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Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

Pik3r1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348926).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Stress response, Transport

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-112399 IRS-mediated signalling
R-MMU-114604 GPVI-mediated activation cascade
R-MMU-1250342 PI3K events in ERBB4 signaling
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1266695 Interleukin-7 signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-180292 GAB1 signalosome
R-MMU-186763 Downstream signal transduction
R-MMU-1963642 PI3K events in ERBB2 signaling
R-MMU-198203 PI3K/AKT activation
R-MMU-202424 Downstream TCR signaling
R-MMU-2029485 Role of phospholipids in phagocytosis
R-MMU-210993 Tie2 Signaling
R-MMU-2424491 DAP12 signaling
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389357 CD28 dependent PI3K/Akt signaling
R-MMU-416476 G alpha (q) signalling events
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-430116 GP1b-IX-V activation signalling
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8851907 MET activates PI3K/AKT signaling
R-MMU-8853659 RET signaling
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Names & Taxonomyi

Protein namesi
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 namesi
Name:Pik3r1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:97583 Pik3r1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3988635

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000807592 – 724Phosphatidylinositol 3-kinase regulatory subunit alphaAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei154PhosphoserineBy similarity1
Modified residuei279PhosphoserineBy similarity1
Modified residuei467PhosphotyrosineCombined sources1
Modified residuei580PhosphotyrosineCombined sources1
Modified residuei608PhosphoserineBy similarity1

Post-translational modificationi

Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.1 Publication
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.By similarity4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP26450
MaxQBiP26450
PaxDbiP26450
PeptideAtlasiP26450
PRIDEiP26450

PTM databases

iPTMnetiP26450
PhosphoSitePlusiP26450
SwissPalmiP26450

Expressioni

Gene expression databases

BgeeiENSMUSG00000041417 Expressed in 304 organ(s), highest expression level in brown adipose tissue
ExpressionAtlasiP26450 baseline and differential
GenevisibleiP26450 MM

Interactioni

Subunit structurei

Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926). 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 (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with FER. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) (Probable). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity).By similarityCurated17 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202162, 52 interactors
CORUMiP26450
DIPiDIP-39593N
IntActiP26450, 46 interactors
MINTiP26450
STRINGi10090.ENSMUSP00000056774

Structurei

3D structure databases

ProteinModelPortaliP26450
SMRiP26450
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 79SH3PROSITE-ProRule annotationAdd BLAST77
Domaini113 – 301Rho-GAPPROSITE-ProRule annotationAdd BLAST189
Domaini333 – 428SH2 1PROSITE-ProRule annotationAdd BLAST96
Domaini624 – 718SH2 2PROSITE-ProRule annotationAdd BLAST95

Domaini

The SH3 domain mediates the binding to CBLB.By similarity

Sequence similaritiesi

Belongs to the PI3K p85 subunit family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4637 Eukaryota
ENOG410XP6R LUCA
GeneTreeiENSGT00390000010431
HOGENOMiHOG000008438
HOVERGENiHBG082100
InParanoidiP26450
KOiK02649
OMAiLNGYNET
OrthoDBiEOG091G0C3Z
TreeFamiTF102033

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11910 SH3_PI3K_p85alpha, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035591 PI3K_p85alpha_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P26450-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP
60 70 80 90 100
EDIGWLNGYN ETTGERGDFP GTYVEYIGRK RISPPTPKPR PPRPLPVAPG
110 120 130 140 150
SSKTEADTEQ QALPLPDLAE QFAPPDVAPP LLIKLLEAIE KKGLECSTLY
160 170 180 190 200
RTQSSSNPAE LRQLLDCDAA SVDLEMIDVH VLADAFKRYL ADLPNPVIPV
210 220 230 240 250
AVYNEMMSLA QELQSPEDCI QLLKKLIRLP NIPHQCWLTL QYLLKHFFKL
260 270 280 290 300
SQASSKNLLN ARVLSEIFSP VLFRFPAASS DNTEHLIKAI EILISTEWNE
310 320 330 340 350
RQPAPALPPK PPKPTTVANN SMNNNMSLQD AEWYWGDISR EEVNEKLRDT
360 370 380 390 400
ADGTFLVRDA STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS
410 420 430 440 450
VVELINHYRN ESLAQYNPKL DVKLLYPVSK YQQDQVVKED NIEAVGKKLH
460 470 480 490 500
EYNTQFQEKS REYDRLYEEY TRTSQEIQMK RTAIEAFNET IKIFEEQCQT
510 520 530 540 550
QERYSKEYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID SRRRLEEDLK
560 570 580 590 600
KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
610 620 630 640 650
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE
660 670 680 690 700
SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH
710 720
TSLVQHNDSL NVTLAYPVYA QQRR
Length:724
Mass (Da):83,517
Last modified:July 27, 2011 - v2
Checksum:i9975D7AD8BABBA9C
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q80UI5Q80UI5_MOUSE
Phosphatidylinositol 3-kinase regul...
Pik3r1
454Annotation score:
A0A087WQM2A0A087WQM2_MOUSE
Phosphatidylinositol 3-kinase regul...
Pik3r1
174Annotation score:
P70305P70305_MOUSE
Phosphatidylinositol 3-kinase regul...
Pik3r1
112Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46Q → P in AAA39886 (PubMed:1849460).Curated1
Sequence conflicti510E → G in AAA39886 (PubMed:1849460).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60651 mRNA Translation: AAA39886.1
CH466567 Genomic DNA Translation: EDL00772.1
BC026146 mRNA Translation: AAH26146.1
CCDSiCCDS36769.1
RefSeqiNP_001070963.1, NM_001077495.2
UniGeneiMm.259333

Genome annotation databases

EnsembliENSMUST00000055518; ENSMUSP00000056774; ENSMUSG00000041417
GeneIDi18708
KEGGimmu:18708
UCSCiuc007rrt.3 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60651 mRNA Translation: AAA39886.1
CH466567 Genomic DNA Translation: EDL00772.1
BC026146 mRNA Translation: AAH26146.1
CCDSiCCDS36769.1
RefSeqiNP_001070963.1, NM_001077495.2
UniGeneiMm.259333

3D structure databases

ProteinModelPortaliP26450
SMRiP26450
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202162, 52 interactors
CORUMiP26450
DIPiDIP-39593N
IntActiP26450, 46 interactors
MINTiP26450
STRINGi10090.ENSMUSP00000056774

Chemistry databases

ChEMBLiCHEMBL3988635

PTM databases

iPTMnetiP26450
PhosphoSitePlusiP26450
SwissPalmiP26450

Proteomic databases

EPDiP26450
MaxQBiP26450
PaxDbiP26450
PeptideAtlasiP26450
PRIDEiP26450

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000055518; ENSMUSP00000056774; ENSMUSG00000041417
GeneIDi18708
KEGGimmu:18708
UCSCiuc007rrt.3 mouse

Organism-specific databases

CTDi5295
MGIiMGI:97583 Pik3r1

Phylogenomic databases

eggNOGiKOG4637 Eukaryota
ENOG410XP6R LUCA
GeneTreeiENSGT00390000010431
HOGENOMiHOG000008438
HOVERGENiHBG082100
InParanoidiP26450
KOiK02649
OMAiLNGYNET
OrthoDBiEOG091G0C3Z
TreeFamiTF102033

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-112399 IRS-mediated signalling
R-MMU-114604 GPVI-mediated activation cascade
R-MMU-1250342 PI3K events in ERBB4 signaling
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1266695 Interleukin-7 signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-180292 GAB1 signalosome
R-MMU-186763 Downstream signal transduction
R-MMU-1963642 PI3K events in ERBB2 signaling
R-MMU-198203 PI3K/AKT activation
R-MMU-202424 Downstream TCR signaling
R-MMU-2029485 Role of phospholipids in phagocytosis
R-MMU-210993 Tie2 Signaling
R-MMU-2424491 DAP12 signaling
R-MMU-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389357 CD28 dependent PI3K/Akt signaling
R-MMU-416476 G alpha (q) signalling events
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-430116 GP1b-IX-V activation signalling
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8851907 MET activates PI3K/AKT signaling
R-MMU-8853659 RET signaling
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912631 Regulation of signaling by CBL
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Miscellaneous databases

ChiTaRSiPik3r1 mouse
PROiPR:P26450
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000041417 Expressed in 304 organ(s), highest expression level in brown adipose tissue
ExpressionAtlasiP26450 baseline and differential
GenevisibleiP26450 MM

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11910 SH3_PI3K_p85alpha, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035591 PI3K_p85alpha_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP85A_MOUSE
AccessioniPrimary (citable) accession number: P26450
Secondary accession number(s): Q8K3B3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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