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 28-JAN-2026, entry version 215. 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=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; 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/auxiliary subunits to form CC alternative complex forms. Alternative complex forms containing a CC fourth regulatory subunit in a mutually exclusive manner are PI3K CC complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) CC containing UVRAG (PubMed:19270696, PubMed:23878393, PubMed:25490155, CC PubMed:8999962). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 CC serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex CC (PubMed:25490155). Both, PI3KC3-C1 and PI3KC3-C2, can associate with CC further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and CC NRBF2 (PubMed:19270696, PubMed:20643123, PubMed:24785657). PI3KC3-C1 CC probably associates with PIK3CB (By similarity). Interacts with RAB7A CC in the presence of PIK3C3/VPS34 (PubMed:14617358). Interacts with NRBF2 CC (PubMed:24785657). Interacts with ARMC3 (By similarity). 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=15; IntAct=EBI-1046979, EBI-2362014; CC Q99570; P31946: YWHAB; NbExp=3; IntAct=EBI-1046979, EBI-359815; 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_014602.3. DR PDB; 7BL1; EM; 9.80 A; CCC=1-1358. DR PDB; 8SOR; EM; 3.96 A; A=1-1358. DR PDB; 9C82; EM; 6.84 A; A=1-1358. DR PDB; 9MHF; EM; 2.73 A; A=1-1358. DR PDB; 9MHG; EM; 3.20 A; A=1-1358. DR PDB; 9MHH; EM; 4.50 A; A=1-1358. DR PDBsum; 7BL1; -. DR PDBsum; 8SOR; -. DR PDBsum; 9C82; -. DR PDBsum; 9MHF; -. DR PDBsum; 9MHG; -. DR PDBsum; 9MHH; -. DR AlphaFoldDB; Q99570; -. DR EMDB; EMD-12214; -. DR EMDB; EMD-2846; -. DR EMDB; EMD-40669; -. DR EMDB; EMD-40738; -. DR EMDB; EMD-45297; -. DR EMDB; EMD-48276; -. DR EMDB; EMD-48277; -. DR EMDB; EMD-48278; -. DR SMR; Q99570; -. DR BioGRID; 119059; 120. 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 FunCoup; Q99570; 3008. DR IntAct; Q99570; 144. DR MINT; Q99570; -. DR STRING; 9606.ENSP00000349205; -. DR BindingDB; Q99570; -. DR ChEMBL; CHEMBL2189144; -. DR GlyGen; Q99570; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q99570; -. DR PhosphoSitePlus; Q99570; -. DR BioMuta; PIK3R4; -. DR DMDM; 74762700; -. DR jPOST; Q99570; -. DR MassIVE; Q99570; -. DR PaxDb; 9606-ENSP00000349205; -. DR PeptideAtlas; Q99570; -. DR ProteomicsDB; 78330; -. DR Pumba; Q99570; -. DR Antibodypedia; 33331; 478 antibodies from 35 providers. DR DNASU; 30849; -. DR Ensembl; ENST00000356763.8; ENSP00000349205.3; ENSG00000196455.9. 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 AGR; HGNC:8982; -. DR ClinPGx; PA33315; -. 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 OpenTargets; ENSG00000196455; -. DR VEuPathDB; HostDB:ENSG00000196455; -. DR eggNOG; KOG1240; Eukaryota. DR GeneTree; ENSGT00390000016225; -. DR HOGENOM; CLU_001696_0_0_1; -. DR InParanoid; Q99570; -. DR OMA; ATNTCRI; -. DR OrthoDB; 242910at2759; -. DR PAN-GO; Q99570; 10 GO annotations based on evolutionary models. DR PhylomeDB; Q99570; -. DR BioCyc; MetaCyc:HS03788-MONOMER; -. 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 Agora; ENSG00000196455; -. DR BioGRID-ORCS; 30849; 374 hits in 1212 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 198 other cell types or tissues. DR ExpressionAtlas; Q99570; baseline and differential. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. DR GO; GO:0005930; C:axoneme; ISS:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:HPA. DR GO; GO:0005929; C:cilium; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0045171; C:intercellular bridge; 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: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:0000425; P:pexophagy; IBA:GO_Central. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:ComplexPortal. DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB. DR GO; GO:0006622; P:protein targeting to lysosome; NAS: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 CDD; cd13980; STKc_Vps15; 1. DR FunFam; 1.25.10.10:FF:000154; Phosphoinositide 3-kinase regulatory subunit 4; 1. DR FunFam; 1.10.510.10:FF:000305; phosphoinositide 3-kinase regulatory subunit 4; 1. DR FunFam; 1.25.10.10:FF:000100; phosphoinositide 3-kinase regulatory subunit 4; 1. DR FunFam; 2.130.10.10:FF:000396; phosphoinositide 3-kinase regulatory subunit 4; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR055231; 2AA_helical. 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; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR17583; PHOSPHOINOSITIDE 3-KINASE REGULATORY SUBUNIT 4; 1. DR PANTHER; PTHR17583:SF0; PHOSPHOINOSITIDE 3-KINASE REGULATORY SUBUNIT 4; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF22956; VPS15-like_hel; 1. DR Pfam; PF00400; WD40; 2. DR SMART; SM00220; S_TKc; 1. DR SMART; SM00320; WD40; 6. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF50978; WD40 repeat-like; 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; Proteomics identification; 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 COMPBIAS 1315..1326 FT /note="Basic and acidic residues" 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" FT HELIX 3..6 FT /evidence="ECO:0007829|PDB:9MHG" FT HELIX 10..14 FT /evidence="ECO:0007829|PDB:9MHG" FT HELIX 17..22 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 24..34 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 39..45 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 48..56 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 65..77 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 92..95 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 96..104 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 110..113 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 122..142 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 162..165 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 181..186 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 189..192 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 199..201 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:9MHG" FT HELIX 229..232 FT /evidence="ECO:0007829|PDB:9MHG" FT HELIX 237..252 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 261..269 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 275..278 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 284..293 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 298..300 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 304..310 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 313..315 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 318..322 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 324..328 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 329..331 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:9MHG" FT HELIX 339..348 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 350..357 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 375..382 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 383..385 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 386..388 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 392..405 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 406..408 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 411..416 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 419..425 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 431..446 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 453..455 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 458..461 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 463..467 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 468..472 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 476..508 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 527..545 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 550..575 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 577..582 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 583..586 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 591..608 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 610..612 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 613..623 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 629..644 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 650..660 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 661..665 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 669..685 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 688..693 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 695..699 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 700..702 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 703..705 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 708..711 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 713..719 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 726..734 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 738..752 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 755..757 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 765..776 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 781..789 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 791..808 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 813..815 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 816..820 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 821..823 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 829..831 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 939..967 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 985..990 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 992..994 FT /evidence="ECO:0007829|PDB:9MHG" FT STRAND 996..1001 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1005..1012 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1017..1021 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 1022..1024 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1035..1038 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1045..1050 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1056..1061 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1064..1071 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1082..1089 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 1092..1095 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1098..1105 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1110..1116 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1119..1136 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 1139..1141 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1144..1149 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1153..1160 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1163..1169 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 1170..1173 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1174..1180 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1187..1192 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1199..1206 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1210..1214 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 1215..1217 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1220..1229 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1242..1248 FT /evidence="ECO:0007829|PDB:9MHF" FT TURN 1250..1252 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1255..1260 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1265..1272 FT /evidence="ECO:0007829|PDB:9MHF" FT HELIX 1273..1275 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1277..1281 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1288..1305 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1332..1349 FT /evidence="ECO:0007829|PDB:9MHF" FT STRAND 1352..1357 FT /evidence="ECO:0007829|PDB:9MHF" 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 //