| Predicate | Object |
|---|---|
| rdf:type | |
| biopax3:comment |
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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (By similarity). Interacts with IRS1 in nuclear extracts (By similarity). Interacts with RUFY3 (By similarity). Interacts with RASD2 (By similarity). Interacts with APPL1 (By similarity). Interacts with HRAS1 and KRAS (By similarity). Interaction with HRAS1/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity). DOMAIN: The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain (By similarity). The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane (By similarity). 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 (By similarity). DISRUPTION PHENOTYPE: Lethal. Embryonic fibroblasts cells are resistant to oncogenic transformation induced by oncogenic receptor tyrosine kinases (RTKs), are unable to differentiate into adipocytes and deficient in cellular signaling in response to various growth factors. Defective responsiveness to insulin led to reduced somatic growth, hyperinsulinaemia, glucose intolerance, hyperphagia and increased adiposity. SIMILARITY: Belongs to the PI3/PI4-kinase family. SIMILARITY: Contains 1 C2 PI3K-type domain. SIMILARITY: Contains 1 PI3K-ABD domain. SIMILARITY: Contains 1 PI3K-RBD domain. SIMILARITY: Contains 1 PI3K/PI4K domain. SIMILARITY: Contains 1 PIK helical domain. GENE SYNONYMS:Pik3ca. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.,
SEQUENCE 1068 AA; 124412 MW; D593283B416ABFD0 CRC64;
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| biopax3:xref | |
| biopax3:displayName |
PK3CA_MOUSE
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| biopax3:name |
2.7.1.153,
2.7.11.1,
PI3-kinase subunit alpha,
PI3K-alpha,
PI3Kalpha,
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha,
Phosphoinositide-3-kinase catalytic alpha polypeptide,
Pik3ca,
PtdIns-3-kinase subunit alpha,
PtdIns-3-kinase subunit p110-alpha,
Serine/threonine protein kinase PIK3CA,
p110alpha
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| biopax3:organism | |
| biopax3:sequence |
MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLVTIKHELFREARKYPLHQLLQDETSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFVIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPIDSFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSYSHTGLSNRLARDNELRENDKEQLRALCTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRSFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRQPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQEYTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHALN
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| biopax3:standardName |
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
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