CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007557
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 
Protein Synonyms/Alias
 PI3-kinase subunit alpha; PI3K-alpha; PI3Kalpha; PtdIns-3-kinase subunit alpha; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; PtdIns-3-kinase subunit p110-alpha; p110alpha; Phosphoinositide-3-kinase catalytic alpha polypeptide; Serine/threonine protein kinase PIK3CA 
Gene Name
 Pik3ca 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
720INLTDILKQEKKDETubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 16 105 PI3K-ABD.
 DOMAIN 187 289 PI3K-RBD.
 DOMAIN 330 487 C2 PI3K-type.
 DOMAIN 517 694 PIK helical.
 DOMAIN 797 1068 PI3K/PI4K.  
Keyword
 3D-structure; Angiogenesis; ATP-binding; Complete proteome; Kinase; Nucleotide-binding; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1068 AA 
Protein Sequence
MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLVTIKHELF REARKYPLHQ 60
LLQDETSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK VIEPVGNREE KILNREIGFV 120
IGMPVCEFDM VKDPEVQDFR RNILNVCKEA VDLRDLNSPH SRAMYVYPPN VESSPELPKH 180
IYNKLDKGQI IVVIWVIVSP NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK 240
LCVLEYQGKY ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPID 300
SFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD IDKIYVRTGI 360
YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA RLCLSICSVK GRKGAKEEHC 420
PLAWGNINLF DYTDTLVSGK MALNLWPVPH GLEDLLNPIG VTGSNPNKET PCLELEFDWF 480
SSVVKFPDMS VIEEHANWSV SREAGFSYSH TGLSNRLARD NELRENDKEQ LRALCTRDPL 540
SEITEQEKDF LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME 600
LLDCNYPDPM VRSFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV RFLLKKALTN 660
QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK HLNRQVEAME KLINLTDILK 720
QEKKDETQKV QMKFLVEQMR QPDFMDALQG FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW 780
LNWENPDIMS ELLFQNNEII FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS 840
IGDCVGLIEV VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS 900
CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE RVPFVLTQDF 960
LIVISKGAQE YTKTREFERF QEMCYKAYLA IRQHANLFIN LFSMMLGSGM PELQSFDDIA 1020
YIRKTLALDK TEQEALEYFT KQMNDAHHGG WTTKMDWIFH TIKQHALN 1068 
Gene Ontology
 GO:0005943; C:1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex; IEA:Compara.
 GO:0030027; C:lamellipodium; IDA:MGI.
 GO:0005942; C:phosphatidylinositol 3-kinase complex; IPI:MGI.
 GO:0005886; C:plasma membrane; IBA:RefGenome.
 GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:MGI.
 GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
 GO:0030295; F:protein kinase activator activity; IDA:BHF-UCL.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0006006; P:glucose metabolic process; IMP:MGI.
 GO:0044029; P:hypomethylation of CpG island; IDA:BHF-UCL.
 GO:2000811; P:negative regulation of anoikis; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
 GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:InterPro.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0043491; P:protein kinase B signaling cascade; IMP:MGI.
 GO:0006468; P:protein phosphorylation; IDA:MGI.
 GO:2000653; P:regulation of genetic imprinting; IDA:BHF-UCL.
 GO:0040014; P:regulation of multicellular organism growth; IMP:MGI. 
Interpro
 IPR016024; ARM-type_fold.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR011009; Kinase-like_dom.
 IPR000403; PI3/4_kinase_cat_dom.
 IPR018936; PI3/4_kinase_CS.
 IPR003113; PI3K_adapt-bd_dom.
 IPR002420; PI3K_C2_dom.
 IPR000341; PI3K_Ras-bd_dom.
 IPR015433; PI_Kinase.
 IPR001263; PInositide-3_kin_accessory_dom. 
Pfam
 PF00454; PI3_PI4_kinase
 PF00792; PI3K_C2
 PF02192; PI3K_p85B
 PF00794; PI3K_rbd
 PF00613; PI3Ka 
SMART
 SM00239; C2
 SM00142; PI3K_C2
 SM00143; PI3K_p85B
 SM00144; PI3K_rbd
 SM00145; PI3Ka
 SM00146; PI3Kc 
PROSITE
 PS50004; C2
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3
 PS51544; PI3K_ABD
 PS51547; PI3K_C2
 PS51546; PI3K_RBD
 PS51545; PIK_HELICAL 
PRINTS