Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q63787

- P85A_RAT

UniProt

Q63787 - P85A_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

Pik3r1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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 (By similarity).By similarity

GO - Molecular functioni

  1. 1-phosphatidylinositol-3-kinase activity Source: RGD
  2. 1-phosphatidylinositol-3-kinase regulator activity Source: RGD
  3. ATPase binding Source: RGD
  4. calmodulin binding Source: RGD
  5. ErbB-3 class receptor binding Source: UniProtKB
  6. estrogen receptor binding Source: RGD
  7. insulin-like growth factor receptor binding Source: UniProtKB
  8. insulin receptor binding Source: UniProtKB
  9. insulin receptor substrate binding Source: UniProtKB
  10. phosphatidylinositol 3-kinase binding Source: RGD
  11. phosphatidylinositol 3-kinase regulator activity Source: UniProtKB
  12. phosphoprotein binding Source: RGD
  13. platelet-derived growth factor receptor binding Source: RGD
  14. protein C-terminus binding Source: RGD
  15. protein domain specific binding Source: RGD
  16. protein kinase binding Source: RGD
  17. receptor binding Source: RGD
  18. receptor tyrosine kinase binding Source: RGD
  19. ubiquitin protein ligase binding Source: RGD

GO - Biological processi

  1. aging Source: RGD
  2. cellular response to fatty acid Source: RGD
  3. cellular response to insulin stimulus Source: RGD
  4. glucose metabolic process Source: RGD
  5. insulin-like growth factor receptor signaling pathway Source: UniProtKB
  6. insulin receptor signaling pathway Source: UniProtKB
  7. negative regulation of blood pressure Source: RGD
  8. negative regulation of cell-cell adhesion Source: RGD
  9. negative regulation of heart rate Source: RGD
  10. negative regulation of muscle cell apoptotic process Source: RGD
  11. negative regulation of proteolysis Source: RGD
  12. negative regulation of smooth muscle cell proliferation Source: RGD
  13. phosphatidylinositol-3-phosphate biosynthetic process Source: GOC
  14. phosphatidylinositol phosphorylation Source: UniProtKB
  15. positive regulation of cell migration Source: RGD
  16. positive regulation of gene expression Source: RGD
  17. positive regulation of myoblast differentiation Source: RGD
  18. positive regulation of protein phosphorylation Source: RGD
  19. regulation of phosphatidylinositol 3-kinase activity Source: RGD
  20. response to amino acid Source: RGD
  21. response to cAMP Source: RGD
  22. response to dexamethasone Source: RGD
  23. response to drug Source: RGD
  24. response to estradiol Source: RGD
  25. response to ethanol Source: RGD
  26. response to fatty acid Source: RGD
  27. response to fructose Source: RGD
  28. response to glucocorticoid Source: RGD
  29. response to growth factor Source: RGD
  30. response to insulin Source: RGD
  31. response to iron(II) ion Source: RGD
  32. response to nutrient Source: RGD
  33. response to progesterone Source: RGD
  34. response to testosterone Source: RGD
  35. response to yeast Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_196225. Regulation of signaling by CBL.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3329. Pik3r1.

Subcellular locationi

GO - Cellular componenti

  1. 1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Source: UniProtKB
  2. cytosol Source: Reactome
  3. membrane Source: RGD
  4. neuron projection Source: RGD
  5. nucleus Source: RGD
  6. phosphatidylinositol 3-kinase complex Source: RGD
  7. plasma membrane Source: RGD
  8. protein complex Source: RGD
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 724723Phosphatidylinositol 3-kinase regulatory subunit alphaPRO_0000080760Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei467 – 4671PhosphotyrosineBy similarity
Modified residuei580 – 5801PhosphotyrosineBy similarity
Modified residuei608 – 6081PhosphoserineBy similarity

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 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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63787.
PRIDEiQ63787.

PTM databases

PhosphoSiteiQ63787.

Expressioni

Tissue specificityi

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.

Gene expression databases

GenevestigatoriQ63787.

Interactioni

Subunit structurei

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.By similarity2 PublicationsCurated

Binary interactionsi

WithEntry#Exp.IntActNotes
A0MZ672EBI-518443,EBI-1392040
Dnm1P215752EBI-518443,EBI-80070
Gabra1P628134EBI-518443,EBI-6258192
Irs1P355703EBI-518443,EBI-520230
Khdrbs1Q91V332EBI-518443,EBI-518436
PDE6GP185452EBI-518443,EBI-2622029From a different organism.

Protein-protein interaction databases

BioGridi247545. 7 interactions.
DIPiDIP-33696N.
IntActiQ63787. 18 interactions.
MINTiMINT-2880471.

Structurei

Secondary structure

1
724
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi324 – 3274
Helixi340 – 3467
Beta strandi347 – 3493
Beta strandi358 – 3603
Beta strandi363 – 3653
Beta strandi371 – 3744
Beta strandi377 – 3804
Beta strandi385 – 3939
Helixi403 – 4075
Beta strandi408 – 4114
Beta strandi415 – 4173

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FU5NMR-A322-431[»]
1FU6NMR-A322-431[»]
ProteinModelPortaliQ63787.
SMRiQ63787. Positions 1-84, 115-309, 328-600, 614-724.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ63787.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 7977SH3PROSITE-ProRule annotationAdd
BLAST
Domaini113 – 301189Rho-GAPPROSITE-ProRule annotationAdd
BLAST
Domaini333 – 42896SH2 1PROSITE-ProRule annotationAdd
BLAST
Domaini624 – 71895SH2 2PROSITE-ProRule annotationAdd
BLAST

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

eggNOGiNOG263689.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiQ63787.
KOiK02649.
PhylomeDBiQ63787.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
PF07653. SH3_2. 1 hit.
[Graphical view]
PRINTSiPR00678. PI3KINASEP85.
PR00401. 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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform p85-alpha (identifier: Q63787) [UniParc]FASTAAdd to Basket

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.

« 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 PVLTLPDLAE QFAPPDVAPP LLIKLLEAIE KKGLECSTLY
160 170 180 190 200
RTQSSSNPAE LRQLLDCDPP SVDLDVFDEH VLADAFKRYL ADLPNPVIPV
210 220 230 240 250
AVYNEMMSLA QEVPSSEDYI QLLKKLIRSP NIPHQYWLTL QYLLKHFFKL
260 270 280 290 300
SQASSKNLLN ARALSEIFSH VLFRFPAASS DNTEHLIKAV ELLISAEWSE
310 320 330 340 350
RQPAPALPPK PPKPTSIANN 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 RTAIEAFNDT IKIFEEQCHP
510 520 530 540 550
QERYSKDYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID SRRRLEEDLK
560 570 580 590 600
KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
610 620 630 640 650
ENTEDQYSLV DDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE
660 670 680 690 700
SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH
710 720
TSLVQHNDSL NVTLAYPVYA QQRR
Length:724
Mass (Da):83,531
Last modified:November 1, 1996 - v1
Checksum:i95C65CF612873B84
GO
Isoform p55-alpha (identifier: Q63787-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-270: Missing.
     271-304: VLFRFPAASSDNTEHLIKAVELLISAEWSERQPA → MYTTVWTMEDLDLECAKTDINCGTDLMFYIEMDP

Show »
Length:455
Mass (Da):53,525
Checksum:iF28B7DCFCB94F170
GO
Isoform p50-alpha (identifier: Q63787-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-300: Missing.
     301-306: RQPAPA → MHNLQT

Show »
Length:425
Mass (Da):50,090
Checksum:i5C77A94F4E24A11D
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 300299Missing in isoform p50-alpha. 2 PublicationsVSP_004711Add
BLAST
Alternative sequencei2 – 270269Missing in isoform p55-alpha. 1 PublicationVSP_004709Add
BLAST
Alternative sequencei271 – 30434VLFRF…ERQPA → MYTTVWTMEDLDLECAKTDI NCGTDLMFYIEMDP in isoform p55-alpha. 1 PublicationVSP_004710Add
BLAST
Alternative sequencei301 – 3066RQPAPA → MHNLQT in isoform p50-alpha. 2 PublicationsVSP_004712

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D64045 mRNA. Translation: BAA18932.1.
D64048 mRNA. Translation: BAA18933.1.
U50412 mRNA. Translation: AAC52846.1.
D78486 mRNA. Translation: BAA24426.1.
RefSeqiNP_037137.1. NM_013005.1. [Q63787-1]
UniGeneiRn.10599.

Genome annotation databases

GeneIDi25513.
KEGGirno:25513.
UCSCiRGD:3329. rat. [Q63787-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D64045 mRNA. Translation: BAA18932.1 .
D64048 mRNA. Translation: BAA18933.1 .
U50412 mRNA. Translation: AAC52846.1 .
D78486 mRNA. Translation: BAA24426.1 .
RefSeqi NP_037137.1. NM_013005.1. [Q63787-1 ]
UniGenei Rn.10599.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FU5 NMR - A 322-431 [» ]
1FU6 NMR - A 322-431 [» ]
ProteinModelPortali Q63787.
SMRi Q63787. Positions 1-84, 115-309, 328-600, 614-724.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247545. 7 interactions.
DIPi DIP-33696N.
IntActi Q63787. 18 interactions.
MINTi MINT-2880471.

PTM databases

PhosphoSitei Q63787.

Proteomic databases

PaxDbi Q63787.
PRIDEi Q63787.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25513.
KEGGi rno:25513.
UCSCi RGD:3329. rat. [Q63787-1 ]

Organism-specific databases

CTDi 5295.
RGDi 3329. Pik3r1.

Phylogenomic databases

eggNOGi NOG263689.
HOGENOMi HOG000008438.
HOVERGENi HBG082100.
InParanoidi Q63787.
KOi K02649.
PhylomeDBi Q63787.

Enzyme and pathway databases

Reactomei REACT_196225. Regulation of signaling by CBL.

Miscellaneous databases

EvolutionaryTracei Q63787.
NextBioi 606957.
PROi Q63787.

Gene expression databases

Genevestigatori Q63787.

Family and domain databases

Gene3Di 1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProi IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view ]
PANTHERi PTHR10155. PTHR10155. 1 hit.
Pfami PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
PF07653. SH3_2. 1 hit.
[Graphical view ]
PRINTSi PR00678. PI3KINASEP85.
PR00401. SH2DOMAIN.
SMARTi SM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view ]
SUPFAMi SSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEi PS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiP85A_RAT
AccessioniPrimary (citable) accession number: Q63787
Secondary accession number(s): O55085, P70544, Q63790
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 139 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

External Data

Dasty 3