Phosphatidylinositol 3-kinase regulatory subunit alpha

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Reviewed, UniProtKB/Swiss-Prot Q63787 (P85A_RAT)

Last modified February 9, 2010. Version 96. History...

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

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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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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Protein attributes

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

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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, 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. Ref.4
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.
Sequence similarities	Belongs to the PI3K p85 subunit family. Contains 1 Rho-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

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Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glucose metabolic process Inferred from mutant phenotype. 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 cell-cell adhesion Inferred from mutant phenotype. Source: RGD negative regulation of proteolysis Inferred from mutant phenotype. Source: RGD phosphoinositide phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of anti-apoptosis Inferred from mutant phenotype. Source: RGD positive regulation of cell migration Inferred from mutant phenotype. Source: RGD positive regulation of myoblast differentiation Inferred from mutant phenotype. Source: RGD response to cAMP Inferred from direct assay. Source: RGD response to estrogen stimulus Inferred from physical interaction. Source: RGD response to glucocorticoid stimulus Inferred from direct assay. Source: RGD
Cellular component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay. Source: RGD
Molecular function	1-phosphatidylinositol-3-kinase activity Ref.1 Traceable author statement. 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 phosphoinositide 3-kinase regulator activity Inferred from sequence or structural similarity. Source: UniProtKB protein C-terminus binding Inferred from direct assay. Source: RGD protein domain specific binding Inferred from physical interaction. Source: RGD protein kinase binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
Khdrbs1	Q91V33	1	EBI-518443,EBI-518436

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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

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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

152

Phosphothreonine By similarity

Modified residue

154

Phosphoserine By similarity

Modified residue

452

Phosphotyrosine By similarity

Modified residue

467

Phosphotyrosine By similarity

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 By similarity

Modified residue

679

Phosphotyrosine 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...

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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. 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. 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

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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: 8621382] [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: 9065454] [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: 8921377] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P50-ALPHA). Tissue: Liver.
[4]	"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: 8628286] [Abstract] Cited for: INTERACTION WITH IRS1.
+	Additional computationally mapped references.

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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.

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	[»]

SMR

Q63787. Positions 1-84, 89-295, 115-309, 431-600, 614-724.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q63787. 2 interactions.

STRING

Q63787.

PTM databases

PhosphoSite

Q63787.

Genome annotation databases

Ensembl

ENSRNOT00000065301; ENSRNOP00000060575; ENSRNOG00000018903; Rattus norvegicus. [Genome view]

GeneID

25513.

KEGG

rno:25513.

Organism-specific databases

CTD

25513.

RGD

3329. Pik3r1.

Phylogenomic databases

HOVERGEN

Q63787.

Gene expression databases

Genevestigator

Q63787.

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

NextBio

606957.

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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:	February 9, 2010
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents