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Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

PIK3R1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

Protein 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-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

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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

WithEntry#Exp.IntActNotes
Inpp5dQ9ES52-12EBI-520244,EBI-1452545From a different organism.
KHDRBS1Q076662EBI-520244,EBI-1364From a different organism.
PDGFRBP096196EBI-520244,EBI-641237From a different organism.
PIK3CAP328714EBI-520244,EBI-1373130
RAB5AP203395EBI-520244,EBI-399437From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi159569. 1 interactor.
DIPiDIP-34247N.
IntActiP23727. 15 interactors.
MINTiMINT-139236.
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[»]
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
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation
Contains 2 SH2 domains.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP23727.
KOiK02649.
OMAiPQYWLTL.
OrthoDBiEOG091G0C3Z.
TreeFamiTF102033.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

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[»]
ProteinModelPortaliP23727.
SMRiP23727.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159569. 1 interactor.
DIPiDIP-34247N.
IntActiP23727. 15 interactors.
MINTiMINT-139236.
STRINGi9913.ENSBTAP00000014594.

PTM databases

iPTMnetiP23727.

Proteomic databases

PaxDbiP23727.
PRIDEiP23727.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000014594; ENSBTAP00000014594; ENSBTAG00000010989.
GeneIDi282307.
KEGGibta:282307.

Organism-specific databases

CTDi5295.

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP23727.
KOiK02649.
OMAiPQYWLTL.
OrthoDBiEOG091G0C3Z.
TreeFamiTF102033.

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-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.

Miscellaneous databases

EvolutionaryTraceiP23727.

Gene expression databases

BgeeiENSBTAG00000010989.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP85A_BOVIN
AccessioniPrimary (citable) accession number: P23727
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 30, 2016
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.