P85A_HUMAN
ID P85A_HUMAN Reviewed; 724 AA.
AC P27986; B3KT19; D3DWA0; E7EX19; Q15747; Q4VBZ7; Q53EM6; Q8IXA2; Q8N1C5;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 252.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit alpha;
DE Short=PI3-kinase regulatory subunit alpha;
DE Short=PI3K regulatory subunit alpha;
DE Short=PtdIns-3-kinase regulatory subunit alpha;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha;
DE Short=PI3-kinase subunit p85-alpha;
DE Short=PtdIns-3-kinase regulatory subunit p85-alpha;
GN Name=PIK3R1; Synonyms=GRB1;
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] (ISOFORM 1).
RX PubMed=1849461; DOI=10.1016/0092-8674(91)90410-z;
RA Skolnik E.Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R.,
RA Drepps A., Ullrich A., Schlessinger J.;
RT "Cloning of PI3 kinase-associated p85 utilizing a novel method for
RT expression/cloning of target proteins for receptor tyrosine kinases.";
RL Cell 65:83-90(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), INTERACTION WITH IRS1, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=8628286; DOI=10.1128/mcb.16.5.2195;
RA Antonetti D.A., Algenstaedt P., Kahn C.R.;
RT "Insulin receptor substrate 1 binds two novel splice variants of the
RT regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain.";
RL Mol. Cell. Biol. 16:2195-2203(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Skeletal muscle;
RA Udelhoven M., Kotzka J., Knebel B., Klein E., Krone W., Mueller-Wieland D.;
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ILE-326.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LYS-451.
RC TISSUE=Placenta, and Skeletal muscle;
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 [9]
RP INTERACTION WITH PDGFRB.
RX PubMed=7692233; DOI=10.1128/mcb.13.11.6889-6896.1993;
RA Nishimura R., Li W., Kashishian A., Mondino A., Zhou M., Cooper J.,
RA Schlessinger J.;
RT "Two signaling molecules share a phosphotyrosine-containing binding site in
RT the platelet-derived growth factor receptor.";
RL Mol. Cell. Biol. 13:6889-6896(1993).
RN [10]
RP INTERACTION WITH INSR.
RX PubMed=8276809; DOI=10.1016/s0021-9258(17)42304-0;
RA Van Horn D.J., Myers M.G. Jr., Backer J.M.;
RT "Direct activation of the phosphatidylinositol 3'-kinase by the insulin
RT receptor.";
RL J. Biol. Chem. 269:29-32(1994).
RN [11]
RP FUNCTION IN FGFR4 SIGNALING.
RX PubMed=7518429; DOI=10.1016/s0021-9258(17)32309-8;
RA Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K.;
RT "Signal transduction by fibroblast growth factor receptor-4 (FGFR-4).
RT Comparison with FGFR-1.";
RL J. Biol. Chem. 269:18320-18326(1994).
RN [12]
RP INTERACTION WITH IGF1R.
RX PubMed=7541045; DOI=10.1074/jbc.270.26.15639;
RA Craparo A., O'Neill T.J., Gustafson T.A.;
RT "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their
RT phosphotyrosine-dependent interaction with the NPEY motif of the insulin-
RT like growth factor I receptor.";
RL J. Biol. Chem. 270:15639-15643(1995).
RN [13]
RP INTERACTION WITH INSR.
RX PubMed=7537849; DOI=10.1128/mcb.15.5.2500;
RA Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J.;
RT "Phosphotyrosine-dependent interaction of SHC and insulin receptor
RT substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2
RT domain.";
RL Mol. Cell. Biol. 15:2500-2508(1995).
RN [14]
RP INTERACTION WITH PDGFRA.
RX PubMed=8940081; DOI=10.1074/jbc.271.48.30942;
RA Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.;
RT "Grb7 is a downstream signaling component of platelet-derived growth factor
RT alpha- and beta-receptors.";
RL J. Biol. Chem. 271:30942-30949(1996).
RN [15]
RP INTERACTION WITH KIT.
RX PubMed=9038210; DOI=10.1074/jbc.272.9.5915;
RA Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.;
RT "Direct association of Csk homologous kinase (CHK) with the
RT diphosphorylated site Tyr568/570 of the activated c-KIT in
RT megakaryocytes.";
RL J. Biol. Chem. 272:5915-5920(1997).
RN [16]
RP INTERACTION WITH AXL.
RX PubMed=9178760; DOI=10.1038/sj.onc.1201123;
RA Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R.,
RA Ullrich A., Bartram C.R., Janssen J.W.;
RT "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is
RT mediated mainly by a multi-substrate docking-site.";
RL Oncogene 14:2619-2631(1997).
RN [17]
RP INTERACTION WITH LAT.
RX PubMed=9489702; DOI=10.1016/s0092-8674(00)80901-0;
RA Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.;
RT "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to
RT cellular activation.";
RL Cell 92:83-92(1998).
RN [18]
RP INTERACTION WITH IRS4.
RX PubMed=9553137; DOI=10.1074/jbc.273.17.10726;
RA Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E.,
RA Lavan B.E.;
RT "Characterization of insulin receptor substrate 4 in human embryonic kidney
RT 293 cells.";
RL J. Biol. Chem. 273:10726-10732(1998).
RN [19]
RP INTERACTION WITH TRAT1.
RX PubMed=9687533; DOI=10.1084/jem.188.3.561;
RA Bruyns E., Marie-Cardine A., Kirchgessner H., Sagolla K., Shevchenko A.,
RA Mann M., Autschbach F., Bensussan A., Meuer S., Schraven B.;
RT "T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-
RT linked dimer associated with the TCR-CD3-zeta complex, recruits
RT intracellular signaling proteins to the plasma membrane.";
RL J. Exp. Med. 188:561-575(1998).
RN [20]
RP INTERACTION WITH HCST.
RX PubMed=10528161;
RA Chang C., Dietrich J., Harpur A.G., Lindquist J.A., Haude A., Loke Y.W.,
RA King A., Colonna M., Trowsdale J., Wilson M.J.;
RT "KAP10, a novel transmembrane adapter protein genetically linked to DAP12
RT but with unique signaling properties.";
RL J. Immunol. 163:4651-4654(1999).
RN [21]
RP INTERACTION WITH CBLB.
RX PubMed=10086340; DOI=10.1038/sj.onc.1202499;
RA Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H.,
RA Lipkowitz S.;
RT "cbl-b inhibits epidermal growth factor receptor signaling.";
RL Oncogene 18:1855-1866(1999).
RN [22]
RP INTERACTION WITH FGR AND HCK.
RX PubMed=10739672; DOI=10.1006/excr.2000.4816;
RA Axelsson L., Hellberg C., Melander F., Smith D., Zheng L., Andersson T.;
RT "Clustering of beta(2)-integrins on human neutrophils activates dual
RT signaling pathways to PtdIns 3-kinase.";
RL Exp. Cell Res. 256:257-263(2000).
RN [23]
RP INTERACTION WITH ERBB4.
RX PubMed=10867024; DOI=10.1074/jbc.c901015199;
RA Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C.,
RA Carraway K.L. III;
RT "Ligand discrimination in signaling through an ErbB4 receptor homodimer.";
RL J. Biol. Chem. 275:19803-19807(2000).
RN [24]
RP INTERACTION WITH TYK2.
RX PubMed=10995743; DOI=10.1074/jbc.m003626200;
RA Kusch A., Tkachuk S., Haller H., Dietz R., Gulba D.C., Lipp M., Dumler I.;
RT "Urokinase stimulates human vascular smooth muscle cell migration via a
RT phosphatidylinositol 3-kinase-Tyk2 interaction.";
RL J. Biol. Chem. 275:39466-39473(2000).
RN [25]
RP INTERACTION WITH CBLB, AND UBIQUITINATION.
RX PubMed=11087752; DOI=10.1074/jbc.m008901200;
RA Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C.;
RT "Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-
RT kinase for ubiquitination in T cells.";
RL J. Biol. Chem. 276:4872-4878(2001).
RN [26]
RP INTERACTION WITH CD3Z AND CD28, AND UBIQUITINATION.
RX PubMed=11526404; DOI=10.1038/ni0901-870;
RA Fang D., Liu Y.-C.;
RT "Proteolysis-independent regulation of PI3K by Cbl-b-mediated
RT ubiquitination in T cells.";
RL Nat. Immunol. 2:870-875(2001).
RN [27]
RP INTERACTION WITH NISCH.
RX PubMed=11912194; DOI=10.1074/jbc.m111838200;
RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.;
RT "Insulin receptor substrate 4 associates with the protein IRAS.";
RL J. Biol. Chem. 277:19439-19447(2002).
RN [28]
RP INTERACTION WITH LAX1.
RX PubMed=12359715; DOI=10.1074/jbc.m208946200;
RA Zhu M., Janssen E., Leung K., Zhang W.;
RT "Molecular cloning of a novel gene encoding a membrane-associated adaptor
RT protein (LAX) in lymphocyte signaling.";
RL J. Biol. Chem. 277:46151-46158(2002).
RN [29]
RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=12009866; DOI=10.1006/viro.2002.1365;
RA Linnemann T., Zheng Y.-H., Mandic R., Peterlin B.M.;
RT "Interaction between Nef and phosphatidylinositol-3-kinase leads to
RT activation of p21-activated kinase and increased production of HIV.";
RL Virology 294:246-255(2002).
RN [30]
RP INTERACTION WITH HCV NS5A (MICROBIAL INFECTION).
RX PubMed=12186904; DOI=10.1128/jvi.76.18.9207-9217.2002;
RA He Y., Nakao H., Tan S.-L., Polyak S.J., Neddermann P., Vijaysri S.,
RA Jacobs B.L., Katze M.G.;
RT "Subversion of cell signaling pathways by hepatitis C virus nonstructural
RT 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-
RT kinase.";
RL J. Virol. 76:9207-9217(2002).
RN [31]
RP INTERACTION WITH NTRK1.
RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011;
RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A.,
RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A.,
RA Mackay A.R.;
RT "TrkA alternative splicing: a regulated tumor-promoting switch in human
RT neuroblastoma.";
RL Cancer Cell 6:347-360(2004).
RN [32]
RP REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [33]
RP INTERACTION WITH BCR.
RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010;
RA Laurent C.E., Smithgall T.E.;
RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region
RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent
RT manner.";
RL Exp. Cell Res. 299:188-198(2004).
RN [34]
RP PHOSPHORYLATION BY FGR.
RX PubMed=15561106; DOI=10.1016/j.yexcr.2004.09.005;
RA Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L.,
RA Lowell C.A., Berton G.;
RT "The proto-oncogene Fgr regulates cell migration and this requires its
RT plasma membrane localization.";
RL Exp. Cell Res. 302:253-269(2005).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [36]
RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPRJ.
RX PubMed=18348712; DOI=10.1042/bj20071317;
RA Tsuboi N., Utsunomiya T., Roberts R.L., Ito H., Takahashi K., Noda M.,
RA Takahashi T.;
RT "The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit
RT of phosphoinositide 3-kinase.";
RL Biochem. J. 413:193-200(2008).
RN [37]
RP INTERACTION WITH ERBB4.
RX PubMed=18721752; DOI=10.1016/j.chembiol.2008.07.006;
RA Kaushansky A., Gordus A., Budnik B.A., Lane W.S., Rush J., MacBeath G.;
RT "System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation
RT that are unusually selective in their recruitment properties.";
RL Chem. Biol. 15:808-817(2008).
RN [38]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [39]
RP INTERACTION WITH FGFR3.
RX PubMed=19286672; DOI=10.1093/hmg/ddp116;
RA Salazar L., Kashiwada T., Krejci P., Muchowski P., Donoghue D.,
RA Wilcox W.R., Thompson L.M.;
RT "A novel interaction between fibroblast growth factor receptor 3 and the
RT p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation
RT of ERK by p85 in multiple myeloma cells.";
RL Hum. Mol. Genet. 18:1951-1961(2009).
RN [40]
RP REVIEW ON ROLE IN FGFR1 SIGNALING.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-580, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [42]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [43]
RP FUNCTION, AND INTERACTION WITH XBP1.
RX PubMed=20348923; DOI=10.1038/nm.2121;
RA Winnay J.N., Boucher J., Mori M.A., Ueki K., Kahn C.R.;
RT "A regulatory subunit of phosphoinositide 3-kinase increases the nuclear
RT accumulation of X-box-binding protein-1 to modulate the unfolded protein
RT response.";
RL Nat. Med. 16:438-445(2010).
RN [44]
RP INTERACTION WITH ALOX5.
RX PubMed=21200133; DOI=10.3858/emm.2011.43.2.012;
RA Ha Y.J., Seul H.J., Lee J.R.;
RT "Ligation of CD40 receptor in human B lymphocytes triggers the 5-
RT lipoxygenase pathway to produce reactive oxygen species and activate p38
RT MAPK.";
RL Exp. Mol. Med. 43:101-110(2011).
RN [45]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL46 (MICROBIAL INFECTION).
RX PubMed=21228233; DOI=10.1128/jvi.01877-10;
RA Wagner M.J., Smiley J.R.;
RT "Herpes simplex virus requires VP11/12 to activate Src family kinase-
RT phosphoinositide 3-kinase-Akt signaling.";
RL J. Virol. 85:2803-2812(2011).
RN [46]
RP INTERACTION WITH CCDC88A.
RX PubMed=21954290; DOI=10.1126/scisignal.2002049;
RA Lin C., Ear J., Pavlova Y., Mittal Y., Kufareva I., Ghassemian M.,
RA Abagyan R., Garcia-Marcos M., Ghosh P.;
RT "Tyrosine phosphorylation of the Galpha-interacting protein GIV promotes
RT activation of phosphoinositide 3-kinase during cell migration.";
RL Sci. Signal. 4:RA64-RA64(2011).
RN [47]
RP INVOLVEMENT IN AGM7.
RX PubMed=22351933; DOI=10.1084/jem.20112533;
RA Conley M.E., Dobbs A.K., Quintana A.M., Bosompem A., Wang Y.D.,
RA Coustan-Smith E., Smith A.M., Perez E.E., Murray P.J.;
RT "Agammaglobulinemia and absent B lineage cells in a patient lacking the
RT p85? subunit of PI3K.";
RL J. Exp. Med. 209:463-470(2012).
RN [48]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [49]
RP INVOLVEMENT IN SHORTS, AND VARIANT SHORTS TRP-649.
RX PubMed=23810382; DOI=10.1016/j.ajhg.2013.06.005;
RG FORGE Canada Consortium;
RA Dyment D.A., Smith A.C., Alcantara D., Schwartzentruber J.A.,
RA Basel-Vanagaite L., Curry C.J., Temple I.K., Reardon W., Mansour S.,
RA Haq M.R., Gilbert R., Lehmann O.J., Vanstone M.R., Beaulieu C.L.,
RA Majewski J., Bulman D.E., O'Driscoll M., Boycott K.M., Innes A.M.,
RA Friedman J., Michaud J., Bernier F., Brudno M., Fernandez B., Knoppers B.,
RA Samuels M., Scherer S.;
RT "Mutations in PIK3R1 cause SHORT syndrome.";
RL Am. J. Hum. Genet. 93:158-166(2013).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-279, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [51]
RP INTERACTION WITH VARICELLA VIRUS ORF12 (MICROBIAL INFECTION).
RX PubMed=23192871; DOI=10.1128/jvi.02395-12;
RA Liu X., Cohen J.I.;
RT "Varicella-zoster virus ORF12 protein activates the phosphatidylinositol 3-
RT kinase/Akt pathway to regulate cell cycle progression.";
RL J. Virol. 87:1842-1848(2013).
RN [52]
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 [53]
RP INVOLVEMENT IN IMD36.
RX PubMed=25133428; DOI=10.1172/jci75746;
RA Deau M.C., Heurtier L., Frange P., Suarez F., Bole-Feysot C., Nitschke P.,
RA Cavazzana M., Picard C., Durandy A., Fischer A., Kracker S.;
RT "A human immunodeficiency caused by mutations in the PIK3R1 gene.";
RL J. Clin. Invest. 124:3923-3928(2014).
RN [54]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [55]
RP INTERACTION WITH SRC.
RX PubMed=28903391; DOI=10.18632/oncotarget.18973;
RA Lu Y., Zheng X., Hu W., Bian S., Zhang Z., Tao D., Liu Y., Ma Y.;
RT "Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating
RT the stability and activity of BMAL1 and CLOCK.";
RL Oncotarget 8:54913-54924(2017).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-85.
RX PubMed=8648629; DOI=10.1006/jmbi.1996.0190;
RA Liang J., Chen J.K., Schreiber S.L., Clardy J.;
RT "Crystal structure of P13K SH3 domain at 2.0-A resolution.";
RL J. Mol. Biol. 257:632-643(1996).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 324-434.
RX PubMed=8599763; DOI=10.1038/nsb0496-364;
RA Nolte R.T., Eck M.J., Schlessinger J., Shoelson S.E., Harrison S.C.;
RT "Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its
RT phosphopeptide complexes.";
RL Nat. Struct. Biol. 3:364-373(1996).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 115-298.
RX PubMed=8962058; DOI=10.1073/pnas.93.25.14373;
RA Musacchio A., Cantley L.C., Harrison S.C.;
RT "Crystal structure of the breakpoint cluster region-homology domain from
RT phosphoinositide 3-kinase p85 alpha subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14373-14378(1996).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 617-724 IN COMPLEX WITH PDGFRB.
RX PubMed=11567151; DOI=10.1107/s0907444901012434;
RA Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A.,
RA Rowsell S., Murshudov G.N.;
RT "NMR trial models: experiences with the colicin immunity protein Im7 and
RT the p85alpha C-terminal SH2-peptide complex.";
RL Acta Crystallogr. D 57:1397-1404(2001).
RN [60]
RP STRUCTURE BY NMR OF 1-79.
RX PubMed=7681364; DOI=10.1016/0092-8674(93)90582-b;
RA Koyama S., Yu H., Dalgarno D.C., Shin T.B., Zydowsky L.D., Schreiber S.L.;
RT "Structure of the PI3K SH3 domain and analysis of the SH3 family.";
RL Cell 72:945-952(1993).
RN [61]
RP STRUCTURE BY NMR OF 91-104.
RX PubMed=8961927; DOI=10.1021/bi9620969;
RA Renzoni D.A., Pugh D.J., Siligardi G., Das P., Morton C.J., Rossi C.,
RA Waterfield M.D., Campbell I.D., Ladbury J.E.;
RT "Structural and thermodynamic characterization of the interaction of the
RT SH3 domain from Fyn with the proline-rich binding site on the p85 subunit
RT of PI3-kinase.";
RL Biochemistry 35:15646-15653(1996).
RN [62]
RP STRUCTURE BY NMR OF 617-724.
RX PubMed=8670861; DOI=10.1002/j.1460-2075.1996.tb00727.x;
RA Breeze A.L., Kara B.V., Barratt D.G., Anderson M., Smith J.C., Luke R.W.,
RA Best J.R., Cartlidge S.A.;
RT "Structure of a specific peptide complex of the carboxy-terminal SH2 domain
RT from the p85 alpha subunit of phosphatidylinositol 3-kinase.";
RL EMBO J. 15:3579-3589(1996).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 431-600, AND FUNCTION.
RX PubMed=17626883; DOI=10.1126/science.1135394;
RA Miled N., Yan Y., Hon W.C., Perisic O., Zvelebil M., Inbar Y.,
RA Schneidman-Duhovny D., Wolfson H.J., Backer J.M., Williams R.L.;
RT "Mechanism of two classes of cancer mutations in the phosphoinositide 3-
RT kinase catalytic subunit.";
RL Science 317:239-242(2007).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 322-600.
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 [65]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 322-694, FUNCTION, AND SUBUNIT.
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 [66]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-83.
RX PubMed=19919182; DOI=10.1515/bc.2010.003;
RA Batra-Safferling R., Granzin J., Modder S., Hoffmann S., Willbold D.;
RT "Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain
RT in complex with a peptide ligand: role of the anchor residue in ligand
RT binding.";
RL Biol. Chem. 391:33-42(2010).
RN [67]
RP VARIANT ILE-326.
RX PubMed=9032108; DOI=10.2337/diab.46.3.494;
RA Hansen T., Andersen C.B., Echwald S.M., Urhammer S.A., Clausen J.O.,
RA Vestergaard H., Owens D., Hansen L., Pedersen O.;
RT "Identification of a common amino acid polymorphism in the p85alpha
RT regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose
RT disappearance constant, glucose effectiveness, and the insulin sensitivity
RT index.";
RL Diabetes 46:494-501(1997).
RN [68]
RP VARIANTS ILE-326 AND GLN-409, AND CHARACTERIZATION OF VARIANTS ILE-326 AND
RP GLN-409.
RX PubMed=10768093; DOI=10.1007/s001250050050;
RA Baynes K.C.R., Beeton C.A., Panayotou G., Stein R., Soos M., Hansen T.,
RA Simpson H., O'Rahilly S., Shepherd P.R., Whitehead J.P.;
RT "Natural variants of human p85 alpha phosphoinositide 3-kinase in severe
RT insulin resistance: a novel variant with impaired insulin-stimulated lipid
RT kinase activity.";
RL Diabetologia 43:321-331(2000).
RN [69]
RP VARIANTS SHORTS LYS-489 AND ILE-539 DEL.
RX PubMed=23810378; DOI=10.1016/j.ajhg.2013.05.019;
RA Thauvin-Robinet C., Auclair M., Duplomb L., Caron-Debarle M., Avila M.,
RA St-Onge J., Le Merrer M., Le Luyer B., Heron D., Mathieu-Dramard M.,
RA Bitoun P., Petit J.M., Odent S., Amiel J., Picot D., Carmignac V.,
RA Thevenon J., Callier P., Laville M., Reznik Y., Fagour C., Nunes M.L.,
RA Capeau J., Lascols O., Huet F., Faivre L., Vigouroux C., Riviere J.B.;
RT "PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy.";
RL Am. J. Hum. Genet. 93:141-149(2013).
RN [70]
RP VARIANT SHORTS TRP-649.
RX PubMed=23810379; DOI=10.1016/j.ajhg.2013.05.023;
RA Chudasama K.K., Winnay J., Johansson S., Claudi T., Konig R., Haldorsen I.,
RA Johansson B., Woo J.R., Aarskog D., Sagen J.V., Kahn C.R., Molven A.,
RA Njolstad P.R.;
RT "SHORT syndrome with partial lipodystrophy due to impaired
RT phosphatidylinositol 3 kinase signaling.";
RL Am. J. Hum. Genet. 93:150-157(2013).
CC -!- FUNCTION: Binds to activated (phosphorylated) protein-Tyr kinases,
CC through its SH2 domain, and acts as an adapter, mediating the
CC association of the p110 catalytic unit to the plasma membrane.
CC Necessary for the insulin-stimulated increase in glucose uptake and
CC glycogen synthesis in insulin-sensitive tissues. Plays an important
CC role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF,
CC KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling
CC (PubMed:17626883, PubMed:19805105, PubMed:7518429). Modulates the
CC cellular response to ER stress by promoting nuclear translocation of
CC XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during
CC metabolic overloading in the liver and hence plays a role in glucose
CC tolerance improvement (PubMed:20348923). {ECO:0000269|PubMed:17626883,
CC ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:20348923,
CC ECO:0000269|PubMed:7518429}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R1 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2
CC domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the
CC interaction enables recruitment of PIK3R1 to the EGFR receptor,
CC enhancing PI3K activity and cell migration (PubMed:21954290). Interacts
CC (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with
CC PIK3R2; the interaction is dissociated in an insulin-dependent manner
CC (By similarity). Interacts with XBP1 isoform 2; the interaction is
CC direct and induces translocation of XBP1 isoform 2 into the nucleus in
CC a ER stress- and/or insulin-dependent but PI3K-independent manner
CC (PubMed:20348923). Interacts with FER. Interacts (via SH2 domain) with
CC TEK/TIE2 (tyrosine phosphorylated). Interacts with PTK2/FAK1 (By
CC similarity). Interacts with phosphorylated TOM1L1. Interacts with
CC phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with
CC SOCS7. Interacts with RUFY3. Interacts (via SH2 domain) with CSF1R
CC (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this
CC enhances enzyme activity (By similarity). Interacts with phosphorylated
CC LAT, LAX1 and TRAT1 upon TCR activation. Interacts with CBLB. The SH2
CC domains interact with the YTHM motif of phosphorylated INSR in vitro.
CC Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts
CC with CD28 and CD3Z upon T-cell activation. Interacts with IRS1 and
CC phosphorylated IRS4, as well as with NISCH and HCST. Interacts with
CC FASLG, KIT and BCR. Interacts with AXL, FGFR1, FGFR2, FGFR3 and FGFR4
CC (phosphorylated). Interacts with FGR and HCK. Interacts with PDGFRA
CC (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated).
CC Interacts with ERBB4 (phosphorylated). Interacts with NTRK1
CC (phosphorylated upon ligand-binding). Interacts with FAM83B; activates
CC the PI3K/AKT signaling cascade (PubMed:23676467). Interacts with APPL1
CC and APPL2 (By similarity). Interacts with SRC (PubMed:28903391).
CC Interacts with ALOX5; this interaction bridges ALOX5 with CD40 after
CC CD40 ligation in B cells and leads to the production of reactive oxygen
CC species (ROS) (PubMed:21200133). Interacts with TYK2 (PubMed:10995743).
CC {ECO:0000250|UniProtKB:P23727, ECO:0000250|UniProtKB:P26450,
CC ECO:0000250|UniProtKB:Q63787, ECO:0000269|PubMed:10086340,
CC ECO:0000269|PubMed:10528161, ECO:0000269|PubMed:10739672,
CC ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:10995743,
CC ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404,
CC ECO:0000269|PubMed:11567151, ECO:0000269|PubMed:11912194,
CC ECO:0000269|PubMed:12359715, ECO:0000269|PubMed:15302586,
CC ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:18721752,
CC ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:19805105,
CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20348923,
CC ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21954290,
CC ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:28903391,
CC ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7541045,
CC ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:8276809,
CC ECO:0000269|PubMed:8628286, ECO:0000269|PubMed:8940081,
CC ECO:0000269|PubMed:9038210, ECO:0000269|PubMed:9178760,
CC ECO:0000269|PubMed:9489702, ECO:0000269|PubMed:9553137,
CC ECO:0000269|PubMed:9687533}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Nef to activate the
CC Nef associated p21-activated kinase (PAK). This interaction depends on
CC the C-terminus of both proteins and leads to increased production of
CC HIV. {ECO:0000269|PubMed:12009866}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HCV NS5A.
CC {ECO:0000269|PubMed:12186904}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC UL46; this interaction activates the PI3K/AKT pathway.
CC {ECO:0000269|PubMed:21228233}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC UL46 and varicella virus ORF12; this interaction activates the PI3K/AKT
CC pathway. {ECO:0000269|PubMed:23192871}.
CC -!- INTERACTION:
CC P27986; Q8IZP0: ABI1; NbExp=8; IntAct=EBI-79464, EBI-375446;
CC P27986; P42684: ABL2; NbExp=2; IntAct=EBI-79464, EBI-1102694;
CC P27986; P10275: AR; NbExp=5; IntAct=EBI-79464, EBI-608057;
CC P27986; P22681: CBL; NbExp=5; IntAct=EBI-79464, EBI-518228;
CC P27986; P10747: CD28; NbExp=10; IntAct=EBI-79464, EBI-4314301;
CC P27986; Q13111: CHAF1A; NbExp=2; IntAct=EBI-79464, EBI-1020839;
CC P27986; Q8IY22: CMIP; NbExp=2; IntAct=EBI-79464, EBI-7689652;
CC P27986; P46108: CRK; NbExp=3; IntAct=EBI-79464, EBI-886;
CC P27986; P16410: CTLA4; NbExp=3; IntAct=EBI-79464, EBI-1030991;
CC P27986; Q9Y2H0: DLGAP4; NbExp=2; IntAct=EBI-79464, EBI-722139;
CC P27986; P00533: EGFR; NbExp=5; IntAct=EBI-79464, EBI-297353;
CC P27986; P41970: ELK3; NbExp=2; IntAct=EBI-79464, EBI-1758534;
CC P27986; P04626: ERBB2; NbExp=11; IntAct=EBI-79464, EBI-641062;
CC P27986; P21860: ERBB3; NbExp=41; IntAct=EBI-79464, EBI-720706;
CC P27986; P48023: FASLG; NbExp=2; IntAct=EBI-79464, EBI-495538;
CC P27986; P11362: FGFR1; NbExp=5; IntAct=EBI-79464, EBI-1028277;
CC P27986; P17948: FLT1; NbExp=3; IntAct=EBI-79464, EBI-1026718;
CC P27986; P36888: FLT3; NbExp=2; IntAct=EBI-79464, EBI-3946257;
CC P27986; Q13480: GAB1; NbExp=33; IntAct=EBI-79464, EBI-517684;
CC P27986; Q13322: GRB10; NbExp=2; IntAct=EBI-79464, EBI-80275;
CC P27986; P62993: GRB2; NbExp=4; IntAct=EBI-79464, EBI-401755;
CC P27986; P42858: HTT; NbExp=7; IntAct=EBI-79464, EBI-466029;
CC P27986; Q9Y6W8: ICOS; NbExp=5; IntAct=EBI-79464, EBI-3922712;
CC P27986; P08069: IGF1R; NbExp=4; IntAct=EBI-79464, EBI-475981;
CC P27986; P06213: INSR; NbExp=3; IntAct=EBI-79464, EBI-475899;
CC P27986; P35568: IRS1; NbExp=12; IntAct=EBI-79464, EBI-517592;
CC P27986; Q9Y4H2: IRS2; NbExp=3; IntAct=EBI-79464, EBI-1049582;
CC P27986; P10721: KIT; NbExp=19; IntAct=EBI-79464, EBI-1379503;
CC P27986; Q86VI4-3: LAPTM4B; NbExp=2; IntAct=EBI-79464, EBI-3267286;
CC P27986; O43561: LAT; NbExp=4; IntAct=EBI-79464, EBI-1222766;
CC P27986; Q92918: MAP4K1; NbExp=2; IntAct=EBI-79464, EBI-881;
CC P27986; P45983: MAPK8; NbExp=6; IntAct=EBI-79464, EBI-286483;
CC P27986; P08581: MET; NbExp=6; IntAct=EBI-79464, EBI-1039152;
CC P27986; Q8WX92: NELFB; NbExp=2; IntAct=EBI-79464, EBI-347721;
CC P27986; P09619: PDGFRB; NbExp=19; IntAct=EBI-79464, EBI-641237;
CC P27986; P42336: PIK3CA; NbExp=23; IntAct=EBI-79464, EBI-2116585;
CC P27986; P42338: PIK3CB; NbExp=4; IntAct=EBI-79464, EBI-2609540;
CC P27986; O00329: PIK3CD; NbExp=8; IntAct=EBI-79464, EBI-718309;
CC P27986; Q13905: RAPGEF1; NbExp=2; IntAct=EBI-79464, EBI-976876;
CC P27986; P26373: RPL13; NbExp=2; IntAct=EBI-79464, EBI-356849;
CC P27986; P19793: RXRA; NbExp=8; IntAct=EBI-79464, EBI-78598;
CC P27986; Q9UPX8: SHANK2; NbExp=2; IntAct=EBI-79464, EBI-1570571;
CC P27986; Q9H0K1: SIK2; NbExp=7; IntAct=EBI-79464, EBI-1181664;
CC P27986; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-79464, EBI-1802965;
CC P27986; Q07889: SOS1; NbExp=3; IntAct=EBI-79464, EBI-297487;
CC P27986; P12931: SRC; NbExp=7; IntAct=EBI-79464, EBI-621482;
CC P27986; P30874: SSTR2; NbExp=5; IntAct=EBI-79464, EBI-6266898;
CC P27986; P58753: TIRAP; NbExp=3; IntAct=EBI-79464, EBI-528644;
CC P27986; O15455: TLR3; NbExp=2; IntAct=EBI-79464, EBI-6116630;
CC P27986; Q15661: TPSAB1; NbExp=2; IntAct=EBI-79464, EBI-1761369;
CC P27986; Q9ULW0: TPX2; NbExp=2; IntAct=EBI-79464, EBI-1037322;
CC P27986; Q9UKW4: VAV3; NbExp=2; IntAct=EBI-79464, EBI-297568;
CC P27986; P35570: Irs1; Xeno; NbExp=2; IntAct=EBI-79464, EBI-520230;
CC P27986; P03496: NS; Xeno; NbExp=6; IntAct=EBI-79464, EBI-2547442;
CC P27986; Q6PFX7: Nyap1; Xeno; NbExp=4; IntAct=EBI-79464, EBI-7447489;
CC P27986; Q8BM65-4: Nyap2; Xeno; NbExp=3; IntAct=EBI-79464, EBI-7447598;
CC P27986; Q99152: VP3; Xeno; NbExp=3; IntAct=EBI-79464, EBI-1776808;
CC P27986; P0DOJ9; Xeno; NbExp=2; IntAct=EBI-79464, EBI-16746307;
CC P27986-2; P01023: A2M; NbExp=3; IntAct=EBI-9090282, EBI-640741;
CC P27986-2; Q9NY61: AATF; NbExp=3; IntAct=EBI-9090282, EBI-372428;
CC P27986-2; O95704: APBB3; NbExp=3; IntAct=EBI-9090282, EBI-286427;
CC P27986-2; P05067: APP; NbExp=3; IntAct=EBI-9090282, EBI-77613;
CC P27986-2; P51451: BLK; NbExp=3; IntAct=EBI-9090282, EBI-2105445;
CC P27986-2; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-9090282, EBI-1383687;
CC P27986-2; P29466-3: CASP1; NbExp=3; IntAct=EBI-9090282, EBI-12248206;
CC P27986-2; P55210: CASP7; NbExp=3; IntAct=EBI-9090282, EBI-523958;
CC P27986-2; P06493: CDK1; NbExp=3; IntAct=EBI-9090282, EBI-444308;
CC P27986-2; P20674: COX5A; NbExp=3; IntAct=EBI-9090282, EBI-715032;
CC P27986-2; P09172: DBH; NbExp=3; IntAct=EBI-9090282, EBI-8589586;
CC P27986-2; P50570-2: DNM2; NbExp=3; IntAct=EBI-9090282, EBI-10968534;
CC P27986-2; P01100: FOS; NbExp=3; IntAct=EBI-9090282, EBI-852851;
CC P27986-2; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-9090282, EBI-11110431;
CC P27986-2; P14136: GFAP; NbExp=3; IntAct=EBI-9090282, EBI-744302;
CC P27986-2; P62993: GRB2; NbExp=3; IntAct=EBI-9090282, EBI-401755;
CC P27986-2; P42858: HTT; NbExp=18; IntAct=EBI-9090282, EBI-466029;
CC P27986-2; P35568: IRS1; NbExp=3; IntAct=EBI-9090282, EBI-517592;
CC P27986-2; P05556: ITGB1; NbExp=3; IntAct=EBI-9090282, EBI-703066;
CC P27986-2; P05412: JUN; NbExp=3; IntAct=EBI-9090282, EBI-852823;
CC P27986-2; P07948: LYN; NbExp=3; IntAct=EBI-9090282, EBI-79452;
CC P27986-2; Q13387-4: MAPK8IP2; NbExp=3; IntAct=EBI-9090282, EBI-12345753;
CC P27986-2; P41227: NAA10; NbExp=3; IntAct=EBI-9090282, EBI-747693;
CC P27986-2; P01111: NRAS; NbExp=3; IntAct=EBI-9090282, EBI-721993;
CC P27986-2; Q9Y6R0: NUMBL; NbExp=3; IntAct=EBI-9090282, EBI-945925;
CC P27986-2; P42336: PIK3CA; NbExp=3; IntAct=EBI-9090282, EBI-2116585;
CC P27986-2; P42338: PIK3CB; NbExp=6; IntAct=EBI-9090282, EBI-2609540;
CC P27986-2; O00329: PIK3CD; NbExp=3; IntAct=EBI-9090282, EBI-718309;
CC P27986-2; P17612: PRKACA; NbExp=3; IntAct=EBI-9090282, EBI-476586;
CC P27986-2; P49810: PSEN2; NbExp=3; IntAct=EBI-9090282, EBI-2010251;
CC P27986-2; P63000: RAC1; NbExp=3; IntAct=EBI-9090282, EBI-413628;
CC P27986-2; P51812: RPS6KA3; NbExp=3; IntAct=EBI-9090282, EBI-1046616;
CC P27986-2; P23443-4: RPS6KB1; NbExp=3; IntAct=EBI-9090282, EBI-25882353;
CC P27986-2; P34741: SDC2; NbExp=3; IntAct=EBI-9090282, EBI-1172957;
CC P27986-2; Q9NP31: SH2D2A; NbExp=3; IntAct=EBI-9090282, EBI-490630;
CC P27986-2; P84022: SMAD3; NbExp=3; IntAct=EBI-9090282, EBI-347161;
CC P27986-2; P12931: SRC; NbExp=3; IntAct=EBI-9090282, EBI-621482;
CC P27986-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-9090282, EBI-357085;
CC P27986-2; Q15583-2: TGIF1; NbExp=3; IntAct=EBI-9090282, EBI-12691451;
CC P27986-2; O60784-2: TOM1; NbExp=3; IntAct=EBI-9090282, EBI-12117154;
CC P27986-2; O14656-2: TOR1A; NbExp=3; IntAct=EBI-9090282, EBI-25847109;
CC P27986-2; P02766: TTR; NbExp=3; IntAct=EBI-9090282, EBI-711909;
CC P27986-2; P42681: TXK; NbExp=3; IntAct=EBI-9090282, EBI-7877438;
CC P27986-2; P60604: UBE2G2; NbExp=3; IntAct=EBI-9090282, EBI-1051028;
CC P27986-2; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-9090282, EBI-11141397;
CC P27986-2; O76024: WFS1; NbExp=3; IntAct=EBI-9090282, EBI-720609;
CC P27986-2; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-9090282, EBI-524753;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P27986-1; Sequence=Displayed;
CC Name=2; Synonyms=AS53;
CC IsoId=P27986-2; Sequence=VSP_021842, VSP_021843;
CC Name=3; Synonyms=p46;
CC IsoId=P27986-3; Sequence=VSP_021841, VSP_021844;
CC Name=4; Synonyms=p85I;
CC IsoId=P27986-4; Sequence=VSP_021845;
CC Name=5;
CC IsoId=P27986-5; Sequence=VSP_045903;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in skeletal muscle and
CC brain, and at lower levels in kidney and cardiac muscle. Isoform 2 and
CC isoform 4 are present in skeletal muscle (at protein level).
CC {ECO:0000269|PubMed:8628286}.
CC -!- DOMAIN: The SH3 domain mediates the binding to CBLB, and to HIV-1 Nef.
CC -!- PTM: Polyubiquitinated in T-cells by CBLB; which does not promote
CC proteasomal degradation but impairs association with CD28 and CD3Z upon
CC T-cell activation. {ECO:0000269|PubMed:11087752,
CC ECO:0000269|PubMed:11526404}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylated in response to signaling
CC by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R.
CC Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by
CC TEK/TIE2. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-
CC 608; phosphorylation is stimulated by insulin and PDGF. The relevance
CC of phosphorylation by PIK3CA is however unclear (By similarity).
CC Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR.
CC {ECO:0000250, ECO:0000269|PubMed:15561106,
CC ECO:0000269|PubMed:18348712}.
CC -!- DISEASE: Agammaglobulinemia 7, autosomal recessive (AGM7) [MIM:615214]:
CC A primary immunodeficiency characterized by profoundly low or absent
CC serum antibodies and low or absent circulating B-cells due to an early
CC block of B-cell development. Affected individuals develop severe
CC infections in the first years of life. {ECO:0000269|PubMed:22351933}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: SHORT syndrome (SHORTS) [MIM:269880]: A rare, multisystem
CC disease characterized by short stature, anomalies of the anterior
CC chamber of the eye, characteristic facial features such as triangular
CC facies, lack of facial fat, and hypoplastic nasal alae with overhanging
CC columella, partial lipodystrophy, hernias, hyperextensibility, and
CC delayed dentition. The clinical phenotype can include insulin
CC resistance, nephrocalcinosis, and hearing deficits. Developmental
CC milestones and cognition are normal. {ECO:0000269|PubMed:23810378,
CC ECO:0000269|PubMed:23810379, ECO:0000269|PubMed:23810382}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Immunodeficiency 36 (IMD36) [MIM:616005]: A primary
CC immunodeficiency characterized by impaired B-cell function,
CC hypogammaglobulinemia and recurrent infections.
CC {ECO:0000269|PubMed:25133428}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PIK3R1ID41717ch5q13.html";
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
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DR EMBL; M61906; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U49349; AAB04140.1; -; mRNA.
DR EMBL; AF279367; AAO15359.1; -; mRNA.
DR EMBL; AK094785; BAG52931.1; -; mRNA.
DR EMBL; AK223613; BAD97333.1; -; mRNA.
DR EMBL; AC016564; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104120; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471137; EAW51312.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51313.1; -; Genomic_DNA.
DR EMBL; BC030815; AAH30815.1; -; mRNA.
DR EMBL; BC094795; AAH94795.1; -; mRNA.
DR CCDS; CCDS3993.1; -. [P27986-1]
DR CCDS; CCDS3994.1; -. [P27986-3]
DR CCDS; CCDS3995.1; -. [P27986-2]
DR CCDS; CCDS56374.1; -. [P27986-5]
DR PIR; A38748; A38748.
DR RefSeq; NP_001229395.1; NM_001242466.1. [P27986-5]
DR RefSeq; NP_852556.2; NM_181504.3. [P27986-2]
DR RefSeq; NP_852664.1; NM_181523.2. [P27986-1]
DR RefSeq; NP_852665.1; NM_181524.1. [P27986-3]
DR RefSeq; XP_005248599.1; XM_005248542.3. [P27986-1]
DR RefSeq; XP_016865074.1; XM_017009585.1. [P27986-1]
DR PDB; 1A0N; NMR; -; A=91-104.
DR PDB; 1AZG; NMR; -; A=91-104.
DR PDB; 1H9O; X-ray; 1.79 A; A=617-724.
DR PDB; 1PBW; X-ray; 2.00 A; A/B=105-319.
DR PDB; 1PHT; X-ray; 2.00 A; A=1-85.
DR PDB; 1PIC; NMR; -; A=617-724.
DR PDB; 1PKS; NMR; -; A=1-79.
DR PDB; 1PKT; NMR; -; A=1-79.
DR PDB; 2IUG; X-ray; 1.89 A; A=321-440.
DR PDB; 2IUH; X-ray; 2.00 A; A=321-440.
DR PDB; 2IUI; X-ray; 2.40 A; A/B=321-440.
DR PDB; 2RD0; X-ray; 3.05 A; B=322-600.
DR PDB; 2V1Y; X-ray; 2.40 A; B=431-600.
DR PDB; 3HHM; X-ray; 2.80 A; B=322-694.
DR PDB; 3HIZ; X-ray; 3.30 A; B=322-694.
DR PDB; 3I5R; X-ray; 1.70 A; A=1-83.
DR PDB; 3I5S; X-ray; 3.00 A; A/B/C/D=1-83.
DR PDB; 4A55; X-ray; 3.50 A; B=322-600.
DR PDB; 4JPS; X-ray; 2.20 A; B=307-593.
DR PDB; 4L1B; X-ray; 2.59 A; B=318-615.
DR PDB; 4L23; X-ray; 2.50 A; B=318-615.
DR PDB; 4L2Y; X-ray; 2.80 A; B=318-615.
DR PDB; 4OVU; X-ray; 2.96 A; B=322-600.
DR PDB; 4OVV; X-ray; 3.50 A; B=322-600.
DR PDB; 4WAF; X-ray; 2.39 A; B=306-617.
DR PDB; 4YKN; X-ray; 2.90 A; A=318-615.
DR PDB; 4ZOP; X-ray; 2.62 A; B=307-590.
DR PDB; 5AUL; X-ray; 1.10 A; A=614-720.
DR PDB; 5FI4; X-ray; 2.50 A; B=306-617.
DR PDB; 5GJI; X-ray; 0.90 A; A=325-430.
DR PDB; 5ITD; X-ray; 3.02 A; B=307-617.
DR PDB; 5M6U; X-ray; 2.85 A; B=1-724.
DR PDB; 5SW8; X-ray; 3.30 A; B=322-600.
DR PDB; 5SWG; X-ray; 3.11 A; B=322-600.
DR PDB; 5SWO; X-ray; 3.50 A; B=322-600.
DR PDB; 5SWP; X-ray; 3.41 A; B=322-600.
DR PDB; 5SWR; X-ray; 3.31 A; B=322-600.
DR PDB; 5SWT; X-ray; 3.49 A; B=322-600.
DR PDB; 5SX8; X-ray; 3.47 A; B=322-600.
DR PDB; 5SX9; X-ray; 3.52 A; B=322-600.
DR PDB; 5SXA; X-ray; 3.35 A; B=322-600.
DR PDB; 5SXB; X-ray; 3.30 A; B=322-600.
DR PDB; 5SXC; X-ray; 3.55 A; B=322-600.
DR PDB; 5SXD; X-ray; 3.50 A; B=322-600.
DR PDB; 5SXE; X-ray; 3.51 A; B=322-600.
DR PDB; 5SXF; X-ray; 3.46 A; B=322-600.
DR PDB; 5SXI; X-ray; 3.40 A; B=322-600.
DR PDB; 5SXJ; X-ray; 3.42 A; B=322-600.
DR PDB; 5SXK; X-ray; 3.55 A; B=322-600.
DR PDB; 5UBT; X-ray; 2.83 A; B=432-599.
DR PDB; 5UK8; X-ray; 2.50 A; B=306-593.
DR PDB; 5UKJ; X-ray; 2.80 A; B=306-593.
DR PDB; 5UL1; X-ray; 3.00 A; B=306-593.
DR PDB; 5VLR; X-ray; 2.80 A; B=431-600.
DR PDB; 5XGH; X-ray; 2.97 A; B=322-598.
DR PDB; 5XGI; X-ray; 2.56 A; B=322-598.
DR PDB; 5XGJ; X-ray; 2.97 A; B=322-599.
DR PDB; 6NCT; X-ray; 3.35 A; B=322-600.
DR PDB; 6PYR; X-ray; 2.21 A; B=431-599.
DR PDB; 6PYU; X-ray; 2.54 A; B=431-599.
DR PDB; 7CIO; X-ray; 1.10 A; A=614-720.
DR PDB; 7LM2; X-ray; 2.79 A; B=431-599.
DR PDB; 7LQ1; X-ray; 2.96 A; B=431-599.
DR PDB; 7MYN; EM; 2.79 A; B=3-724.
DR PDB; 7MYO; EM; 2.92 A; B=3-724.
DR PDB; 7RNS; X-ray; 1.14 A; A=321-434.
DR PDBsum; 1A0N; -.
DR PDBsum; 1AZG; -.
DR PDBsum; 1H9O; -.
DR PDBsum; 1PBW; -.
DR PDBsum; 1PHT; -.
DR PDBsum; 1PIC; -.
DR PDBsum; 1PKS; -.
DR PDBsum; 1PKT; -.
DR PDBsum; 2IUG; -.
DR PDBsum; 2IUH; -.
DR PDBsum; 2IUI; -.
DR PDBsum; 2RD0; -.
DR PDBsum; 2V1Y; -.
DR PDBsum; 3HHM; -.
DR PDBsum; 3HIZ; -.
DR PDBsum; 3I5R; -.
DR PDBsum; 3I5S; -.
DR PDBsum; 4A55; -.
DR PDBsum; 4JPS; -.
DR PDBsum; 4L1B; -.
DR PDBsum; 4L23; -.
DR PDBsum; 4L2Y; -.
DR PDBsum; 4OVU; -.
DR PDBsum; 4OVV; -.
DR PDBsum; 4WAF; -.
DR PDBsum; 4YKN; -.
DR PDBsum; 4ZOP; -.
DR PDBsum; 5AUL; -.
DR PDBsum; 5FI4; -.
DR PDBsum; 5GJI; -.
DR PDBsum; 5ITD; -.
DR PDBsum; 5M6U; -.
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; 5UBT; -.
DR PDBsum; 5UK8; -.
DR PDBsum; 5UKJ; -.
DR PDBsum; 5UL1; -.
DR PDBsum; 5VLR; -.
DR PDBsum; 5XGH; -.
DR PDBsum; 5XGI; -.
DR PDBsum; 5XGJ; -.
DR PDBsum; 6NCT; -.
DR PDBsum; 6PYR; -.
DR PDBsum; 6PYU; -.
DR PDBsum; 7CIO; -.
DR PDBsum; 7LM2; -.
DR PDBsum; 7LQ1; -.
DR PDBsum; 7MYN; -.
DR PDBsum; 7MYO; -.
DR PDBsum; 7RNS; -.
DR AlphaFoldDB; P27986; -.
DR BMRB; P27986; -.
DR SMR; P27986; -.
DR BioGRID; 111313; 335.
DR ComplexPortal; CPX-2384; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p85alpha.
DR ComplexPortal; CPX-5970; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p55alpha. [P27986-2]
DR ComplexPortal; CPX-5971; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p50alpha. [P27986-3]
DR ComplexPortal; CPX-5972; Phosphatidylinositol 3-kinase complex class IA, p110beta/p50alpha. [P27986-3]
DR ComplexPortal; CPX-5974; Phosphatidylinositol 3-kinase complex class IA, p110beta/p55alpha. [P27986-2]
DR ComplexPortal; CPX-5975; Phosphatidylinositol 3-kinase complex class IA, p110beta/p85alpha.
DR ComplexPortal; CPX-5983; Phosphatidylinositol 3-kinase complex class IA, p110delta/p85alpha.
DR ComplexPortal; CPX-5984; Phosphatidylinositol 3-kinase complex class IA, p110delta/p55alpha.
DR ComplexPortal; CPX-5985; Phosphatidylinositol 3-kinase complex class IA, p110delta/p50alpha. [P27986-3]
DR CORUM; P27986; -.
DR DIP; DIP-119N; -.
DR IntAct; P27986; 332.
DR MINT; P27986; -.
DR STRING; 9606.ENSP00000428056; -.
DR BindingDB; P27986; -.
DR ChEMBL; CHEMBL2506; -.
DR DrugBank; DB06486; Enzastaurin.
DR DrugBank; DB05210; SF1126.
DR DrugBank; DB08059; Wortmannin.
DR DrugCentral; P27986; -.
DR MoonDB; P27986; Predicted.
DR iPTMnet; P27986; -.
DR PhosphoSitePlus; P27986; -.
DR BioMuta; PIK3R1; -.
DR DMDM; 118572681; -.
DR CPTAC; CPTAC-1539; -.
DR CPTAC; CPTAC-1626; -.
DR CPTAC; CPTAC-1740; -.
DR EPD; P27986; -.
DR jPOST; P27986; -.
DR MassIVE; P27986; -.
DR MaxQB; P27986; -.
DR PaxDb; P27986; -.
DR PeptideAtlas; P27986; -.
DR PRIDE; P27986; -.
DR ProteomicsDB; 18961; -.
DR ProteomicsDB; 54429; -. [P27986-1]
DR ProteomicsDB; 54430; -. [P27986-2]
DR ProteomicsDB; 54431; -. [P27986-3]
DR ProteomicsDB; 54432; -. [P27986-4]
DR Antibodypedia; 717; 1140 antibodies from 46 providers.
DR DNASU; 5295; -.
DR Ensembl; ENST00000320694.12; ENSP00000323512.8; ENSG00000145675.15. [P27986-3]
DR Ensembl; ENST00000336483.9; ENSP00000338554.5; ENSG00000145675.15. [P27986-2]
DR Ensembl; ENST00000521381.6; ENSP00000428056.1; ENSG00000145675.15. [P27986-1]
DR Ensembl; ENST00000521657.5; ENSP00000429277.1; ENSG00000145675.15. [P27986-1]
DR Ensembl; ENST00000523872.1; ENSP00000430098.1; ENSG00000145675.15. [P27986-5]
DR GeneID; 5295; -.
DR KEGG; hsa:5295; -.
DR MANE-Select; ENST00000521381.6; ENSP00000428056.1; NM_181523.3; NP_852664.1.
DR UCSC; uc003jva.4; human. [P27986-1]
DR CTD; 5295; -.
DR DisGeNET; 5295; -.
DR GeneCards; PIK3R1; -.
DR GeneReviews; PIK3R1; -.
DR HGNC; HGNC:8979; PIK3R1.
DR HPA; ENSG00000145675; Low tissue specificity.
DR MalaCards; PIK3R1; -.
DR MIM; 171833; gene.
DR MIM; 269880; phenotype.
DR MIM; 615214; phenotype.
DR MIM; 616005; phenotype.
DR neXtProt; NX_P27986; -.
DR OpenTargets; ENSG00000145675; -.
DR Orphanet; 397596; Activated PI3K-delta syndrome.
DR Orphanet; 33110; Autosomal agammaglobulinemia.
DR Orphanet; 3163; SHORT syndrome.
DR PharmGKB; PA33312; -.
DR VEuPathDB; HostDB:ENSG00000145675; -.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000155553; -.
DR HOGENOM; CLU_007031_1_0_1; -.
DR InParanoid; P27986; -.
DR OMA; VIPVQWY; -.
DR OrthoDB; 737926at2759; -.
DR PhylomeDB; P27986; -.
DR TreeFam; TF102033; -.
DR BioCyc; MetaCyc:ENSG00000145675-MON; -.
DR BRENDA; 2.7.1.153; 2681.
DR PathwayCommons; P27986; -.
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-1266695; Interleukin-7 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-430116; GP1b-IX-V activation signalling.
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-6785807; Interleukin-4 and Interleukin-13 signaling.
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-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV 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-9035034; RHOF GTPase cycle.
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-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
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 Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P27986; -.
DR SIGNOR; P27986; -.
DR BioGRID-ORCS; 5295; 27 hits in 1099 CRISPR screens.
DR ChiTaRS; PIK3R1; human.
DR EvolutionaryTrace; P27986; -.
DR GeneWiki; PIK3R1; -.
DR GenomeRNAi; 5295; -.
DR Pharos; P27986; Tchem.
DR PRO; PR:P27986; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P27986; protein.
DR Bgee; ENSG00000145675; Expressed in calcaneal tendon and 222 other tissues.
DR ExpressionAtlas; P27986; baseline and differential.
DR Genevisible; P27986; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005801; C:cis-Golgi network; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1990578; C:perinuclear endoplasmic reticulum membrane; 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; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; IDA:UniProtKB.
DR GO; GO:0043559; F:insulin binding; IDA:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; IPI:UniProtKB.
DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:Ensembl.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IPI:UniProtKB.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:BHF-UCL.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISS:UniProtKB.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; ISS:BHF-UCL.
DR GO; GO:0030183; P:B cell differentiation; IC:ComplexPortal.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0097529; P:myeloid leukocyte migration; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISS:BHF-UCL.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; IMP:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:BHF-UCL.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; ISS:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:BHF-UCL.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; ISS:BHF-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:BHF-UCL.
DR GO; GO:0030217; P:T cell differentiation; IC:ComplexPortal.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd12924; iSH2_PIK3R1; 1.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11910; SH3_PI3K_p85alpha; 1.
DR DisProt; DP01112; -.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR044124; ISH2_PIK3R1.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035591; PI3K_p85alpha_SH3.
DR InterPro; IPR035020; PI3kinase_P85_cSH2.
DR InterPro; IPR035022; PI3kinase_P85_nSH2.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF16454; PI3K_P85_iSH2; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00017; SH2; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Disease variant; Dwarfism;
KW Host-virus interaction; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Stress response;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..724
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT alpha"
FT /id="PRO_0000080758"
FT DOMAIN 3..79
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 113..301
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 333..428
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 624..718
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 80..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..98
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 467
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26450"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23727"
FT VAR_SEQ 1..363
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045903"
FT VAR_SEQ 1..300
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021841"
FT VAR_SEQ 1..270
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8628286, ECO:0000303|Ref.5"
FT /id="VSP_021842"
FT VAR_SEQ 271..304
FT /note="MLFRFSAASSDNTENLIKVIEILISTEWNERQPA -> MYNTVWNMEDLDLE
FT YAKTDINCGTDLMFYIEMDP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8628286, ECO:0000303|Ref.5"
FT /id="VSP_021843"
FT VAR_SEQ 301..306
FT /note="RQPAPA -> MHNLQT (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021844"
FT VAR_SEQ 605
FT /note="D -> ENFLSCLPS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8628286"
FT /id="VSP_021845"
FT VARIANT 326
FT /note="M -> I (does not affect insulin-stimulated lipid
FT kinase activity; dbSNP:rs3730089)"
FT /evidence="ECO:0000269|PubMed:10768093,
FT ECO:0000269|PubMed:9032108, ECO:0000269|Ref.5"
FT /id="VAR_010023"
FT VARIANT 409
FT /note="R -> Q (in a patient with severe insulin resistance;
FT lower insulin-stimulated lipid kinase activity compared
FT with wild-type; dbSNP:rs748784250)"
FT /evidence="ECO:0000269|PubMed:10768093"
FT /id="VAR_010024"
FT VARIANT 451
FT /note="E -> K (in dbSNP:rs17852841)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_029562"
FT VARIANT 489
FT /note="E -> K (in SHORTS; there is 70 to 90% reduction in
FT the effect of insulin on AKT1 activation, glycogen
FT synthesis and glucose uptake, indicating severe insulin
FT resistance for both proximal and distal PI3K-dependent
FT signaling; dbSNP:rs397514047)"
FT /evidence="ECO:0000269|PubMed:23810378"
FT /id="VAR_070221"
FT VARIANT 539
FT /note="Missing (in SHORTS; there is 70 to 90% reduction in
FT the effect of insulin on AKT1 activation, glycogen
FT synthesis and glucose uptake, indicating severe insulin
FT resistance for both proximal and distal PI3K-dependent
FT signaling)"
FT /evidence="ECO:0000269|PubMed:23810378"
FT /id="VAR_070222"
FT VARIANT 649
FT /note="R -> W (in SHORTS; impairs interaction between
FT PIK3R1 and IRS1 and reduces AKT1-mediated insulin
FT signaling; dbSNP:rs397515453)"
FT /evidence="ECO:0000269|PubMed:23810379,
FT ECO:0000269|PubMed:23810382"
FT /id="VAR_070223"
FT CONFLICT 330
FT /note="D -> N (in Ref. 1; M61906)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="S -> G (in Ref. 4; BAG52931)"
FT /evidence="ECO:0000305"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:3I5R"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:3I5R"
FT HELIX 34..40
FT /evidence="ECO:0007829|PDB:3I5R"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:3I5R"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3I5R"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:3I5R"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:3I5R"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:3I5R"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:3I5R"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3I5R"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:3I5R"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:1AZG"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:1PBW"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 160..164
FT /evidence="ECO:0007829|PDB:1PBW"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 179..191
FT /evidence="ECO:0007829|PDB:1PBW"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 200..209
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 234..252
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 261..273
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 280..295
FT /evidence="ECO:0007829|PDB:1PBW"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:4L23"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:5GJI"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:6NCT"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:4WAF"
FT HELIX 340..347
FT /evidence="ECO:0007829|PDB:5GJI"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:5GJI"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:7RNS"
FT STRAND 368..374
FT /evidence="ECO:0007829|PDB:5GJI"
FT STRAND 377..386
FT /evidence="ECO:0007829|PDB:5GJI"
FT STRAND 389..395
FT /evidence="ECO:0007829|PDB:5GJI"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:5GJI"
FT HELIX 401..409
FT /evidence="ECO:0007829|PDB:5GJI"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:5GJI"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:5GJI"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:4YKN"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:2IUG"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:4WAF"
FT HELIX 442..515
FT /evidence="ECO:0007829|PDB:4JPS"
FT HELIX 518..587
FT /evidence="ECO:0007829|PDB:4JPS"
FT HELIX 591..597
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 617..619
FT /evidence="ECO:0007829|PDB:5AUL"
FT HELIX 621..623
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 625..629
FT /evidence="ECO:0007829|PDB:1PIC"
FT HELIX 631..638
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 645..650
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 652..655
FT /evidence="ECO:0007829|PDB:1PIC"
FT STRAND 657..663
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 666..675
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 678..682
FT /evidence="ECO:0007829|PDB:5AUL"
FT STRAND 688..690
FT /evidence="ECO:0007829|PDB:5AUL"
FT HELIX 691..698
FT /evidence="ECO:0007829|PDB:5AUL"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:5AUL"
FT TURN 708..710
FT /evidence="ECO:0007829|PDB:1PIC"
FT STRAND 716..719
FT /evidence="ECO:0007829|PDB:1PIC"
SQ SEQUENCE 724 AA; 83598 MW; B9DAD8416C33140F CRC64;
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EEIGWLNGYN
ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE
QFAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE LRQLLDCDTP SVDLEMIDVH
VLADAFKRYL LDLPNPVIPA AVYSEMISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL
QYLLKHFFKL SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE
RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA
STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS VVELINHYRN ESLAQYNPKL
DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK
RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID
SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS
VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA
QQRR
