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

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P32871 (PK3CA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 114. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	1068 AA.
Sequence status	Complete.
Protein existence	Evidence 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 HRAS1 and KRAS By similarity. Interaction with HRAS1/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 process	Angiogenesis
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW glucose metabolic process Inferred from electronic annotation. Source: Compara hypomethylation of CpG island Inferred from electronic annotation. Source: Compara negative regulation of anoikis Inferred from electronic annotation. Source: Compara phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: InterPro positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara regulation of genetic imprinting Inferred from electronic annotation. Source: Compara regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from electronic annotation. Source: Compara lamellipodium Inferred from electronic annotation. Source: Compara phosphatidylinositol 3-kinase complex Inferred from direct assay Ref.1. Source: BHF-UCL plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	1-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-4,5-bisphosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome protein kinase activator activity Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIK3R1	P23727	4	EBI-1373130,EBI-520244
PIK3R2	P23726	3	EBI-1373130,EBI-1555978

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1068

1068

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

PRO_0000088784

Regions

Domain

16 – 105

PI3K-ABD

Domain

187 – 289

103

PI3K-RBD

Domain

330 – 487

158

C2 PI3K-type

Domain

517 – 694

178

PIK helical

Domain

797 – 1068

272

PI3K/PI4K

Secondary structure

1068

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P32871 [UniParc].

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

FASTA

1,068

124,328

        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.

IPI

IPI00686923.

PIR

A43322.

RefSeq

NP_776999.1. NM_174574.1.

UniGene

Bt.447.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V1Y	X-ray	2.40	A	1-108	[»]

ProteinModelPortal

P32871.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39319N.

IntAct

P32871. 3 interactions.

STRING

9913.ENSBTAP00000012168.

Proteomic databases

PRIDE

P32871.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSBTAT00000012168; ENSBTAP00000012168; ENSBTAG00000009232.

GeneID

282306.

KEGG

bta:282306.

Organism-specific databases

CTD

5290.

Phylogenomic databases

eggNOG

COG5032.

GeneTree

ENSGT00620000087742.

HOGENOM

HOG000252911.

HOVERGEN

HBG052721.

InParanoid

P32871.

K00922.

OMA

AFAVRCL.

OrthoDB

EOG45TCMC.

Enzyme and pathway databases

BRENDA

2.7.1.137. 908.

Family and domain databases

Gene3D

1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.

InterPro

IPR016024. ARM-type_fold.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
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.
[Graphical view]

PANTHER

PTHR10048. PTHR10048. 1 hit.

Pfam

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]

SMART

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]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS50004. C2. False negative.
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]

ProtoNet

Search...

Other

BindingDB

P32871.

ChEMBL

CHEMBL2498.

EvolutionaryTrace

P32871.

NextBio

20806105.

Entry information

Entry name

PK3CA_BOVIN

Accession

Primary (citable) accession number: P32871

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Entry information

Relevant documents