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P27986

- P85A_HUMAN

UniProt

P27986 - P85A_HUMAN

Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

PIK3R1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 181 (01 Oct 2014)
      Sequence version 2 (28 Nov 2006)
      Previous versions | rss
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    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.3 Publications

    GO - Molecular functioni

    1. ErbB-3 class receptor binding Source: UniProtKB
    2. insulin binding Source: UniProtKB
    3. insulin-like growth factor receptor binding Source: UniProtKB
    4. insulin receptor binding Source: UniProtKB
    5. insulin receptor substrate binding Source: BHF-UCL
    6. neurotrophin TRKA receptor binding Source: UniProtKB
    7. phosphatidylinositol 3-kinase binding Source: BHF-UCL
    8. phosphatidylinositol 3-kinase regulator activity Source: UniProtKB
    9. protein binding Source: IntAct
    10. protein phosphatase binding Source: UniProtKB
    11. transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL

    GO - Biological processi

    1. B cell differentiation Source: Ensembl
    2. blood coagulation Source: Reactome
    3. cellular response to UV Source: Ensembl
    4. epidermal growth factor receptor signaling pathway Source: Reactome
    5. extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
    6. Fc-epsilon receptor signaling pathway Source: Reactome
    7. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    8. fibroblast growth factor receptor signaling pathway Source: Reactome
    9. growth hormone receptor signaling pathway Source: BHF-UCL
    10. innate immune response Source: Reactome
    11. insulin-like growth factor receptor signaling pathway Source: UniProtKB
    12. insulin receptor signaling pathway Source: Reactome
    13. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
    14. leukocyte migration Source: Reactome
    15. negative regulation of apoptotic process Source: Ensembl
    16. negative regulation of cell-matrix adhesion Source: Ensembl
    17. negative regulation of osteoclast differentiation Source: Ensembl
    18. neurotrophin TRK receptor signaling pathway Source: Reactome
    19. NFAT protein import into nucleus Source: Ensembl
    20. phosphatidylinositol 3-kinase signaling Source: BHF-UCL
    21. phosphatidylinositol biosynthetic process Source: Reactome
    22. phosphatidylinositol-mediated signaling Source: Reactome
    23. phosphatidylinositol phosphorylation Source: UniProtKB
    24. phospholipid metabolic process Source: Reactome
    25. platelet activation Source: Reactome
    26. positive regulation of cell migration Source: Ensembl
    27. positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
    28. positive regulation of glucose import Source: BHF-UCL
    29. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    30. positive regulation of tumor necrosis factor production Source: Ensembl
    31. protein phosphorylation Source: Ensembl
    32. regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
    33. small molecule metabolic process Source: Reactome
    34. T cell costimulation Source: Reactome
    35. T cell receptor signaling pathway Source: Reactome
    36. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Host-virus interaction

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000145675-MONOMER.
    ReactomeiREACT_111040. Signaling by SCF-KIT.
    REACT_115529. Interleukin-7 signaling.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115961. PI3K events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_121141. Signaling by FGFR1 fusion mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_12464. PI3K/AKT activation.
    REACT_12555. Downstream TCR signaling.
    REACT_12578. GAB1 signalosome.
    REACT_12621. Tie2 Signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_160158. Role of phospholipids in phagocytosis.
    REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_17025. Downstream signal transduction.
    REACT_18283. G alpha (q) signalling events.
    REACT_18407. G alpha (12/13) signalling events.
    REACT_19344. Costimulation by the CD28 family.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_21270. PI-3K cascade.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23832. Nephrin interactions.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23847. GP1b-IX-V activation signalling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_976. PI3K Cascade.
    SignaLinkiP27986.

    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
    Synonyms:GRB1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:8979. 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: UniProtKB
    4. phosphatidylinositol 3-kinase complex Source: BHF-UCL
    5. plasma membrane Source: Reactome

    Pathology & Biotechi

    Involvement in diseasei

    Agammaglobulinemia 7, autosomal recessive (AGM7) [MIM:615214]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    SHORT syndrome (SHORTS) [MIM:269880]: A rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti489 – 4891E → K in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication
    VAR_070221
    Natural varianti539 – 5391Missing in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication
    VAR_070222
    Natural varianti649 – 6491R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 1 Publication
    VAR_070223

    Keywords - Diseasei

    Disease mutation, Dwarfism

    Organism-specific databases

    MIMi269880. phenotype.
    615214. phenotype.
    Orphaneti33110. Autosomal agammaglobulinemia.
    3163. SHORT syndrome.
    PharmGKBiPA33312.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 724723Phosphatidylinositol 3-kinase regulatory subunit alphaPRO_0000080758Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    Modified residuei467 – 4671PhosphotyrosineBy similarity
    Modified residuei580 – 5801Phosphotyrosine1 Publication
    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.2 Publications
    Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R. Phosphorylated by ERBB4. 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 By similarity. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR.By similarity3 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP27986.
    PaxDbiP27986.
    PRIDEiP27986.

    PTM databases

    PhosphoSiteiP27986.

    Expressioni

    Tissue specificityi

    Isoform 2 is expressed in skeletal muscle and brain, and at lower levels in kidney and cardiac muscle. Isoform 2 and isoform 4 are present in skeletal muscle (at protein level).1 Publication

    Gene expression databases

    ArrayExpressiP27986.
    BgeeiP27986.
    CleanExiHS_PIK3R1.
    GenevestigatoriP27986.

    Organism-specific databases

    HPAiCAB004268.
    HPA001216.

    Interactioni

    Subunit structurei

    Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with FER. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with PTK2/FAK1 By similarity. Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with SOCS7. Interacts with RUFY3. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity By similarity. Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. Interacts with CBLB. Interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK). This interaction depends on the C-terminus of both proteins and leads to increased production of HIV. Interacts with HCV NS5A. 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 IRS1 and phosphorylated IRS4, as well as with NISCH and HCST. Interacts with FASLG, KIT and BCR. Interacts with AXL, FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated). Interacts with FGR and HCK. Interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated). Interacts with NTRK1 (phosphorylated upon ligand-binding).By similarity28 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ABI1Q8IZP08EBI-79464,EBI-375446
    ABL2P426842EBI-79464,EBI-1102694
    ARP102755EBI-79464,EBI-608057
    CBLP226815EBI-79464,EBI-518228
    CD28P107478EBI-79464,EBI-4314301
    CMIPQ8IY222EBI-79464,EBI-7689652
    CRKP461082EBI-79464,EBI-886
    CRKLP461092EBI-79464,EBI-910
    CTLA4P164103EBI-79464,EBI-1030991
    DLGAP4Q9Y2H02EBI-79464,EBI-722139
    EGFRP005335EBI-79464,EBI-297353
    ERBB2P0462611EBI-79464,EBI-641062
    ERBB3P2186040EBI-79464,EBI-720706
    ESR1P033726EBI-79464,EBI-78473
    FASLGP480232EBI-79464,EBI-495538
    FGFR1P113625EBI-79464,EBI-1028277
    FLT1P179482EBI-79464,EBI-1026718
    FLT3P368882EBI-79464,EBI-3946257
    GAB1Q1348033EBI-79464,EBI-517684
    GRB2P629933EBI-79464,EBI-401755
    HTTP428587EBI-79464,EBI-466029
    IGF1RP080694EBI-79464,EBI-475981
    INSRP062133EBI-79464,EBI-475899
    IRS1P3556812EBI-79464,EBI-517592
    Irs1P355702EBI-79464,EBI-520230From a different organism.
    IRS2Q9Y4H22EBI-79464,EBI-1049582
    KITP1072119EBI-79464,EBI-1379503
    LAPTM4BQ86VI4-32EBI-79464,EBI-3267286
    LATO435614EBI-79464,EBI-1222766
    MAP4K1Q929182EBI-79464,EBI-881
    MAPK8P459832EBI-79464,EBI-286483
    METP085816EBI-79464,EBI-1039152
    NELFBQ8WX922EBI-79464,EBI-347721
    Nyap1Q6PFX74EBI-79464,EBI-7447489From a different organism.
    Nyap2Q8BM65-43EBI-79464,EBI-7447598From a different organism.
    PDGFRBP0961919EBI-79464,EBI-641237
    PIK3CAP4233613EBI-79464,EBI-2116585
    PLCG2P168852EBI-79464,EBI-617403
    PXNP490232EBI-79464,EBI-702209
    RAPGEF1Q139052EBI-79464,EBI-976876
    RPL13P263732EBI-79464,EBI-356849
    RXRAP197938EBI-79464,EBI-78598
    SHANK2Q9UPX82EBI-79464,EBI-1570571
    SHC1P293533EBI-79464,EBI-78835
    SIRT1Q96EB63EBI-79464,EBI-1802965
    SOS1Q078893EBI-79464,EBI-297487
    SRCP129316EBI-79464,EBI-621482
    SSTR2P308745EBI-79464,EBI-6266898
    TIRAPP587533EBI-79464,EBI-528644
    TLR3O154552EBI-79464,EBI-6116630
    TPSAB1Q156612EBI-79464,EBI-1761369
    TPX2Q9ULW02EBI-79464,EBI-1037322
    VAV3Q9UKW42EBI-79464,EBI-297568
    VP3Q991523EBI-79464,EBI-1776808From a different organism.
    ZDHHC17Q8IUH52EBI-9090282,EBI-524753

    Protein-protein interaction databases

    BioGridi111313. 126 interactions.
    DIPiDIP-119N.
    IntActiP27986. 196 interactions.
    MINTiMINT-93751.
    STRINGi9606.ENSP00000274335.

    Structurei

    Secondary structure

    1
    724
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 107
    Beta strandi29 – 335
    Helixi34 – 407
    Turni43 – 453
    Helixi46 – 483
    Helixi50 – 534
    Beta strandi55 – 606
    Turni61 – 644
    Beta strandi65 – 706
    Helixi71 – 733
    Beta strandi74 – 818
    Turni100 – 1023
    Helixi118 – 1214
    Helixi130 – 14314
    Turni147 – 1504
    Helixi160 – 1645
    Beta strandi167 – 1704
    Helixi174 – 1763
    Helixi179 – 19113
    Beta strandi193 – 1953
    Helixi200 – 20910
    Helixi210 – 2123
    Helixi216 – 22712
    Helixi234 – 25219
    Helixi254 – 2574
    Helixi261 – 27313
    Helixi280 – 29516
    Helixi323 – 3253
    Helixi326 – 3294
    Beta strandi334 – 3374
    Helixi340 – 3478
    Beta strandi354 – 3596
    Helixi363 – 3653
    Beta strandi367 – 3748
    Beta strandi377 – 38610
    Beta strandi389 – 3957
    Beta strandi398 – 4003
    Helixi401 – 41010
    Helixi413 – 4153
    Helixi418 – 4203
    Turni430 – 4323
    Helixi433 – 4364
    Helixi442 – 51574
    Helixi518 – 58770
    Helixi591 – 5988
    Helixi617 – 6193
    Helixi621 – 6233
    Beta strandi625 – 6295
    Helixi631 – 6388
    Beta strandi645 – 6506
    Beta strandi652 – 6554
    Beta strandi657 – 6637
    Beta strandi666 – 67510
    Beta strandi678 – 6825
    Beta strandi688 – 6903
    Helixi691 – 70010
    Helixi703 – 7053
    Turni708 – 7103
    Beta strandi716 – 7194

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1A0NNMR-A91-104[»]
    1AZGNMR-A91-104[»]
    1H9OX-ray1.79A617-724[»]
    1PBWX-ray2.00A/B105-319[»]
    1PHTX-ray2.00A1-85[»]
    1PICNMR-A617-724[»]
    1PKSNMR-A1-79[»]
    1PKTNMR-A1-79[»]
    2IUGX-ray1.89A321-440[»]
    2IUHX-ray2.00A321-440[»]
    2IUIX-ray2.40A/B321-440[»]
    2RD0X-ray3.05B322-600[»]
    2V1YX-ray2.40B431-600[»]
    3HHMX-ray2.80B322-694[»]
    3HIZX-ray3.30B322-694[»]
    3I5RX-ray1.70A1-83[»]
    3I5SX-ray3.00A/B/C/D1-83[»]
    4A55X-ray3.50B322-600[»]
    4JPSX-ray2.20B307-593[»]
    4L1BX-ray2.59B318-615[»]
    4L23X-ray2.50B318-615[»]
    4L2YX-ray2.80B318-615[»]
    ProteinModelPortaliP27986.
    SMRiP27986. Positions 3-85, 115-309, 322-724.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27986.

    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, and to HIV-1 Nef.

    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.
    HOVERGENiHBG082100.
    KOiK02649.
    OMAiLNGYNET.
    OrthoDBiEOG7BP831.
    PhylomeDBiP27986.
    TreeFamiTF102033.

    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 (5)i

    Sequence statusi: Complete.

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

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P27986-1) [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

    MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP    50
    EEIGWLNGYN ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG 100
    SSKTEADVEQ QALTLPDLAE QFAPPDIAPP LLIKLVEAIE KKGLECSTLY 150
    RTQSSSNLAE LRQLLDCDTP SVDLEMIDVH VLADAFKRYL LDLPNPVIPA 200
    AVYSEMISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL QYLLKHFFKL 250
    SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE 300
    RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT 350
    ADGTFLVRDA STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS 400
    VVELINHYRN ESLAQYNPKL DVKLLYPVSK YQQDQVVKED NIEAVGKKLH 450
    EYNTQFQEKS REYDRLYEEY TRTSQEIQMK RTAIEAFNET IKIFEEQCQT 500
    QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID SRRRLEEDLK 550
    KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 600
    ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE 650
    SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH 700
    TSLVQHNDSL NVTLAYPVYA QQRR 724
    Length:724
    Mass (Da):83,598
    Last modified:November 28, 2006 - v2
    Checksum:iB9DAD8416C33140F
    GO
    Isoform 2 (identifier: P27986-2) [UniParc]FASTAAdd to Basket

    Also known as: AS53

    The sequence of this isoform differs from the canonical sequence as follows:
         1-270: Missing.
         271-304: MLFRFSAASSDNTENLIKVIEILISTEWNERQPA → MYNTVWNMEDLDLEYAKTDINCGTDLMFYIEMDP

    Show »
    Length:454
    Mass (Da):53,486
    Checksum:i33BB0F88AA47CB3F
    GO
    Isoform 3 (identifier: P27986-3) [UniParc]FASTAAdd to Basket

    Also known as: p46

    The sequence of this isoform differs from the canonical sequence as follows:
         1-300: Missing.
         301-306: RQPAPA → MHNLQT

    Show »
    Length:424
    Mass (Da):49,965
    Checksum:iEF2D6D4D668C62D8
    GO
    Isoform 4 (identifier: P27986-4) [UniParc]FASTAAdd to Basket

    Also known as: p85I

    The sequence of this isoform differs from the canonical sequence as follows:
         605-605: D → ENFLSCLPS

    Show »
    Length:732
    Mass (Da):84,474
    Checksum:iF4820A783035803A
    GO
    Isoform 5 (identifier: P27986-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-363: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:361
    Mass (Da):42,838
    Checksum:i100325CF4D673C4B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti330 – 3301D → N in M61906. (PubMed:1849461)Curated
    Sequence conflicti460 – 4601S → G in BAG52931. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti326 – 3261M → I Does not affect insulin-stimulated lipid kinase activity. 3 Publications
    Corresponds to variant rs3730089 [ dbSNP | Ensembl ].
    VAR_010023
    Natural varianti409 – 4091R → Q in a patient with severe insulin resistance; lower insulin-stimulated lipid kinase activity compared with wild-type. 1 Publication
    VAR_010024
    Natural varianti451 – 4511E → K.1 Publication
    Corresponds to variant rs17852841 [ dbSNP | Ensembl ].
    VAR_029562
    Natural varianti489 – 4891E → K in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication
    VAR_070221
    Natural varianti539 – 5391Missing in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication
    VAR_070222
    Natural varianti649 – 6491R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 1 Publication
    VAR_070223

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 363363Missing in isoform 5. 1 PublicationVSP_045903Add
    BLAST
    Alternative sequencei1 – 300300Missing in isoform 3. 1 PublicationVSP_021841Add
    BLAST
    Alternative sequencei1 – 270270Missing in isoform 2. 3 PublicationsVSP_021842Add
    BLAST
    Alternative sequencei271 – 30434MLFRF…ERQPA → MYNTVWNMEDLDLEYAKTDI NCGTDLMFYIEMDP in isoform 2. 3 PublicationsVSP_021843Add
    BLAST
    Alternative sequencei301 – 3066RQPAPA → MHNLQT in isoform 3. 1 PublicationVSP_021844
    Alternative sequencei605 – 6051D → ENFLSCLPS in isoform 4. 1 PublicationVSP_021845

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M61906 mRNA. No translation available.
    U49349 mRNA. Translation: AAB04140.1.
    AF279367 mRNA. Translation: AAO15359.1.
    AK094785 mRNA. Translation: BAG52931.1.
    AK223613 mRNA. Translation: BAD97333.1.
    AC016564 Genomic DNA. No translation available.
    AC104120 Genomic DNA. No translation available.
    CH471137 Genomic DNA. Translation: EAW51312.1.
    CH471137 Genomic DNA. Translation: EAW51313.1.
    BC030815 mRNA. Translation: AAH30815.1.
    BC094795 mRNA. Translation: AAH94795.1.
    CCDSiCCDS3993.1. [P27986-1]
    CCDS3994.1. [P27986-3]
    CCDS3995.1. [P27986-2]
    CCDS56374.1. [P27986-5]
    PIRiA38748.
    RefSeqiNP_001229395.1. NM_001242466.1. [P27986-5]
    NP_852556.2. NM_181504.3. [P27986-2]
    NP_852664.1. NM_181523.2. [P27986-1]
    NP_852665.1. NM_181524.1. [P27986-3]
    XP_005248599.1. XM_005248542.1. [P27986-1]
    UniGeneiHs.132225.
    Hs.604502.
    Hs.734132.

    Genome annotation databases

    EnsembliENST00000320694; ENSP00000323512; ENSG00000145675. [P27986-3]
    ENST00000336483; ENSP00000338554; ENSG00000145675. [P27986-2]
    ENST00000521381; ENSP00000428056; ENSG00000145675. [P27986-1]
    ENST00000521657; ENSP00000429277; ENSG00000145675. [P27986-1]
    ENST00000523872; ENSP00000430098; ENSG00000145675. [P27986-5]
    GeneIDi5295.
    KEGGihsa:5295.
    UCSCiuc003jva.3. human. [P27986-1]
    uc003jvc.3. human. [P27986-3]
    uc003jvd.3. human. [P27986-2]

    Polymorphism databases

    DMDMi118572681.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M61906 mRNA. No translation available.
    U49349 mRNA. Translation: AAB04140.1 .
    AF279367 mRNA. Translation: AAO15359.1 .
    AK094785 mRNA. Translation: BAG52931.1 .
    AK223613 mRNA. Translation: BAD97333.1 .
    AC016564 Genomic DNA. No translation available.
    AC104120 Genomic DNA. No translation available.
    CH471137 Genomic DNA. Translation: EAW51312.1 .
    CH471137 Genomic DNA. Translation: EAW51313.1 .
    BC030815 mRNA. Translation: AAH30815.1 .
    BC094795 mRNA. Translation: AAH94795.1 .
    CCDSi CCDS3993.1. [P27986-1 ]
    CCDS3994.1. [P27986-3 ]
    CCDS3995.1. [P27986-2 ]
    CCDS56374.1. [P27986-5 ]
    PIRi A38748.
    RefSeqi NP_001229395.1. NM_001242466.1. [P27986-5 ]
    NP_852556.2. NM_181504.3. [P27986-2 ]
    NP_852664.1. NM_181523.2. [P27986-1 ]
    NP_852665.1. NM_181524.1. [P27986-3 ]
    XP_005248599.1. XM_005248542.1. [P27986-1 ]
    UniGenei Hs.132225.
    Hs.604502.
    Hs.734132.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1A0N NMR - A 91-104 [» ]
    1AZG NMR - A 91-104 [» ]
    1H9O X-ray 1.79 A 617-724 [» ]
    1PBW X-ray 2.00 A/B 105-319 [» ]
    1PHT X-ray 2.00 A 1-85 [» ]
    1PIC NMR - A 617-724 [» ]
    1PKS NMR - A 1-79 [» ]
    1PKT NMR - A 1-79 [» ]
    2IUG X-ray 1.89 A 321-440 [» ]
    2IUH X-ray 2.00 A 321-440 [» ]
    2IUI X-ray 2.40 A/B 321-440 [» ]
    2RD0 X-ray 3.05 B 322-600 [» ]
    2V1Y X-ray 2.40 B 431-600 [» ]
    3HHM X-ray 2.80 B 322-694 [» ]
    3HIZ X-ray 3.30 B 322-694 [» ]
    3I5R X-ray 1.70 A 1-83 [» ]
    3I5S X-ray 3.00 A/B/C/D 1-83 [» ]
    4A55 X-ray 3.50 B 322-600 [» ]
    4JPS X-ray 2.20 B 307-593 [» ]
    4L1B X-ray 2.59 B 318-615 [» ]
    4L23 X-ray 2.50 B 318-615 [» ]
    4L2Y X-ray 2.80 B 318-615 [» ]
    ProteinModelPortali P27986.
    SMRi P27986. Positions 3-85, 115-309, 322-724.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111313. 126 interactions.
    DIPi DIP-119N.
    IntActi P27986. 196 interactions.
    MINTi MINT-93751.
    STRINGi 9606.ENSP00000274335.

    Chemistry

    BindingDBi P27986.
    ChEMBLi CHEMBL2506.
    DrugBanki DB01064. Isoproterenol.

    PTM databases

    PhosphoSitei P27986.

    Polymorphism databases

    DMDMi 118572681.

    Proteomic databases

    MaxQBi P27986.
    PaxDbi P27986.
    PRIDEi P27986.

    Protocols and materials databases

    DNASUi 5295.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000320694 ; ENSP00000323512 ; ENSG00000145675 . [P27986-3 ]
    ENST00000336483 ; ENSP00000338554 ; ENSG00000145675 . [P27986-2 ]
    ENST00000521381 ; ENSP00000428056 ; ENSG00000145675 . [P27986-1 ]
    ENST00000521657 ; ENSP00000429277 ; ENSG00000145675 . [P27986-1 ]
    ENST00000523872 ; ENSP00000430098 ; ENSG00000145675 . [P27986-5 ]
    GeneIDi 5295.
    KEGGi hsa:5295.
    UCSCi uc003jva.3. human. [P27986-1 ]
    uc003jvc.3. human. [P27986-3 ]
    uc003jvd.3. human. [P27986-2 ]

    Organism-specific databases

    CTDi 5295.
    GeneCardsi GC05P067511.
    HGNCi HGNC:8979. PIK3R1.
    HPAi CAB004268.
    HPA001216.
    MIMi 171833. gene.
    269880. phenotype.
    615214. phenotype.
    neXtProti NX_P27986.
    Orphaneti 33110. Autosomal agammaglobulinemia.
    3163. SHORT syndrome.
    PharmGKBi PA33312.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG263689.
    HOVERGENi HBG082100.
    KOi K02649.
    OMAi LNGYNET.
    OrthoDBi EOG7BP831.
    PhylomeDBi P27986.
    TreeFami TF102033.

    Enzyme and pathway databases

    BioCyci MetaCyc:ENSG00000145675-MONOMER.
    Reactomei REACT_111040. Signaling by SCF-KIT.
    REACT_115529. Interleukin-7 signaling.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115961. PI3K events in ERBB4 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_121141. Signaling by FGFR1 fusion mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_12464. PI3K/AKT activation.
    REACT_12555. Downstream TCR signaling.
    REACT_12578. GAB1 signalosome.
    REACT_12621. Tie2 Signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_160158. Role of phospholipids in phagocytosis.
    REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_17025. Downstream signal transduction.
    REACT_18283. G alpha (q) signalling events.
    REACT_18407. G alpha (12/13) signalling events.
    REACT_19344. Costimulation by the CD28 family.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_21270. PI-3K cascade.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23832. Nephrin interactions.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23847. GP1b-IX-V activation signalling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_976. PI3K Cascade.
    SignaLinki P27986.

    Miscellaneous databases

    ChiTaRSi PIK3R1. human.
    EvolutionaryTracei P27986.
    GeneWikii PIK3R1.
    GenomeRNAii 5295.
    NextBioi 20462.
    PROi P27986.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P27986.
    Bgeei P27986.
    CleanExi HS_PIK3R1.
    Genevestigatori P27986.

    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. "Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases."
      Skolnik E.Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R., Drepps A., Ullrich A., Schlessinger J.
      Cell 65:83-90(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), INTERACTION WITH IRS1, TISSUE SPECIFICITY.
      Tissue: Skeletal muscle.
    3. Udelhoven M., Kotzka J., Knebel B., Klein E., Krone W., Mueller-Wieland D.
      Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
      Tissue: Skeletal muscle.
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
      Tissue: Brain.
    5. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-326.
      Tissue: Brain.
    6. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LYS-451.
      Tissue: Placenta and Skeletal muscle.
    9. "Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor."
      Nishimura R., Li W., Kashishian A., Mondino A., Zhou M., Cooper J., Schlessinger J.
      Mol. Cell. Biol. 13:6889-6896(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PDGFRB.
    10. "Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor."
      Van Horn D.J., Myers M.G. Jr., Backer J.M.
      J. Biol. Chem. 269:29-32(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INSR.
    11. "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: FUNCTION IN FGFR4 SIGNALING.
    12. "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor."
      Craparo A., O'Neill T.J., Gustafson T.A.
      J. Biol. Chem. 270:15639-15643(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IGF1R.
    13. "Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain."
      Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J.
      Mol. Cell. Biol. 15:2500-2508(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INSR.
    14. "Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors."
      Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.
      J. Biol. Chem. 271:30942-30949(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PDGFRA.
    15. "Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes."
      Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.
      J. Biol. Chem. 272:5915-5920(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KIT.
    16. "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site."
      Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W.
      Oncogene 14:2619-2631(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXL.
    17. "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation."
      Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.
      Cell 92:83-92(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LAT.
    18. "Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells."
      Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E., Lavan B.E.
      J. Biol. Chem. 273:10726-10732(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS4.
    19. "T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane."
      Bruyns E., Marie-Cardine A., Kirchgessner H., Sagolla K., Shevchenko A., Mann M., Autschbach F., Bensussan A., Meuer S., Schraven B.
      J. Exp. Med. 188:561-575(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TRAT1.
    20. "KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties."
      Chang C., Dietrich J., Harpur A.G., Lindquist J.A., Haude A., Loke Y.W., King A., Colonna M., Trowsdale J., Wilson M.J.
      J. Immunol. 163:4651-4654(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCST.
    21. Cited for: INTERACTION WITH CBLB.
    22. "Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase."
      Axelsson L., Hellberg C., Melander F., Smith D., Zheng L., Andersson T.
      Exp. Cell Res. 256:257-263(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGR AND HCK.
    23. "Ligand discrimination in signaling through an ErbB4 receptor homodimer."
      Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., Carraway K.L. III
      J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERBB4.
    24. "Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells."
      Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C.
      J. Biol. Chem. 276:4872-4878(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBLB, UBIQUITINATION.
    25. "Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells."
      Fang D., Liu Y.-C.
      Nat. Immunol. 2:870-875(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD3Z AND CD28, UBIQUITINATION.
    26. "Insulin receptor substrate 4 associates with the protein IRAS."
      Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.
      J. Biol. Chem. 277:19439-19447(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NISCH.
    27. "Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling."
      Zhu M., Janssen E., Leung K., Zhang W.
      J. Biol. Chem. 277:46151-46158(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LAX1.
    28. "Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV."
      Linnemann T., Zheng Y.-H., Mandic R., Peterlin B.M.
      Virology 294:246-255(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 NEF.
    29. "Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase."
      He Y., Nakao H., Tan S.-L., Polyak S.J., Neddermann P., Vijaysri S., Jacobs B.L., Katze M.G.
      J. Virol. 76:9207-9217(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCV NS5A.
    30. Cited for: INTERACTION WITH NTRK1.
    31. "Signal transduction via the stem cell factor receptor/c-Kit."
      Ronnstrand L.
      Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
    32. "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner."
      Laurent C.E., Smithgall T.E.
      Exp. Cell Res. 299:188-198(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BCR.
    33. "The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization."
      Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L., Lowell C.A., Berton G.
      Exp. Cell Res. 302:253-269(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY FGR.
    34. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    35. "The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase."
      Tsuboi N., Utsunomiya T., Roberts R.L., Ito H., Takahashi K., Noda M., Takahashi T.
      Biochem. J. 413:193-200(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ.
    36. "System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties."
      Kaushansky A., Gordus A., Budnik B.A., Lane W.S., Rush J., MacBeath G.
      Chem. Biol. 15:808-817(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERBB4.
    37. "Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
      Voss M., Lettau M., Janssen O.
      BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FASLG.
    38. "A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells."
      Salazar L., Kashiwada T., Krejci P., Muchowski P., Donoghue D., Wilcox W.R., Thompson L.M.
      Hum. Mol. Genet. 18:1951-1961(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGFR3.
    39. "Cellular signaling by fibroblast growth factor receptors."
      Eswarakumar V.P., Lax I., Schlessinger J.
      Cytokine Growth Factor Rev. 16:139-149(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN FGFR1 SIGNALING AND PHOSPHORYLATION.
    40. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-580, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    41. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    42. "Agammaglobulinemia and absent B lineage cells in a patient lacking the p85? subunit of PI3K."
      Conley M.E., Dobbs A.K., Quintana A.M., Bosompem A., Wang Y.D., Coustan-Smith E., Smith A.M., Perez E.E., Murray P.J.
      J. Exp. Med. 209:463-470(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN AGM7.
    43. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    44. "Crystal structure of P13K SH3 domain at 2.0-A resolution."
      Liang J., Chen J.K., Schreiber S.L., Clardy J.
      J. Mol. Biol. 257:632-643(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-85.
    45. "Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes."
      Nolte R.T., Eck M.J., Schlessinger J., Shoelson S.E., Harrison S.C.
      Nat. Struct. Biol. 3:364-373(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 324-434.
    46. "Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit."
      Musacchio A., Cantley L.C., Harrison S.C.
      Proc. Natl. Acad. Sci. U.S.A. 93:14373-14378(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 115-298.
    47. "NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex."
      Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A., Rowsell S., Murshudov G.N.
      Acta Crystallogr. D 57:1397-1404(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 617-724 IN COMPLEX WITH PDGFRB.
    48. "Structure of the PI3K SH3 domain and analysis of the SH3 family."
      Koyama S., Yu H., Dalgarno D.C., Shin T.B., Zydowsky L.D., Schreiber S.L.
      Cell 72:945-952(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-79.
    49. "Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase."
      Renzoni D.A., Pugh D.J., Siligardi G., Das P., Morton C.J., Rossi C., Waterfield M.D., Campbell I.D., Ladbury J.E.
      Biochemistry 35:15646-15653(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 91-104.
    50. "Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase."
      Breeze A.L., Kara B.V., Barratt D.G., Anderson M., Smith J.C., Luke R.W., Best J.R., Cartlidge S.A.
      EMBO J. 15:3579-3589(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 617-724.
    51. "Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit."
      Miled N., Yan Y., Hon W.C., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson H.J., Backer J.M., Williams R.L.
      Science 317:239-242(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 431-600, FUNCTION.
    52. "The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations."
      Huang C.-H., Mandelker D., Schmidt-Kittler O., Samuels Y., Velculescu V.E., Kinzler K.W., Vogelstein B., Gabelli S.B., Amzel L.M.
      Science 318:1744-1748(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 322-600.
    53. "A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane."
      Mandelker D., Gabelli S.B., Schmidt-Kittler O., Zhu J., Cheong I., Huang C.H., Kinzler K.W., Vogelstein B., Amzel L.M.
      Proc. Natl. Acad. Sci. U.S.A. 106:16996-17001(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 322-694, FUNCTION, SUBUNIT.
    54. "Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding."
      Batra-Safferling R., Granzin J., Modder S., Hoffmann S., Willbold D.
      Biol. Chem. 391:33-42(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-83.
    55. "Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index."
      Hansen T., Andersen C.B., Echwald S.M., Urhammer S.A., Clausen J.O., Vestergaard H., Owens D., Hansen L., Pedersen O.
      Diabetes 46:494-501(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ILE-326.
    56. "Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity."
      Baynes K.C.R., Beeton C.A., Panayotou G., Stein R., Soos M., Hansen T., Simpson H., O'Rahilly S., Shepherd P.R., Whitehead J.P.
      Diabetologia 43:321-331(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ILE-326 AND GLN-409, CHARACTERIZATION OF VARIANTS ILE-326 AND GLN-409.
    57. Cited for: VARIANTS SHORTS LYS-489 AND ILE-539 DEL.
    58. "SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling."
      Chudasama K.K., Winnay J., Johansson S., Claudi T., Konig R., Haldorsen I., Johansson B., Woo J.R., Aarskog D., Sagen J.V., Kahn C.R., Molven A., Njolstad P.R.
      Am. J. Hum. Genet. 93:150-157(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SHORTS TRP-649.

    Entry informationi

    Entry nameiP85A_HUMAN
    AccessioniPrimary (citable) accession number: P27986
    Secondary accession number(s): B3KT19
    , D3DWA0, E7EX19, Q15747, Q4VBZ7, Q53EM6, Q8IXA2, Q8N1C5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: November 28, 2006
    Last modified: October 1, 2014
    This is version 181 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3