Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P32871 (PK3CA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

Short name=PI3-kinase subunit alpha
Short name=PI3K-alpha
Short name=PI3Kalpha
Short name=PtdIns-3-kinase subunit alpha
EC=2.7.1.153
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 names
Name:PIK3CA
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length1068 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.3

Catalytic activity

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.

Subunit structure

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

Domain

The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain By similarity. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane By similarity. 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 similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 C2 PI3K-type domain.

Contains 1 PI3K-ABD domain.

Contains 1 PI3K-RBD domain.

Contains 1 PI3K/PI4K domain.

Contains 1 PIK helical domain.

Ontologies

Keywords
   Biological processAngiogenesis
   DiseaseProto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

hypomethylation of CpG island

Inferred from electronic annotation. Source: Ensembl

negative regulation of anoikis

Inferred from electronic annotation. Source: Ensembl

negative regulation of fibroblast apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol phosphorylation

Inferred from direct assay Ref.1. Source: BHF-UCL

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from Biological aspect of Ancestor. Source: GOC

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: InterPro

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

regulation of genetic imprinting

Inferred from electronic annotation. Source: Ensembl

regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

   Cellular_component1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex

Inferred from electronic annotation. Source: Ensembl

lamellipodium

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase complex

Inferred from direct assay Ref.1. Source: BHF-UCL

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_function1-phosphatidylinositol-3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

1-phosphatidylinositol-4-phosphate 3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylinositol 3-kinase activity

Inferred from direct assay Ref.1. Source: BHF-UCL

phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 8313896. Source: IntAct

protein kinase activator activity

Inferred from electronic annotation. Source: Ensembl

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PIK3R1P237274EBI-1373130,EBI-520244
PIK3R2P237263EBI-1373130,EBI-1555978

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10681068Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
PRO_0000088784

Regions

Domain16 – 10590PI3K-ABD
Domain187 – 289103PI3K-RBD
Domain330 – 487158C2 PI3K-type
Domain517 – 694178PIK helical
Domain797 – 1068272PI3K/PI4K

Secondary structure

.................... 1068
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P32871 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: C753DCC2F39FDDF0

FASTA1,068124,328
        10         20         30         40         50         60 
MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLITIKHELF KEARKYPLHQ 

        70         80         90        100        110        120 
LLQDESSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK VIEPVGNREE KILNREIGFA 

       130        140        150        160        170        180 
IGMPVCEFDM VKDPEVQDFR RNILNVCKEA VDLRDLNSPH SRAMYVYPPN VESSPELPKH 

       190        200        210        220        230        240 
IYNKLDKGQI IVVIWVIVSP NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK 

       250        260        270        280        290        300 
LCVLEYQGKY ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPMD 

       310        320        330        340        350        360 
CFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD IDKIYVRTGI 

       370        380        390        400        410        420 
YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA RLCLSICSVK GRKGAKEEHC 

       430        440        450        460        470        480 
PLAWGNINLF DYTDTLVSGK MALNLWPVPH GLEDLLNPIG VTGSNPNKET PCLELEFDWF 

       490        500        510        520        530        540 
SSVVKFPDMS VIEEHANWSV SREAGFSYSH AGLSNRLARD NELRENDKEQ LRAICTRDPL 

       550        560        570        580        590        600 
SEITEQEKDF LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME 

       610        620        630        640        650        660 
LLDCNYPDPM VRGFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV RFLLKKALTN 

       670        680        690        700        710        720 
QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK HLNRQVEAME KLINLTDILK 

       730        740        750        760        770        780 
QEKKDETQKV QMKFLVEQMR RPDFMDALQG FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW 

       790        800        810        820        830        840 
LNWENPDIMS ELLFQNNEII FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS 

       850        860        870        880        890        900 
IGDCVGLIEV VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS 

       910        920        930        940        950        960 
CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE RVPFVLTQDF 

       970        980        990       1000       1010       1020 
LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN LFSMMLGSGM PELQSFDDIA 

      1030       1040       1050       1060 
YIRKTLALDK TEQEALEYFM KQMNDAHHGG WTTKMDWIFH TIKQHALN 

« Hide

References

[1]"Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit."
Hiles I.D., Otsu M., Volinia S., Fry M.J., Gout I., Dhand R., Panayotou G., Ruiz-Larrea F., Thompson A., Totty N.F., Hsuan J.J., Courtneidge S.A., Parker P.J., Waterfield M.D.
Cell 70:419-429(1992) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M93252 mRNA. Translation: AAA30698.1.
PIRA43322.
RefSeqNP_776999.1. NM_174574.1.
UniGeneBt.447.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2V1YX-ray2.40A1-108[»]
ProteinModelPortalP32871.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-39319N.
IntActP32871. 3 interactions.
MINTMINT-1518096.
STRING9913.ENSBTAP00000012168.

Chemistry

BindingDBP32871.
ChEMBLCHEMBL2498.

Proteomic databases

PRIDEP32871.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000012168; ENSBTAP00000012168; ENSBTAG00000009232.
GeneID282306.
KEGGbta:282306.

Organism-specific databases

CTD5290.

Phylogenomic databases

eggNOGCOG5032.
GeneTreeENSGT00620000087742.
HOGENOMHOG000252911.
HOVERGENHBG052721.
InParanoidP32871.
KOK00922.
OMAAFAVRCL.
OrthoDBEOG70CR65.
TreeFamTF102031.

Enzyme and pathway databases

BRENDA2.7.1.137. 908.

Family and domain databases

Gene3D1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProIPR016024. 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]
PANTHERPTHR10048. PTHR10048. 1 hit.
PfamPF00454. 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]
SMARTSM00239. 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]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00915. 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]
ProtoNetSearch...

Other

EvolutionaryTraceP32871.
NextBio20806105.

Entry information

Entry namePK3CA_BOVIN
AccessionPrimary (citable) accession number: P32871
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 11, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references