE IQRIMHNHDK LKSRISEIID SRRRLEEDLK KQAAEYREID KRMNSIKPDL 310 320 330 340 350 360 IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN ENTEDQYSLV DDDEDLPHHD EKTWNVGSSN 370 380 390 400 410 420 RNKAENLLRG KRDGTFLVRE SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS 430 440 450 LKELVLHYQH TSLVQHNDSL NVTLAYPVYA QQRR « Hide
Isoform p50-alpha [UniParc]. Checksum: C2E52B0D385D99E9 Show »	FASTA	424	49,959
10 20 30 40 50 60 MHNLQTLPPK PPKPTSIANN SMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA 70 80 90 100 110 120 STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS VVELINHYRN ESLAQYNPKL 130 140 150 160 170 180 DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK 190 200 210 220 230 240 RTAIEAFNDT IKIFEEQCHP QERYSKDYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID 250 260 270 280 290 300 SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 310 320 330 340 350 360 ENTEDQYSLV DDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS 370 380 390 400 410 420 VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA QQRR « Hide

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.

IPI

IPI00211946.
IPI00231820.
IPI00231821.

RefSeq

NP_037137.1. NM_013005.1.

UniGene

Rn.10599.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FU5	NMR	-	A	322-431	[»]
1FU6	NMR	-	A	322-431	[»]

ProteinModelPortal

Q63787.

SMR

Q63787. Positions 1-84, 115-309, 328-600, 614-724.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q63787. 3 interactions.

MINT

MINT-2880471.

PTM databases

PhosphoSite

Q63787.

Proteomic databases

PaxDb

Q63787.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25513.

KEGG

rno:25513.

UCSC

RGD:3329. rat.

Organism-specific databases

CTD

5295.

RGD

3329. Pik3r1.

Phylogenomic databases

eggNOG

NOG263689.

HOGENOM

HOG000008438.

HOVERGEN

HBG082100.

K02649.

OrthoDB

EOG4GXFM8.

Enzyme and pathway databases

Reactome

REACT_109781. Immune System.

Gene expression databases

ArrayExpress

Q63787.

Genevestigator

Q63787.

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

EvolutionaryTrace

Q63787.

NextBio

606957.

Entry information

Entry name

P85A_RAT

Accession

Primary (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 3, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Alt products·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

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Secondary structure

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