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

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P42336 (PK3CA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 141. History...

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

Documents (7) |

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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Ref.5
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). Interacts with IRS1 in nuclear extracts. Interacts with RUFY3 By similarity. Interacts with RASD2 By similarity. Interacts with APPL1. 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. Ref.4 Ref.11
Domain	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. Ref.9 Ref.11
Involvement in disease	Most of the cancer-derived mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS1/KRAS. Interaction with HRAS1/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note: The gene represented in this entry may be involved in disease pathogenesis. Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.21 Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27
Miscellaneous	The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA (Ref.6).
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
Coding sequence diversity	Polymorphism
Disease	Disease mutation Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cardiac muscle contraction Traceable author statement PubMed 19147653. Source: UniProtKB endothelial cell migration Traceable author statement Ref.8. Source: UniProtKB epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome glucose metabolic process Inferred from electronic annotation. Source: Compara hypomethylation of CpG island Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade Traceable author statement Ref.8. Source: UniProtKB leukocyte migration Traceable author statement. Source: Reactome negative regulation of anoikis Inferred from mutant phenotype PubMed 22402981. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome platelet activation Traceable author statement PubMed 21035500. Source: UniProtKB 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 small molecule metabolic process Traceable author statement. Source: Reactome vasculature development Traceable author statement Ref.8. Source: UniProtKB
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from direct assay PubMed 22402981. Source: UniProtKB lamellipodium Inferred from electronic annotation. Source: Compara plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	1-phosphatidylinositol-3-kinase activity Inferred from direct assay PubMed 2174051. Source: UniProtKB 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 Traceable author statement. Source: Reactome 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	P27986	2	EBI-2116585,EBI-79464

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_0000088785

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

Natural variations

Natural variant

R → H in cancer; shows an increase in lipid kinase activity; may disrupt the interaction between the PI3K-ABD domain and the N-terminal lobe of PI3K/PI4K kinase domain possibly affecting the conformation of the kinase domain. Ref.17

VAR_026166

Natural variant

I → V. Ref.1
Corresponds to variant rs1051399 [ dbSNP | Ensembl ].

VAR_042942

Natural variant

R → Q in cancer; may disrupt the interaction between the PI3K-ABD domain and the N-terminal lobe of PI3K/PI4K kinase domain possibly affecting the conformation of the kinase domain. Ref.15

VAR_026167

Natural variant

106

G → V in cancer; shows an increase in lipid kinase activity. Ref.17

VAR_026168

Natural variant

332

S → R. Ref.1
Corresponds to variant rs1051407 [ dbSNP | Ensembl ].

VAR_042943

Natural variant

343

Y → C in cancer. Ref.22

VAR_026169

Natural variant

391

I → M. Ref.22
Corresponds to variant rs3729680 [ dbSNP | Ensembl ].

VAR_026170

Natural variant

420

C → R in CLOVE and cancer; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. Ref.17 Ref.27

VAR_026171

Natural variant

453

E → Q in cancer; shows an increase in lipid kinase activity; may disrupt the interaction of the C2 PI3K-type domain with the iSH2 region of the p85 regulatory subunit. Ref.17

VAR_026172

Natural variant

542

E → K in CLOVE and KERSEB; shows an increase in lipid kinase activity; oncogenic in vivo; occurs in the interface between the PI3K helical domain and the nSH2 (N-terminal SH2) region of the p85 regulatory subunit and may reduce the inhibitory effect of p85; requires interaction with RAS to induce cellular transformation. Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22 Ref.24 Ref.25 Ref.26 Ref.27

VAR_026173

Natural variant

542

E → Q in cancer. Ref.18

VAR_026174

Natural variant

542

E → V in cancer. Ref.24

VAR_026175

Natural variant

545

E → A in cancer. Ref.15 Ref.21

VAR_026176

Natural variant

545

E → G in KERSEB. Ref.13 Ref.18 Ref.19 Ref.26

VAR_026177

Natural variant

545

E → K in KERSEB; shows an increase in lipid kinase activity; oncogenic in vivo; occurs in the interface between the PI3K helical domain and the nSH2 (N-terminal SH2) region of the p85 regulatory subunit and may reduce the inhibitory effect of p85; requires interaction with RAS to induce cellular transformation; enhances invadopodia-mediated extracellular matrix degradation and invasion in breast cancer cells. Ref.5 Ref.12 Ref.13 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.26

VAR_026178

Natural variant

546

Q → E in cancer. Ref.13

VAR_026179

Natural variant

546

Q → K in cancer. Ref.13

VAR_026180

Natural variant

546

Q → P in cancer. Ref.12

VAR_026181

Natural variant

546

Q → R in cancer. Ref.24

VAR_026182

Natural variant

1007

G → R in cancer. Ref.18

VAR_026183

Natural variant

1021

Y → C in cancer. Ref.18

VAR_026184

Natural variant

1021

Y → H in cancer. Ref.18

VAR_026185

Natural variant

1021

Y → N in cancer. Ref.12

VAR_026186

Natural variant

1023

R → Q in cancer. Ref.19

VAR_026187

Natural variant

1025

T → N in cancer. Ref.15

VAR_026188

Natural variant

1035

A → V in cancer. Ref.18

VAR_026189

Natural variant

1043

M → I in cancer; shows an increase in lipid kinase activity. Ref.17 Ref.18

VAR_026190

Natural variant

1047

H → L in cancer. Ref.12 Ref.13 Ref.19 Ref.24

VAR_026191

Natural variant

1047

H → R in CLOVE and KERSEB; shows an increase in lipid kinase activity; oncogenic in vivo; requires binding to p85 regulatory subunit to induce cellular transformation but not interaction with RAS; may mimic the conformatitonal change triggered by the interaction with RAS; enhances invadopodia-mediated extracellular matrix degradation and invasion in breast cancer cells; increases lipid kinase activity; may alter the interaction of the PI3K/PI4K kinase domain with the cell membrane. Ref.5 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27

VAR_026192

Natural variant

1047

H → Y in cancer. Ref.18

VAR_026193

Natural variant

1050

G → D in cancer. Ref.18

VAR_026194

Natural variant

1052

T → K in cancer. Ref.18

VAR_026195

Natural variant

1065

H → L in cancer. Ref.18

VAR_026196

Natural variant

1065

H → Y in cancer. Ref.12

VAR_026197

Experimental info

Sequence conflict

170

N → H in CAA82333. Ref.1

Sequence conflict

187

K → R in CAA82333. Ref.1

Sequence conflict

286 – 287

ML → KM in CAA82333. Ref.1

Sequence conflict

346

V → L in CAA82333. Ref.1

Sequence conflict

723

K → R in CAA82333. Ref.1

Sequence conflict

751

F → L in CAA82333. Ref.1

Sequence conflict

767

E → K in CAA82333. Ref.1

Secondary structure

1068

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P42336 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: 041487231A9A1207
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FASTA

1,068

124,284

        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 LKAISTRDPL 

       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

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene." Volinia S., Hiles I., Ormondroyd E., Nizetic D., Antonacci R., Rocchi M., Waterfield M. Genomics 24:472-477(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-43 AND ARG-332.
[2]	"Cloning and mutagenesis of the p110 alpha subunit of human phosphoinositide 3'-hydroxykinase." Stirdivant S.M., Ahern J., Conroy R.R., Barnett S.F., Ledder L.M., Oliff A., Heimbrook D.C. Bioorg. Med. Chem. 5:65-74(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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]. Tissue: Lung.
[4]	"Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2." Mitsuuchi Y., Johnson S.W., Sonoda G., Tanno S., Golemis E.A., Testa J.R. Oncogene 18:4891-4898(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APPL1.
[5]	"Phosphoinositide 3-kinase signaling pathway mediated by p110{alpha} regulates invadopodia formation." Yamaguchi H., Yoshida S., Muroi E., Yoshida N., Kawamura M., Kouchi Z., Nakamura Y., Sakai R., Fukami K. J. Cell Biol. 193:1275-1288(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INVADOPODIA FORMATION, CHARACTERIZATION OF VARIANTS LYS-545 AND ARG-1047.
[6]	"Insights into the oncogenic effects of PIK3CA mutations from the structure of p110alpha/p85alpha." Huang C.-H., Mandelker D., Gabelli S.B., Amzel L.M. Cell Cycle 7:1151-1156(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON CANCER.
[7]	"Class I PI3K in oncogenic cellular transformation." Zhao L., Vogt P.K. Oncogene 27:5486-5496(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION, REVIEW ON CANCER.
[8]	"Should individual PI3 kinase isoforms be targeted in cancer?" Jia S., Roberts T.M., Zhao J.J. Curr. Opin. Cell Biol. 21:199-208(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[9]	"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 ANGSTROMS) IN A COMPLEX WITH PIK3R1, DOMAINS.
[10]	"Solution structure of the C2 domain from human PI3-kinase p110 subunit alpha." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 331-481.
[11]	"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 (2.8 ANGSTROMS) OF MUTANT HIS-1047 IN COMPLEX WITH WORTMANNIN AND PIK3R1, INTERACTION WITH PIK3R1, CHARACTERIZATION OF VARIANT ARG-1047, DOMAINS.
[12]	"Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas." Broderick D.K., Di C., Parrett T.J., Samuels Y.R., Cummins J.M., McLendon R.E., Fults D.W., Velculescu V.E., Bigner D.D., Yan H. Cancer Res. 64:5048-5050(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER LYS-542; LYS-545; PRO-546; ASN-1021; ARG-1047; LEU-1047 AND TYR-1065.
[13]	"Mutation of the PIK3CA gene in ovarian and breast cancer." Campbell I.G., Russell S.E., Choong D.Y.H., Montgomery K.G., Ciavarella M.L., Hooi C.S.F., Cristiano B.E., Pearson R.B., Phillips W.A. Cancer Res. 64:7678-7681(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER GLY-545; LYS-545; LYS-546; GLU-546; ARG-1047 AND LEU-1047.
[14]	"High frequency of mutations of the PIK3CA gene in human cancers." Samuels Y., Wang Z., Bardelli A., Silliman N., Ptak J., Szabo S., Yan H., Gazdar A., Powell S.M., Riggins G.J., Willson J.K.V., Markowitz S., Kinzler K.W., Vogelstein B., Velculescu V.E. Science 304:554-554(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CANCER ARG-1047.
[15]	"PIK3CA mutations in glioblastoma multiforme." Hartmann C., Bartels G., Gehlhaar C., Holtkamp N., von Deimling A. Acta Neuropathol. 109:639-642(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER GLN-88; LYS-542; ALA-545 AND ASN-1025.
[16]	"Mutations of PIK3CA in gastric adenocarcinoma." Li V.S.W., Wong C.W., Chan T.L., Chan A.S.W., Zhao W., Chu K.-M., So S., Chen X., Yuen S.T., Leung S.Y. BMC Cancer 5:29-29(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047.
[17]	"Functional analysis of PIK3CA gene mutations in human colorectal cancer." Ikenoue T., Kanai F., Hikiba Y., Obata T., Tanaka Y., Imamura J., Ohta M., Jazag A., Guleng B., Tateishi K., Asaoka Y., Matsumura M., Kawabe T., Omata M. Cancer Res. 65:4562-4567(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CANCER HIS-38; VAL-106; ARG-420; GLN-453; LYS-542; LYS-545; ILE-1043 AND ARG-1047.
[18]	"High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma." Oda K., Stokoe D., Taketani Y., McCormick F. Cancer Res. 65:10669-10673(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER GLN-542; LYS-542; GLY-545; LYS-545; ARG-1007; HIS-1021; CYS-1021; VAL-1035; ILE-1043; TYR-1047; ARG-1047; ASP-1050; LYS-1052 AND LEU-1065.
[19]	"The prevalence of PIK3CA mutations in gastric and colon cancer." Velho S., Oliveira C., Ferreira A., Ferreira A.C., Suriano G., Schwartz S. Jr., Duval A., Carneiro F., Machado J.C., Hamelin R., Seruca R. Eur. J. Cancer 41:1649-1654(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER LYS-542; GLY-545; LYS-545; GLN-1023; ARG-1047 AND LEU-1047.
[20]	"PIK3CA mutations in advanced ovarian carcinomas." Wang Y., Helland A., Holm R., Kristensen G.B., Boerresen-Dale A.-L. Hum. Mutat. 25:322-322(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER LYS-545 AND ARG-1047.
[21]	"PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas." Lee J.W., Soung Y.H., Kim S.Y., Lee H.W., Park W.S., Nam S.W., Kim S.H., Lee J.Y., Yoo N.J., Lee S.H. Oncogene 24:1477-1480(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HCC ALA-545.
[22]	"PIK3CA mutations in head and neck squamous cell carcinoma." Qiu W., Schoenleben F., Li X., Ho D.J., Close L.G., Manolidis S., Bennett B.P., Su G.H. Clin. Cancer Res. 12:1441-1446(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER CYS-343; LYS-542; LYS-545 AND ARG-1047, VARIANT MET-391.
[23]	"PIK3CA mutations in nasopharyngeal carcinoma." Or Y.Y.-Y., Hui A.B.-Y., To K.-F., Lam C.N.-Y., Lo K.-W. Int. J. Cancer 118:1065-1067(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CANCER ARG-1047.
[24]	"PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma." Buttitta F., Felicioni L., Barassi F., Martella C., Paolizzi D., Fresu G., Salvatore S., Cuccurullo F., Mezzetti A., Campani D., Marchetti A. J. Pathol. 208:350-355(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CANCER LYS-542; VAL-542; LYS-545; ARG-546; ARG-1047 AND LEU-1047.
[25]	"Cancer-specific mutations in PIK3CA are oncogenic in vivo." Bader A.G., Kang S., Vogt P.K. Proc. Natl. Acad. Sci. U.S.A. 103:1475-1479(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047.
[26]	"Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern." Hafner C., Lopez-Knowles E., Luis N.M., Toll A., Baselga E., Fernandez-Casado A., Hernandez S., Ribe A., Mentzel T., Stoehr R., Hofstaedter F., Landthaler M., Vogt T., Pujol R.M., Hartmann A., Real F.X. Proc. Natl. Acad. Sci. U.S.A. 104:13450-13454(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS KERSEB LYS-542; LYS-545; GLY-545 AND ARG-1047.
[27]	"Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome." Kurek K.C., Luks V.L., Ayturk U.M., Alomari A.I., Fishman S.J., Spencer S.A., Mulliken J.B., Bowen M.E., Yamamoto G.L., Kozakewich H.P., Warman M.L. Am. J. Hum. Genet. 90:1108-1115(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLOVE ARG-420; LYS-542 AND ARG-1047.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z29090 mRNA. Translation: CAA82333.1.
U79143 mRNA. Translation: AAB39753.1.
BC113601 mRNA. Translation: AAI13602.1.
BC113603 mRNA. Translation: AAI13604.1.

IPI

IPI00031386.

PIR

I38110.

RefSeq

NP_006209.2. NM_006218.2.

UniGene

Hs.553498.
Hs.715194.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ENQ	NMR	-	A	331-481	[»]
2RD0	X-ray	3.05	A	1-1068	[»]
3HHM	X-ray	2.80	A	1-1068	[»]
3HIZ	X-ray	3.30	A	1-1068	[»]
3ZIM	X-ray	2.85	A	107-1046	[»]

ProteinModelPortal

P42336.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42728N.

IntAct

P42336. 23 interactions.

MINT

MINT-1367228.

STRING

9606.ENSP00000263967.

PTM databases

PhosphoSite

P42336.

Polymorphism databases

DMDM

126302584.

Proteomic databases

PaxDb

P42336.

PRIDE

P42336.

Protocols and materials databases

DNASU

5290.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263967; ENSP00000263967; ENSG00000121879.

GeneID

5290.

KEGG

hsa:5290.

UCSC

uc003fjk.3. human.

Organism-specific databases

CTD

5290.

GeneCards

GC03P178865.

HGNC

HGNC:8975. PIK3CA.

HPA

CAB017804.
HPA009985.

MIM

114480. phenotype.
114500. phenotype.
114550. phenotype.
167000. phenotype.
171834. gene.
182000. phenotype.
612918. phenotype.

neXtProt

NX_P42336.

Orphanet

140944. CLOVE syndrome.
144. Hereditary nonpolyposis colon cancer.

PharmGKB

PA33308.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5032.

HOVERGEN

HBG052721.

InParanoid

P42336.

K00922.

OMA

AFAVRCL.

OrthoDB

EOG45TCMC.

PhylomeDB

P42336.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04527-MONOMER.

BRENDA

2.7.1.137. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
arf6cyclingpathway. Arf6 signaling events.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
epha2_fwdpathway. EPHA2 forward signaling.
ephbfwdpathway. EPHB forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
il1pathway. IL1-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
insulin_pathway. Insulin Pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
mtor_4pathway. mTOR signaling pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
avb3_opn_pathway. Osteopontin-mediated events.
p75ntrpathway. p75(NTR)-mediated signaling.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrapathway. PDGFR-alpha signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
trail_pathway. TRAIL signaling pathway.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
vegfr1_pathway. VEGFR1 specific signals.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P42336.

Bgee

P42336.

CleanEx

HS_PIK3CA.

Genevestigator

P42336.

GermOnline

ENSG00000121879. Homo sapiens.

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

P42336.

ChEMBL

CHEMBL4005.

ChiTaRS

PIK3CA. human.

EvolutionaryTrace

P42336.

GenomeRNAi

5290.

NextBio

20442.

SOURCE

Search...

Entry information

Entry name

PK3CA_HUMAN

Accession

Primary (citable) accession number: P42336
Secondary accession number(s): Q14CW1, Q99762

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents