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P32871

- PK3CA_BOVIN

UniProt

P32871 - PK3CA_BOVIN

Protein

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

Gene

PIK3CA

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Oct 1993)
      Previous versions | rss
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    Functioni

    Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway By similarity. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.By similarity2 Publications

    Catalytic activityi

    ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.
    ATP + a protein = ADP + a phosphoprotein.

    GO - Molecular functioni

    1. 1-phosphatidylinositol-3-kinase activity Source: RefGenome
    2. 1-phosphatidylinositol-4-phosphate 3-kinase activity Source: RefGenome
    3. ATP binding Source: UniProtKB-KW
    4. phosphatidylinositol 3-kinase activity Source: BHF-UCL
    5. phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: RefGenome
    6. protein binding Source: IntAct
    7. protein kinase activator activity Source: Ensembl
    8. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. glucose metabolic process Source: Ensembl
    3. hypomethylation of CpG island Source: Ensembl
    4. negative regulation of anoikis Source: Ensembl
    5. negative regulation of fibroblast apoptotic process Source: Ensembl
    6. negative regulation of neuron apoptotic process Source: Ensembl
    7. phosphatidylinositol-3-phosphate biosynthetic process Source: GOC
    8. phosphatidylinositol-mediated signaling Source: InterPro
    9. phosphatidylinositol phosphorylation Source: BHF-UCL
    10. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    11. protein kinase B signaling Source: Ensembl
    12. regulation of genetic imprinting Source: Ensembl
    13. regulation of multicellular organism growth Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Angiogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.137. 908.
    ReactomeiREACT_203011. Signaling by constitutively active EGFR.
    REACT_204114. Signaling by SCF-KIT.
    REACT_204467. PI-3K cascade.
    REACT_204566. Tie2 Signaling.
    REACT_205384. G alpha (12/13) signalling events.
    REACT_205423. Downstream TCR signaling.
    REACT_208171. PIP3 activates AKT signaling.
    REACT_209521. G alpha (q) signalling events.
    REACT_209911. PI3K Cascade.
    REACT_211267. Interleukin-3, 5 and GM-CSF signaling.
    REACT_211504. Nephrin interactions.
    REACT_212750. Downstream signal transduction.
    REACT_213843. Costimulation by the CD28 family.
    REACT_214988. DAP12 signaling.
    REACT_215783. Role of phospholipids in phagocytosis.
    REACT_215895. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_217559. CD28 dependent PI3K/Akt signaling.
    REACT_218512. Regulation of signaling by CBL.
    REACT_219098. GPVI-mediated activation cascade.
    REACT_219416. PI3K events in ERBB2 signaling.
    REACT_222082. GAB1 signalosome.
    REACT_222492. PI3K events in ERBB4 signaling.
    REACT_223657. Interleukin receptor SHC signaling.
    REACT_224097. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_225332. PI3K/AKT activation.
    REACT_226907. Signaling by FGFR mutants.
    REACT_227241. Signaling by FGFR1 fusion mutants.
    REACT_227888. Synthesis of PIPs at the plasma membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (EC:2.7.1.153)
    Short name:
    PI3-kinase subunit alpha
    Short name:
    PI3K-alpha
    Short name:
    PI3Kalpha
    Short name:
    PtdIns-3-kinase subunit alpha
    Alternative name(s):
    Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha
    Short name:
    PtdIns-3-kinase subunit p110-alpha
    Short name:
    p110alpha
    Phosphoinositide-3-kinase catalytic alpha polypeptide
    Serine/threonine protein kinase PIK3CA (EC:2.7.11.1)
    Gene namesi
    Name:PIK3CA
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 1

    Subcellular locationi

    GO - Cellular componenti

    1. 1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Source: Ensembl
    2. lamellipodium Source: Ensembl
    3. phosphatidylinositol 3-kinase complex Source: BHF-UCL
    4. plasma membrane Source: RefGenome

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10681068Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformPRO_0000088784Add
    BLAST

    Proteomic databases

    PRIDEiP32871.

    Interactioni

    Subunit structurei

    Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with IRS1 in nuclear extracts. Interacts with RUFY3. Interacts with RASD2. Interacts with APPL1. Interacts with HRAS and KRAS. Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PIK3R1P237274EBI-1373130,EBI-520244
    PIK3R2P237263EBI-1373130,EBI-1555978

    Protein-protein interaction databases

    DIPiDIP-39319N.
    IntActiP32871. 3 interactions.
    MINTiMINT-1518096.
    STRINGi9913.ENSBTAP00000012168.

    Structurei

    Secondary structure

    1
    1068
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi18 – 258
    Beta strandi31 – 377
    Helixi42 – 5211
    Helixi53 – 553
    Helixi59 – 613
    Helixi65 – 673
    Beta strandi69 – 746
    Beta strandi79 – 824
    Helixi89 – 913
    Beta strandi94 – 1029

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2V1YX-ray2.40A1-108[»]
    ProteinModelPortaliP32871.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP32871.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 10590PI3K-ABDPROSITE-ProRule annotationAdd
    BLAST
    Domaini187 – 289103PI3K-RBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini330 – 487158C2 PI3K-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini517 – 694178PIK helicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini797 – 1068272PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1.By similarity

    Sequence similaritiesi

    Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
    Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
    Contains 1 PI3K-ABD domain.PROSITE-ProRule annotation
    Contains 1 PI3K-RBD domain.PROSITE-ProRule annotation
    Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
    Contains 1 PIK helical domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5032.
    GeneTreeiENSGT00620000087742.
    HOGENOMiHOG000252911.
    HOVERGENiHBG052721.
    InParanoidiP32871.
    KOiK00922.
    OMAiAFAVRCL.
    OrthoDBiEOG70CR65.
    TreeFamiTF102031.

    Family and domain databases

    Gene3Di1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    2.60.40.150. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003113. PI3K_adapt-bd_dom.
    IPR002420. PI3K_C2_dom.
    IPR000341. PI3K_Ras-bd_dom.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PANTHERiPTHR10048. PTHR10048. 1 hit.
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF02192. PI3K_p85B. 1 hit.
    PF00794. PI3K_rbd. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view]
    SMARTiSM00239. C2. 1 hit.
    SM00142. PI3K_C2. 1 hit.
    SM00143. PI3K_p85B. 1 hit.
    SM00144. PI3K_rbd. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 1 hit.
    SSF49562. SSF49562. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51544. PI3K_ABD. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51546. PI3K_RBD. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P32871-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLITIKHELF     50
    KEARKYPLHQ LLQDESSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK 100
    VIEPVGNREE KILNREIGFA IGMPVCEFDM VKDPEVQDFR RNILNVCKEA 150
    VDLRDLNSPH SRAMYVYPPN VESSPELPKH IYNKLDKGQI IVVIWVIVSP 200
    NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK LCVLEYQGKY 250
    ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPMD 300
    CFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD 350
    IDKIYVRTGI YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA 400
    RLCLSICSVK GRKGAKEEHC PLAWGNINLF DYTDTLVSGK MALNLWPVPH 450
    GLEDLLNPIG VTGSNPNKET PCLELEFDWF SSVVKFPDMS VIEEHANWSV 500
    SREAGFSYSH AGLSNRLARD NELRENDKEQ LRAICTRDPL SEITEQEKDF 550
    LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME 600
    LLDCNYPDPM VRGFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV 650
    RFLLKKALTN QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK 700
    HLNRQVEAME KLINLTDILK QEKKDETQKV QMKFLVEQMR RPDFMDALQG 750
    FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW LNWENPDIMS ELLFQNNEII 800
    FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS IGDCVGLIEV 850
    VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS 900
    CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE 950
    RVPFVLTQDF LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN 1000
    LFSMMLGSGM PELQSFDDIA YIRKTLALDK TEQEALEYFM KQMNDAHHGG 1050
    WTTKMDWIFH TIKQHALN 1068
    Length:1,068
    Mass (Da):124,328
    Last modified:October 1, 1993 - v1
    Checksum:iC753DCC2F39FDDF0
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93252 mRNA. Translation: AAA30698.1.
    PIRiA43322.
    RefSeqiNP_776999.1. NM_174574.1.
    UniGeneiBt.447.

    Genome annotation databases

    EnsembliENSBTAT00000012168; ENSBTAP00000012168; ENSBTAG00000009232.
    GeneIDi282306.
    KEGGibta:282306.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93252 mRNA. Translation: AAA30698.1 .
    PIRi A43322.
    RefSeqi NP_776999.1. NM_174574.1.
    UniGenei Bt.447.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2V1Y X-ray 2.40 A 1-108 [» ]
    ProteinModelPortali P32871.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-39319N.
    IntActi P32871. 3 interactions.
    MINTi MINT-1518096.
    STRINGi 9913.ENSBTAP00000012168.

    Chemistry

    BindingDBi P32871.
    ChEMBLi CHEMBL2498.

    Proteomic databases

    PRIDEi P32871.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000012168 ; ENSBTAP00000012168 ; ENSBTAG00000009232 .
    GeneIDi 282306.
    KEGGi bta:282306.

    Organism-specific databases

    CTDi 5290.

    Phylogenomic databases

    eggNOGi COG5032.
    GeneTreei ENSGT00620000087742.
    HOGENOMi HOG000252911.
    HOVERGENi HBG052721.
    InParanoidi P32871.
    KOi K00922.
    OMAi AFAVRCL.
    OrthoDBi EOG70CR65.
    TreeFami TF102031.

    Enzyme and pathway databases

    BRENDAi 2.7.1.137. 908.
    Reactomei REACT_203011. Signaling by constitutively active EGFR.
    REACT_204114. Signaling by SCF-KIT.
    REACT_204467. PI-3K cascade.
    REACT_204566. Tie2 Signaling.
    REACT_205384. G alpha (12/13) signalling events.
    REACT_205423. Downstream TCR signaling.
    REACT_208171. PIP3 activates AKT signaling.
    REACT_209521. G alpha (q) signalling events.
    REACT_209911. PI3K Cascade.
    REACT_211267. Interleukin-3, 5 and GM-CSF signaling.
    REACT_211504. Nephrin interactions.
    REACT_212750. Downstream signal transduction.
    REACT_213843. Costimulation by the CD28 family.
    REACT_214988. DAP12 signaling.
    REACT_215783. Role of phospholipids in phagocytosis.
    REACT_215895. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_217559. CD28 dependent PI3K/Akt signaling.
    REACT_218512. Regulation of signaling by CBL.
    REACT_219098. GPVI-mediated activation cascade.
    REACT_219416. PI3K events in ERBB2 signaling.
    REACT_222082. GAB1 signalosome.
    REACT_222492. PI3K events in ERBB4 signaling.
    REACT_223657. Interleukin receptor SHC signaling.
    REACT_224097. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_225332. PI3K/AKT activation.
    REACT_226907. Signaling by FGFR mutants.
    REACT_227241. Signaling by FGFR1 fusion mutants.
    REACT_227888. Synthesis of PIPs at the plasma membrane.

    Miscellaneous databases

    EvolutionaryTracei P32871.
    NextBioi 20806105.

    Family and domain databases

    Gene3Di 1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    2.60.40.150. 1 hit.
    InterProi IPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003113. PI3K_adapt-bd_dom.
    IPR002420. PI3K_C2_dom.
    IPR000341. PI3K_Ras-bd_dom.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    PANTHERi PTHR10048. PTHR10048. 1 hit.
    Pfami PF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF02192. PI3K_p85B. 1 hit.
    PF00794. PI3K_rbd. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view ]
    SMARTi SM00239. C2. 1 hit.
    SM00142. PI3K_C2. 1 hit.
    SM00143. PI3K_p85B. 1 hit.
    SM00144. PI3K_rbd. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    SSF49562. SSF49562. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51544. PI3K_ABD. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51546. PI3K_RBD. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Brain.
    2. "eIF4E binding protein 1 and H-Ras are novel substrates for the protein kinase activity of class-I phosphoinositide 3-kinase."
      Foukas L.C., Shepherd P.R.
      Biochem. Biophys. Res. Commun. 319:541-549(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS PROTEIN KINASE.
    3. "Regulation of phosphoinositide 3-kinase by its intrinsic serine kinase activity in vivo."
      Foukas L.C., Beeton C.A., Jensen J., Phillips W.A., Shepherd P.R.
      Mol. Cell. Biol. 24:966-975(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS PROTEIN KINASE.

    Entry informationi

    Entry nameiPK3CA_BOVIN
    AccessioniPrimary (citable) accession number: P32871
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1993
    Last modified: October 1, 2014
    This is version 124 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, Direct protein sequencing, 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