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P32871

- PK3CA_BOVIN

UniProt

P32871 - PK3CA_BOVIN

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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

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 kinase activator activity Source: Ensembl
  7. 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-mediated signaling Source: InterPro
  8. phosphatidylinositol phosphorylation Source: BHF-UCL
  9. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  10. protein kinase B signaling Source: Ensembl
  11. regulation of genetic imprinting Source: Ensembl
  12. regulation of multicellular organism growth Source: Ensembl
Complete GO annotation...

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
Complete GO annotation...

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.
GeneTreeiENSGT00760000119110.
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

        10         20         30         40         50
MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLITIKHELF
60 70 80 90 100
KEARKYPLHQ LLQDESSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK
110 120 130 140 150
VIEPVGNREE KILNREIGFA IGMPVCEFDM VKDPEVQDFR RNILNVCKEA
160 170 180 190 200
VDLRDLNSPH SRAMYVYPPN VESSPELPKH IYNKLDKGQI IVVIWVIVSP
210 220 230 240 250
NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK LCVLEYQGKY
260 270 280 290 300
ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPMD
310 320 330 340 350
CFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD
360 370 380 390 400
IDKIYVRTGI YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA
410 420 430 440 450
RLCLSICSVK GRKGAKEEHC PLAWGNINLF DYTDTLVSGK MALNLWPVPH
460 470 480 490 500
GLEDLLNPIG VTGSNPNKET PCLELEFDWF SSVVKFPDMS VIEEHANWSV
510 520 530 540 550
SREAGFSYSH AGLSNRLARD NELRENDKEQ LRAICTRDPL SEITEQEKDF
560 570 580 590 600
LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME
610 620 630 640 650
LLDCNYPDPM VRGFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV
660 670 680 690 700
RFLLKKALTN QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK
710 720 730 740 750
HLNRQVEAME KLINLTDILK QEKKDETQKV QMKFLVEQMR RPDFMDALQG
760 770 780 790 800
FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW LNWENPDIMS ELLFQNNEII
810 820 830 840 850
FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS IGDCVGLIEV
860 870 880 890 900
VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS
910 920 930 940 950
CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE
960 970 980 990 1000
RVPFVLTQDF LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN
1010 1020 1030 1040 1050
LFSMMLGSGM PELQSFDDIA YIRKTLALDK TEQEALEYFM KQMNDAHHGG
1060
WTTKMDWIFH TIKQHALN
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 ENSGT00760000119110.
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 29, 2014
This is version 125 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