Gene/Proteome Database (LMPD)

LMPD ID
LMP001325
Gene ID
5290
Species
Homo sapiens (Human)
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Gene Symbol
PIK3CA
Synonyms
CLOVE; CWS5; MCAP; MCM; MCMTC; PI3K; p110-alpha
Alternate Names
phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; PI3K-alpha; PI3-kinase p110 subunit alpha; ptdIns-3-kinase subunit p110-alpha; serine/threonine protein kinase PIK3CA; phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha; phosphoinositide-3-kinase, catalytic, alpha polypeptide; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide; phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform
Chromosome
3
Map Location
3q26.3
EC Number
2.7.1.153
Summary
Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PIK3CA

Proteins

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Refseq ID NP_006209
Protein GI 54792082
UniProt ID P42336
mRNA ID NM_006218
Length 1068
RefSeq Status REVIEWED
MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN

Gene Information

Entrez Gene ID
5290
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Gene Symbol
PIK3CA
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005829 TAS:Reactome C cytosol
GO:0030027 IEA:Ensembl C lamellipodium
GO:0005942 ISS:BHF-UCL C phosphatidylinositol 3-kinase complex
GO:0005943 IDA:UniProtKB C phosphatidylinositol 3-kinase complex, class IA
GO:0005886 IBA:RefGenome C plasma membrane
GO:0016303 IDA:UniProtKB F 1-phosphatidylinositol-3-kinase activity
GO:0035005 IBA:RefGenome F 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0016301 TAS:Reactome F kinase activity
GO:0035004 TAS:UniProtKB F phosphatidylinositol 3-kinase activity
GO:0046934 TAS:Reactome F phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0030295 IEA:Ensembl F protein kinase activator activity
GO:0004674 IEA:UniProtKB-KW F protein serine/threonine kinase activity
GO:0038095 TAS:Reactome P Fc-epsilon receptor signaling pathway
GO:0038096 TAS:Reactome P Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0031295 TAS:Reactome P T cell costimulation
GO:0050852 TAS:Reactome P T cell receptor signaling pathway
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0007596 TAS:Reactome P blood coagulation
GO:0060048 TAS:UniProtKB P cardiac muscle contraction
GO:0043542 TAS:UniProtKB P endothelial cell migration
GO:0007173 TAS:Reactome P epidermal growth factor receptor signaling pathway
GO:0008543 TAS:Reactome P fibroblast growth factor receptor signaling pathway
GO:0006006 IEA:Ensembl P glucose metabolic process
GO:0044029 IEA:Ensembl P hypomethylation of CpG island
GO:0045087 TAS:Reactome P innate immune response
GO:0008286 TAS:Reactome P insulin receptor signaling pathway
GO:0038028 TAS:UniProtKB P insulin receptor signaling pathway via phosphatidylinositol 3-kinase
GO:0050900 TAS:Reactome P leukocyte migration
GO:2000811 IMP:UniProtKB P negative regulation of anoikis
GO:2000270 IEA:Ensembl P negative regulation of fibroblast apoptotic process
GO:0043524 IEA:Ensembl P negative regulation of neuron apoptotic process
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0006661 TAS:Reactome P phosphatidylinositol biosynthetic process
GO:0046854 ISS:BHF-UCL P phosphatidylinositol phosphorylation
GO:0048015 TAS:Reactome P phosphatidylinositol-mediated signaling
GO:0006644 TAS:Reactome P phospholipid metabolic process
GO:0030168 TAS:UniProtKB P platelet activation
GO:0033138 IEA:Ensembl P positive regulation of peptidyl-serine phosphorylation
GO:0043491 IEA:Ensembl P protein kinase B signaling
GO:2000653 IEA:Ensembl P regulation of genetic imprinting
GO:0040014 IEA:Ensembl P regulation of multicellular organism growth
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0001944 TAS:UniProtKB P vasculature development

KEGG Pathway Links

KEGG Pathway ID Description
hsa04152 AMPK signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04024 cAMP signaling pathway
hsa04022 cGMP-PKG signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR016024 Armadillo-type fold
IPR000008 C2 domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR018936 Phosphatidylinositol 3/4-kinase, conserved site
IPR015433 Phosphatidylinositol Kinase
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR011009 Protein kinase-like domain
IPR029071 Ubiquitin-related domain

UniProt Annotations

Entry Information

Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Protein Entry
PK3CA_HUMAN
UniProt ID
P42336
Species
Human

Comments

Comment Type Description
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.
Disease Breast cancer (BC) [MIM
Disease Colorectal cancer (CRC) [MIM
Disease Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM
Disease Cowden syndrome 5 (CWS5) [MIM
Disease Hepatocellular carcinoma (HCC) [MIM
Disease Keratosis, seborrheic (KERSEB) [MIM
Disease Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM
Disease 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.
Disease Ovarian cancer (OC) [MIM
Domain 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. {ECO
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.
Interaction P21860:ERBB3; NbExp=3; IntAct=EBI-2116585, EBI-720706; P35568:IRS1; NbExp=20; IntAct=EBI-2116585, EBI-517592; P27986:PIK3R1; NbExp=13; IntAct=EBI-2116585, EBI-79464;
Miscellaneous The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA.
Similarity Belongs to the PI3/PI4-kinase family. {ECO
Similarity Contains 1 C2 PI3K-type domain. {ECO
Similarity Contains 1 PI3K-ABD domain. {ECO
Similarity Contains 1 PI3K-RBD domain. {ECO
Similarity Contains 1 PI3K/PI4K domain. {ECO
Similarity Contains 1 PIK helical domain. {ECO
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).
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PIK3CAID415ch3q26.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP001325 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
54792082 RefSeq NP_006209 1068 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

Identical Sequences to LMP001325 proteins

Reference Database Accession Length Protein Name
GI:54792082 RefSeq XP_007970228.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Chlorocebus sabaeus]
GI:54792082 RefSeq XP_007970229.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Chlorocebus sabaeus]
GI:54792082 RefSeq XP_007970230.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Chlorocebus sabaeus]
GI:54792082 RefSeq XP_009199591.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Papio anubis]
GI:54792082 RefSeq XP_009199592.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Papio anubis]
GI:54792082 RefSeq XP_009445164.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Pan troglodytes]

Related Sequences to LMP001325 proteins

Reference Database Accession Length Protein Name
GI:54792082 DBBJ BAE06102.1 1069 PIK3CA variant protein, partial [Homo sapiens]
GI:54792082 GenBank AAQ02532.1 1069 phosphoinositide-3-kinase, catalytic, alpha polypeptide, partial [synthetic construct]
GI:54792082 GenBank AEL91080.1 1068 Sequence 15 from patent US 7981605
GI:54792082 GenBank AGY15662.1 1068 Sequence 15 from patent US 8546107
GI:54792082 RefSeq XP_010372245.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Rhinopithecus roxellana]
GI:54792082 RefSeq XP_010372252.1 1068 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Rhinopithecus roxellana]