InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIK3CA

Summary

InnateDB Protein

IDBP-66005.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PIK3CA

Protein Name

phosphoinositide-3-kinase, catalytic, alpha polypeptide

Synonyms

CLOVE; CWS5; MCAP; MCM; MCMTC; p110-alpha; PI3K;

Species

Homo sapiens

Ensembl Protein

ENSP00000263967

InnateDB Gene

IDBG-66003 (PIK3CA)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:21708979}.

Subcellular Localization

Disease Associations

Note=PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis.Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269PubMed:16353168}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269PubMed:15608678}. Note=The gene represented in this entry may be involved in disease pathogenesis.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. {ECO:0000269PubMed:17673550}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:22729224}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:22729224}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:22658544}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269PubMed:23246288}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 70 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	70 [view]
Protein-Protein	68 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	11 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004674	protein serine/threonine kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016303	1-phosphatidylinositol-3-kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0030295	protein kinase activator activity
GO:0035004	phosphatidylinositol 3-kinase activity
GO:0035005	1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0043560	insulin receptor substrate binding
GO:0046934	phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process

GO:0001525	angiogenesis
GO:0001944	vasculature development
GO:0006006	glucose metabolic process
GO:0006468	protein phosphorylation
GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007596	blood coagulation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0030168	platelet activation
GO:0031295	T cell costimulation
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0038028	insulin receptor signaling pathway via phosphatidylinositol 3-kinase
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0040014	regulation of multicellular organism growth
GO:0043491	protein kinase B signaling
GO:0043524	negative regulation of neuron apoptotic process
GO:0043542	endothelial cell migration
GO:0044029	hypomethylation of CpG island
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045860	positive regulation of protein kinase activity
GO:0046854	phosphatidylinositol phosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050852	T cell receptor signaling pathway
GO:0050900	leukocyte migration
GO:0060048	cardiac muscle contraction
GO:2000270	negative regulation of fibroblast apoptotic process
GO:2000653	regulation of genetic imprinting
GO:2000811	negative regulation of anoikis

Cellular Component

GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005942	phosphatidylinositol 3-kinase complex
GO:0005943	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex
GO:0030027	lamellipodium

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR011009 Protein kinase-like domain
IPR016024 Armadillo-type fold
IPR029071 Ubiquitin-related domain

PFAM

PF00168
PF00794
PF00454
PF00613
PF00792
PF02192

PRINTS

PR00360

PIRSF

SMART

SM00239
SM00144
SM00146
SM00145
SM00142
SM00143

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt