ID PK3CA_HUMAN Reviewed; 1068 AA. AC P42336; Q14CW1; Q99762; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 2. DT 27-MAR-2024, entry version 234. DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; DE Short=PI3-kinase subunit alpha; DE Short=PI3K-alpha; DE Short=PI3Kalpha {ECO:0000303|PubMed:28676499}; DE Short=PtdIns-3-kinase subunit alpha; DE EC=2.7.1.137 {ECO:0000269|PubMed:23936502}; DE EC=2.7.1.153 {ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:28676499}; DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; DE Short=PtdIns-3-kinase subunit p110-alpha; DE Short=p110alpha {ECO:0000303|PubMed:15135396}; DE AltName: Full=Phosphoinositide 3-kinase alpha {ECO:0000303|PubMed:28676499}; DE AltName: Full=Phosphoinositide-3-kinase catalytic alpha polypeptide; DE AltName: Full=Serine/threonine protein kinase PIK3CA; DE EC=2.7.11.1 {ECO:0000269|PubMed:23936502, ECO:0000269|PubMed:28676499}; GN Name=PIK3CA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-43 AND ARG-332. RX PubMed=7713498; DOI=10.1006/geno.1994.1655; RA Volinia S., Hiles I., Ormondroyd E., Nizetic D., Antonacci R., Rocchi M., RA Waterfield M.; RT "Molecular cloning, cDNA sequence, and chromosomal localization of the RT human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene."; RL Genomics 24:472-477(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9043658; DOI=10.1016/s0968-0896(96)00196-4; RA Stirdivant S.M., Ahern J., Conroy R.R., Barnett S.F., Ledder L.M., RA Oliff A., Heimbrook D.C.; RT "Cloning and mutagenesis of the p110 alpha subunit of human RT phosphoinositide 3'-hydroxykinase."; RL Bioorg. Med. Chem. 5:65-74(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH APPL1. RX PubMed=10490823; DOI=10.1038/sj.onc.1203080; RA Mitsuuchi Y., Johnson S.W., Sonoda G., Tanno S., Golemis E.A., Testa J.R.; RT "Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor RT molecule that interacts with the oncoprotein-serine/threonine kinase RT AKT2."; RL Oncogene 18:4891-4898(1999). RN [5] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15135396; DOI=10.1016/j.pep.2003.12.010; RA Meier T.I., Cook J.A., Thomas J.E., Radding J.A., Horn C., Lingaraj T., RA Smith M.C.; RT "Cloning, expression, purification, and characterization of the human Class RT Ia phosphoinositide 3-kinase isoforms."; RL Protein Expr. Purif. 35:218-224(2004). RN [6] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23936502; DOI=10.1371/journal.pone.0071337; RA Buchanan C.M., Dickson J.M., Lee W.J., Guthridge M.A., Kendall J.D., RA Shepherd P.R.; RT "Oncogenic mutations of p110alpha isoform of PI 3-kinase upregulate its RT protein kinase activity."; RL PLoS ONE 8:e71337-e71337(2013). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=28676499; DOI=10.1074/jbc.m116.772426; RA Maheshwari S., Miller M.S., O'Meally R., Cole R.N., Amzel L.M., RA Gabelli S.B.; RT "Kinetic and structural analyses reveal residues in phosphoinositide 3- RT kinase alpha that are critical for catalysis and substrate recognition."; RL J. Biol. Chem. 292:13541-13550(2017). RN [8] RP FUNCTION IN INVADOPODIA FORMATION, AND CHARACTERIZATION OF VARIANTS LYS-545 RP AND ARG-1047. RX PubMed=21708979; DOI=10.1083/jcb.201009126; RA Yamaguchi H., Yoshida S., Muroi E., Yoshida N., Kawamura M., Kouchi Z., RA Nakamura Y., Sakai R., Fukami K.; RT "Phosphoinositide 3-kinase signaling pathway mediated by p110{alpha} RT regulates invadopodia formation."; RL J. Cell Biol. 193:1275-1288(2011). RN [9] RP INVOLVEMENT IN MADAC, AND VARIANTS MADAC PRO-115; LYS-542; ARG-1047 AND RP LEU-1047. RX PubMed=23100325; DOI=10.1093/hmg/dds440; RA Rios J.J., Paria N., Burns D.K., Israel B.A., Cornelia R., Wise C.A., RA Ezaki M.; RT "Somatic gain-of-function mutations in PIK3CA in patients with RT macrodactyly."; RL Hum. Mol. Genet. 22:444-451(2013). RN [10] RP INTERACTION WITH FAM83B. RX PubMed=23676467; DOI=10.18632/oncotarget.1027; RA Cipriano R., Miskimen K.L., Bryson B.L., Foy C.R., Bartel C.A., RA Jackson M.W.; RT "FAM83B-mediated activation of PI3K/AKT and MAPK signaling cooperates to RT promote epithelial cell transformation and resistance to targeted RT therapies."; RL Oncotarget 4:729-738(2013). RN [11] RP REVIEW ON CANCER. RX PubMed=18418043; DOI=10.4161/cc.7.9.5817; RA Huang C.-H., Mandelker D., Gabelli S.B., Amzel L.M.; RT "Insights into the oncogenic effects of PIK3CA mutations from the structure RT of p110alpha/p85alpha."; RL Cell Cycle 7:1151-1156(2008). RN [12] RP REVIEW ON FUNCTION, AND REVIEW ON CANCER. RX PubMed=18794883; DOI=10.1038/onc.2008.244; RA Zhao L., Vogt P.K.; RT "Class I PI3K in oncogenic cellular transformation."; RL Oncogene 27:5486-5496(2008). RN [13] RP REVIEW ON FUNCTION. RX PubMed=19200708; DOI=10.1016/j.ceb.2008.12.007; RA Jia S., Roberts T.M., Zhao J.J.; RT "Should individual PI3 kinase isoforms be targeted in cancer?"; RL Curr. Opin. Cell Biol. 21:199-208(2009). RN [14] RP INVOLVEMENT IN CLAPO, AND VARIANTS CLAPO SER-83; PRO-115; ARG-420; LYS-542 RP AND LEU-1047. RX PubMed=29446767; DOI=10.1038/gim.2017.200; RA Rodriguez-Laguna L., Ibanez K., Gordo G., Garcia-Minaur S., RA Santos-Simarro F., Agra N., Vallespin E., Fernandez-Montano V.E., RA Martin-Arenas R., Del Pozo A., Gonzalez-Pecellin H., Mena R., RA Rueda-Arenas I., Gomez M.V., Villaverde C., Bustamante A., Ayuso C., RA Ruiz-Perez V.L., Nevado J., Lapunzina P., Lopez-Gutierrez J.C., RA Martinez-Glez V.; RT "CLAPO syndrome: identification of somatic activating PIK3CA mutations and RT delineation of the natural history and phenotype."; RL Genet. Med. 20:882-889(2018). RN [15] RP INVOLVEMENT IN CCM4, AND VARIANTS CCM4 LYS-542; ARG-1047 AND LEU-1047. RX PubMed=34496175; DOI=10.1056/nejmoa2100440; RA Peyre M., Miyagishima D., Bielle F., Chapon F., Sierant M., Venot Q., RA Lerond J., Marijon P., Abi-Jaoude S., Le Van T., Labreche K., Houlston R., RA Faisant M., Clemenceau S., Boch A.L., Nouet A., Carpentier A., Boetto J., RA Louvi A., Kalamarides M.; RT "Somatic PIK3CA mutations in sporadic cerebral cavernous malformations."; RL N. Engl. J. Med. 385:996-996(2021). RN [16] RP X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS) IN A COMPLEX WITH PIK3R1, AND DOMAINS. RX PubMed=18079394; DOI=10.1126/science.1150799; RA Huang C.-H., Mandelker D., Schmidt-Kittler O., Samuels Y., Velculescu V.E., RA Kinzler K.W., Vogelstein B., Gabelli S.B., Amzel L.M.; RT "The structure of a human p110alpha/p85alpha complex elucidates the effects RT of oncogenic PI3Kalpha mutations."; RL Science 318:1744-1748(2007). RN [17] RP STRUCTURE BY NMR OF 331-481. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the C2 domain from human PI3-kinase p110 subunit RT alpha."; RL Submitted (APR-2008) to the PDB data bank. RN [18] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF MUTANT HIS-1047 IN COMPLEX WITH RP WORTMANNIN AND PIK3R1, INTERACTION WITH PIK3R1, CHARACTERIZATION OF VARIANT RP ARG-1047, AND DOMAINS. RX PubMed=19805105; DOI=10.1073/pnas.0908444106; RA Mandelker D., Gabelli S.B., Schmidt-Kittler O., Zhu J., Cheong I., RA Huang C.H., Kinzler K.W., Vogelstein B., Amzel L.M.; RT "A frequent kinase domain mutation that changes the interaction between RT PI3Kalpha and the membrane."; RL Proc. Natl. Acad. Sci. U.S.A. 106:16996-17001(2009). RN [19] RP VARIANTS CANCER LYS-542; LYS-545; PRO-546; ASN-1021; ARG-1047; LEU-1047 AND RP TYR-1065. RX PubMed=15289301; DOI=10.1158/0008-5472.can-04-1170; RA Broderick D.K., Di C., Parrett T.J., Samuels Y.R., Cummins J.M., RA McLendon R.E., Fults D.W., Velculescu V.E., Bigner D.D., Yan H.; RT "Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade RT astrocytomas, and medulloblastomas."; RL Cancer Res. 64:5048-5050(2004). RN [20] RP INVOLVEMENT IN OC, AND VARIANTS CANCER GLY-545; LYS-545; LYS-546; GLU-546; RP ARG-1047 AND LEU-1047. RX PubMed=15520168; DOI=10.1158/0008-5472.can-04-2933; RA Campbell I.G., Russell S.E., Choong D.Y.H., Montgomery K.G., RA Ciavarella M.L., Hooi C.S.F., Cristiano B.E., Pearson R.B., Phillips W.A.; RT "Mutation of the PIK3CA gene in ovarian and breast cancer."; RL Cancer Res. 64:7678-7681(2004). RN [21] RP VARIANT CANCER ARG-1047. RX PubMed=15016963; DOI=10.1126/science.1096502; RA Samuels Y., Wang Z., Bardelli A., Silliman N., Ptak J., Szabo S., Yan H., RA Gazdar A., Powell S.M., Riggins G.J., Willson J.K.V., Markowitz S., RA Kinzler K.W., Vogelstein B., Velculescu V.E.; RT "High frequency of mutations of the PIK3CA gene in human cancers."; RL Science 304:554-554(2004). RN [22] RP VARIANTS CANCER GLN-88; LYS-542; ALA-545 AND ASN-1025. RX PubMed=15924253; DOI=10.1007/s00401-005-1000-1; RA Hartmann C., Bartels G., Gehlhaar C., Holtkamp N., von Deimling A.; RT "PIK3CA mutations in glioblastoma multiforme."; RL Acta Neuropathol. 109:639-642(2005). RN [23] RP VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047. RX PubMed=15784156; DOI=10.1186/1471-2407-5-29; RA Li V.S.W., Wong C.W., Chan T.L., Chan A.S.W., Zhao W., Chu K.-M., So S., RA Chen X., Yuen S.T., Leung S.Y.; RT "Mutations of PIK3CA in gastric adenocarcinoma."; RL BMC Cancer 5:29-29(2005). RN [24] RP INVOLVEMENT IN CRC, AND CHARACTERIZATION OF VARIANTS CRC HIS-38; VAL-106; RP ARG-420; GLN-453; LYS-542; LYS-545; ILE-1043 AND ARG-1047. RX PubMed=15930273; DOI=10.1158/0008-5472.can-04-4114; RA Ikenoue T., Kanai F., Hikiba Y., Obata T., Tanaka Y., Imamura J., Ohta M., RA Jazag A., Guleng B., Tateishi K., Asaoka Y., Matsumura M., Kawabe T., RA Omata M.; RT "Functional analysis of PIK3CA gene mutations in human colorectal cancer."; RL Cancer Res. 65:4562-4567(2005). RN [25] RP VARIANTS CANCER GLN-542; LYS-542; GLY-545; LYS-545; ARG-1007; HIS-1021; RP CYS-1021; VAL-1035; ILE-1043; TYR-1047; ARG-1047; ASP-1050; LYS-1052 AND RP LEU-1065. RX PubMed=16322209; DOI=10.1158/0008-5472.can-05-2620; RA Oda K., Stokoe D., Taketani Y., McCormick F.; RT "High frequency of coexistent mutations of PIK3CA and PTEN genes in RT endometrial carcinoma."; RL Cancer Res. 65:10669-10673(2005). RN [26] RP INVOLVEMENT IN CRC, AND VARIANTS CANCER LYS-542; GLY-545; LYS-545; RP GLN-1023; ARG-1047 AND LEU-1047. RX PubMed=15994075; DOI=10.1016/j.ejca.2005.04.022; RA Velho S., Oliveira C., Ferreira A., Ferreira A.C., Suriano G., RA Schwartz S. Jr., Duval A., Carneiro F., Machado J.C., Hamelin R., RA Seruca R.; RT "The prevalence of PIK3CA mutations in gastric and colon cancer."; RL Eur. J. Cancer 41:1649-1654(2005). RN [27] RP VARIANTS CANCER LYS-545 AND ARG-1047. RX PubMed=15712344; DOI=10.1002/humu.9316; RA Wang Y., Helland A., Holm R., Kristensen G.B., Boerresen-Dale A.-L.; RT "PIK3CA mutations in advanced ovarian carcinomas."; RL Hum. Mutat. 25:322-322(2005). RN [28] RP VARIANT HCC ALA-545. RX PubMed=15608678; DOI=10.1038/sj.onc.1208304; RA Lee J.W., Soung Y.H., Kim S.Y., Lee H.W., Park W.S., Nam S.W., Kim S.H., RA Lee J.Y., Yoo N.J., Lee S.H.; RT "PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular RT carcinomas."; RL Oncogene 24:1477-1480(2005). RN [29] RP VARIANTS CANCER CYS-343; LYS-542; LYS-545 AND ARG-1047, AND VARIANT RP MET-391. RX PubMed=16533766; DOI=10.1158/1078-0432.ccr-05-2173; RA Qiu W., Schoenleben F., Li X., Ho D.J., Close L.G., Manolidis S., RA Bennett B.P., Su G.H.; RT "PIK3CA mutations in head and neck squamous cell carcinoma."; RL Clin. Cancer Res. 12:1441-1446(2006). RN [30] RP VARIANT CANCER ARG-1047. RX PubMed=16114017; DOI=10.1002/ijc.21444; RA Or Y.Y.-Y., Hui A.B.-Y., To K.-F., Lam C.N.-Y., Lo K.-W.; RT "PIK3CA mutations in nasopharyngeal carcinoma."; RL Int. J. Cancer 118:1065-1067(2006). RN [31] RP VARIANTS BC LYS-542; VAL-542; LYS-545; ARG-546; ARG-1047 AND LEU-1047. RX PubMed=16353168; DOI=10.1002/path.1908; RA Buttitta F., Felicioni L., Barassi F., Martella C., Paolizzi D., Fresu G., RA Salvatore S., Cuccurullo F., Mezzetti A., Campani D., Marchetti A.; RT "PIK3CA mutation and histological type in breast carcinoma: high frequency RT of mutations in lobular carcinoma."; RL J. Pathol. 208:350-355(2006). RN [32] RP CHARACTERIZATION OF VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047. RX PubMed=16432179; DOI=10.1073/pnas.0510857103; RA Bader A.G., Kang S., Vogt P.K.; RT "Cancer-specific mutations in PIK3CA are oncogenic in vivo."; RL Proc. Natl. Acad. Sci. U.S.A. 103:1475-1479(2006). RN [33] RP VARIANTS KERSEB LYS-542; LYS-545; GLY-545 AND ARG-1047. RX PubMed=17673550; DOI=10.1073/pnas.0705218104; RA Hafner C., Lopez-Knowles E., Luis N.M., Toll A., Baselga E., RA Fernandez-Casado A., Hernandez S., Ribe A., Mentzel T., Stoehr R., RA Hofstaedter F., Landthaler M., Vogt T., Pujol R.M., Hartmann A., Real F.X.; RT "Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic RT keratoses with a characteristic mutation pattern."; RL Proc. Natl. Acad. Sci. U.S.A. 104:13450-13454(2007). RN [34] RP VARIANTS CLOVE ARG-420; LYS-542 AND ARG-1047. RX PubMed=22658544; DOI=10.1016/j.ajhg.2012.05.006; RA Kurek K.C., Luks V.L., Ayturk U.M., Alomari A.I., Fishman S.J., RA Spencer S.A., Mulliken J.B., Bowen M.E., Yamamoto G.L., Kozakewich H.P., RA Warman M.L.; RT "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome."; RL Am. J. Hum. Genet. 90:1108-1115(2012). RN [35] RP VARIANTS MCAP LYS-81; GLN-88; ARG-364; LYS-365; TYR-378; GLU-453 DEL; RP LYS-545; LYS-726; ARG-914; CYS-1021; ALA-1025; VAL-1035; ILE-1043; TYR-1047 RP AND SER-1049. RX PubMed=22729224; DOI=10.1038/ng.2331; RA Riviere J.B., Mirzaa G.M., O'Roak B.J., Beddaoui M., Alcantara D., RA Conway R.L., St-Onge J., Schwartzentruber J.A., Gripp K.W., Nikkel S.M., RA Worthylake T., Sullivan C.T., Ward T.R., Butler H.E., Kramer N.A., RA Albrecht B., Armour C.M., Armstrong L., Caluseriu O., Cytrynbaum C., RA Drolet B.A., Innes A.M., Lauzon J.L., Lin A.E., Mancini G.M., RA Meschino W.S., Reggin J.D., Saggar A.K., Lerman-Sagie T., Uyanik G., RA Weksberg R., Zirn B., Beaulieu C.L., Majewski J., Bulman D.E., RA O'Driscoll M., Shendure J., Graham J.M. Jr., Boycott K.M., Dobyns W.B.; RT "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA RT cause a spectrum of related megalencephaly syndromes."; RL Nat. Genet. 44:934-940(2012). RN [36] RP VARIANTS CWS5 ASP-118; LYS-135; LYS-218; ILE-356; LYS-382 AND ALA-545. RX PubMed=23246288; DOI=10.1016/j.ajhg.2012.10.021; RA Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L., Eng C.; RT "Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes."; RL Am. J. Hum. Genet. 92:76-80(2013). RN [37] RP VARIANT MCAP ASN-112, CHARACTERIZATION OF VARIANT MCAP ASN-112, FUNCTION, RP AND SUBUNIT. RX PubMed=26593112; DOI=10.1002/humu.22933; RA Donato N.D., Rump A., Mirzaa G.M., Alcantara D., Oliver A., Schrock E., RA Dobyns W.B., O'Driscoll M.; RT "Identification and characterisation of a novel constitutional PIK3CA RT mutation in a child lacking the typical segmental overgrowth of 'PIK3CA- RT related overgrowth spectrum' (PROS)."; RL Hum. Mutat. 37:242-245(2016). CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates CC phosphatidylinositol (PI) and its phosphorylated derivatives at CC position 3 of the inositol ring to produce 3-phosphoinositides CC (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and CC PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate CC phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, CC PubMed:28676499). PIP3 plays a key role by recruiting PH domain- CC containing proteins to the membrane, including AKT1 and PDPK1, CC activating signaling cascades involved in cell growth, survival, CC proliferation, motility and morphology. Participates in cellular CC signaling in response to various growth factors. Involved in the CC activation of AKT1 upon stimulation by receptor tyrosine kinases CC ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in CC signaling via insulin-receptor substrate (IRS) proteins. Essential in CC endothelial cell migration during vascular development through VEGFA CC signaling, possibly by regulating RhoA activity. Required for lymphatic CC vasculature development, possibly by binding to RAS and by activation CC by EGF and FGF2, but not by PDGF. Regulates invadopodia formation CC through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in CC embryonic stem cells through a AKT1 pathway. Participates in CC vasculogenesis in embryonic stem cells through PDK1 and protein kinase CC C pathway. In addition to its lipid kinase activity, it displays a CC serine-protein kinase activity that results in the autophosphorylation CC of the p85alpha regulatory subunit as well as phosphorylation of other CC proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly CC others (PubMed:23936502, PubMed:28676499). Plays a role in the positive CC regulation of phagocytosis and pinocytosis (By similarity). CC {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:15135396, CC ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:23936502, CC ECO:0000269|PubMed:26593112, ECO:0000269|PubMed:28676499}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836, CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153; CC Evidence={ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:28676499}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293; CC Evidence={ECO:0000305|PubMed:15135396, ECO:0000305|PubMed:28676499}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; CC EC=2.7.1.137; Evidence={ECO:0000269|PubMed:23936502}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; CC Evidence={ECO:0000305|PubMed:23936502}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:23936502, ECO:0000269|PubMed:28676499}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000305|PubMed:23936502, ECO:0000305|PubMed:28676499}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- CC bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55632, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83416, CC ChEBI:CHEBI:83419, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:28676499}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55633; CC Evidence={ECO:0000305|PubMed:28676499}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero- CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2- CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo- CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137, CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:15135396}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397; CC Evidence={ECO:0000305|PubMed:15135396}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.77 uM for PIP2 CC (1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)) CC {ECO:0000269|PubMed:28676499}; CC KM=2 uM for ATP {ECO:0000269|PubMed:28676499}; CC Vmax=1.7 pmol/min/ng enzyme for the phosphorylation of PIP2 CC (1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)) CC {ECO:0000269|PubMed:28676499}; CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate CC biosynthesis. {ECO:0000305|PubMed:15135396, CC ECO:0000305|PubMed:28676499}. CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory CC subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112). Interacts with CC IRS1 in nuclear extracts (By similarity). Interacts with RUFY3 (By CC similarity). Interacts with RASD2 (By similarity). Interacts with CC APPL1. Interacts with HRAS and KRAS (By similarity). Interaction with CC HRAS/KRAS is required for PI3K pathway signaling and cell proliferation CC stimulated by EGF and FGF2 (By similarity). Interacts with FAM83B; CC activates the PI3K/AKT signaling cascade (PubMed:23676467). CC {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:23676467, CC ECO:0000269|PubMed:26593112}. CC -!- INTERACTION: CC P42336; P54253: ATXN1; NbExp=3; IntAct=EBI-2116585, EBI-930964; CC P42336; P54252: ATXN3; NbExp=3; IntAct=EBI-2116585, EBI-946046; CC P42336; P21860: ERBB3; NbExp=18; IntAct=EBI-2116585, EBI-720706; CC P42336; P01100: FOS; NbExp=3; IntAct=EBI-2116585, EBI-852851; CC P42336; P62993: GRB2; NbExp=5; IntAct=EBI-2116585, EBI-401755; CC P42336; P42858: HTT; NbExp=3; IntAct=EBI-2116585, EBI-466029; CC P42336; P35568: IRS1; NbExp=41; IntAct=EBI-2116585, EBI-517592; CC P42336; P27986: PIK3R1; NbExp=63; IntAct=EBI-2116585, EBI-79464; CC P42336; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-2116585, EBI-9090282; CC P42336; O00459: PIK3R2; NbExp=48; IntAct=EBI-2116585, EBI-346930; CC P42336; Q92569: PIK3R3; NbExp=45; IntAct=EBI-2116585, EBI-79893; CC -!- DOMAIN: The PI3K-ABD domain and the PI3K-RBD domain interact with the CC PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the CC recruitment to the plasma membrane. The inhibitory interactions with CC PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain CC with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type CC domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with CC the nSH2 (N-terminal SH2) region of PIK3R1. CC {ECO:0000269|PubMed:18079394, ECO:0000269|PubMed:19805105}. CC -!- DISEASE: Note=PIK3CA mutations are involved in various type of cancer. CC Most of the cancer-associated mutations are missense mutations and map CC to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated CC isoforms participate in cellular transformation and tumorigenesis CC induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. CC Interaction with HRAS/KRAS is required for Ras-driven tumor formation. CC Mutations increasing the lipid kinase activity are required for CC oncogenic signaling. The protein kinase activity may not be required CC for tumorigenesis. {ECO:0000269|PubMed:15016963, CC ECO:0000269|PubMed:15289301, ECO:0000269|PubMed:15520168, CC ECO:0000269|PubMed:15712344, ECO:0000269|PubMed:15784156, CC ECO:0000269|PubMed:15924253, ECO:0000269|PubMed:15930273, CC ECO:0000269|PubMed:15994075, ECO:0000269|PubMed:16114017, CC ECO:0000269|PubMed:16322209, ECO:0000269|PubMed:16353168, CC ECO:0000269|PubMed:16432179, ECO:0000269|PubMed:16533766, CC ECO:0000269|PubMed:17673550, ECO:0000269|PubMed:19805105, CC ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:22658544, CC ECO:0000269|PubMed:22729224}. CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease CC characterized by malignant lesions arising from the inner wall of the CC large intestine (the colon) and the rectum. Genetic alterations are CC often associated with progression from premalignant lesion (adenoma) to CC invasive adenocarcinoma. Risk factors for cancer of the colon and CC rectum include colon polyps, long-standing ulcerative colitis, and CC genetic family history. {ECO:0000269|PubMed:15930273, CC ECO:0000269|PubMed:15994075}. Note=The gene represented in this entry CC may be involved in disease pathogenesis. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:16353168}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer CC defines malignancies originating from ovarian tissue. Although many CC histologic types of ovarian tumors have been described, epithelial CC ovarian carcinoma is the most common form. Ovarian cancers are often CC asymptomatic and the recognized signs and symptoms, even of late-stage CC disease, are vague. Consequently, most patients are diagnosed with CC advanced disease. {ECO:0000269|PubMed:15520168}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary CC malignant neoplasm of epithelial liver cells. The major risk factors CC for HCC are chronic hepatitis B virus (HBV) infection, chronic CC hepatitis C virus (HCV) infection, prolonged dietary aflatoxin CC exposure, alcoholic cirrhosis, and cirrhosis due to other causes. CC {ECO:0000269|PubMed:15608678}. Note=The gene represented in this entry CC may be involved in disease pathogenesis. CC -!- DISEASE: Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign CC skin tumor. Seborrheic keratoses usually begin with the appearance of CC one or more sharply defined, light brown, flat macules. The lesions may CC be sparse or numerous. As they initially grow, they develop a velvety CC to finely verrucous surface, followed by an uneven warty surface with CC multiple plugged follicles and a dull or lackluster appearance. CC {ECO:0000269|PubMed:17673550}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Megalencephaly-capillary malformation-polymicrogyria syndrome CC (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of CC anomalies including primary megalencephaly, prenatal overgrowth, brain CC and body asymmetry, cutaneous vascular malformations, digital anomalies CC consisting of syndactyly with or without postaxial polydactyly, CC connective tissue dysplasia involving the skin, subcutaneous tissue, CC and joints, and cortical brain malformations, most distinctively CC polymicrogyria. {ECO:0000269|PubMed:22729224, CC ECO:0000269|PubMed:26593112}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Congenital lipomatous overgrowth, vascular malformations, and CC epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non- CC hereditary disorder characterized by asymmetric somatic hypertrophy and CC anomalies in multiple organs. It is defined by four main clinical CC findings: congenital lipomatous overgrowth, vascular malformations, CC epidermal nevi, and skeletal/spinal abnormalities. The presence of CC truncal overgrowth and characteristic patterned macrodactyly at birth CC differentiates CLOVE from other syndromic forms of overgrowth. CC {ECO:0000269|PubMed:22658544}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden CC syndrome, a hamartomatous polyposis syndrome with age-related CC penetrance. Cowden syndrome is characterized by hamartomatous lesions CC affecting derivatives of ectodermal, mesodermal and endodermal layers, CC macrocephaly, facial trichilemmomas (benign tumors of the hair follicle CC infundibulum), acral keratoses, papillomatous papules, and elevated CC risk for development of several types of malignancy, particularly CC breast carcinoma in women and thyroid carcinoma in both men and women. CC Colon cancer and renal cell carcinoma have also been reported. CC Hamartomas can be found in virtually every organ, but most commonly in CC the skin, gastrointestinal tract, breast and thyroid. CC {ECO:0000269|PubMed:23246288}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: CLAPO syndrome (CLAPO) [MIM:613089]: A syndrome characterized CC by capillary malformation of the lower lip, lymphatic malformation of CC the face and neck, asymmetry of face and limbs and partial or CC generalised overgrowth. {ECO:0000269|PubMed:29446767}. Note=The disease CC may be caused by variants affecting the gene represented in this entry. CC The tissue distribution of the clinical manifestations in CLAPO seems CC to follow a pattern of somatic mosaicism. CC {ECO:0000269|PubMed:29446767}. CC -!- DISEASE: Macrodactyly (MADAC) [MIM:155500]: A congenital anomaly CC characterized by fibrofatty tissue enlargement and bony overgrowth CC affecting the digits or the entire hand or foot. CC {ECO:0000269|PubMed:23100325}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. The tissue CC distribution of the clinical manifestations in MADAC seems to follow a CC pattern of somatic mosaicism. {ECO:0000269|PubMed:23100325}. CC -!- DISEASE: Cerebral cavernous malformations 4 (CCM4) [MIM:619538]: A form CC of cerebral cavernous malformations, a congenital vascular anomaly of CC the central nervous system that can result in hemorrhagic stroke, CC seizures, recurrent headaches, and focal neurologic deficits. The CC lesions are characterized by grossly enlarged blood vessels consisting CC of a single layer of endothelium and without any intervening neural CC tissue, ranging in diameter from a few millimeters to several CC centimeters. CCM4 cases occur sporadically. CC {ECO:0000269|PubMed:34496175}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The avian sarcoma virus 16 genome encodes an oncogene CC derived from PIK3CA. {ECO:0000305|PubMed:18418043}. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE- CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879, CC ECO:0000255|PROSITE-ProRule:PRU00880}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/415/PIK3CA"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z29090; CAA82333.1; -; mRNA. DR EMBL; U79143; AAB39753.1; -; mRNA. DR EMBL; BC113601; AAI13602.1; -; mRNA. DR EMBL; BC113603; AAI13604.1; -; mRNA. DR CCDS; CCDS43171.1; -. DR PIR; I38110; I38110. DR RefSeq; NP_006209.2; NM_006218.3. DR RefSeq; XP_006713721.1; XM_006713658.3. DR RefSeq; XP_011511196.1; XM_011512894.2. DR PDB; 2ENQ; NMR; -; A=331-481. DR PDB; 2RD0; X-ray; 3.05 A; A=1-1068. DR PDB; 3HHM; X-ray; 2.80 A; A=1-1068. DR PDB; 3HIZ; X-ray; 3.30 A; A=1-1068. DR PDB; 3ZIM; X-ray; 2.85 A; A=107-1046. DR PDB; 4JPS; X-ray; 2.20 A; A=1-1068. DR PDB; 4L1B; X-ray; 2.59 A; A=1-1068. DR PDB; 4L23; X-ray; 2.50 A; A=1-1068. DR PDB; 4L2Y; X-ray; 2.80 A; A=1-1068. DR PDB; 4OVU; X-ray; 2.96 A; A=1-1068. DR PDB; 4OVV; X-ray; 3.50 A; A=1-1068. DR PDB; 4TUU; X-ray; 2.64 A; A=105-1048. DR PDB; 4TV3; X-ray; 2.85 A; A=105-1048. DR PDB; 4WAF; X-ray; 2.39 A; A=2-1068. DR PDB; 4YKN; X-ray; 2.90 A; A=2-1068. DR PDB; 4ZOP; X-ray; 2.62 A; A=1-1068. DR PDB; 5DXH; X-ray; 3.00 A; A/D=2-1068. DR PDB; 5DXT; X-ray; 2.25 A; A=107-1068. DR PDB; 5FI4; X-ray; 2.50 A; A=1-1068. DR PDB; 5ITD; X-ray; 3.02 A; A=1-1068. DR PDB; 5SW8; X-ray; 3.30 A; A=1-1068. DR PDB; 5SWG; X-ray; 3.11 A; A=1-1068. DR PDB; 5SWO; X-ray; 3.50 A; A=1-1068. DR PDB; 5SWP; X-ray; 3.41 A; A=1-1068. DR PDB; 5SWR; X-ray; 3.31 A; A=1-1068. DR PDB; 5SWT; X-ray; 3.49 A; A=1-1068. DR PDB; 5SX8; X-ray; 3.47 A; A=1-1068. DR PDB; 5SX9; X-ray; 3.52 A; A=1-1068. DR PDB; 5SXA; X-ray; 3.35 A; A=1-1068. DR PDB; 5SXB; X-ray; 3.30 A; A=1-1068. DR PDB; 5SXC; X-ray; 3.55 A; A=1-1068. DR PDB; 5SXD; X-ray; 3.50 A; A=1-1068. DR PDB; 5SXE; X-ray; 3.51 A; A=1-1068. DR PDB; 5SXF; X-ray; 3.46 A; A=1-1068. DR PDB; 5SXI; X-ray; 3.40 A; A=1-1068. DR PDB; 5SXJ; X-ray; 3.42 A; A=1-1068. DR PDB; 5SXK; X-ray; 3.55 A; A=1-1068. DR PDB; 5UBR; X-ray; 2.40 A; A=107-1050. DR PDB; 5UK8; X-ray; 2.50 A; A=1-1068. DR PDB; 5UKJ; X-ray; 2.80 A; A=1-1068. DR PDB; 5UL1; X-ray; 3.00 A; A=1-1068. DR PDB; 5XGH; X-ray; 2.97 A; A=8-1055. DR PDB; 5XGI; X-ray; 2.56 A; A=8-1059. DR PDB; 5XGJ; X-ray; 2.97 A; A=8-1055. DR PDB; 6GVF; X-ray; 2.50 A; A=107-1051. DR PDB; 6GVG; X-ray; 3.00 A; A=107-1068. DR PDB; 6GVH; X-ray; 2.74 A; A=107-1068. DR PDB; 6GVI; X-ray; 2.90 A; A=107-1068. DR PDB; 6NCT; X-ray; 3.35 A; A=1-1068. DR PDB; 6OAC; X-ray; 3.15 A; A=105-1048. DR PDB; 6PYS; X-ray; 2.19 A; A=107-1051. DR PDB; 6VO7; X-ray; 2.31 A; A=157-300. DR PDB; 7JIU; X-ray; 2.12 A; A=107-1052. DR PDB; 7K6M; X-ray; 2.41 A; A=105-1048. DR PDB; 7K6N; X-ray; 2.77 A; A=105-1048. DR PDB; 7K6O; X-ray; 2.74 A; A=105-1048. DR PDB; 7K71; X-ray; 2.90 A; A=105-1048. DR PDB; 7L1B; X-ray; 2.04 A; C=1046-1054. DR PDB; 7L1C; X-ray; 1.96 A; C=1046-1054. DR PDB; 7L1D; X-ray; 3.11 A; C=1046-1054. DR PDB; 7MLK; X-ray; 2.91 A; A=105-1048. DR PDB; 7MYN; EM; 2.79 A; A=1-1068. DR PDB; 7MYO; EM; 2.92 A; A=1-1068. DR PDB; 7PG5; X-ray; 2.20 A; A=1-1068. DR PDB; 7PG6; X-ray; 2.50 A; A=1-1068. DR PDB; 7R9V; X-ray; 2.69 A; A=105-1048. DR PDB; 7R9Y; X-ray; 2.85 A; A=105-1048. DR PDB; 7RRG; X-ray; 2.12 A; C=1046-1054. DR PDB; 7TZ7; X-ray; 2.41 A; A=1-1068. DR PDB; 8BFU; X-ray; 2.41 A; A=105-1048. DR PDB; 8DCP; EM; 2.41 A; A=1-1068. DR PDB; 8DCX; EM; 2.80 A; A=1-1068. DR PDB; 8DD4; EM; 3.10 A; A=1-1068. DR PDB; 8DD8; EM; 3.40 A; A=1-1068. DR PDB; 8EXL; X-ray; 1.99 A; A=7-1052. DR PDB; 8EXO; X-ray; 2.46 A; A=7-1052. DR PDB; 8EXU; X-ray; 2.68 A; A=7-1052. DR PDB; 8EXV; X-ray; 2.48 A; A=7-1052. DR PDB; 8GUA; EM; 2.77 A; A=1-1068. DR PDB; 8GUB; EM; 2.73 A; A=1-1068. DR PDB; 8GUD; EM; 2.62 A; A=1-1068. DR PDB; 8ILR; EM; 3.05 A; A=1-1068. DR PDB; 8ILS; EM; 3.10 A; A=1-1068. DR PDB; 8ILV; EM; 3.19 A; A=1-1068. DR PDB; 8OW2; X-ray; 2.57 A; A=105-1048. DR PDB; 8SBC; X-ray; 2.30 A; A=1-1068. DR PDB; 8SBJ; X-ray; 3.10 A; A=1-1068. DR PDB; 8TDU; X-ray; 3.11 A; A/C=1-1068. DR PDB; 8TGD; X-ray; 2.93 A; A/C=1-1068. DR PDB; 8TS7; X-ray; 2.71 A; A=2-1053. DR PDB; 8TS8; X-ray; 2.72 A; A=2-1053. DR PDB; 8TS9; X-ray; 2.83 A; A=2-1050. DR PDB; 8TSA; X-ray; 2.51 A; A=2-1050. DR PDB; 8TSB; X-ray; 3.53 A; A=2-1053. DR PDB; 8TSC; X-ray; 3.62 A; A=2-1050. DR PDB; 8TSD; X-ray; 2.70 A; A=2-1053. DR PDB; 8TU6; EM; 3.12 A; A=2-1068. DR PDBsum; 2ENQ; -. DR PDBsum; 2RD0; -. DR PDBsum; 3HHM; -. DR PDBsum; 3HIZ; -. DR PDBsum; 3ZIM; -. DR PDBsum; 4JPS; -. DR PDBsum; 4L1B; -. DR PDBsum; 4L23; -. DR PDBsum; 4L2Y; -. DR PDBsum; 4OVU; -. DR PDBsum; 4OVV; -. DR PDBsum; 4TUU; -. DR PDBsum; 4TV3; -. DR PDBsum; 4WAF; -. DR PDBsum; 4YKN; -. DR PDBsum; 4ZOP; -. DR PDBsum; 5DXH; -. DR PDBsum; 5DXT; -. DR PDBsum; 5FI4; -. DR PDBsum; 5ITD; -. DR PDBsum; 5SW8; -. DR PDBsum; 5SWG; -. DR PDBsum; 5SWO; -. DR PDBsum; 5SWP; -. DR PDBsum; 5SWR; -. DR PDBsum; 5SWT; -. DR PDBsum; 5SX8; -. DR PDBsum; 5SX9; -. DR PDBsum; 5SXA; -. DR PDBsum; 5SXB; -. DR PDBsum; 5SXC; -. DR PDBsum; 5SXD; -. DR PDBsum; 5SXE; -. DR PDBsum; 5SXF; -. DR PDBsum; 5SXI; -. DR PDBsum; 5SXJ; -. DR PDBsum; 5SXK; -. DR PDBsum; 5UBR; -. DR PDBsum; 5UK8; -. DR PDBsum; 5UKJ; -. DR PDBsum; 5UL1; -. DR PDBsum; 5XGH; -. DR PDBsum; 5XGI; -. DR PDBsum; 5XGJ; -. DR PDBsum; 6GVF; -. DR PDBsum; 6GVG; -. DR PDBsum; 6GVH; -. DR PDBsum; 6GVI; -. DR PDBsum; 6NCT; -. DR PDBsum; 6OAC; -. DR PDBsum; 6PYS; -. DR PDBsum; 6VO7; -. DR PDBsum; 7JIU; -. DR PDBsum; 7K6M; -. DR PDBsum; 7K6N; -. DR PDBsum; 7K6O; -. DR PDBsum; 7K71; -. DR PDBsum; 7L1B; -. DR PDBsum; 7L1C; -. DR PDBsum; 7L1D; -. DR PDBsum; 7MLK; -. DR PDBsum; 7MYN; -. DR PDBsum; 7MYO; -. DR PDBsum; 7PG5; -. DR PDBsum; 7PG6; -. DR PDBsum; 7R9V; -. DR PDBsum; 7R9Y; -. DR PDBsum; 7RRG; -. DR PDBsum; 7TZ7; -. DR PDBsum; 8BFU; -. DR PDBsum; 8DCP; -. DR PDBsum; 8DCX; -. DR PDBsum; 8DD4; -. DR PDBsum; 8DD8; -. DR PDBsum; 8EXL; -. DR PDBsum; 8EXO; -. DR PDBsum; 8EXU; -. DR PDBsum; 8EXV; -. DR PDBsum; 8GUA; -. DR PDBsum; 8GUB; -. DR PDBsum; 8GUD; -. DR PDBsum; 8ILR; -. DR PDBsum; 8ILS; -. DR PDBsum; 8ILV; -. DR PDBsum; 8OW2; -. DR PDBsum; 8SBC; -. DR PDBsum; 8SBJ; -. DR PDBsum; 8TDU; -. DR PDBsum; 8TGD; -. DR PDBsum; 8TS7; -. DR PDBsum; 8TS8; -. DR PDBsum; 8TS9; -. DR PDBsum; 8TSA; -. DR PDBsum; 8TSB; -. DR PDBsum; 8TSC; -. DR PDBsum; 8TSD; -. DR PDBsum; 8TU6; -. DR AlphaFoldDB; P42336; -. DR EMDB; EMD-24081; -. DR EMDB; EMD-24082; -. DR EMDB; EMD-27327; -. DR EMDB; EMD-27330; -. DR EMDB; EMD-27334; -. DR EMDB; EMD-27336; -. DR EMDB; EMD-35543; -. DR EMDB; EMD-35545; -. DR EMDB; EMD-35547; -. DR EMDB; EMD-41617; -. DR SMR; P42336; -. DR BioGRID; 111308; 174. DR ComplexPortal; CPX-1917; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p85beta. DR ComplexPortal; CPX-1918; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p55gamma. DR ComplexPortal; CPX-2384; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p85alpha. DR ComplexPortal; CPX-5970; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p55alpha. DR ComplexPortal; CPX-5971; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p50alpha. DR CORUM; P42336; -. DR DIP; DIP-42728N; -. DR IntAct; P42336; 196. DR MINT; P42336; -. DR STRING; 9606.ENSP00000263967; -. DR BindingDB; P42336; -. DR ChEMBL; CHEMBL4005; -. DR DrugBank; DB12015; Alpelisib. DR DrugBank; DB00171; ATP. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB12483; Copanlisib. DR DrugBank; DB11772; Pilaralisib. DR DrugBank; DB08059; Wortmannin. DR DrugBank; DB05241; XL765. DR DrugCentral; P42336; -. DR GuidetoPHARMACOLOGY; 2153; -. DR iPTMnet; P42336; -. DR MetOSite; P42336; -. DR PhosphoSitePlus; P42336; -. DR BioMuta; PIK3CA; -. DR DMDM; 126302584; -. DR CPTAC; CPTAC-1631; -. DR CPTAC; CPTAC-3127; -. DR CPTAC; CPTAC-3128; -. DR CPTAC; CPTAC-3129; -. DR EPD; P42336; -. DR jPOST; P42336; -. DR MassIVE; P42336; -. DR MaxQB; P42336; -. DR PaxDb; 9606-ENSP00000263967; -. DR PeptideAtlas; P42336; -. DR ProteomicsDB; 55509; -. DR Pumba; P42336; -. DR Antibodypedia; 1374; 861 antibodies from 43 providers. DR CPTC; P42336; 1 antibody. DR DNASU; 5290; -. DR Ensembl; ENST00000263967.4; ENSP00000263967.3; ENSG00000121879.6. DR GeneID; 5290; -. DR KEGG; hsa:5290; -. DR MANE-Select; ENST00000263967.4; ENSP00000263967.3; NM_006218.4; NP_006209.2. DR UCSC; uc003fjk.4; human. DR AGR; HGNC:8975; -. DR CTD; 5290; -. DR DisGeNET; 5290; -. DR GeneCards; PIK3CA; -. DR GeneReviews; PIK3CA; -. DR HGNC; HGNC:8975; PIK3CA. DR HPA; ENSG00000121879; Low tissue specificity. DR MalaCards; PIK3CA; -. DR MIM; 114480; phenotype. DR MIM; 114500; phenotype. DR MIM; 114550; phenotype. DR MIM; 155500; phenotype. DR MIM; 167000; phenotype. DR MIM; 171834; gene. DR MIM; 182000; phenotype. DR MIM; 602501; phenotype. DR MIM; 612918; phenotype. DR MIM; 613089; phenotype. DR MIM; 615108; phenotype. DR MIM; 619538; phenotype. DR neXtProt; NX_P42336; -. DR OpenTargets; ENSG00000121879; -. DR Orphanet; 210159; Adult hepatocellular carcinoma. DR Orphanet; 168984; CLAPO syndrome. DR Orphanet; 140944; CLOVES syndrome. DR Orphanet; 201; Cowden syndrome. DR Orphanet; 221061; Familial cerebral cavernous malformation. DR Orphanet; 276280; Hemihyperplasia-multiple lipomatosis syndrome. DR Orphanet; 99802; Hemimegalencephaly. DR Orphanet; 144; Lynch syndrome. DR Orphanet; 295239; Macrodactyly of fingers, unilateral. DR Orphanet; 295243; Macrodactyly of toes, unilateral. DR Orphanet; 60040; Megalencephaly-capillary malformation-polymicrogyria syndrome. DR Orphanet; 2495; Meningioma. DR Orphanet; 314662; Segmental progressive overgrowth syndrome with fibroadipose hyperplasia. DR PharmGKB; PA33308; -. DR VEuPathDB; HostDB:ENSG00000121879; -. DR eggNOG; KOG0904; Eukaryota. DR GeneTree; ENSGT00940000155531; -. DR HOGENOM; CLU_002191_1_1_1; -. DR InParanoid; P42336; -. DR OMA; WSEWLNY; -. DR OrthoDB; 10350at2759; -. DR PhylomeDB; P42336; -. DR TreeFam; TF102031; -. DR BioCyc; MetaCyc:HS04527-MONOMER; -. DR BRENDA; 2.7.1.137; 2681. DR BRENDA; 2.7.1.153; 2681. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; P42336; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-112399; IRS-mediated signalling. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1250342; PI3K events in ERBB4 signaling. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-HSA-180292; GAB1 signalosome. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling. DR Reactome; R-HSA-198203; PI3K/AKT activation. DR Reactome; R-HSA-201556; Signaling by ALK. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-HSA-210993; Tie2 Signaling. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-HSA-373753; Nephrin family interactions. DR Reactome; R-HSA-388841; Costimulation by the CD28 family. DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655291; Signaling by FGFR4 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8851907; MET activates PI3K/AKT signaling. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K). DR Reactome; R-HSA-9028335; Activated NTRK2 signals through PI3K. DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. DR Reactome; R-HSA-912631; Regulation of signaling by CBL. DR Reactome; R-HSA-9603381; Activated NTRK3 signals through PI3K. DR Reactome; R-HSA-9607240; FLT3 Signaling. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants. DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants. DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins. DR Reactome; R-HSA-9703648; Signaling by FLT3 ITD and TKD mutants. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SABIO-RK; P42336; -. DR SignaLink; P42336; -. DR SIGNOR; P42336; -. DR UniPathway; UPA00220; -. DR BioGRID-ORCS; 5290; 275 hits in 1174 CRISPR screens. DR ChiTaRS; PIK3CA; human. DR EvolutionaryTrace; P42336; -. DR GeneWiki; P110%CE%B1; -. DR GenomeRNAi; 5290; -. DR Pharos; P42336; Tclin. DR PRO; PR:P42336; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P42336; Protein. DR Bgee; ENSG00000121879; Expressed in calcaneal tendon and 201 other cell types or tissues. DR ExpressionAtlas; P42336; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL. DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL. DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; ISS:BHF-UCL. DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IDA:UniProtKB. DR GO; GO:0005944; C:phosphatidylinositol 3-kinase complex, class IB; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:UniProtKB. DR GO; GO:0046934; F:1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IDA:UniProt. DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:Ensembl. DR GO; GO:0016301; F:kinase activity; IDA:MGI. DR GO; GO:0030295; F:protein kinase activator activity; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:BHF-UCL. DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0043276; P:anoikis; NAS:ParkinsonsUK-UCL. DR GO; GO:0141068; P:autosome genomic imprinting; IEA:Ensembl. DR GO; GO:0086003; P:cardiac muscle cell contraction; ISS:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; TAS:UniProtKB. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0071464; P:cellular response to hydrostatic pressure; ISS:BHF-UCL. DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProt. DR GO; GO:0043542; P:endothelial cell migration; TAS:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; ISS:BHF-UCL. DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB. DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0016242; P:negative regulation of macroautophagy; NAS:ParkinsonsUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IGI:BHF-UCL. DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:BHF-UCL. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IDA:MGI. DR GO; GO:0030168; P:platelet activation; TAS:UniProtKB. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IGI:BHF-UCL. DR GO; GO:1905477; P:positive regulation of protein localization to membrane; IDA:UniProt. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0032008; P:positive regulation of TOR signaling; NAS:ParkinsonsUK-UCL. DR GO; GO:0110053; P:regulation of actin filament organization; ISS:BHF-UCL. DR GO; GO:0043457; P:regulation of cellular respiration; IEA:Ensembl. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0055119; P:relaxation of cardiac muscle; ISS:BHF-UCL. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:1903544; P:response to butyrate; IEA:Ensembl. DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl. DR GO; GO:0043201; P:response to leucine; IEA:Ensembl. DR GO; GO:0014870; P:response to muscle inactivity; IEA:Ensembl. DR GO; GO:0035994; P:response to muscle stretch; ISS:BHF-UCL. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IGI:BHF-UCL. DR GO; GO:0001944; P:vasculature development; TAS:UniProtKB. DR CDD; cd08398; C2_PI3K_class_I_alpha; 1. DR CDD; cd00872; PI3Ka_I; 1. DR CDD; cd05175; PI3Kc_IA_alpha; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 1. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000403; PI3/4_kinase_cat_dom. DR InterPro; IPR036940; PI3/4_kinase_cat_sf. DR InterPro; IPR018936; PI3/4_kinase_CS. DR InterPro; IPR002420; PI3K-type_C2_dom. DR InterPro; IPR003113; PI3K_ABD. DR InterPro; IPR001263; PI3K_accessory_dom. DR InterPro; IPR042236; PI3K_accessory_sf. DR InterPro; IPR000341; PI3K_Ras-bd_dom. DR InterPro; IPR037704; PI3Kalpha_dom. DR InterPro; IPR015433; PI_Kinase. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR10048:SF107; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT ALPHA ISOFORM; 1. DR PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR Pfam; PF00792; PI3K_C2; 1. DR Pfam; PF02192; PI3K_p85B; 1. DR Pfam; PF00794; PI3K_rbd; 1. DR Pfam; PF00613; PI3Ka; 1. DR SMART; SM00142; PI3K_C2; 1. DR SMART; SM00143; PI3K_p85B; 1. DR SMART; SM00144; PI3K_rbd; 1. DR SMART; SM00145; PI3Ka; 1. DR SMART; SM00146; PI3Kc; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS51547; C2_PI3K; 1. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. DR PROSITE; PS51544; PI3K_ABD; 1. DR PROSITE; PS51546; PI3K_RBD; 1. DR PROSITE; PS51545; PIK_HELICAL; 1. DR Genevisible; P42336; HS. PE 1: Evidence at protein level; KW 3D-structure; Angiogenesis; ATP-binding; Disease variant; Kinase; KW Lipid metabolism; Nucleotide-binding; Phagocytosis; Proto-oncogene; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1..1068 FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase FT catalytic subunit alpha isoform" FT /id="PRO_0000088785" FT DOMAIN 16..105 FT /note="PI3K-ABD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877" FT DOMAIN 187..289 FT /note="PI3K-RBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879" FT DOMAIN 330..487 FT /note="C2 PI3K-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880" FT DOMAIN 517..694 FT /note="PIK helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878" FT DOMAIN 765..1051 FT /note="PI3K/PI4K catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 771..777 FT /note="G-loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 912..920 FT /note="Catalytic loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 931..957 FT /note="Activation loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT SITE 776 FT /note="Implicated in the recognition of ATP as well as FT PIP2. Also crucial for autophosphorylation of the p85alpha FT subunit" FT /evidence="ECO:0000305|PubMed:23936502" FT VARIANT 38 FT /note="R -> H (in CRC; likely involved in disease FT pathogenesis; shows an increase in lipid kinase activity; FT may disrupt the interaction between the PI3K-ABD domain and FT the N-terminal lobe of PI3K/PI4K kinase domain possibly FT affecting the conformation of the kinase domain; FT dbSNP:rs772110575)" FT /evidence="ECO:0000269|PubMed:15930273" FT /id="VAR_026166" FT VARIANT 43 FT /note="I -> V (in dbSNP:rs1051399)" FT /evidence="ECO:0000269|PubMed:7713498" FT /id="VAR_042942" FT VARIANT 81 FT /note="E -> K (in MCAP; dbSNP:rs1057519929)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069251" FT VARIANT 83 FT /note="F -> S (in CLAPO; uncertain significance; somatic FT mutation; dbSNP:rs1560137208)" FT /evidence="ECO:0000269|PubMed:29446767" FT /id="VAR_081475" FT VARIANT 88 FT /note="R -> Q (in MCAP; also found in a glioblastoma FT multiforme sample; dbSNP:rs121913287)" FT /evidence="ECO:0000269|PubMed:15924253, FT ECO:0000269|PubMed:22729224" FT /id="VAR_026167" FT VARIANT 106 FT /note="G -> V (in CRC; likely involved in disease FT pathogenesis; shows an increase in lipid kinase activity; FT dbSNP:rs1057519930)" FT /evidence="ECO:0000269|PubMed:15930273" FT /id="VAR_026168" FT VARIANT 112 FT /note="I -> N (in MCAP; increased phosphatidylinositol FT 3-kinase signaling; decreased interaction with p85 FT regulatory subunit; no effect on protein abundance; FT dbSNP:rs863225460)" FT /evidence="ECO:0000269|PubMed:26593112" FT /id="VAR_075634" FT VARIANT 115 FT /note="R -> P (in CLAPO and MADAC; uncertain significance; FT somatic mutation in CLAPO and MADAC patients)" FT /evidence="ECO:0000269|PubMed:23100325, FT ECO:0000269|PubMed:29446767" FT /id="VAR_081476" FT VARIANT 118 FT /note="G -> D (in CWS5; dbSNP:rs587777790)" FT /evidence="ECO:0000269|PubMed:23246288" FT /id="VAR_069786" FT VARIANT 135 FT /note="E -> K (in CWS5; dbSNP:rs587777791)" FT /evidence="ECO:0000269|PubMed:23246288" FT /id="VAR_069787" FT VARIANT 218 FT /note="E -> K (in CWS5; dbSNP:rs587777792)" FT /evidence="ECO:0000269|PubMed:23246288" FT /id="VAR_069788" FT VARIANT 332 FT /note="S -> R (in dbSNP:rs1051407)" FT /evidence="ECO:0000269|PubMed:7713498" FT /id="VAR_042943" FT VARIANT 343 FT /note="Y -> C (found in a cancer sample; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:16533766" FT /id="VAR_026169" FT VARIANT 356 FT /note="V -> I (in CWS5; dbSNP:rs587777793)" FT /evidence="ECO:0000269|PubMed:23246288" FT /id="VAR_069789" FT VARIANT 364 FT /note="G -> R (in MCAP; dbSNP:rs1576935161)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069252" FT VARIANT 365 FT /note="E -> K (in MCAP; dbSNP:rs1064793732)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069253" FT VARIANT 378 FT /note="C -> Y (in MCAP; dbSNP:rs397514565)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069254" FT VARIANT 382 FT /note="R -> K (in CWS5; dbSNP:rs587777794)" FT /evidence="ECO:0000269|PubMed:23246288" FT /id="VAR_069790" FT VARIANT 391 FT /note="I -> M (in dbSNP:rs2230461)" FT /evidence="ECO:0000269|PubMed:16533766" FT /id="VAR_026170" FT VARIANT 420 FT /note="C -> R (in CLOVE, CRC and CLAPO; uncertain FT significance; somatic mutation in CLAPO patients; shows an FT increase in lipid kinase activity; may increase the FT affinity for lipid membranes; dbSNP:rs121913272)" FT /evidence="ECO:0000269|PubMed:15930273, FT ECO:0000269|PubMed:22658544, ECO:0000269|PubMed:29446767" FT /id="VAR_026171" FT VARIANT 453 FT /note="E -> Q (in CRC; likely involved in disease FT pathogenesis; shows an increase in lipid kinase activity; FT may disrupt the interaction of the C2 PI3K-type domain with FT the iSH2 region of the p85 regulatory subunit; FT dbSNP:rs1057519925)" FT /evidence="ECO:0000269|PubMed:15930273" FT /id="VAR_026172" FT VARIANT 453 FT /note="Missing (in MCAP)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069255" FT VARIANT 542 FT /note="E -> K (in CLOVE, KERSEB, CRC, BC, CLAPO, MADAC and FT CCM4; also found in glioblastoma multiforme and endometrial FT carcinoma; somatic mutation; shows an increase in lipid FT kinase activity; oncogenic in vivo; occurs in the interface FT between the PI3K helical domain and the nSH2 (N-terminal FT SH2) region of the p85 regulatory subunit and may reduce FT the inhibitory effect of p85; requires interaction with RAS FT to induce cellular transformation; dbSNP:rs121913273)" FT /evidence="ECO:0000269|PubMed:15289301, FT ECO:0000269|PubMed:15784156, ECO:0000269|PubMed:15924253, FT ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075, FT ECO:0000269|PubMed:16322209, ECO:0000269|PubMed:16353168, FT ECO:0000269|PubMed:16432179, ECO:0000269|PubMed:16533766, FT ECO:0000269|PubMed:17673550, ECO:0000269|PubMed:22658544, FT ECO:0000269|PubMed:23100325, ECO:0000269|PubMed:29446767, FT ECO:0000269|PubMed:34496175" FT /id="VAR_026173" FT VARIANT 542 FT /note="E -> Q (found in an endometrial carcinoma sample; FT uncertain significance; dbSNP:rs121913273)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026174" FT VARIANT 542 FT /note="E -> V (in BC; uncertain significance; FT dbSNP:rs1057519927)" FT /evidence="ECO:0000269|PubMed:16353168" FT /id="VAR_026175" FT VARIANT 545 FT /note="E -> A (in CWS5 and HCC; also found in a FT glioblastoma multiforme sample; dbSNP:rs121913274)" FT /evidence="ECO:0000269|PubMed:15608678, FT ECO:0000269|PubMed:15924253, ECO:0000269|PubMed:23246288" FT /id="VAR_026176" FT VARIANT 545 FT /note="E -> G (in KERSEB; also found in an endometrial FT carcinoma sample; dbSNP:rs121913274)" FT /evidence="ECO:0000269|PubMed:15520168, FT ECO:0000269|PubMed:15994075, ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:17673550" FT /id="VAR_026177" FT VARIANT 545 FT /note="E -> K (in MCAP, KERSEB, CRC and BC; shows an FT increase in lipid kinase activity; oncogenic in vivo; FT occurs in the interface between the PI3K helical domain and FT the nSH2 (N-terminal SH2) region of the p85 regulatory FT subunit and may reduce the inhibitory effect of p85; FT requires interaction with RAS to induce cellular FT transformation; enhances invadopodia-mediated extracellular FT matrix degradation and invasion in breast cancer cells; FT dbSNP:rs104886003)" FT /evidence="ECO:0000269|PubMed:15289301, FT ECO:0000269|PubMed:15520168, ECO:0000269|PubMed:15712344, FT ECO:0000269|PubMed:15784156, ECO:0000269|PubMed:15930273, FT ECO:0000269|PubMed:15994075, ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:16353168, ECO:0000269|PubMed:16432179, FT ECO:0000269|PubMed:16533766, ECO:0000269|PubMed:17673550, FT ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:22729224" FT /id="VAR_026178" FT VARIANT 546 FT /note="Q -> E (in BC; uncertain significance; FT dbSNP:rs121913286)" FT /evidence="ECO:0000269|PubMed:15520168" FT /id="VAR_026179" FT VARIANT 546 FT /note="Q -> K (in OC; uncertain significance; FT dbSNP:rs121913286)" FT /evidence="ECO:0000269|PubMed:15520168" FT /id="VAR_026180" FT VARIANT 546 FT /note="Q -> P (found in an anaplastic astrocytoma sample; FT uncertain significance; dbSNP:rs397517201)" FT /evidence="ECO:0000269|PubMed:15289301" FT /id="VAR_026181" FT VARIANT 546 FT /note="Q -> R (in BC; uncertain significance; FT dbSNP:rs397517201)" FT /evidence="ECO:0000269|PubMed:16353168" FT /id="VAR_026182" FT VARIANT 726 FT /note="E -> K (in MCAP; dbSNP:rs867262025)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069256" FT VARIANT 914 FT /note="G -> R (in MCAP; dbSNP:rs587776932)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069257" FT VARIANT 1007 FT /note="G -> R (found in an endometrial carcinoma sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026183" FT VARIANT 1021 FT /note="Y -> C (in MCAP; also found in an endometrial FT carcinoma sample; dbSNP:rs121913288)" FT /evidence="ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:22729224" FT /id="VAR_026184" FT VARIANT 1021 FT /note="Y -> H (found in an endometrial carcinoma sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026185" FT VARIANT 1021 FT /note="Y -> N (found in a glioblastoma multiforme sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:15289301" FT /id="VAR_026186" FT VARIANT 1023 FT /note="R -> Q (in CRC; uncertain significance)" FT /evidence="ECO:0000269|PubMed:15994075" FT /id="VAR_026187" FT VARIANT 1025 FT /note="T -> A (in MCAP; dbSNP:rs397517202)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069258" FT VARIANT 1025 FT /note="T -> N (found in a glioblastoma multiforme sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:15924253" FT /id="VAR_026188" FT VARIANT 1035 FT /note="A -> V (in MCAP; also found in an endometrial FT carcinoma sample; dbSNP:rs1242945375)" FT /evidence="ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:22729224" FT /id="VAR_026189" FT VARIANT 1043 FT /note="M -> I (in MCAP and CRC; also found in an FT endometrial carcinoma sample; shows an increase in lipid FT kinase activity; dbSNP:rs121913283)" FT /evidence="ECO:0000269|PubMed:15930273, FT ECO:0000269|PubMed:16322209, ECO:0000269|PubMed:22729224" FT /id="VAR_026190" FT VARIANT 1047 FT /note="H -> L (in BC, CLAPO, MADAC and CCM4; somatic FT mutation; dbSNP:rs121913279)" FT /evidence="ECO:0000269|PubMed:15289301, FT ECO:0000269|PubMed:15520168, ECO:0000269|PubMed:15994075, FT ECO:0000269|PubMed:16353168, ECO:0000269|PubMed:23100325, FT ECO:0000269|PubMed:29446767, ECO:0000269|PubMed:34496175" FT /id="VAR_026191" FT VARIANT 1047 FT /note="H -> R (in CLOVE, KERSEB, CRC, BC, OC, MADAC and FT CCM4; also found in an endometrial carcinoma sample; FT somatic mutation; shows an increase in lipid kinase FT activity; oncogenic in vivo; requires binding to p85 FT regulatory subunit to induce cellular transformation but FT not interaction with RAS; may mimic the conformatitonal FT change triggered by the interaction with RAS; enhances FT invadopodia-mediated extracellular matrix degradation and FT invasion in breast cancer cells; may alter the interaction FT of the PI3K/PI4K kinase domain with the cell membrane; FT dbSNP:rs121913279)" FT /evidence="ECO:0000269|PubMed:15016963, FT ECO:0000269|PubMed:15289301, ECO:0000269|PubMed:15520168, FT ECO:0000269|PubMed:15712344, ECO:0000269|PubMed:15784156, FT ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075, FT ECO:0000269|PubMed:16114017, ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:16353168, ECO:0000269|PubMed:16432179, FT ECO:0000269|PubMed:16533766, ECO:0000269|PubMed:17673550, FT ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:21708979, FT ECO:0000269|PubMed:22658544, ECO:0000269|PubMed:23100325, FT ECO:0000269|PubMed:34496175" FT /id="VAR_026192" FT VARIANT 1047 FT /note="H -> Y (in MCAP; also found in an endometrial FT carcinoma sample; dbSNP:rs121913281)" FT /evidence="ECO:0000269|PubMed:16322209, FT ECO:0000269|PubMed:22729224" FT /id="VAR_026193" FT VARIANT 1049 FT /note="G -> S (in MCAP; dbSNP:rs121913277)" FT /evidence="ECO:0000269|PubMed:22729224" FT /id="VAR_069259" FT VARIANT 1050 FT /note="G -> D (found in an endometrial carcinoma sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026194" FT VARIANT 1052 FT /note="T -> K (found in an endometrial carcinoma sample; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026195" FT VARIANT 1065 FT /note="H -> L (found in an endometrial carcinoma sample; FT uncertain significance; dbSNP:rs1560150596)" FT /evidence="ECO:0000269|PubMed:16322209" FT /id="VAR_026196" FT VARIANT 1065 FT /note="H -> Y (found in brain tumors; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:15289301" FT /id="VAR_026197" FT CONFLICT 170 FT /note="N -> H (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 187 FT /note="K -> R (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 286..287 FT /note="ML -> KM (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 346 FT /note="V -> L (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 723 FT /note="K -> R (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 751 FT /note="F -> L (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT CONFLICT 767 FT /note="E -> K (in Ref. 1; CAA82333)" FT /evidence="ECO:0000305" FT STRAND 5..10 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 13..15 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 18..25 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:7MYN" FT STRAND 31..37 FT /evidence="ECO:0007829|PDB:4JPS" FT HELIX 42..52 FT /evidence="ECO:0007829|PDB:4JPS" FT HELIX 53..55 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:2RD0" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:4JPS" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:4OVU" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:5SW8" FT HELIX 89..91 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 94..102 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:5SXA" FT HELIX 108..121 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 126..129 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 134..142 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 144..154 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 155..159 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 160..166 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 179..182 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:3HHM" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:8BFU" FT STRAND 189..197 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 199..202 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 204..212 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 217..230 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:6GVH" FT HELIX 236..246 FT /evidence="ECO:0007829|PDB:7PG5" FT HELIX 247..249 FT /evidence="ECO:0007829|PDB:7JIU" FT STRAND 250..254 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 255..258 FT /evidence="ECO:0007829|PDB:3HIZ" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:8TGD" FT HELIX 267..269 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 271..279 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 284..289 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 290..294 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:5SXA" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 332..343 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 348..350 FT /evidence="ECO:0007829|PDB:4JPS" FT STRAND 353..362 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 365..368 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:6PYS" FT STRAND 382..392 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 400..408 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:7TZ7" FT STRAND 420..430 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 434..436 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 439..444 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 446..448 FT /evidence="ECO:0007829|PDB:8GUA" FT STRAND 454..456 FT /evidence="ECO:0007829|PDB:6GVF" FT STRAND 458..460 FT /evidence="ECO:0007829|PDB:6GVH" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 472..477 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 481..485 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 489..504 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 508..511 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 515..517 FT /evidence="ECO:0007829|PDB:4TUU" FT TURN 520..522 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 525..536 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:4TUU" FT HELIX 545..553 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 555..558 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 562..564 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 565..569 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 577..588 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 595..598 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 599..602 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 603..605 FT /evidence="ECO:0007829|PDB:8GUA" FT HELIX 609..622 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 625..630 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 632..638 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 639..641 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 643..646 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 648..657 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 661..672 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 673..676 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 678..680 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 681..694 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 698..721 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 723..726 FT /evidence="ECO:0007829|PDB:7K6M" FT HELIX 728..739 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 742..747 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 749..753 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 756..761 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 766..768 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 774..776 FT /evidence="ECO:0007829|PDB:7R9V" FT STRAND 779..784 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 786..789 FT /evidence="ECO:0007829|PDB:7MYN" FT HELIX 790..792 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 795..805 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 808..826 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 838..842 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 845..849 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 852..856 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 857..860 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 863..865 FT /evidence="ECO:0007829|PDB:7K6N" FT STRAND 868..870 FT /evidence="ECO:0007829|PDB:7R9V" FT HELIX 871..873 FT /evidence="ECO:0007829|PDB:2RD0" FT HELIX 876..884 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 887..889 FT /evidence="ECO:0007829|PDB:7JIU" FT HELIX 890..911 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 920..924 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 929..931 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 938..941 FT /evidence="ECO:0007829|PDB:7PG5" FT HELIX 942..945 FT /evidence="ECO:0007829|PDB:4JPS" FT HELIX 948..950 FT /evidence="ECO:0007829|PDB:7K6M" FT STRAND 951..954 FT /evidence="ECO:0007829|PDB:7K6M" FT HELIX 958..964 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 965..967 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 971..973 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 975..993 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 995..1003 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 1004..1007 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 1013..1015 FT /evidence="ECO:0007829|PDB:8EXV" FT HELIX 1016..1025 FT /evidence="ECO:0007829|PDB:8EXL" FT TURN 1026..1029 FT /evidence="ECO:0007829|PDB:8EXL" FT HELIX 1032..1047 FT /evidence="ECO:0007829|PDB:8EXL" FT STRAND 1048..1050 FT /evidence="ECO:0007829|PDB:5SW8" FT STRAND 1053..1055 FT /evidence="ECO:0007829|PDB:3HHM" FT STRAND 1056..1058 FT /evidence="ECO:0007829|PDB:4JPS" SQ SEQUENCE 1068 AA; 124284 MW; 041487231A9A1207 CRC64; MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLITIKHELF KEARKYPLHQ LLQDESSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK VIEPVGNREE KILNREIGFA IGMPVCEFDM VKDPEVQDFR RNILNVCKEA VDLRDLNSPH SRAMYVYPPN VESSPELPKH IYNKLDKGQI IVVIWVIVSP NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK LCVLEYQGKY ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPMD CFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD IDKIYVRTGI YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA RLCLSICSVK GRKGAKEEHC PLAWGNINLF DYTDTLVSGK MALNLWPVPH GLEDLLNPIG VTGSNPNKET PCLELEFDWF SSVVKFPDMS VIEEHANWSV SREAGFSYSH AGLSNRLARD NELRENDKEQ LKAISTRDPL SEITEQEKDF LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME LLDCNYPDPM VRGFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV RFLLKKALTN QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK HLNRQVEAME KLINLTDILK QEKKDETQKV QMKFLVEQMR RPDFMDALQG FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW LNWENPDIMS ELLFQNNEII FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS IGDCVGLIEV VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE RVPFVLTQDF LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN LFSMMLGSGM PELQSFDDIA YIRKTLALDK TEQEALEYFM KQMNDAHHGG WTTKMDWIFH TIKQHALN //