P85B_HUMAN
ID P85B_HUMAN Reviewed; 728 AA.
AC O00459; Q5EAT5; Q9UPH9;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit beta;
DE Short=PI3-kinase regulatory subunit beta;
DE Short=PI3K regulatory subunit beta;
DE Short=PtdIns-3-kinase regulatory subunit beta;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta;
DE Short=PI3-kinase subunit p85-beta;
DE Short=PtdIns-3-kinase regulatory subunit p85-beta;
GN Name=PIK3R2;
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 [GENOMIC DNA], AND VARIANTS ARG-234 AND PRO-313.
RX PubMed=1314371;
RA Volinia S., Patracchini P., Otsu M., Hiles I., Gout I., Calzolari E.,
RA Bernardi F., Rooke L., Waterfield M.D.;
RT "Chromosomal localization of human p85 alpha, a subunit of
RT phosphatidylinositol 3-kinase, and its homologue p85 beta.";
RL Oncogene 7:789-793(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-234 AND PRO-313.
RX PubMed=9582025; DOI=10.1038/sj.onc.1201695;
RA Janssen J.W.G., Schleithhoff L., Bartram C.R., Schulz A.S.;
RT "An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta
RT subunit and HUMORF8, a putative deubiquitinating enzyme.";
RL Oncogene 16:1767-1772(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-234 AND PRO-313.
RC TISSUE=Brain, and Placenta;
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 [5]
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 [6]
RP INTERACTION WITH FLT1.
RX PubMed=9600074; DOI=10.1006/bbrc.1998.8578;
RA Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I.;
RT "Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2.";
RL Biochem. Biophys. Res. Commun. 246:95-99(1998).
RN [7]
RP INTERACTION WITH FLT4.
RX PubMed=15102829; DOI=10.1074/jbc.m314015200;
RA Wang J.F., Zhang X., Groopman J.E.;
RT "Activation of vascular endothelial growth factor receptor-3 and its
RT downstream signaling promote cell survival under oxidative stress.";
RL J. Biol. Chem. 279:27088-27097(2004).
RN [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-605, AND IDENTIFICATION BY
RP 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464, AND IDENTIFICATION BY
RP 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 [15]
RP FUNCTION, INTERACTION WITH FBXL2 AND PTPN13, PHOSPHORYLATION AT TYR-655,
RP DEPHOSPHORYLATION AT TYR-655 BY PTPN13, UBIQUITINATION, DOMAIN, AND
RP MUTAGENESIS OF GLN-651; ARG-652 AND TYR-655.
RX PubMed=23604317; DOI=10.1038/ncb2731;
RA Kuchay S., Duan S., Schenkein E., Peschiaroli A., Saraf A., Florens L.,
RA Washburn M.P., Pagano M.;
RT "FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory
RT subunit controls the PI(3)K signalling cascade.";
RL Nat. Cell Biol. 15:472-480(2013).
RN [16]
RP INVOLVEMENT IN MPPH1, AND VARIANT MPPH1 PRO-401.
RX PubMed=23745724; DOI=10.1111/cge.12188;
RA Nakamura K., Kato M., Tohyama J., Shiohama T., Hayasaka K., Nishiyama K.,
RA Kodera H., Nakashima M., Tsurusaki Y., Miyake N., Matsumoto N., Saitsu H.;
RT "AKT3 and PIK3R2 mutations in two patients with megalencephaly-related
RT syndromes: MCAP and MPPH.";
RL Clin. Genet. 85:396-398(2014).
RN [17]
RP INVOLVEMENT IN MPPH1, AND VARIANT MPPH1 ARG-373.
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 [18]
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 [19]
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 [20]
RP VARIANTS MPPH1 ARG-373 AND GLU-376.
RX PubMed=26520804; DOI=10.1016/s1474-4422(15)00278-1;
RA Mirzaa G.M., Conti V., Timms A.E., Smyser C.D., Ahmed S., Carter M.,
RA Barnett S., Hufnagel R.B., Goldstein A., Narumi-Kishimoto Y., Olds C.,
RA Collins S., Johnston K., Deleuze J.F., Nitschke P., Friend K., Harris C.,
RA Goetsch A., Martin B., Boyle E.A., Parrini E., Mei D., Tattini L.,
RA Slavotinek A., Blair E., Barnett C., Shendure J., Chelly J., Dobyns W.B.,
RA Guerrini R.;
RT "Characterisation of mutations of the phosphoinositide-3-kinase regulatory
RT subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation
RT sequencing study.";
RL Lancet Neurol. 14:1182-1195(2015).
RN [21]
RP VARIANT MPPH1 HIS-557.
RX PubMed=26860062; DOI=10.1038/ejhg.2016.7;
RA Terrone G., Voisin N., Abdullah Alfaiz A., Cappuccio G., Vitiello G.,
RA Guex N., D'Amico A., James Barkovich A., Brunetti-Pierri N.,
RA Del Giudice E., Reymond A.;
RT "De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia
RT and focal cortical dysplasia.";
RL Eur. J. Hum. Genet. 24:1359-1362(2016).
CC -!- FUNCTION: Regulatory subunit of phosphoinositide-3-kinase (PI3K), a
CC kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-
CC bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate
CC (PIP3). PIP3 plays a key role by recruiting PH domain-containing
CC proteins to the membrane, including AKT1 and PDPK1, activating
CC signaling cascades involved in cell growth, survival, proliferation,
CC motility and morphology. Binds to activated (phosphorylated) protein-
CC tyrosine kinases, through its SH2 domain, and acts as an adapter,
CC mediating the association of the p110 catalytic unit to the plasma
CC membrane. Indirectly regulates autophagy (PubMed:23604317). Promotes
CC nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-
CC dependent manner during metabolic overloading in the liver and hence
CC plays a role in glucose tolerance improvement (By similarity).
CC {ECO:0000250|UniProtKB:O08908, ECO:0000269|PubMed:23604317}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R2 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD) (PubMed:23604317).
CC Interacts with AXL (PubMed:9178760). Interacts with FLT1 (tyrosine-
CC phosphorylated) and FLT4 (tyrosine-phosphorylated) (PubMed:9600074,
CC PubMed:15102829). Interacts with NYAP1, NYAP2 and MYO16 (By
CC similarity). Interacts with FBXL2; PIK3R2 is a substrate of the
CC SCF(FBXL2) complex (PubMed:23604317). Interacts with PTPN13;
CC dephosphorylates PIK3R2 (PubMed:23604317). Interacts with XBP1 isoform
CC 2; the interaction is direct and induces translocation of XBP1 isoform
CC 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-
CC independent manner (By similarity). Interacts with PIK3R1; the
CC interaction is dissociated in an insulin-dependent manner (By
CC similarity). Interacts with SRC (PubMed:28903391).
CC {ECO:0000250|UniProtKB:O08908, ECO:0000269|PubMed:15102829,
CC ECO:0000269|PubMed:23604317, ECO:0000269|PubMed:28903391,
CC ECO:0000269|PubMed:9178760, ECO:0000269|PubMed:9600074}.
CC -!- INTERACTION:
CC O00459; P10275: AR; NbExp=14; IntAct=EBI-346930, EBI-608057;
CC O00459; P22681: CBL; NbExp=4; IntAct=EBI-346930, EBI-518228;
CC O00459; P46108: CRK; NbExp=5; IntAct=EBI-346930, EBI-886;
CC O00459; G5E9A7: DMWD; NbExp=3; IntAct=EBI-346930, EBI-10976677;
CC O00459; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-346930, EBI-740680;
CC O00459; P00533: EGFR; NbExp=4; IntAct=EBI-346930, EBI-297353;
CC O00459; P04626: ERBB2; NbExp=6; IntAct=EBI-346930, EBI-641062;
CC O00459; P21860: ERBB3; NbExp=16; IntAct=EBI-346930, EBI-720706;
CC O00459; Q13480: GAB1; NbExp=23; IntAct=EBI-346930, EBI-517684;
CC O00459; Q08379: GOLGA2; NbExp=3; IntAct=EBI-346930, EBI-618309;
CC O00459; P62993: GRB2; NbExp=4; IntAct=EBI-346930, EBI-401755;
CC O00459; P42858: HTT; NbExp=6; IntAct=EBI-346930, EBI-466029;
CC O00459; Q9UKT9: IKZF3; NbExp=4; IntAct=EBI-346930, EBI-747204;
CC O00459; P10721: KIT; NbExp=19; IntAct=EBI-346930, EBI-1379503;
CC O00459; P19012: KRT15; NbExp=3; IntAct=EBI-346930, EBI-739566;
CC O00459; P35900: KRT20; NbExp=3; IntAct=EBI-346930, EBI-742094;
CC O00459; O76015: KRT38; NbExp=5; IntAct=EBI-346930, EBI-1047263;
CC O00459; P08581: MET; NbExp=11; IntAct=EBI-346930, EBI-1039152;
CC O00459; Q96HT8: MRFAP1L1; NbExp=4; IntAct=EBI-346930, EBI-748896;
CC O00459; P42338: PIK3CB; NbExp=5; IntAct=EBI-346930, EBI-2609540;
CC O00459; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-346930, EBI-726876;
CC O00459; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-346930, EBI-5235340;
CC O00459; P36406: TRIM23; NbExp=3; IntAct=EBI-346930, EBI-740098;
CC O00459; P03496: NS; Xeno; NbExp=13; IntAct=EBI-346930, EBI-2547442;
CC O00459; Q82506: NS; Xeno; NbExp=2; IntAct=EBI-346930, EBI-6149498;
CC -!- DOMAIN: The SH2 2 domain is required for interaction with FBXL2 and
CC PTPN13. {ECO:0000269|PubMed:23604317}.
CC -!- PTM: Phosphorylated in response to signaling from activated receptor-
CC type protein kinases (PubMed:19690332, PubMed:20068231).
CC Dephosphorylated by PTPRJ (PubMed:18348712). Dephosphorylated at Tyr-
CC 655 by PTPN13. Phosphorylation of Tyr-655 impairs while its
CC dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-
CC mediated polyubiquitination (PubMed:23604317).
CC {ECO:0000269|PubMed:18348712, ECO:0000269|PubMed:23604317}.
CC -!- PTM: Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex
CC probably promotes proteasomal degradation of PIK3R2.
CC {ECO:0000303|PubMed:23604317}.
CC -!- DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus
CC syndrome 1 (MPPH1) [MIM:603387]: A syndrome characterized by
CC megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also
CC be seen. There is considerable phenotypic similarity between this
CC disorder and the megalencephaly-capillary malformation syndrome.
CC {ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:23745724,
CC ECO:0000269|PubMed:26520804, ECO:0000269|PubMed:26860062}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
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DR EMBL; X80907; CAA56868.1; -; mRNA.
DR EMBL; AC007192; AAD22671.1; -; Genomic_DNA.
DR EMBL; BC070082; AAH70082.1; -; mRNA.
DR EMBL; BC090249; AAH90249.1; -; mRNA.
DR CCDS; CCDS12371.1; -.
DR PIR; H59435; H59435.
DR RefSeq; NP_005018.1; NM_005027.3.
DR PDB; 2KT1; NMR; -; A=1-80.
DR PDB; 2XS6; X-ray; 2.09 A; A=108-298.
DR PDB; 3MTT; X-ray; 3.30 A; A=433-610.
DR PDB; 3O5Z; X-ray; 2.01 A; A/B=1-85.
DR PDB; 6OX7; X-ray; 2.75 A; C/D=435-597.
DR PDB; 6U28; X-ray; 2.95 A; C/D=435-597.
DR PDB; 7RNU; X-ray; 1.45 A; A/C/E/G=318-428.
DR PDBsum; 2KT1; -.
DR PDBsum; 2XS6; -.
DR PDBsum; 3MTT; -.
DR PDBsum; 3O5Z; -.
DR PDBsum; 6OX7; -.
DR PDBsum; 6U28; -.
DR PDBsum; 7RNU; -.
DR AlphaFoldDB; O00459; -.
DR BMRB; O00459; -.
DR SMR; O00459; -.
DR BioGRID; 111314; 188.
DR ComplexPortal; CPX-1917; Phosphatidylinositol 3-kinase complex class IA, p110alpha/p85beta.
DR ComplexPortal; CPX-5976; Phosphatidylinositol 3-kinase complex class IA, p110beta/p85beta.
DR ComplexPortal; CPX-5980; Phosphatidylinositol 3-kinase complex class IA, p110delta/p85beta.
DR DIP; DIP-31811N; -.
DR IntAct; O00459; 95.
DR MINT; O00459; -.
DR STRING; 9606.ENSP00000222254; -.
DR BindingDB; O00459; -.
DR ChEMBL; CHEMBL4437; -.
DR DrugBank; DB05210; SF1126.
DR iPTMnet; O00459; -.
DR PhosphoSitePlus; O00459; -.
DR BioMuta; PIK3R2; -.
DR CPTAC; CPTAC-1538; -.
DR EPD; O00459; -.
DR jPOST; O00459; -.
DR MassIVE; O00459; -.
DR MaxQB; O00459; -.
DR PaxDb; O00459; -.
DR PeptideAtlas; O00459; -.
DR PRIDE; O00459; -.
DR ProteomicsDB; 47910; -.
DR ABCD; O00459; 6 sequenced antibodies.
DR Antibodypedia; 14986; 641 antibodies from 40 providers.
DR DNASU; 5296; -.
DR Ensembl; ENST00000222254.13; ENSP00000222254.6; ENSG00000105647.19.
DR GeneID; 5296; -.
DR KEGG; hsa:5296; -.
DR MANE-Select; ENST00000222254.13; ENSP00000222254.6; NM_005027.4; NP_005018.2.
DR UCSC; uc002nia.3; human.
DR CTD; 5296; -.
DR DisGeNET; 5296; -.
DR GeneCards; PIK3R2; -.
DR GeneReviews; PIK3R2; -.
DR HGNC; HGNC:8980; PIK3R2.
DR HPA; ENSG00000105647; Low tissue specificity.
DR MalaCards; PIK3R2; -.
DR MIM; 603157; gene.
DR MIM; 603387; phenotype.
DR neXtProt; NX_O00459; -.
DR OpenTargets; ENSG00000105647; -.
DR OpenTargets; ENSG00000268173; -.
DR Orphanet; 83473; Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome.
DR PharmGKB; PA33313; -.
DR VEuPathDB; HostDB:ENSG00000105647; -.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000157050; -.
DR HOGENOM; CLU_007031_1_0_1; -.
DR InParanoid; O00459; -.
DR OMA; CIYPQLQ; -.
DR OrthoDB; 737926at2759; -.
DR PhylomeDB; O00459; -.
DR TreeFam; TF102033; -.
DR BioCyc; MetaCyc:ENSG00000105647-MON; -.
DR BRENDA; 2.7.1.137; 2681.
DR PathwayCommons; O00459; -.
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-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-186763; Downstream signal transduction.
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-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate 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-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-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
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-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 SignaLink; O00459; -.
DR SIGNOR; O00459; -.
DR BioGRID-ORCS; 5296; 59 hits in 1077 CRISPR screens.
DR ChiTaRS; PIK3R2; human.
DR EvolutionaryTrace; O00459; -.
DR GeneWiki; PIK3R2; -.
DR GenomeRNAi; 5296; -.
DR Pharos; O00459; Tbio.
DR PRO; PR:O00459; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O00459; protein.
DR Bgee; ENSG00000105647; Expressed in cortical plate and 99 other tissues.
DR ExpressionAtlas; O00459; baseline and differential.
DR Genevisible; O00459; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IPI:ComplexPortal.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
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; ISS:ParkinsonsUK-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
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:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:BHF-UCL.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; IBA:GO_Central.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IC:ComplexPortal.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11909; SH3_PI3K_p85beta; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035586; PI3K_p85beta_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; Disease variant; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Stress response;
KW Transport; Ubl conjugation.
FT CHAIN 1..728
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT beta"
FT /id="PRO_0000080763"
FT DOMAIN 4..80
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 109..295
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 330..425
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 622..716
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 81..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..102
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 254..273
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 464
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 605
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 655
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:23604317"
FT VARIANT 234
FT /note="S -> R (in dbSNP:rs2241088)"
FT /evidence="ECO:0000269|PubMed:1314371,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9582025"
FT /id="VAR_030679"
FT VARIANT 313
FT /note="S -> P (in dbSNP:rs1011320)"
FT /evidence="ECO:0000269|PubMed:1314371,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9582025"
FT /id="VAR_030680"
FT VARIANT 373
FT /note="G -> R (in MPPH1; dbSNP:rs587776934)"
FT /evidence="ECO:0000269|PubMed:22729224,
FT ECO:0000269|PubMed:26520804"
FT /id="VAR_069262"
FT VARIANT 376
FT /note="K -> E (in MPPH1; unknown pathological significance;
FT dbSNP:rs886041591)"
FT /evidence="ECO:0000269|PubMed:26520804"
FT /id="VAR_075556"
FT VARIANT 401
FT /note="L -> P (in MPPH1; dbSNP:rs587777624)"
FT /evidence="ECO:0000269|PubMed:23745724"
FT /id="VAR_075683"
FT VARIANT 557
FT /note="D -> H (in MPPH1; dbSNP:rs372272045)"
FT /evidence="ECO:0000269|PubMed:26860062"
FT /id="VAR_075684"
FT MUTAGEN 651
FT /note="Q->A: Loss of interaction with FBXL2 and increased
FT half-life; when associated with A-652."
FT /evidence="ECO:0000269|PubMed:23604317"
FT MUTAGEN 652
FT /note="R->A: Loss of interaction with FBXL2 and increased
FT half-life; when associated with A-651."
FT /evidence="ECO:0000269|PubMed:23604317"
FT MUTAGEN 655
FT /note="Y->A: Stabilized interaction with FBXL2 and
FT decreased half-life."
FT /evidence="ECO:0000269|PubMed:23604317"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:3O5Z"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:3O5Z"
FT HELIX 35..40
FT /evidence="ECO:0007829|PDB:3O5Z"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:3O5Z"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:3O5Z"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:3O5Z"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:3O5Z"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:3O5Z"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:3O5Z"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:3O5Z"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:2XS6"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:2XS6"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 216..235
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 239..255
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 279..293
FT /evidence="ECO:0007829|PDB:2XS6"
FT HELIX 337..344
FT /evidence="ECO:0007829|PDB:7RNU"
FT STRAND 351..356
FT /evidence="ECO:0007829|PDB:7RNU"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:7RNU"
FT STRAND 374..383
FT /evidence="ECO:0007829|PDB:7RNU"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:7RNU"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:7RNU"
FT HELIX 398..405
FT /evidence="ECO:0007829|PDB:7RNU"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:7RNU"
FT HELIX 435..492
FT /evidence="ECO:0007829|PDB:6OX7"
FT HELIX 523..531
FT /evidence="ECO:0007829|PDB:6OX7"
FT HELIX 535..561
FT /evidence="ECO:0007829|PDB:6OX7"
FT HELIX 564..583
FT /evidence="ECO:0007829|PDB:6OX7"
FT HELIX 588..594
FT /evidence="ECO:0007829|PDB:6OX7"
SQ SEQUENCE 728 AA; 81545 MW; ADAC3E4B61F3F44A CRC64;
MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGGERC PQSVGWMPGL
NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP RDGAPEPGLT LPDLPEQFSP
PDVAPPLLVK LVEAIERTGL DSESHYRPEL PAPRTDWSLS DVDQWDTAAL ADGIKSFLLA
LPAPLVTPEA SAEARRALRE AAGPVGPALE PPTLPLHRAL TLRFLLQHLG RVASRAPALG
PAVRALGATF GPLLLRAPPP PSSPPPGGAP DGSEPSPDFP ALLVEKLLQE HLEEQEVAPP
ALPPKPPKAK PASTVLANGG SPPSLQDAEW YWGDISREEV NEKLRDTPDG TFLVRDASSK
IQGEYTLTLR KGGNNKLIKV FHRDGHYGFS EPLTFCSVVD LINHYRHESL AQYNAKLDTR
LLYPVSKYQQ DQIVKEDSVE AVGAQLKVYH QQYQDKSREY DQLYEEYTRT SQELQMKRTA
IEAFNETIKI FEEQGQTQEK CSKEYLERFR REGNEKEMQR ILLNSERLKS RIAEIHESRT
KLEQQLRAQA SDNREIDKRM NSLKPDLMQL RKIRDQYLVW LTQKGARQKK INEWLGIKNE
TEDQYALMED EDDLPHHEER TWYVGKINRT QAEEMLSGKR DGTFLIRESS QRGCYACSVV
VDGDTKHCVI YRTATGFGFA EPYNLYGSLK ELVLHYQHAS LVQHNDALTV TLAHPVRAPG
PGPPPAAR
