PK3CA_HUMAN
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 03-AUG-2022, entry version 225.
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 (1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) {ECO:0000269|PubMed:28676499};
CC KM=2.00 uM for ATP {ECO:0000269|PubMed:28676499};
CC Vmax=1.70 pmol/min/ng enzyme for the phosphorylation of PIP2 (1,2-
CC 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=3; 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=20; IntAct=EBI-2116585, EBI-517592;
CC P42336; P27986: PIK3R1; NbExp=23; IntAct=EBI-2116585, EBI-79464;
CC P42336; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-2116585, EBI-9090282;
CC P42336; Q92569: PIK3R3; NbExp=5; 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="http://atlasgeneticsoncology.org/Genes/PIK3CAID415ch3q26.html";
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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; 7MYN; EM; 2.79 A; A=1-1068.
DR PDB; 7MYO; EM; 2.92 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 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; 7MYN; -.
DR PDBsum; 7MYO; -.
DR PDBsum; 7R9V; -.
DR PDBsum; 7R9Y; -.
DR PDBsum; 7RRG; -.
DR AlphaFoldDB; P42336; -.
DR SMR; P42336; -.
DR BioGRID; 111308; 152.
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; 74.
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 EPD; P42336; -.
DR jPOST; P42336; -.
DR MassIVE; P42336; -.
DR MaxQB; P42336; -.
DR PaxDb; P42336; -.
DR PeptideAtlas; P42336; -.
DR PRIDE; P42336; -.
DR ProteomicsDB; 55509; -.
DR Antibodypedia; 1374; 754 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 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; 140944; CLOVES syndrome.
DR Orphanet; 201; Cowden syndrome.
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 Orphanet; 357191; Selection of therapeutic option in non-small cell lung carcinoma.
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; EHANWTV; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; P42336; -.
DR TreeFam; TF102031; -.
DR BioCyc; MetaCyc:HS04527-MON; -.
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-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 SignaLink; P42336; -.
DR SIGNOR; P42336; -.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 5290; 270 hits in 1086 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 200 other tissues.
DR ExpressionAtlas; P42336; baseline and differential.
DR Genevisible; P42336; HS.
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:0016020; C:membrane; IBA:GO_Central.
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: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:0035004; F:phosphatidylinositol 3-kinase activity; ISS:BHF-UCL.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome.
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:0086003; P:cardiac muscle cell contraction; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; TAS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
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: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:0044029; P:hypomethylation of CpG island; IEA:Ensembl.
DR GO; GO:0038028; P:insulin receptor signaling pathway via phosphatidylinositol 3-kinase; TAS:UniProtKB.
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:0014065; P:phosphatidylinositol 3-kinase signaling; 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:0048015; P:phosphatidylinositol-mediated signaling; 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:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:BHF-UCL.
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:0043491; P:protein kinase B signaling; IEA:Ensembl.
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:2000653; P:regulation of genetic imprinting; IEA:Ensembl.
DR GO; GO:0040014; P:regulation of multicellular organism growth; 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; cd05175; PI3Kc_IA_alpha; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 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; PTHR10048; 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; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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; unknown pathological significance;
FT somatic 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 3-
FT kinase signaling; decreased interaction with p85 regulatory
FT 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; unknown pathological
FT significance; somatic mutation in CLAPO and MADAC
FT 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; unknown
FT pathological 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; unknown
FT pathological significance; somatic mutation in CLAPO
FT patients; shows an increase in lipid kinase activity; may
FT increase the affinity for lipid membranes;
FT 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 unknown pathological significance; dbSNP:rs121913273)"
FT /evidence="ECO:0000269|PubMed:16322209"
FT /id="VAR_026174"
FT VARIANT 542
FT /note="E -> V (in BC; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs121913286)"
FT /evidence="ECO:0000269|PubMed:15520168"
FT /id="VAR_026179"
FT VARIANT 546
FT /note="Q -> K (in OC; unknown pathological 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 unknown pathological significance; dbSNP:rs397517201)"
FT /evidence="ECO:0000269|PubMed:15289301"
FT /id="VAR_026181"
FT VARIANT 546
FT /note="Q -> R (in BC; unknown pathological 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 unknown pathological 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 unknown pathological 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 unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:15289301"
FT /id="VAR_026186"
FT VARIANT 1023
FT /note="R -> Q (in CRC; unknown pathological 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 unknown pathological 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 unknown pathological 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 unknown pathological 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 unknown pathological significance; dbSNP:rs1560150596)"
FT /evidence="ECO:0000269|PubMed:16322209"
FT /id="VAR_026196"
FT VARIANT 1065
FT /note="H -> Y (found in brain tumors; unknown pathological
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:7JIU"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 156..159
FT /evidence="ECO:0007829|PDB:4JPS"
FT HELIX 160..166
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:3HHM"
FT STRAND 188..197
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:4JPS"
FT STRAND 204..212
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 217..231
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:6GVH"
FT HELIX 237..242
FT /evidence="ECO:0007829|PDB:4WAF"
FT TURN 243..246
FT /evidence="ECO:0007829|PDB:4WAF"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 255..258
FT /evidence="ECO:0007829|PDB:3HIZ"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:5DXH"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 271..279
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 290..294
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 320..323
FT /evidence="ECO:0007829|PDB:4OVU"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 333..343
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:4JPS"
FT STRAND 353..362
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:6PYS"
FT STRAND 382..392
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 400..409
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 412..415
FT /evidence="ECO:0007829|PDB:7MYN"
FT STRAND 420..430
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 439..444
FT /evidence="ECO:0007829|PDB:7JIU"
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:7JIU"
FT STRAND 472..477
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 489..504
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 508..512
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 515..517
FT /evidence="ECO:0007829|PDB:4TUU"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 525..535
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 539..541
FT /evidence="ECO:0007829|PDB:4TUU"
FT HELIX 545..553
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 555..558
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 562..564
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 565..569
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 577..588
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 599..602
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 609..622
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 625..638
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 639..641
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 643..646
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 648..659
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 661..672
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 673..676
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 678..680
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 681..694
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 698..719
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 721..725
FT /evidence="ECO:0007829|PDB:4JPS"
FT HELIX 728..740
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 742..747
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 749..752
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 759..761
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 766..768
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 773..776
FT /evidence="ECO:0007829|PDB:7MYN"
FT STRAND 779..784
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 786..789
FT /evidence="ECO:0007829|PDB:7MYN"
FT HELIX 790..792
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 795..805
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 808..826
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 838..842
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 845..849
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 854..856
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 857..862
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 863..865
FT /evidence="ECO:0007829|PDB:7K6N"
FT HELIX 869..871
FT /evidence="ECO:0007829|PDB:7K6N"
FT HELIX 876..884
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 887..889
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 890..911
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 920..924
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 929..931
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 938..940
FT /evidence="ECO:0007829|PDB:6GVH"
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:7JIU"
FT TURN 965..967
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 971..973
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 975..992
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 995..1004
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 1005..1007
FT /evidence="ECO:0007829|PDB:7JIU"
FT STRAND 1013..1015
FT /evidence="ECO:0007829|PDB:5UK8"
FT HELIX 1016..1025
FT /evidence="ECO:0007829|PDB:7JIU"
FT TURN 1026..1029
FT /evidence="ECO:0007829|PDB:7JIU"
FT HELIX 1032..1047
FT /evidence="ECO:0007829|PDB:7JIU"
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
