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Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

PIK3R1

Organism
Bos taurus (Bovine)
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. Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Stress response, Transport

Enzyme and pathway databases

ReactomeiR-BTA-109704 PI3K Cascade
R-BTA-114604 GPVI-mediated activation cascade
R-BTA-1250342 PI3K events in ERBB4 signaling
R-BTA-1257604 PIP3 activates AKT signaling
R-BTA-1266695 Interleukin-7 signaling
R-BTA-1433557 Signaling by SCF-KIT
R-BTA-1660499 Synthesis of PIPs at the plasma membrane
R-BTA-180292 GAB1 signalosome
R-BTA-186763 Downstream signal transduction
R-BTA-1963642 PI3K events in ERBB2 signaling
R-BTA-198203 PI3K/AKT activation
R-BTA-202424 Downstream TCR signaling
R-BTA-2029485 Role of phospholipids in phagocytosis
R-BTA-210993 Tie2 Signaling
R-BTA-2424491 DAP12 signaling
R-BTA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-BTA-388841 Costimulation by the CD28 family
R-BTA-389357 CD28 dependent PI3K/Akt signaling
R-BTA-392451 G beta:gamma signalling through PI3Kgamma
R-BTA-416476 G alpha (q) signalling events
R-BTA-416482 G alpha (12/13) signalling events
R-BTA-430116 GP1b-IX-V activation signalling
R-BTA-4420097 VEGFA-VEGFR2 Pathway
R-BTA-512988 Interleukin-3, 5 and GM-CSF signaling
R-BTA-5654689 PI-3K cascade:FGFR1
R-BTA-5654695 PI-3K cascade:FGFR2
R-BTA-5654710 PI-3K cascade:FGFR3
R-BTA-5654720 PI-3K cascade:FGFR4
R-BTA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-BTA-8851907 MET activates PI3K/AKT signaling
R-BTA-8853659 RET signaling
R-BTA-912526 Interleukin receptor SHC signaling
R-BTA-912631 Regulation of signaling by CBL
R-BTA-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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 20

Organism-specific databases

VGNCiVGNC:32894 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000807572 – 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 residuei467PhosphotyrosineBy similarity1
Modified residuei580PhosphotyrosineBy similarity1
Modified residuei608Phosphoserine1 Publication1

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.By similarity
Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated by FGR. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Dephosphorylated by PTPRJ (By similarity). Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear.By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP23727
PRIDEiP23727

PTM databases

iPTMnetiP23727

Expressioni

Gene expression databases

BgeeiENSBTAG00000010989

Interactioni

Subunit structurei

Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (By similarity). Interacts with XBP1; the interaction is direct and induces translocation of XBP1 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). 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 BCR activation. 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 SOCS7. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST. Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated) (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (By similarity). Interacts with PDGFRB (tyrosine phosphorylated) (PubMed:1375321). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi1595691 interactor.
CORUMiP23727
DIPiDIP-34247N
IntActiP23727 17 interactors.
MINTiP23727
STRINGi9913.ENSBTAP00000014594

Structurei

Secondary structure

1724
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 10Combined sources4
Beta strandi29 – 31Combined sources3
Helixi37 – 39Combined sources3
Turni50 – 52Combined sources3
Beta strandi55 – 60Combined sources6
Turni61 – 64Combined sources4
Beta strandi65 – 78Combined sources14
Beta strandi331 – 333Combined sources3
Turni341 – 344Combined sources4
Helixi345 – 349Combined sources5
Beta strandi354 – 357Combined sources4
Turni362 – 364Combined sources3
Beta strandi370 – 378Combined sources9
Beta strandi386 – 388Combined sources3
Beta strandi393 – 395Combined sources3
Turni403 – 405Combined sources3
Turni408 – 411Combined sources4
Helixi413 – 415Combined sources3
Turni418 – 420Combined sources3
Helixi442 – 513Combined sources72
Turni514 – 516Combined sources3
Helixi518 – 586Combined sources69
Helixi591 – 598Combined sources8
Helixi617 – 619Combined sources3
Helixi621 – 623Combined sources3
Beta strandi625 – 628Combined sources4
Helixi631 – 638Combined sources8
Beta strandi645 – 650Combined sources6
Beta strandi652 – 655Combined sources4
Beta strandi657 – 663Combined sources7
Beta strandi666 – 675Combined sources10
Beta strandi678 – 682Combined sources5
Beta strandi688 – 690Combined sources3
Helixi691 – 700Combined sources10
Helixi703 – 705Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BFINMR-A614-724[»]
1BFJNMR-A614-724[»]
1OO3NMR-A321-431[»]
1OO4NMR-A321-431[»]
1PNJNMR-A1-84[»]
1QADX-ray1.80A614-724[»]
2PNANMR-A328-431[»]
2PNBNMR-A328-431[»]
2PNINMR-A1-84[»]
5DXHX-ray3.00B/E431-599[»]
5DXUX-ray2.64B431-599[»]
5T8FX-ray2.91B431-599[»]
ProteinModelPortaliP23727
SMRiP23727
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23727

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
InParanoidiP23727
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
Gene3Di1.10.555.101 hit
3.30.505.102 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

Sequencei

Sequence statusi: Complete.

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

P23727-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEAKP
60 70 80 90 100
EEIGWLNGYN ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG
110 120 130 140 150
PSKTEADSEQ QASTLPDLAE QFAPPDVAPP LLIKLVEAIE KKGLECSTLY
160 170 180 190 200
RTQSSSNPAE LRQLLDCDTA SLDLEMFDVH VLADAFKRYL LDLPNPVIPV
210 220 230 240 250
AVSSELISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL QYLLKHFFKL
260 270 280 290 300
SQTSSKNLLN ARVLSELFSP LLFRFPAASS ENTEHLIKII EILISTEWNE
310 320 330 340 350
RQPAPALPPK PPKPTTVANN GMNNNMSLQD 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 REYDRLYEDY TRTSQEIQMK RTAIEAFNET IKIFEEQCQT
510 520 530 540 550
QERYSKEYIE KFKREGNETE IQRIMHNYEK LKSRISEIVD 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):83,497
Last modified:November 1, 1991 - v1
Checksum:iEBDF6E754BBF7321
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61745 mRNA Translation: AAA79511.1
PIRiA38749
RefSeqiNP_777000.1, NM_174575.1
XP_005221493.1, XM_005221436.3
UniGeneiBt.109755

Genome annotation databases

EnsembliENSBTAT00000014594; ENSBTAP00000014594; ENSBTAG00000010989
GeneIDi282307
KEGGibta:282307

Similar proteinsi

Entry informationi

Entry nameiP85A_BOVIN
AccessioniPrimary (citable) accession number: P23727
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: April 25, 2018
This is version 180 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome