PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

Gene

• Entrez ID: 5290
• Gene name: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
• Gene symbol: PIK3CA
• Synonyms: CLAPO, CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, PI3K-alpha, p110-alpha
• Chromosome: 3
• Chromosome location: 3q26.32
• 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. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104886003	G>A,C	Pathogenic, pathogenic-likely-pathogenic, likely-pathogenic, drug-response, not-provided	Missense variant, coding sequence variant
rs121913272	T>C,G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913273	G>A,C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913274	A>C,G,T	Pathogenic, pathogenic-likely-pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913275	G>A,C,T	Pathogenic, likely-pathogenic, likely-benign	Missense variant, synonymous variant, coding sequence variant
rs121913277	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs121913279	A>G,T	Pathogenic, pathogenic-likely-pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913281	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913282	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs121913283	G>A,T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913284	T>A,G	Likely-pathogenic	Missense variant, coding sequence variant
rs121913285	C>G	Likely-pathogenic	Missense variant, coding sequence variant
rs121913286	C>A,G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913287	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs121913288	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs201884756	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs397514565	G>A	Pathogenic	Missense variant, coding sequence variant
rs397517200	AGATTTGCTGAACCC>-	Likely-pathogenic	Coding sequence variant, inframe indel
rs397517201	A>C,G,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397517202	A>G	Pathogenic	Missense variant, coding sequence variant
rs587776802	->A	Pathogenic	Coding sequence variant, frameshift variant
rs587776932	G>A	Pathogenic, pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs587776933	AGA>-	Pathogenic	Coding sequence variant, inframe deletion
rs587777790	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs587777791	G>A	Pathogenic	Missense variant, coding sequence variant
rs587777792	G>A	Pathogenic	Missense variant, coding sequence variant
rs587777793	G>A	Pathogenic	Missense variant, coding sequence variant
rs587777794	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs587777795	GT>C	Pathogenic	Coding sequence variant, frameshift variant
rs587777796	T>G	Pathogenic	Stop gained, coding sequence variant
rs749415085	C>A,G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs772110575	G>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs863225060	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs863225460	T>A	Pathogenic	Missense variant, coding sequence variant
rs867262025	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs886042002	G>A	Pathogenic	Missense variant, coding sequence variant
rs1057518041	->GTC	Likely-pathogenic	Inframe insertion, coding sequence variant
rs1057519699	G>A	Pathogenic	Missense variant, coding sequence variant
rs1057519925	G>A,C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1057519926	A>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519927	A>C,G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519928	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519929	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519930	G>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1057519931	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519932	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519933	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519934	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519935	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519936	A>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519937	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519938	A>C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519939	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519940	G>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519941	T>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519942	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1064793349	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1064793663	G>A	Pathogenic	Missense variant, coding sequence variant
rs1064793732	G>A	Pathogenic	Missense variant, coding sequence variant
rs1064793838	A>G	Pathogenic	Missense variant, coding sequence variant
rs1064795304	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1553820381	CAGTAGGCAACC>-	Likely-pathogenic	Inframe deletion, coding sequence variant
rs1553825266	->A	Pathogenic	Frameshift variant, coding sequence variant
rs1553826166	C>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1553826184	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1560137208	T>C	Pathogenic	Missense variant, coding sequence variant
rs1560137609	->T	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1576935161	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1576947658	T>G	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006837	hsa-miR-124-3p	Luciferase reporter assay, qRT-PCR, Western blot	22940133
MIRT007316	hsa-miR-148b-3p	Western blot	23238785
MIRT007316	hsa-miR-148b-3p	Luciferase reporter assay	23233531
MIRT017306	hsa-miR-335-5p	Microarray	18185580
MIRT050839	hsa-miR-17-5p	CLASH	23622248
MIRT054839	hsa-miR-375	Luciferase reporter assay, qRT-PCR, Quantitative proteomic approach, Western blot	24440701
MIRT054889	hsa-miR-1-3p	Luciferase reporter assay, qRT-PCR, Western blot	24486107
MIRT161793	hsa-miR-155-5p	HITS-CLIP	22473208
MIRT161796	hsa-miR-490-5p	Luciferase reporter assay, qRT-PCR	26559013
MIRT209229	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	24996183
MIRT209229	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26617776
MIRT438492	hsa-miR-139-5p	Luciferase reporter assay	24158791
MIRT731192	hsa-miR-373-3p	Western blot, Luciferase reporter assay, Microarray	25591738
MIRT732765	hsa-miR-422a	Luciferase reporter assay, qRT-PCR, Western blot	27648359
MIRT734311	hsa-miR-19a-3p	In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	26058752
MIRT734680	hsa-miR-10b-5p	Luciferase reporter assay, Western blot	25896413

Transcription factors

Transcription factor	Regulation	Reference
FOXO3	Unknown	19299143
HIF1A	Unknown	23060442

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0001889	Process	Liver development	IEA
GO:0001944	Process	Vasculature development	TAS	19200708
GO:0005515	Function	Protein binding	IPI	10490823, 16043515, 17475214, 19411071, 19574958, 19805105, 20018188, 20713702, 21706016, 22402981, 23643389, 23676467, 24189400, 25253337, 25814554, 26496610, 28514442, 30568254, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005942	Component	Phosphatidylinositol 3-kinase complex	IBA	21873635
GO:0005942	Component	Phosphatidylinositol 3-kinase complex	ISS
GO:0005943	Component	Phosphatidylinositol 3-kinase complex, class IA	IBA	21873635
GO:0005943	Component	Phosphatidylinositol 3-kinase complex, class IA	IDA	22402981
GO:0005944	Component	Phosphatidylinositol 3-kinase complex, class IB	IBA	21873635
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006468	Process	Protein phosphorylation	IEA
GO:0006661	Process	Phosphatidylinositol biosynthetic process	TAS
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007411	Process	Axon guidance	TAS
GO:0010468	Process	Regulation of gene expression	IEA
GO:0010592	Process	Positive regulation of lamellipodium assembly	ISS
GO:0014065	Process	Phosphatidylinositol 3-kinase signaling	IBA	21873635
GO:0014065	Process	Phosphatidylinositol 3-kinase signaling	IGI	30496354
GO:0014065	Process	Phosphatidylinositol 3-kinase signaling	ISS	30568254
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	TAS
GO:0014704	Component	Intercalated disc	ISS
GO:0016020	Component	Membrane	IBA	21873635
GO:0016242	Process	Negative regulation of macroautophagy	NAS	23778976
GO:0016301	Function	Kinase activity	IDA	25327288
GO:0016301	Function	Kinase activity	TAS
GO:0016303	Function	1-phosphatidylinositol-3-kinase activity	IBA	21873635
GO:0016303	Function	1-phosphatidylinositol-3-kinase activity	IDA	2174051
GO:0016310	Process	Phosphorylation	IDA	25327288
GO:0016477	Process	Cell migration	IBA	21873635
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030027	Component	Lamellipodium	IEA
GO:0030036	Process	Actin cytoskeleton organization	ISS
GO:0030168	Process	Platelet activation	TAS	21035500
GO:0030295	Function	Protein kinase activator activity	IEA
GO:0030835	Process	Negative regulation of actin filament depolymerization	ISS
GO:0031295	Process	T cell costimulation	TAS
GO:0032008	Process	Positive regulation of TOR signaling	NAS	23778976
GO:0032147	Process	Activation of protein kinase activity	IEA
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IEA
GO:0035004	Function	Phosphatidylinositol 3-kinase activity	ISS
GO:0035004	Function	Phosphatidylinositol 3-kinase activity	TAS	19200708
GO:0035005	Function	1-phosphatidylinositol-4-phosphate 3-kinase activity	IBA	21873635
GO:0035994	Process	Response to muscle stretch	ISS
GO:0036092	Process	Phosphatidylinositol-3-phosphate biosynthetic process	IBA	21873635
GO:0038028	Process	Insulin receptor signaling pathway via phosphatidylinositol 3-kinase	TAS	19200708
GO:0038084	Process	Vascular endothelial growth factor signaling pathway	IGI	30496354
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0040014	Process	Regulation of multicellular organism growth	IEA
GO:0043276	Process	Anoikis	NAS	23778976
GO:0043457	Process	Regulation of cellular respiration	IEA
GO:0043491	Process	Protein kinase B signaling	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043542	Process	Endothelial cell migration	TAS	19200708
GO:0043560	Function	Insulin receptor substrate binding	IEA
GO:0044029	Process	Hypomethylation of CpG island	IEA
GO:0046854	Process	Phosphatidylinositol phosphorylation	IBA	21873635
GO:0046854	Process	Phosphatidylinositol phosphorylation	ISS
GO:0046934	Function	Phosphatidylinositol-4,5-bisphosphate 3-kinase activity	TAS
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0048015	Process	Phosphatidylinositol-mediated signaling	IBA	21873635
GO:0048015	Process	Phosphatidylinositol-mediated signaling	TAS
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050900	Process	Leukocyte migration	TAS
GO:0051897	Process	Positive regulation of protein kinase B signaling	IGI	30496354
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0052742	Function	Phosphatidylinositol kinase activity	IBA	21873635
GO:0052812	Function	Phosphatidylinositol-3,4-bisphosphate 5-kinase activity	IEA
GO:0055119	Process	Relaxation of cardiac muscle	ISS
GO:0060048	Process	Cardiac muscle contraction	TAS	19147653
GO:0060612	Process	Adipose tissue development	IEA
GO:0071333	Process	Cellular response to glucose stimulus	IEA
GO:0071464	Process	Cellular response to hydrostatic pressure	ISS	30568254
GO:0086003	Process	Cardiac muscle cell contraction	ISS
GO:0097009	Process	Energy homeostasis	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:0110053	Process	Regulation of actin filament organization	ISS
GO:2000270	Process	Negative regulation of fibroblast apoptotic process	IEA
GO:2000653	Process	Regulation of genetic imprinting	IEA
GO:2000811	Process	Negative regulation of anoikis	IMP	22402981

Other IDs

• MIM: 171834
• HGNC: 8975
• e!Ensembl: ENSG00000121879

Protein

• UniProt ID: P42336
• Protein name: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PI3-kinase subunit alpha) (PI3K-alpha) (PI3Kalpha) (PtdIns-3-kinase subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha) (PtdIns-3-kinase subunit p110-alpha) (p110alpha) (Phosphoinositide 3-kinase alpha) (Phosphoinositide-3-kinase catalytic alpha polypeptide) (Serine/threonine protein kinase PIK3CA) (EC 2.7.11.1)
• Protein function: Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). 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. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity).
• PDB: 2ENQ, 2RD0, 3HHM, 3HIZ, 3ZIM, 4JPS, 4L1B, 4L23, 4L2Y, 4OVU, 4OVV, 4TUU, 4TV3, 4WAF, 4YKN, 4ZOP, 5DXH, 5DXT, 5FI4, 5ITD, 5SW8, 5SWG, 5SWO, 5SWP, 5SWR, 5SWT, 5SX8, 5SX9, 5SXA, 5SXB, 5SXC, 5SXD, 5SXE, 5SXF, 5SXI, 5SXJ, 5SXK, 5UBR, 5UK8, 5UKJ, 5UL1, 5XGH, 5XGI, 5XGJ, 6GVF, 6GVG, 6GVH, 6GVI, 6NCT, 6OAC, 6PYS
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02192	PI3K_p85B	32 → 107	PI3-kinase family, p85-binding domain	Family
  PF00794	PI3K_rbd	173 → 292	PI3-kinase family, ras-binding domain	Domain
  PF00792	PI3K_C2	350 → 485	Phosphoinositide 3-kinase C2	Domain
  PF00613	PI3Ka	519 → 704	Phosphoinositide 3-kinase family, accessory domain (PIK domain)	Family
  PF00454	PI3_PI4_kinase	796 → 1015	Phosphatidylinositol 3- and 4-kinase	Family

• Sequence:

  MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQ
  LLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFA
  IGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKH
  IYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLK
  LCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMD
  CFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGI
  YHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHC
  PLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWF
  SSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPL
  SEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAME
  LLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTN
  QRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILK
  QEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW
  LNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLS
  IGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRS
  CAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDF
  LIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA
  YIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN

• Sequence length: 1068