Gene content
Symbol	PIK3CA ( by HUGO)
Name	Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic...
Category	Oncogene
Alias	Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Phosphoinositide-3-Kinase Catalytic Alpha Polypeptide PtdIns-3-Kinase Subunit P110-Alpha Serine/Threonine Protein Kinase PIK3CA PI3K-alpha CLOVE CWS5 MCAP MCM MCMTC PI3K p110-alpha Phosphatidylinositol 3-Kinase Catalytic 110-KD Alpha Phosphatidylinositol 3-Kinase Catalytic Alpha Polypeptide Phosphatidylinositol 4 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform Phosphatidylinositol-4 5-Bisphosphate 3-Kinase 110 KDa Catalytic Subunit Alpha Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform PI3-Kinase P110 Subunit Alpha EC 2.7.1.153 EC 2.7.11.1 PI3Kalpha p110alpha Phosphatidylinositol 4 5-Bisphosphate 3-Kinase 110 KDa Catalytic Subunit Alpha Phosphoinositide-3-Kinase Catalytic Alpha Polypeptide PI3-Kinase Subunit Alpha PtdIns-3-Kinase Subunit Alpha EC 2.7.1
Cytogenetic band	NCBI: 3q26.3    Ensembl: 3q26.32
Protein information	PK3CA_HUMAN Size: 1068 amino acids Mass: 124284 Da Subunit: Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with IRS1 in nuclear extracts. Interacts with RUFY3 (By similarity). Interacts with RASD2 (By similarity). Interacts with APPL1. Interacts with HRAS and KRAS (By similarity). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity) Miscellaneous: The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA (PubMed:18418043) Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for PIK3CA (see all 8): 2ENQ (3D) [IMAGE] 2RD0 (3D) [IMAGE] 3HHM (3D) [IMAGE] 3HIZ (3D) [IMAGE] 3ZIM (3D) [IMAGE] 4L1B (3D) [IMAGE] Function: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS Catalytic activity: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate                        Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS Catalytic activity: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate                        ATP + a protein = ADP + a phosphoprotein Similarity: Belongs to the PI3/PI4-kinase family                        Contains 1 C2 PI3K-type domain                        Contains 1 PI3K-ABD domain                        Contains 1 PI3K-RBD domain                        Contains 1 PI3K/PI4K domain                        Contains 1 PIK helical domain [IMAGE]

Protein Domain/Family
Source	ID	Domain	Name	Type
InterPro	IPR000008	C2_dom	C2	Domain
	IPR000341	PI3K_Ras-bd_dom	Phosphoinositide 3-kinase, ras-binding	Domain
	IPR000403	PI3/4_kinase_cat_dom	Phosphatidylinositol 3- and 4-kinase, catalytic	Domain
	IPR001263	PInositide-3_kin_accessory_dom	Phosphoinositide 3-kinase accessory region PIK	Domain
	IPR002420	PI3K_C2_dom	Phosphoinositide 3-kinase, C2	Domain
	IPR003113	PI3K_adapt-bd_dom	Phosphatidylinositol 3-kinase, p85-binding	Domain
	IPR011009	Kinase-like_dom	Protein kinase-like	Domain
Blocks	IPB000341	Phosphoinositide 3-kinase	Phosphoinositide 3-kinase, ras-binding domain
	IPB000403	Phosphatidylinositol 3- and 4-kinase	Phosphatidylinositol 3- and 4-kinase
	IPB003113	Phosphatidylinositol 3-kinase	Phosphatidylinositol 3-kinase, p85-binding

Gene Ontology
Type	Term	Evidence	Source	Pub
Biological Process	cardiac muscle contraction	TAS	GOA	19147653
	endothelial cell migration	TAS	GOA	19200708
	vasculature development	TAS	GOA	19200708
Molecular Function	1-phosphatidylinositol-3-kinase activity	IDA	GOA	2174051
	phosphatidylinositol 3-kinase activity	TAS	GOA	19200708
	protein binding	IPI	GOA	10490823

Disorder & Mutation
Source	Disease
SWISS-PROT	Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis
SWISS-PROT	Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
SWISS-PROT	Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
SWISS-PROT	Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The gene represented in this entry may be involved in disease pathogenesis
SWISS-PROT	Note=Most of the cancer-derived mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis
SWISS-PROT	Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. Note=The disease is caused by mutations affecting the gene represented in this entry
SWISS-PROT	Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. Note=The disease is caused by mutations affecting the gene represented in this entry
SWISS-PROT	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry
SWISS-PROT	Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. Note=The disease is caused by mutations affecting the gene represented in this entry

PIK3CA cross reference
PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene