Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

PIK3CA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA.1 Publication

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

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAngiogenesis, Phagocytosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc: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 family 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-9028335 Activated NTRK2 signals through PI3K
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

EuPathDBiHostDB:ENSG00000121879.3
HGNCiHGNC:8975 PIK3CA
MIMi171834 gene
neXtProtiNX_P42336

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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.18 Publications
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 dbSNP:rs772110575EnsemblClinVar.1
Natural variantiVAR_026168106G → V in CRC; likely involved in disease pathogenesis; shows an increase in lipid kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1057519930Ensembl.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 PublicationCorresponds to variant dbSNP:rs1057519925Ensembl.1
Natural variantiVAR_0261871023R → Q in CRC; unknown pathological significance. 1 Publication1
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_026175542E → V in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519927Ensembl.1
Natural variantiVAR_026179546Q → E in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121913286EnsemblClinVar.1
Natural variantiVAR_026182546Q → R in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397517201EnsemblClinVar.1
Natural variantiVAR_0261911047H → L in BC; unknown pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs121913279EnsemblClinVar.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 dbSNP:rs121913286EnsemblClinVar.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
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_026177545E → G in KERSEB; also found in an endometrial carcinoma sample. 4 PublicationsCorresponds to variant dbSNP:rs121913274EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs1057519929Ensembl.1
Natural variantiVAR_02616788R → Q in MCAP; also found in a glioblastoma multiforme sample. 2 PublicationsCorresponds to variant dbSNP:rs121913287EnsemblClinVar.1
Natural variantiVAR_075634112I → N in MCAP; increased phosphatidylinositol 3-kinase signaling; decreased interaction with p85 regulatory subunit; no effect on protein abundance. 1 PublicationCorresponds to variant dbSNP:rs863225460EnsemblClinVar.1
Natural variantiVAR_069252364G → R in MCAP. 1 Publication1
Natural variantiVAR_069253365E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs1064793732Ensembl.1
Natural variantiVAR_069254378C → Y in MCAP. 1 PublicationCorresponds to variant dbSNP:rs397514565EnsemblClinVar.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 dbSNP:rs104886003EnsemblClinVar.1
Natural variantiVAR_069256726E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs867262025EnsemblClinVar.1
Natural variantiVAR_069257914G → R in MCAP. 1 PublicationCorresponds to variant dbSNP:rs587776932EnsemblClinVar.1
Natural variantiVAR_0261841021Y → C in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant dbSNP:rs121913288EnsemblClinVar.1
Natural variantiVAR_0692581025T → A in MCAP. 1 PublicationCorresponds to variant dbSNP:rs397517202EnsemblClinVar.1
Natural variantiVAR_0261891035A → V in MCAP; also found in an endometrial carcinoma sample. 2 Publications1
Natural variantiVAR_0261931047H → Y in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant dbSNP:rs121913281EnsemblClinVar.1
Natural variantiVAR_0692591049G → S in MCAP. 1 PublicationCorresponds to variant dbSNP:rs121913277EnsemblClinVar.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_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 dbSNP:rs121913273EnsemblClinVar.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 dbSNP:rs121913279EnsemblClinVar.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 dbSNP:rs587777790EnsemblClinVar.1
Natural variantiVAR_069787135E → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777791EnsemblClinVar.1
Natural variantiVAR_069788218E → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777792EnsemblClinVar.1
Natural variantiVAR_069789356V → I in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777793EnsemblClinVar.1
Natural variantiVAR_069790382R → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777794EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi5290
GeneReviewsiPIK3CA
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
DB05240 XL147
DB05241 XL765
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
ProteomicsDBi55509

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111308, 92 interactors
ComplexPortaliCPX-1917 Phosphatidylinositol 3-kinase complex class I, variant 1
CPX-1918 Phosphatidylinositol 3-kinase complex class I, variant 2
CORUMiP42336
DIPiDIP-42728N
IntActiP42336, 53 interactors
MINTiP42336
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 strandi27 – 29Combined sources3
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
Beta strandi86 – 88Combined sources3
Helixi89 – 91Combined sources3
Beta strandi94 – 102Combined sources9
Beta strandi105 – 107Combined sources3
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 strandi319 – 321Combined sources3
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
Beta strandi504 – 506Combined sources3
Helixi508 – 512Combined sources5
Helixi513 – 515Combined sources3
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
Beta strandi862 – 864Combined sources3
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 strandi1048 – 1050Combined sources3
Beta strandi1053 – 1055Combined sources3
Beta strandi1056 – 1058Combined sources3

3D structure databases

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

Phylogenomic databases

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

Family and domain databases

CDDicd05175 PI3Kc_IA_alpha, 1 hit
Gene3Di1.10.1070.11, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003113 PI3K_adapt-bd_dom
IPR002420 PI3K_C2_dom
IPR000341 PI3K_Ras-bd_dom
IPR008290 PI3K_Vps34
IPR037704 PI3Kalpha_dom
IPR015433 PI_Kinase
IPR001263 PInositide-3_kin_accessory_dom
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR10048 PTHR10048, 1 hit
PfamiView protein in 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
PIRSFiPIRSF000587 PI3K_Vps34, 1 hit
SMARTiView protein in SMART
SM00142 PI3K_C2, 1 hit
SM00143 PI3K_p85B, 1 hit
SM00144 PI3K_rbd, 1 hit
SM00145 PI3Ka, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

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 dbSNP:rs772110575EnsemblClinVar.1
Natural variantiVAR_04294243I → V1 PublicationCorresponds to variant dbSNP:rs1051399Ensembl.1
Natural variantiVAR_06925181E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs1057519929Ensembl.1
Natural variantiVAR_02616788R → Q in MCAP; also found in a glioblastoma multiforme sample. 2 PublicationsCorresponds to variant dbSNP:rs121913287EnsemblClinVar.1
Natural variantiVAR_026168106G → V in CRC; likely involved in disease pathogenesis; shows an increase in lipid kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1057519930Ensembl.1
Natural variantiVAR_075634112I → N in MCAP; increased phosphatidylinositol 3-kinase signaling; decreased interaction with p85 regulatory subunit; no effect on protein abundance. 1 PublicationCorresponds to variant dbSNP:rs863225460EnsemblClinVar.1
Natural variantiVAR_069786118G → D in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777790EnsemblClinVar.1
Natural variantiVAR_069787135E → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777791EnsemblClinVar.1
Natural variantiVAR_069788218E → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777792EnsemblClinVar.1
Natural variantiVAR_042943332S → R1 PublicationCorresponds to variant dbSNP:rs1051407Ensembl.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 dbSNP:rs587777793EnsemblClinVar.1
Natural variantiVAR_069252364G → R in MCAP. 1 Publication1
Natural variantiVAR_069253365E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs1064793732Ensembl.1
Natural variantiVAR_069254378C → Y in MCAP. 1 PublicationCorresponds to variant dbSNP:rs397514565EnsemblClinVar.1
Natural variantiVAR_069790382R → K in CWS5. 1 PublicationCorresponds to variant dbSNP:rs587777794EnsemblClinVar.1
Natural variantiVAR_026170391I → M1 PublicationCorresponds to variant dbSNP:rs2230461EnsemblClinVar.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 dbSNP:rs121913272EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs1057519925Ensembl.1
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 PublicationsCorresponds to variant dbSNP:rs121913273EnsemblClinVar.1
Natural variantiVAR_026174542E → Q Found in an endometrial carcinoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_026175542E → V in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519927Ensembl.1
Natural variantiVAR_026176545E → A in CWS5 and HCC; also found in a glioblastoma multiforme sample. 3 PublicationsCorresponds to variant dbSNP:rs121913274EnsemblClinVar.1
Natural variantiVAR_026177545E → G in KERSEB; also found in an endometrial carcinoma sample. 4 PublicationsCorresponds to variant dbSNP:rs121913274EnsemblClinVar.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 dbSNP:rs104886003EnsemblClinVar.1
Natural variantiVAR_026179546Q → E in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121913286EnsemblClinVar.1
Natural variantiVAR_026180546Q → K in OC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121913286EnsemblClinVar.1
Natural variantiVAR_026181546Q → P Found in an anaplastic astrocytoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_026182546Q → R in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397517201EnsemblClinVar.1
Natural variantiVAR_069256726E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs867262025EnsemblClinVar.1
Natural variantiVAR_069257914G → R in MCAP. 1 PublicationCorresponds to variant dbSNP:rs587776932EnsemblClinVar.1
Natural variantiVAR_0261831007G → R Found in an endometrial carcinoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_0261841021Y → C in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant dbSNP:rs121913288EnsemblClinVar.1
Natural variantiVAR_0261851021Y → H Found in an endometrial carcinoma sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_0261861021Y → N Found in a glioblastoma multiforme sample; unknown pathological significance. 1 Publication1
Natural variantiVAR_0261871023R → Q in CRC; unknown pathological significance. 1 Publication1
Natural variantiVAR_0692581025T → A in MCAP. 1 PublicationCorresponds to variant dbSNP:rs397517202EnsemblClinVar.1
Natural variantiVAR_0261881025T → N Found in a glioblastoma multiforme sample; unknown pathological significance. 1 Publication1
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 dbSNP:rs121913283EnsemblClinVar.1
Natural variantiVAR_0261911047H → L in BC; unknown pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs121913279EnsemblClinVar.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 dbSNP:rs121913279EnsemblClinVar.1
Natural variantiVAR_0261931047H → Y in MCAP; also found in an endometrial carcinoma sample. 2 PublicationsCorresponds to variant dbSNP:rs121913281EnsemblClinVar.1
Natural variantiVAR_0692591049G → S in MCAP. 1 Publication