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Entry version 210 (16 Oct 2019)
Sequence version 2 (20 Feb 2007)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS04527-MONOMER

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.1.137 2681
2.7.1.153 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-109704 PI3K Cascade
R-HSA-112399 IRS-mediated signalling
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-416476 G alpha (q) signalling events
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-512988 Interleukin-3, Interleukin-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-9009391 Extra-nuclear estrogen signaling
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-9028335 Activated NTRK2 signals through PI3K
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-9603381 Activated NTRK3 signals through PI3K

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P42336

SIGNOR Signaling Network Open Resource

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SIGNORi
P42336

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:PIK3CA
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 3

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:8975 PIK3CA

Online Mendelian Inheritance in Man (OMIM)

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MIMi
171834 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P42336

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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:rs1057519930EnsemblClinVar.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:rs1057519925EnsemblClinVar.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 dbSNP:rs121913283EnsemblClinVar.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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026175542E → V in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519927EnsemblClinVar.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_026182546Q → R in BC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397517201EnsemblClinVar.1
Natural variantiVAR_0261911047H → L in BC, CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO patients. 6 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.
Related information in OMIM
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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026176545E → A in CWS5 and HCC; also found in a glioblastoma multiforme sample. 3 PublicationsCorresponds to variant dbSNP:rs121913274EnsemblClinVar.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.
Related information in OMIM
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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06925181E → K in MCAP. 1 PublicationCorresponds to variant dbSNP:rs1057519929EnsemblClinVar.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:rs1064793732EnsemblClinVar.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 PublicationsCorresponds to variant dbSNP:rs1242945375Ensembl.1
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_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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026171420C → R in CLOVE, CRC and CLAPO; unknown pathological significance; somatic mutation in CLAPO patients; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 3 PublicationsCorresponds to variant dbSNP:rs121913272EnsemblClinVar.1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC, BC, CLAPO and MADAC; also found in glioblastoma multiforme and endometrial carcinoma; unknown pathological significance; somatic mutation in CLAPO and MADAC patients; 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. 13 PublicationsCorresponds to variant dbSNP:rs121913273EnsemblClinVar.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC, OC and MADAC; also found in an endometrial carcinoma sample; unknown pathological significance; somatic mutation in MADAC patients; 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; may alter the interaction of the PI3K/PI4K kinase domain with the cell membrane. 17 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.
Related information in OMIM
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
Natural variantiVAR_026176545E → A in CWS5 and HCC; also found in a glioblastoma multiforme sample. 3 PublicationsCorresponds to variant dbSNP:rs121913274EnsemblClinVar.1
CLAPO syndrome (CLAPO)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.1 Publication
Disease descriptionA syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08147583F → S in CLAPO; unknown pathological significance; somatic mutation. 1 Publication1
Natural variantiVAR_081476115R → P in CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO and MADAC patients. 2 Publications1
Natural variantiVAR_026171420C → R in CLOVE, CRC and CLAPO; unknown pathological significance; somatic mutation in CLAPO patients; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 3 PublicationsCorresponds to variant dbSNP:rs121913272EnsemblClinVar.1
Macrodactyly (MADAC)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in MADAC seems to follow a pattern of somatic mosaicism.1 Publication
Disease descriptionA congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081476115R → P in CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO and MADAC patients. 2 Publications1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC, BC, CLAPO and MADAC; also found in glioblastoma multiforme and endometrial carcinoma; unknown pathological significance; somatic mutation in CLAPO and MADAC patients; 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. 13 PublicationsCorresponds to variant dbSNP:rs121913273EnsemblClinVar.1
Natural variantiVAR_0261911047H → L in BC, CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO patients. 6 PublicationsCorresponds to variant dbSNP:rs121913279EnsemblClinVar.1
Natural variantiVAR_0261921047H → R in CLOVE, KERSEB, CRC, BC, OC and MADAC; also found in an endometrial carcinoma sample; unknown pathological significance; somatic mutation in MADAC patients; 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; may alter the interaction of the PI3K/PI4K kinase domain with the cell membrane. 17 PublicationsCorresponds to variant dbSNP:rs121913279EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNET

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DisGeNETi
5290

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
PIK3CA

MalaCards human disease database

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MalaCardsi
PIK3CA
MIMi114480 phenotype
114500 phenotype
114550 phenotype
155500 phenotype
167000 phenotype
182000 phenotype
602501 phenotype
612918 phenotype
613089 phenotype
615108 phenotype

Open Targets

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OpenTargetsi
ENSG00000121879

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
210159 Adult hepatocellular carcinoma
140944 CLOVES syndrome
201 Cowden syndrome
276280 Hemihyperplasia-multiple lipomatosis syndrome
99802 Hemimegalencephaly
144 Lynch syndrome
295239 Macrodactyly of fingers, unilateral
295243 Macrodactyly of toes, unilateral
60040 Megalencephaly-capillary malformation-polymicrogyria syndrome
314662 Segmental progressive overgrowth syndrome with fibroadipose hyperplasia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA33308

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P42336

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL4005

Drug and drug target database

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DrugBanki
DB12015 Alpelisib
DB00171 ATP
DB00201 Caffeine
DB12483 Copanlisib
DB11772 Pilaralisib
DB08059 Wortmannin
DB05241 XL765

DrugCentral

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DrugCentrali
P42336

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2153

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
PIK3CA

Domain mapping of disease mutations (DMDM)

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DMDMi
126302584

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000887851 – 1068Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformAdd BLAST1068

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P42336

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P42336

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P42336

MaxQB - The MaxQuant DataBase

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MaxQBi
P42336

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P42336

PeptideAtlas

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PeptideAtlasi
P42336

PRoteomics IDEntifications database

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PRIDEi
P42336

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
55509

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P42336

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P42336

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000121879 Expressed in 220 organ(s), highest expression level in adrenal tissue

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P42336 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P42336 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB017804
HPA009985

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111308, 125 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-1917 Phosphatidylinositol 3-kinase complex class I, variant 1
CPX-1918 Phosphatidylinositol 3-kinase complex class I, variant 2

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P42336

Database of interacting proteins

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DIPi
DIP-42728N

Protein interaction database and analysis system

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IntActi
P42336, 65 interactors

Molecular INTeraction database

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MINTi
P42336

STRING: functional protein association networks

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STRINGi
9606.ENSP00000263967

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P42336

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11068
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P42336

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P42336

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>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

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0904 Eukaryota
COG5032 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155531

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P42336

KEGG Orthology (KO)

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KOi
K00922

Identification of Orthologs from Complete Genome Data

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OMAi
EEHANWN

Database of Orthologous Groups

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OrthoDBi
204282at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P42336

TreeFam database of animal gene trees

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TreeFami
TF102031

Family and domain databases

Conserved Domains Database

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CDDi
cd05175 PI3Kc_IA_alpha, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.1070.11, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View 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
IPR001263 PI3K_accessory_dom
IPR003113 PI3K_adapt-bd_dom
IPR002420 PI3K_C2_dom
IPR000341 PI3K_Ras-bd_dom
IPR008290 PI3K_Vps34
IPR037704 PI3Kalpha_dom
IPR015433 PI_Kinase
IPR029071 Ubiquitin-like_domsf

The PANTHER Classification System

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PANTHERi
PTHR10048 PTHR10048, 1 hit

Pfam protein domain database

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Pfami
View 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

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF000587 PI3K_Vps34, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View 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

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48371 SSF48371, 1 hit
SSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View 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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i041487231A9A1207
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y2F6A0A2R8Y2F6_HUMAN
Phosphatidylinositol 4,5-bisphospha...
PIK3CA
1,000Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9JAM9C9JAM9_HUMAN
Phosphatidylinositol 4,5-bisphospha...
PIK3CA
118Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9J951C9J951_HUMAN
Phosphatidylinositol 4,5-bisphospha...
PIK3CA
21Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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:rs1057519929EnsemblClinVar.1
Natural variantiVAR_08147583F → S in CLAPO; unknown pathological significance; somatic mutation. 1 Publication1
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:rs1057519930EnsemblClinVar.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_081476115R → P in CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO and MADAC patients. 2 Publications1
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:rs1064793732EnsemblClinVar.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, CRC and CLAPO; unknown pathological significance; somatic mutation in CLAPO patients; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes. 3 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:rs1057519925EnsemblClinVar.1
Natural variantiVAR_069255453Missing in MCAP. 1 Publication1
Natural variantiVAR_026173542E → K in CLOVE, KERSEB, CRC, BC, CLAPO and MADAC; also found in glioblastoma multiforme and endometrial carcinoma; unknown pathological significance; somatic mutation in CLAPO and MADAC patients; 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. 13 Publications