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P42336 (PK3CA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. 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 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. 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

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

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 HRAS/KRAS. Interaction with HRAS/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.

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

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28

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

Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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 processAngiogenesis
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Proto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Fc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

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

blood coagulation

Traceable author statement. Source: Reactome

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: Ensembl

hypomethylation of CpG island

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

insulin receptor signaling pathway via phosphatidylinositol 3-kinase

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

negative regulation of fibroblast apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from direct assay PubMed 2174051. Source: GOC

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

phospholipid metabolic process

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: 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

small molecule metabolic process

Traceable author statement. Source: Reactome

vasculature development

Traceable author statement Ref.8. Source: UniProtKB

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

Inferred from direct assay PubMed 22402981. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

lamellipodium

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase complex

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_function1-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

kinase activity

Traceable author statement. Source: Reactome

phosphatidylinositol 3-kinase activity

Traceable author statement Ref.8. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Traceable author statement. Source: Reactome

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10681068Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
PRO_0000088785

Regions

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

Natural variations

Natural variant381R → 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 variant431I → V. Ref.1
Corresponds to variant rs1051399 [ dbSNP | Ensembl ].
VAR_042942
Natural variant811E → K in MCAP. Ref.28
VAR_069251
Natural variant881R → Q in MCAP and 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 Ref.28
VAR_026167
Natural variant1061G → V in cancer; shows an increase in lipid kinase activity. Ref.17
VAR_026168
Natural variant1181G → D in CWD5. Ref.29
VAR_069786
Natural variant1351E → K in CWD5. Ref.29
VAR_069787
Natural variant2181E → K in CWD5. Ref.29
VAR_069788
Natural variant3321S → R. Ref.1
Corresponds to variant rs1051407 [ dbSNP | Ensembl ].
VAR_042943
Natural variant3431Y → C in cancer. Ref.22
VAR_026169
Natural variant3561V → I in CWD5. Ref.29
VAR_069789
Natural variant3641G → R in MCAP. Ref.28
VAR_069252
Natural variant3651E → K in MCAP. Ref.28
VAR_069253
Natural variant3781C → Y in MCAP. Ref.28
VAR_069254
Natural variant3821R → K in CWD5. Ref.29
VAR_069790
Natural variant3911I → M. Ref.22
Corresponds to variant rs3729680 [ dbSNP | Ensembl ].
VAR_026170
Natural variant4201C → 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 variant4531E → 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 variant4531Missing in MCAP and MPPH. Ref.28
VAR_069255
Natural variant5421E → 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 variant5421E → Q in cancer. Ref.18
VAR_026174
Natural variant5421E → V in cancer. Ref.24
VAR_026175
Natural variant5451E → A in cancer and CWD5. Ref.15 Ref.21 Ref.29
VAR_026176
Natural variant5451E → G in KERSEB. Ref.13 Ref.18 Ref.19 Ref.26
VAR_026177
Natural variant5451E → K in MCAP 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; 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 Ref.28
VAR_026178
Natural variant5461Q → E in cancer. Ref.13
VAR_026179
Natural variant5461Q → K in cancer. Ref.13
VAR_026180
Natural variant5461Q → P in cancer. Ref.12
VAR_026181
Natural variant5461Q → R in cancer. Ref.24
VAR_026182
Natural variant7261E → K in MCAP. Ref.28
VAR_069256
Natural variant9141G → R in MCAP. Ref.28
VAR_069257
Natural variant10071G → R in cancer. Ref.18
VAR_026183
Natural variant10211Y → C in MCAP and cancer. Ref.18 Ref.28
VAR_026184
Natural variant10211Y → H in cancer. Ref.18
VAR_026185
Natural variant10211Y → N in cancer. Ref.12
VAR_026186
Natural variant10231R → Q in cancer. Ref.19
VAR_026187
Natural variant10251T → A in MCAP. Ref.28
VAR_069258
Natural variant10251T → N in cancer. Ref.15
VAR_026188
Natural variant10351A → V in MCAP and cancer. Ref.18 Ref.28
VAR_026189
Natural variant10431M → I in MCAP and cancer; shows an increase in lipid kinase activity. Ref.17 Ref.18 Ref.28
VAR_026190
Natural variant10471H → L in cancer. Ref.12 Ref.13 Ref.19 Ref.24
VAR_026191
Natural variant10471H → 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 variant10471H → Y in MCAP and cancer. Ref.18 Ref.28
VAR_026193
Natural variant10491G → S in MCAP. Ref.28
VAR_069259
Natural variant10501G → D in cancer. Ref.18
VAR_026194
Natural variant10521T → K in cancer. Ref.18
VAR_026195
Natural variant10651H → L in cancer. Ref.18
VAR_026196
Natural variant10651H → Y in cancer. Ref.12
VAR_026197

Experimental info

Sequence conflict1701N → H in CAA82333. Ref.1
Sequence conflict1871K → R in CAA82333. Ref.1
Sequence conflict286 – 2872ML → KM in CAA82333. Ref.1
Sequence conflict3461V → L in CAA82333. Ref.1
Sequence conflict7231K → R in CAA82333. Ref.1
Sequence conflict7511F → L in CAA82333. Ref.1
Sequence conflict7671E → K in CAA82333. Ref.1

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P42336 [UniParc].

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

FASTA1,068124,284
        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 

« Hide

References

« Hide '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.
[28]"De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes."
Riviere J.B., Mirzaa G.M., O'Roak B.J., Beddaoui M., Alcantara D., Conway R.L., St-Onge J., Schwartzentruber J.A., Gripp K.W., Nikkel S.M., Worthylake T., Sullivan C.T., Ward T.R., Butler H.E., Kramer N.A., Albrecht B., Armour C.M., Armstrong L. expand/collapse author list , Caluseriu O., Cytrynbaum C., Drolet B.A., Innes A.M., Lauzon J.L., Lin A.E., Mancini G.M., Meschino W.S., Reggin J.D., Saggar A.K., Lerman-Sagie T., Uyanik G., Weksberg R., Zirn B., Beaulieu C.L., Majewski J., Bulman D.E., O'Driscoll M., Shendure J., Graham J.M. Jr., Boycott K.M., Dobyns W.B.
Nat. Genet. 44:934-940(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCAP LYS-81; GLN-88; ARG-364; LYS-365; TYR-378; GLU-453 DEL; LYS-545; LYS-726; ARG-914; CYS-1021; ALA-1025; VAL-1035; ILE-1043; TYR-1047 AND SER-1049, VARIANT MPPH GLU-453 DEL.
[29]"Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes."
Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L., Eng C.
Am. J. Hum. Genet. 92:76-80(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CWD5 ASP-118; LYS-135; LYS-218; ILE-356; LYS-382 AND ALA-545.
+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.
PIRI38110.
RefSeqNP_006209.2. NM_006218.2.
UniGeneHs.553498.
Hs.715194.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ENQNMR-A331-481[»]
2RD0X-ray3.05A1-1068[»]
3HHMX-ray2.80A1-1068[»]
3HIZX-ray3.30A1-1068[»]
3ZIMX-ray2.85A107-1046[»]
4L1BX-ray2.59A1-1068[»]
4L23X-ray2.50A1-1068[»]
4L2YX-ray2.80A1-1068[»]
ProteinModelPortalP42336.
SMRP42336. Positions 16-105, 107-1046.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111308. 49 interactions.
DIPDIP-42728N.
IntActP42336. 25 interactions.
MINTMINT-1367228.
STRING9606.ENSP00000263967.

Chemistry

BindingDBP42336.
ChEMBLCHEMBL2111367.
GuidetoPHARMACOLOGY2153.

PTM databases

PhosphoSiteP42336.

Polymorphism databases

DMDM126302584.

Proteomic databases

PaxDbP42336.
PRIDEP42336.

Protocols and materials databases

DNASU5290.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263967; ENSP00000263967; ENSG00000121879.
GeneID5290.
KEGGhsa:5290.
UCSCuc003fjk.3. human.

Organism-specific databases

CTD5290.
GeneCardsGC03P178865.
HGNCHGNC:8975. PIK3CA.
HPACAB017804.
HPA009985.
MIM114480. phenotype.
114500. phenotype.
114550. phenotype.
167000. phenotype.
171834. gene.
182000. phenotype.
602501. phenotype.
603387. phenotype.
612918. phenotype.
615108. phenotype.
neXtProtNX_P42336.
Orphanet140944. CLOVE syndrome.
201. Cowden syndrome.
99802. Hemimegalencephaly.
144. Hereditary nonpolyposis colon cancer.
295239. Macrodactyly of fingers, unilateral.
60040. Megalencephaly-capillary malformation-polymicrogyria syndrome.
314662. Segmental progressive overgrowth syndrome with fibroadipose hyperplasia.
PharmGKBPA33308.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOVERGENHBG052721.
InParanoidP42336.
KOK00922.
OMAAFAVRCL.
OrthoDBEOG70CR65.
PhylomeDBP42336.
TreeFamTF102031.

Enzyme and pathway databases

BioCycMetaCyc:HS04527-MONOMER.
BRENDA2.7.1.137. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP42336.

Gene expression databases

ArrayExpressP42336.
BgeeP42336.
CleanExHS_PIK3CA.
GenevestigatorP42336.

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.
[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.
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

ChiTaRSPIK3CA. human.
EvolutionaryTraceP42336.
GeneWikiP110%CE%B1.
GenomeRNAi5290.
NextBio20442.
PROP42336.
SOURCESearch...

Entry information

Entry namePK3CA_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

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