PI3R4_HUMAN
ID PI3R4_HUMAN Reviewed; 1358 AA.
AC Q99570; Q2TBF4;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Phosphoinositide 3-kinase regulatory subunit 4;
DE Short=PI3-kinase regulatory subunit 4;
DE EC=2.7.11.1;
DE AltName: Full=PI3-kinase p150 subunit;
DE AltName: Full=Phosphoinositide 3-kinase adaptor protein;
GN Name=PIK3R4; Synonyms=VPS15 {ECO:0000303|PubMed:23878393};
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], PROTEIN SEQUENCE OF 53-63; 333-343; 540-554 AND
RP 786-791, MYRISTOYLATION AT GLY-2, PHOSPHORYLATION, COFACTOR, TISSUE
RP SPECIFICITY, AND INTERACTION WITH PIK3C3.
RX PubMed=8999962; DOI=10.1074/jbc.272.4.2477;
RA Panaretou C., Domin J., Cockcroft S., Waterfield M.D.;
RT "Characterization of p150, an adaptor protein for the human
RT phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by
RT phosphatidylinositol transfer protein to the p150.PtdIns 3-kinase
RT complex.";
RL J. Biol. Chem. 272:2477-2485(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP INTERACTION WITH RAB7A AND PIK3C3/VPS34, AND SUBCELLULAR LOCATION.
RX PubMed=14617358; DOI=10.1034/j.1600-0854.2003.00133.x;
RA Stein M.P., Feng Y., Cooper K.L., Welford A.M., Wandinger-Ness A.;
RT "Human VPS34 and p150 are Rab7 interacting partners.";
RL Traffic 4:754-771(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1316, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [5]
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-808; SER-853 AND SER-865, AND
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 [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=20643123; DOI=10.1016/j.yexcr.2010.07.008;
RA Thoresen S.B., Pedersen N.M., Liestol K., Stenmark H.;
RT "A phosphatidylinositol 3-kinase class III sub-complex containing VPS15,
RT VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative
RT endocytic traffic.";
RL Exp. Cell Res. 316:3368-3378(2010).
RN [8]
RP INTERACTION WITH BECN1; RUBCN; ATG14; PIK3C3 AND UVRAG.
RX PubMed=19270696; DOI=10.1038/ncb1846;
RA Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N.,
RA Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T.,
RA Yoshimori T.;
RT "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate
RT autophagy at different stages.";
RL Nat. Cell Biol. 11:385-396(2009).
RN [9]
RP IDENTIFICATION BY 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 [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-813, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [12]
RP INTERACTION WITH BECN1.
RX PubMed=23878393; DOI=10.1128/mcb.00079-13;
RA Fogel A.I., Dlouhy B.J., Wang C., Ryu S.W., Neutzner A., Hasson S.A.,
RA Sideris D.P., Abeliovich H., Youle R.J.;
RT "Role of membrane association and Atg14-dependent phosphorylation in
RT beclin-1-mediated autophagy.";
RL Mol. Cell. Biol. 33:3675-3688(2013).
RN [13]
RP INTERACTION WITH NRBF2.
RX PubMed=24785657; DOI=10.1042/bj20140515;
RA Cao Y., Wang Y., Abi Saab W.F., Yang F., Pessin J.E., Backer J.M.;
RT "NRBF2 regulates macroautophagy as a component of Vps34 Complex I.";
RL Biochem. J. 461:315-322(2014).
RN [14]
RP RECONSTITUTION OF THE PI3K COMPLEX I, AND ELECTRON MICROSCOPY OF THE PI3K
RP COMPLEX I.
RX PubMed=25490155; DOI=10.7554/elife.05115;
RA Baskaran S., Carlson L.A., Stjepanovic G., Young L.N., Kim do J., Grob P.,
RA Stanley R.E., Nogales E., Hurley J.H.;
RT "Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase
RT complex.";
RL Elife 3:0-0(2014).
RN [15]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-936.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-273; HIS-342; TRP-347; ILE-388;
RP ASN-393; VAL-699 AND VAL-1043.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Regulatory subunit of the PI3K complex that mediates
CC formation of phosphatidylinositol 3-phosphate; different complex forms
CC are believed to play a role in multiple membrane trafficking pathways:
CC PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in
CC maturation of autophagosomes and endocytosis. Involved in regulation of
CC degradative endocytic trafficking and cytokinesis, probably in the
CC context of PI3KC3-C2 (PubMed:20643123). {ECO:0000269|PubMed:20643123}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:8999962};
CC -!- SUBUNIT: Component of the PI3K (PI3KC3/PI3K-III/class III
CC phosphatidylinositol 3-kinase) complex the core of which is composed of
CC the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1
CC associating with additional regulatory/auxilliary subunits to form
CC alternative complex forms. Alternative complex forms containing a forth
CC regulatory subunit in a mutually exclusive manner are PI3K complex I
CC (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2)
CC containing UVRAG (PubMed:8999962, PubMed:19270696, PubMed:23878393,
CC PubMed:25490155). PI3KC3-C1 displays a V-shaped architecture with
CC PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1
CC subcomplex (PubMed:25490155). Both, PI3KC3-C1 and PI3KC3-C2, can
CC associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-
CC 1, AMBRA1 and NRBF2 (PubMed:19270696, PubMed:20643123,
CC PubMed:24785657). PI3KC3-C1 probably associates with PIK3CB (By
CC similarity). Interacts with RAB7A in the presence of PIK3C3/VPS34
CC (PubMed:14617358). Interacts with NRBF2 (PubMed:24785657).
CC {ECO:0000250|UniProtKB:Q8VD65, ECO:0000269|PubMed:14617358,
CC ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20643123,
CC ECO:0000269|PubMed:23878393, ECO:0000269|PubMed:24785657,
CC ECO:0000269|PubMed:25490155, ECO:0000269|PubMed:8999962}.
CC -!- INTERACTION:
CC Q99570; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-1046979, EBI-10242151;
CC Q99570; Q96F24: NRBF2; NbExp=13; IntAct=EBI-1046979, EBI-2362014;
CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000269|PubMed:14617358}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000305}. Membrane
CC {ECO:0000305}; Lipid-anchor {ECO:0000305}. Note=As component of the
CC PI3K complex I localized to pre-autophagosome structures. As component
CC of the PI3K complex II localized predominantly to endosomes. Localizes
CC also to discrete punctae along the ciliary axoneme (By similarity).
CC {ECO:0000250|UniProtKB:Q8VD65, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:8999962}.
CC -!- PTM: Myristoylated. {ECO:0000269|PubMed:8999962}.
CC -!- PTM: Probably autophosphorylated. {ECO:0000269|PubMed:8999962}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y08991; CAA70176.1; -; mRNA.
DR EMBL; BC110318; AAI10319.1; -; mRNA.
DR EMBL; BC127106; AAI27107.1; -; mRNA.
DR CCDS; CCDS3067.1; -.
DR RefSeq; NP_055417.1; NM_014602.2.
DR PDB; 7BL1; EM; 9.80 A; CCC=1-1358.
DR PDBsum; 7BL1; -.
DR AlphaFoldDB; Q99570; -.
DR SMR; Q99570; -.
DR BioGRID; 119059; 87.
DR ComplexPortal; CPX-73; Phosphatidylinositol 3-kinase complex, class III, ATG14 variant.
DR ComplexPortal; CPX-74; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant.
DR CORUM; Q99570; -.
DR DIP; DIP-42310N; -.
DR ELM; Q99570; -.
DR IntAct; Q99570; 47.
DR MINT; Q99570; -.
DR STRING; 9606.ENSP00000349205; -.
DR BindingDB; Q99570; -.
DR ChEMBL; CHEMBL2189144; -.
DR iPTMnet; Q99570; -.
DR PhosphoSitePlus; Q99570; -.
DR BioMuta; PIK3R4; -.
DR DMDM; 74762700; -.
DR EPD; Q99570; -.
DR jPOST; Q99570; -.
DR MassIVE; Q99570; -.
DR MaxQB; Q99570; -.
DR PaxDb; Q99570; -.
DR PeptideAtlas; Q99570; -.
DR PRIDE; Q99570; -.
DR ProteomicsDB; 78330; -.
DR Antibodypedia; 33331; 490 antibodies from 34 providers.
DR DNASU; 30849; -.
DR Ensembl; ENST00000356763.8; ENSP00000349205.3; ENSG00000196455.8.
DR GeneID; 30849; -.
DR KEGG; hsa:30849; -.
DR MANE-Select; ENST00000356763.8; ENSP00000349205.3; NM_014602.3; NP_055417.1.
DR UCSC; uc003enj.4; human.
DR CTD; 30849; -.
DR DisGeNET; 30849; -.
DR GeneCards; PIK3R4; -.
DR HGNC; HGNC:8982; PIK3R4.
DR HPA; ENSG00000196455; Low tissue specificity.
DR MIM; 602610; gene.
DR neXtProt; NX_Q99570; -.
DR OpenTargets; ENSG00000196455; -.
DR PharmGKB; PA33315; -.
DR VEuPathDB; HostDB:ENSG00000196455; -.
DR eggNOG; KOG1240; Eukaryota.
DR GeneTree; ENSGT00390000016225; -.
DR HOGENOM; CLU_001696_0_0_1; -.
DR InParanoid; Q99570; -.
DR OMA; RELILHM; -.
DR OrthoDB; 1312453at2759; -.
DR PhylomeDB; Q99570; -.
DR TreeFam; TF102034; -.
DR BioCyc; MetaCyc:HS03788-MON; -.
DR PathwayCommons; Q99570; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-HSA-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-9679504; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR Reactome; R-HSA-9694676; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; Q99570; -.
DR SIGNOR; Q99570; -.
DR BioGRID-ORCS; 30849; 367 hits in 1125 CRISPR screens.
DR ChiTaRS; PIK3R4; human.
DR GeneWiki; PIK3R4; -.
DR GenomeRNAi; 30849; -.
DR Pharos; Q99570; Tbio.
DR PRO; PR:Q99570; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q99570; protein.
DR Bgee; ENSG00000196455; Expressed in right lobe of liver and 196 other tissues.
DR ExpressionAtlas; Q99570; baseline and differential.
DR Genevisible; Q99570; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0071561; C:nucleus-vacuole junction; IBA:GO_Central.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; IPI:ComplexPortal.
DR GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central.
DR GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; NAS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0097352; P:autophagosome maturation; IDA:ComplexPortal.
DR GO; GO:0030242; P:autophagy of peroxisome; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; IDA:ComplexPortal.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0006622; P:protein targeting to lysosome; IC:ComplexPortal.
DR GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central.
DR GO; GO:0032801; P:receptor catabolic process; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:ComplexPortal.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; IDA:ComplexPortal.
DR Gene3D; 1.25.10.10; -; 2.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045162; Vps15-like.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR17583; PTHR17583; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasmic vesicle; Direct protein sequencing;
KW Endosome; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..1358
FT /note="Phosphoinositide 3-kinase regulatory subunit 4"
FT /id="PRO_0000086524"
FT DOMAIN 26..324
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 413..450
FT /note="HEAT 1"
FT REPEAT 458..495
FT /note="HEAT 2"
FT REPEAT 572..610
FT /note="HEAT 3"
FT REPEAT 991..1030
FT /note="WD 1"
FT REPEAT 1040..1079
FT /note="WD 2"
FT REPEAT 1093..1134
FT /note="WD 3"
FT REPEAT 1139..1178
FT /note="WD 4"
FT REPEAT 1182..1223
FT /note="WD 5"
FT REPEAT 1237..1278
FT /note="WD 6"
FT REPEAT 1327..1358
FT /note="WD 7"
FT REGION 875..898
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1307..1326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 148
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 32..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 853
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 865
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 1316
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000269|PubMed:8999962"
FT VARIANT 273
FT /note="F -> L (in dbSNP:rs55951445)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040997"
FT VARIANT 342
FT /note="R -> H (in dbSNP:rs56295394)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040998"
FT VARIANT 347
FT /note="R -> W (in dbSNP:rs34797184)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040999"
FT VARIANT 388
FT /note="T -> I (in dbSNP:rs34663155)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041000"
FT VARIANT 393
FT /note="D -> N (in dbSNP:rs34633532)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041001"
FT VARIANT 699
FT /note="L -> V (in dbSNP:rs56369596)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041002"
FT VARIANT 936
FT /note="R -> Q (in a breast cancer sample; somatic mutation;
FT dbSNP:rs181132426)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035632"
FT VARIANT 1043
FT /note="G -> V (in dbSNP:rs56160735)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041003"
FT CONFLICT 342..343
FT /note="RI -> EK (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 553..554
FT /note="KQ -> FK (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1358 AA; 153103 MW; 5B402175265B21F7 CRC64;
MGNQLAGIAP SQILSVESYF SDIHDFEYDK SLGSTRFFKV ARAKHREGLV VVKVFAIQDP
TLPLTSYKQE LEELKIRLNS AQNCLPFQKA SEKASEKAAM LFRQYVRDNL YDRISTRPFL
NNIEKRWIAF QILTAVDQAH KSGVRHGDIK TENVMVTSWN WVLLTDFASF KPTYLPEDNP
ADFNYFFDTS RRRTCYIAPE RFVDGGMFAT ELEYMRDPST PLVDLNSNQR TRGELKRAMD
IFSAGCVIAE LFTEGVPLFD LSQLLAYRNG HFFPEQVLNK IEDHSIRELV TQMIHREPDK
RLEAEDYLKQ QRGNAFPEIF YTFLQPYMAQ FAKETFLSAD ERILVIRKDL GNIIHNLCGH
DLPEKAEGEP KENGLVILVS VITSCLQTLK YCDSKLAALE LILHLAPRLS VEILLDRITP
YLLHFSNDSV PRVRAEALRT LTKVLALVKE VPRNDINIYP EYILPGIAHL AQDDATIVRL
AYAENIALLA ETALRFLELV QLKNLNMEND PNNEEIDEVT HPNGNYDTEL QALHEMVQQK
VVTLLSDPEN IVKQTLMENG ITRLCVFFGR QKANDVLLSH MITFLNDKND WHLRGAFFDS
IVGVAAYVGW QSSSILKPLL QQGLSDAEEF VIVKALYALT CMCQLGLLQK PHVYEFASDI
APFLCHPNLW IRYGAVGFIT VVARQISTAD VYCKLMPYLD PYITQPIIQI ERKLVLLSVL
KEPVSRSIFD YALRSKDITS LFRHLHMRQK KRNGSLPDCP PPEDPAIAQL LKKLLSQGMT
EEEEDKLLAL KDFMMKSNKA KANIVDQSHL HDSSQKGVID LAALGITGRQ VDLVKTKQEP
DDKRARKHVK QDSNVNEEWK SMFGSLDPPN MPQALPKGSD QEVIQTGKPP RSESSAGICV
PLSTSSQVPE VTTVQNKKPV IPVLSSTILP STYQIRITTC KTELQQLIQQ KREQCNAERI
AKQMMENAEW ESKPPPPGWR PKGLLVAHLH EHKSAVNRIR VSDEHSLFAT CSNDGTVKIW
NSQKMEGKTT TTRSILTYSR IGGRVKTLTF CQGSHYLAIA SDNGAVQLLG IEASKLPKSP
KIHPLQSRIL DQKEDGCVVD MHHFNSGAQS VLAYATVNGS LVGWDLRSSS NAWTLKHDLK
SGLITSFAVD IHQCWLCIGT SSGTMACWDM RFQLPISSHC HPSRARIRRL SMHPLYQSWV
IAAVQGNNEV SMWDMETGDR RFTLWASSAP PLSELQPSPH SVHGIYCSPA DGNPILLTAG
SDMKIRFWDL AYPERSYVVA GSTSSPSVSY YRKIIEGTEV VQEIQNKQKV GPSDDTPRRG
PESLPVGHHD IITDVATFQT TQGFIVTASR DGIVKVWK
