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Protein

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

Gene

PIK3CA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation 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. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity).By similarity2 Publications

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.By similarity
ATP + a protein = ADP + a phosphoprotein.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Angiogenesis, Phagocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04527-MONOMER.
ZFISH:HS04527-MONOMER.
BRENDAi2.7.1.137. 2681.
2.7.1.153. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1236382. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
R-HSA-1250342. PI3K events in ERBB4 signaling.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-180292. GAB1 signalosome.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-198203. PI3K/AKT activation.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2029485. Role of phospholipids in phagocytosis.
R-HSA-210993. Tie2 Signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-2424491. DAP12 signaling.
R-HSA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-HSA-373753. Nephrin interactions.
R-HSA-388841. Costimulation by the CD28 family.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
R-HSA-416476. G alpha (q) signalling events.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-512988. Interleukin-3, 5 and GM-CSF signaling.
R-HSA-5637810. Constitutive Signaling by EGFRvIII.
R-HSA-5654689. PI-3K cascade:FGFR1.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654710. PI-3K cascade:FGFR3.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5655291. Signaling by FGFR4 in disease.
R-HSA-5655302. Signaling by FGFR1 in disease.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851907. MET activates PI3K/AKT signaling.
R-HSA-8853334. Signaling by FGFR3 fusions in cancer.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
R-HSA-8853659. RET signaling.
R-HSA-912526. Interleukin receptor SHC signaling.
R-HSA-912631. Regulation of signaling by CBL.
SignaLinkiP42336.
SIGNORiP42336.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (EC:2.7.1.153By similarity)
Short name:
PI3-kinase subunit alpha
Short name:
PI3K-alpha
Short name:
PI3Kalpha
Short name:
PtdIns-3-kinase subunit alpha
Alternative name(s):
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha
Short name:
PtdIns-3-kinase subunit p110-alpha
Short name:
p110alpha
Phosphoinositide-3-kinase catalytic alpha polypeptide
Serine/threonine protein kinase PIK3CA (EC:2.7.11.1By similarity)
Gene namesi
Name:PIK3CA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:8975. PIK3CA.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated 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.

Colorectal cancer (CRC)2 Publications
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:114500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02616638R → H in CRC; likely involved in disease pathogenesis; 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. 1 PublicationCorresponds to variant rs772110575dbSNPEnsembl.1
Natural variantiVAR_026168106G → V in CRC; likely involved in disease pathogenesis; shows an increase in lipid kinase activity. 1 Publication1
Natural variantiVAR_026171420C → R in CLOVE and CRC; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 2 PublicationsCorresponds to variant rs121913272dbSNPEnsembl.1
Natural variantiVAR_026172453E → Q in CRC; likely involved in disease pathogenesis; 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. 1 Publication1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC and BC; also found in glioblastoma multiforme and endometrial carcinoma; 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. 11 PublicationsCorresponds to variant rs121913273dbSNPEnsembl.1
Natural variantiVAR_026178545E → K in MCAP, KERSEB, CRC and BC; 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. 13 PublicationsCorresponds to variant rs104886003dbSNPEnsembl.1
Natural variantiVAR_0261871023R → Q in CRC; unknown pathological significance. 1 Publication1
Natural variantiVAR_0261901043M → I in MCAP and CRC; also found in an endometrial carcinoma sample; shows an increase in lipid kinase activity. 3 PublicationsCorresponds to variant rs121913283dbSNPEnsembl.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC and OC; also found in an endometrial carcinoma sample; 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. 16 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Breast cancer (BC)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:114480
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC and BC; also found in glioblastoma multiforme and endometrial carcinoma; 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. 11 PublicationsCorresponds to variant rs121913273dbSNPEnsembl.1
Natural variantiVAR_026175542E → V in BC; unknown pathological significance. 1 Publication1
Natural variantiVAR_026178545E → K in MCAP, KERSEB, CRC and BC; 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. 13 PublicationsCorresponds to variant rs104886003dbSNPEnsembl.1
Natural variantiVAR_026179546Q → E in BC; unknown pathological significance. 1 PublicationCorresponds to variant rs121913286dbSNPEnsembl.1
Natural variantiVAR_026182546Q → R in BC; unknown pathological significance. 1 PublicationCorresponds to variant rs397517201dbSNPEnsembl.1
Natural variantiVAR_0261911047H → L in BC; unknown pathological significance. 4 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC and OC; also found in an endometrial carcinoma sample; 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. 16 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Ovarian cancer (OC)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionThe 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.
See also OMIM:167000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026180546Q → K in OC; unknown pathological significance. 1 PublicationCorresponds to variant rs121913286dbSNPEnsembl.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC and OC; also found in an endometrial carcinoma sample; 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. 16 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Hepatocellular carcinoma (HCC)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:114550
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026176545E → A in CWS5 and HCC; also found in a glioblastoma multiforme sample. 3 PublicationsCorresponds to variant rs121913274dbSNPEnsembl.1
Keratosis, seborrheic (KERSEB)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:182000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC and BC; also found in glioblastoma multiforme and endometrial carcinoma; 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. 11 PublicationsCorresponds to variant rs121913273dbSNPEnsembl.1
Natural variantiVAR_026177545E → G in KERSEB; also found in an endometrial carcinoma sample. 4 PublicationsCorresponds to variant rs121913274dbSNPEnsembl.1
Natural variantiVAR_026178545E → K in MCAP, KERSEB, CRC and BC; 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. 13 PublicationsCorresponds to variant rs104886003dbSNPEnsembl.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC and OC; also found in an endometrial carcinoma sample; 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. 16 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:602501
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06925181E → K in MCAP. 1 Publication1
Natural variantiVAR_02616788R → Q in MCAP; also found in a glioblastoma multiforme sample. 2 PublicationsCorresponds to variant rs121913287dbSNPEnsembl.1
Natural variantiVAR_075634112I → N in MCAP; increased phosphatidylinositol 3-kinase signaling; decreased interaction with p85 regulatory subunit; no effect on protein abundance. 1 Publication1
Natural variantiVAR_069252364G → R in MCAP. 1 Publication1
Natural variantiVAR_069253365E → K in MCAP. 1 Publication1
Natural variantiVAR_069254378C → Y in MCAP. 1 PublicationCorresponds to variant rs397514565dbSNPEnsembl.1
Natural variantiVAR_069255453Missing in MCAP. 1 Publication1
Natural variantiVAR_026178545E → K in MCAP, KERSEB, CRC and BC; 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. 13 PublicationsCorresponds to variant rs104886003dbSNPEnsembl.1
Natural variantiVAR_069256726E → K in MCAP. 1 Publication1
Natural variantiVAR_069257914G → R in MCAP. 1 PublicationCorresponds to variant rs587776932dbSNPEnsembl.1
Natural variantiVAR_0261841021Y → C in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant rs121913288dbSNPEnsembl.1
Natural variantiVAR_0692581025T → A in MCAP. 1 PublicationCorresponds to variant rs397517202dbSNPEnsembl.1
Natural variantiVAR_0261891035A → V in MCAP; also found in an endometrial carcinoma sample. 2 Publications1
Natural variantiVAR_0261901043M → I in MCAP and CRC; also found in an endometrial carcinoma sample; shows an increase in lipid kinase activity. 3 PublicationsCorresponds to variant rs121913283dbSNPEnsembl.1
Natural variantiVAR_0261931047H → Y in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant rs121913281dbSNPEnsembl.1
Natural variantiVAR_0692591049G → S in MCAP. 1 PublicationCorresponds to variant rs121913277dbSNPEnsembl.1
Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612918
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026171420C → R in CLOVE and CRC; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 2 PublicationsCorresponds to variant rs121913272dbSNPEnsembl.1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC and BC; also found in glioblastoma multiforme and endometrial carcinoma; 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. 11 PublicationsCorresponds to variant rs121913273dbSNPEnsembl.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC and OC; also found in an endometrial carcinoma sample; 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. 16 PublicationsCorresponds to variant rs121913279dbSNPEnsembl.1
Cowden syndrome 5 (CWS5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615108
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069786118G → D in CWS5. 1 PublicationCorresponds to variant rs587777790dbSNPEnsembl.1
Natural variantiVAR_069787135E → K in CWS5. 1 PublicationCorresponds to variant rs587777791dbSNPEnsembl.1
Natural variantiVAR_069788218E → K in CWS5. 1 PublicationCorresponds to variant rs587777792dbSNPEnsembl.1
Natural variantiVAR_069789356V → I in CWS5. 1 PublicationCorresponds to variant rs587777793dbSNPEnsembl.1
Natural variantiVAR_069790382R → K in CWS5. 1 PublicationCorresponds to variant rs587777794dbSNPEnsembl.1
Natural variantiVAR_026176545E → A in CWS5 and HCC; also found in a glioblastoma multiforme sample. 3 PublicationsCorresponds to variant rs121913274dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi5290.
MalaCardsiPIK3CA.
MIMi114480. phenotype.
114500. phenotype.
114550. phenotype.
167000. phenotype.
182000. phenotype.
602501. phenotype.
612918. phenotype.
615108. phenotype.
OpenTargetsiENSG00000121879.
Orphaneti140944. CLOVE syndrome.
201. Cowden syndrome.
276280. Hemihyperplasia-multiple lipomatosis syndrome.
99802. Hemimegalencephaly.
144. Hereditary nonpolyposis colon cancer.
295239. Macrodactyly of fingers, unilateral.
295243. Macrodactyly of toes, unilateral.
60040. Megalencephaly-capillary malformation-polymicrogyria syndrome.
314662. Segmental progressive overgrowth syndrome with fibroadipose hyperplasia.
PharmGKBiPA33308.

Chemistry databases

ChEMBLiCHEMBL4005.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi2153.

Polymorphism and mutation databases

BioMutaiPI3KCA.
DMDMi126302584.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000887851 – 1068Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformAdd BLAST1068

Proteomic databases

EPDiP42336.
MaxQBiP42336.
PaxDbiP42336.
PeptideAtlasiP42336.
PRIDEiP42336.

PTM databases

iPTMnetiP42336.
PhosphoSitePlusiP42336.

Expressioni

Gene expression databases

BgeeiENSG00000121879.
CleanExiHS_PIK3CA.
ExpressionAtlasiP42336. baseline and differential.
GenevisibleiP42336. HS.

Organism-specific databases

HPAiCAB017804.
HPA009985.

Interactioni

Subunit structurei

Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112). Interacts with IRS1 in nuclear extracts (By similarity). 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). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ERBB3P218603EBI-2116585,EBI-720706
IRS1P3556820EBI-2116585,EBI-517592
PIK3R1P2798614EBI-2116585,EBI-79464
PIK3R3Q925694EBI-2116585,EBI-79893

Protein-protein interaction databases

BioGridi111308. 73 interactors.
DIPiDIP-42728N.
IntActiP42336. 45 interactors.
MINTiMINT-1367228.
STRINGi9606.ENSP00000263967.

Chemistry databases

BindingDBiP42336.

Structurei

Secondary structure

11068
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 10Combined sources6
Beta strandi13 – 15Combined sources3
Beta strandi18 – 25Combined sources8
Beta strandi31 – 37Combined sources7
Helixi42 – 52Combined sources11
Helixi53 – 55Combined sources3
Beta strandi56 – 58Combined sources3
Helixi59 – 61Combined sources3
Helixi65 – 67Combined sources3
Beta strandi69 – 74Combined sources6
Beta strandi75 – 77Combined sources3
Beta strandi79 – 82Combined sources4
Helixi89 – 91Combined sources3
Beta strandi94 – 102Combined sources9
Helixi108 – 121Combined sources14
Helixi126 – 130Combined sources5
Helixi134 – 142Combined sources9
Helixi144 – 155Combined sources12
Turni156 – 159Combined sources4
Helixi160 – 166Combined sources7
Helixi179 – 182Combined sources4
Beta strandi185 – 198Combined sources14
Turni199 – 202Combined sources4
Beta strandi203 – 212Combined sources10
Helixi217 – 226Combined sources10
Turni228 – 230Combined sources3
Beta strandi232 – 234Combined sources3
Helixi237 – 242Combined sources6
Turni243 – 245Combined sources3
Helixi246 – 248Combined sources3
Beta strandi249 – 254Combined sources6
Turni255 – 258Combined sources4
Beta strandi263 – 265Combined sources3
Helixi267 – 269Combined sources3
Helixi271 – 279Combined sources9
Beta strandi284 – 289Combined sources6
Helixi290 – 294Combined sources5
Helixi306 – 309Combined sources4
Beta strandi323 – 326Combined sources4
Helixi327 – 329Combined sources3
Beta strandi332 – 342Combined sources11
Turni348 – 350Combined sources3
Beta strandi353 – 362Combined sources10
Beta strandi365 – 368Combined sources4
Beta strandi376 – 379Combined sources4
Beta strandi382 – 392Combined sources11
Helixi393 – 395Combined sources3
Beta strandi401 – 413Combined sources13
Beta strandi416 – 430Combined sources15
Beta strandi434 – 436Combined sources3
Beta strandi439 – 444Combined sources6
Beta strandi454 – 456Combined sources3
Beta strandi458 – 460Combined sources3
Beta strandi468 – 470Combined sources3
Beta strandi472 – 477Combined sources6
Beta strandi481 – 485Combined sources5
Helixi489 – 492Combined sources4
Helixi495 – 498Combined sources4
Helixi508 – 512Combined sources5
Helixi517 – 520Combined sources4
Helixi526 – 536Combined sources11
Beta strandi539 – 541Combined sources3
Helixi545 – 553Combined sources9
Turni554 – 557Combined sources4
Helixi558 – 560Combined sources3
Helixi562 – 564Combined sources3
Helixi565 – 571Combined sources7
Helixi577 – 589Combined sources13
Helixi595 – 598Combined sources4
Helixi599 – 602Combined sources4
Helixi609 – 622Combined sources14
Helixi625 – 638Combined sources14
Helixi639 – 641Combined sources3
Beta strandi643 – 646Combined sources4
Helixi648 – 657Combined sources10
Helixi661 – 672Combined sources12
Turni673 – 676Combined sources4
Turni678 – 680Combined sources3
Helixi681 – 694Combined sources14
Helixi698 – 720Combined sources23
Turni721 – 725Combined sources5
Helixi728 – 739Combined sources12
Helixi742 – 748Combined sources7
Beta strandi749 – 753Combined sources5
Beta strandi756 – 761Combined sources6
Helixi766 – 768Combined sources3
Beta strandi774 – 776Combined sources3
Beta strandi779 – 784Combined sources6
Helixi790 – 792Combined sources3
Beta strandi795 – 805Combined sources11
Helixi808 – 825Combined sources18
Turni826 – 828Combined sources3
Beta strandi838 – 842Combined sources5
Beta strandi845 – 849Combined sources5
Beta strandi852 – 856Combined sources5
Helixi857 – 861Combined sources5
Turni865 – 867Combined sources3
Helixi871 – 873Combined sources3
Helixi876 – 884Combined sources9
Helixi887 – 889Combined sources3
Helixi890 – 911Combined sources22
Beta strandi920 – 924Combined sources5
Beta strandi929 – 931Combined sources3
Turni938 – 941Combined sources4
Helixi942 – 945Combined sources4
Helixi958 – 964Combined sources7
Turni965 – 967Combined sources3
Beta strandi969 – 971Combined sources3
Beta strandi972 – 974Combined sources3
Helixi975 – 993Combined sources19
Helixi995 – 1003Combined sources9
Turni1004 – 1007Combined sources4
Beta strandi1013 – 1015Combined sources3
Helixi1016 – 1025Combined sources10
Turni1026 – 1029Combined sources4
Helixi1032 – 1047Combined sources16
Beta strandi1053 – 1055Combined sources3
Beta strandi1056 – 1058Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ENQNMR-A331-481[»]
2RD0X-ray3.05A1-1068[»]
3HHMX-ray2.80A1-1068[»]
3HIZX-ray3.30A1-1068[»]
3ZIMX-ray2.85A107-1046[»]
4JPSX-ray2.20A1-1068[»]
4L1BX-ray2.59A1-1068[»]
4L23X-ray2.50A1-1068[»]
4L2YX-ray2.80A1-1068[»]
4OVUX-ray2.96A1-1068[»]
4OVVX-ray3.50A1-1068[»]
4TUUX-ray2.64A105-1048[»]
4TV3X-ray2.85A105-1048[»]
4WAFX-ray2.39A2-1068[»]
4YKNX-ray2.90A2-1068[»]
4ZOPX-ray2.62A1-1068[»]
5DXHX-ray3.00A/D2-1068[»]
5DXTX-ray2.25A107-1068[»]
5FI4X-ray2.50A1-1068[»]
5ITDX-ray3.02A1-1068[»]
ProteinModelPortaliP42336.
SMRiP42336.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42336.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 105PI3K-ABDPROSITE-ProRule annotationAdd BLAST90
Domaini187 – 289PI3K-RBDPROSITE-ProRule annotationAdd BLAST103
Domaini330 – 487C2 PI3K-typePROSITE-ProRule annotationAdd BLAST158
Domaini517 – 694PIK helicalPROSITE-ProRule annotationAdd BLAST178
Domaini797 – 1068PI3K/PI4KPROSITE-ProRule annotationAdd BLAST272

Domaini

The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1.2 Publications

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
Contains 1 PI3K-ABD domain.PROSITE-ProRule annotation
Contains 1 PI3K-RBD domain.PROSITE-ProRule annotation
Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
Contains 1 PIK helical domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0904. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00760000119110.
HOVERGENiHBG052721.
InParanoidiP42336.
KOiK00922.
OMAiPMVRAFA.
OrthoDBiEOG091G027R.
PhylomeDBiP42336.
TreeFamiTF102031.

Family and domain databases

Gene3Di1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR000008. C2_dom.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003113. PI3K_adapt-bd_dom.
IPR002420. PI3K_C2_dom.
IPR000341. PI3K_Ras-bd_dom.
IPR015433. PI_Kinase.
IPR001263. PInositide-3_kin_accessory_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10048. PTHR10048. 1 hit.
PfamiPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF02192. PI3K_p85B. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
SMARTiSM00142. PI3K_C2. 1 hit.
SM00143. PI3K_p85B. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
PS51544. PI3K_ABD. 1 hit.
PS51547. PI3K_C2. 1 hit.
PS51546. PI3K_RBD. 1 hit.
PS51545. PIK_HELICAL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P42336-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLITIKHELF
60 70 80 90 100
KEARKYPLHQ LLQDESSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK
110 120 130 140 150
VIEPVGNREE KILNREIGFA IGMPVCEFDM VKDPEVQDFR RNILNVCKEA
160 170 180 190 200
VDLRDLNSPH SRAMYVYPPN VESSPELPKH IYNKLDKGQI IVVIWVIVSP
210 220 230 240 250
NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK LCVLEYQGKY
260 270 280 290 300
ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPMD
310 320 330 340 350
CFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD
360 370 380 390 400
IDKIYVRTGI YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA
410 420 430 440 450
RLCLSICSVK GRKGAKEEHC PLAWGNINLF DYTDTLVSGK MALNLWPVPH
460 470 480 490 500
GLEDLLNPIG VTGSNPNKET PCLELEFDWF SSVVKFPDMS VIEEHANWSV
510 520 530 540 550
SREAGFSYSH AGLSNRLARD NELRENDKEQ LKAISTRDPL SEITEQEKDF
560 570 580 590 600
LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME
610 620 630 640 650
LLDCNYPDPM VRGFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV
660 670 680 690 700
RFLLKKALTN QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK
710 720 730 740 750
HLNRQVEAME KLINLTDILK QEKKDETQKV QMKFLVEQMR RPDFMDALQG
760 770 780 790 800
FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW LNWENPDIMS ELLFQNNEII
810 820 830 840 850
FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS IGDCVGLIEV
860 870 880 890 900
VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS
910 920 930 940 950
CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE
960 970 980 990 1000
RVPFVLTQDF LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN
1010 1020 1030 1040 1050
LFSMMLGSGM PELQSFDDIA YIRKTLALDK TEQEALEYFM KQMNDAHHGG
1060
WTTKMDWIFH TIKQHALN
Length:1,068
Mass (Da):124,284
Last modified:February 20, 2007 - v2
Checksum:i041487231A9A1207
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti170N → H in CAA82333 (PubMed:7713498).Curated1
Sequence conflicti187K → R in CAA82333 (PubMed:7713498).Curated1
Sequence conflicti286 – 287ML → KM in CAA82333 (PubMed:7713498).Curated2
Sequence conflicti346V → L in CAA82333 (PubMed:7713498).Curated1
Sequence conflicti723K → R in CAA82333 (PubMed:7713498).Curated1
Sequence conflicti751F → L in CAA82333 (PubMed:7713498).Curated1
Sequence conflicti767E → K in CAA82333 (PubMed:7713498).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02616638R → H in CRC; likely involved in disease pathogenesis; 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. 1 PublicationCorresponds to variant rs772110575dbSNPEnsembl.1
Natural variantiVAR_04294243I → V.1 PublicationCorresponds to variant rs1051399dbSNPEnsembl.1
Natural variantiVAR_06925181E → K in MCAP. 1 Publication1
Natural variantiVAR_02616788R → Q in MCAP; also found in a glioblastoma multiforme sample. 2 PublicationsCorresponds to variant rs121913287dbSNPEnsembl.1
Natural variantiVAR_026168106G → V in CRC; likely involved in disease pathogenesis; shows an increase in lipid kinase activity. 1 Publication1
Natural variantiVAR_075634112I → N in MCAP; increased phosphatidylinositol 3-kinase signaling; decreased interaction with p85 regulatory subunit; no effect on protein abundance. 1 Publication1
Natural variantiVAR_069786118G → D in CWS5. 1 PublicationCorresponds to variant rs587777790dbSNPEnsembl.1
Natural variantiVAR_069787135E → K in CWS5. 1 PublicationCorresponds to variant rs587777791dbSNPEnsembl.1
Natural variantiVAR_069788218E → K in CWS5. 1 PublicationCorresponds to variant rs587777792dbSNPEnsembl.1
Natural variantiVAR_042943332S → R.1 PublicationCorresponds to variant rs1051407dbSNPEnsembl.1
Natural variantiVAR_026169343Y → C Found in a cancer sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_069789356V → I in CWS5. 1 PublicationCorresponds to variant rs587777793dbSNPEnsembl.1
Natural variantiVAR_069252364G → R in MCAP. 1 Publication1
Natural variantiVAR_069253365E → K in MCAP. 1 Publication1
Natural variantiVAR_069254378C → Y in MCAP. 1 PublicationCorresponds to variant rs397514565dbSNPEnsembl.1
Natural variantiVAR_069790382R → K in CWS5. 1 PublicationCorresponds to variant rs587777794dbSNPEnsembl.1
Natural variantiVAR_026170391I → M.1 PublicationCorresponds to variant rs2230461dbSNPEnsembl.1
Natural variantiVAR_026171420C → R in CLOVE and CRC; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 2 PublicationsCorresponds to variant rs121913272dbSNPEnsembl.1
Natural variantiVAR_026172453E → Q in CRC; likely involved in disease pathogenesis; 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. 1 Publication1
Natural variantiVAR_069255453Missing in MCAP. 1 Publication1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC and BC; also found in glioblastoma multiforme and endometrial carcinoma; 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. 11 Publications