true2005-12-062024-01-24162PK3C3_MOUSEThe status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)Mammary glandAmbra1 regulates autophagy and development of the nervous system.Maria Fimia G.Stoykova A.Romagnoli A.Giunta L.Di Bartolomeo S.Nardacci R.Corazzari M.Fuoco C.Ucar A.Schwartz P.Gruss P.Piacentini M.Chowdhury K.Cecconi F.doi:10.1038/nature059252007Nature4471121-1125INTERACTION WITH BECN1 AND AMBRA1A tissue-specific atlas of mouse protein phosphorylation and expression.Huttlin E.L.Jedrychowski M.P.Elias J.E.Goswami T.Rad R.Beausoleil S.A.Villen J.Haas W.Sowa M.E.Gygi S.P.doi:10.1016/j.cell.2010.12.0012010Cell1431174-1189IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]BrainBrown adipose tissueLungSpleenTestisThe class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy.Dou Z.Chattopadhyay M.Pan J.-A.Guerriero J.L.Jiang Y.-P.Ballou L.M.Yue Z.Lin R.Z.Zong W.-X.doi:10.1083/jcb.2010060562010J. Cell Biol.191827-843IDENTIFICATION IN A COMPLEX WITH PIK3R4 AND PIK3CBReceptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex.Ma C.Wang N.Detre C.Wang G.O'Keeffe M.Terhorst C.doi:10.1074/jbc.m112.3670602012J. Biol. Chem.28718359-18365SUBCELLULAR LOCATIONINTERACTION WITH SLAMF1Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.Kim J.Kim Y.C.Fang C.Russell R.C.Kim J.H.Fan W.Liu R.Zhong Q.Guan K.L.doi:10.1016/j.cell.2012.12.0162013Cell152290-303PHOSPHORYLATION AT THR-163 AND SER-165MUTAGENESIS OF THR-163 AND SER-165IDENTIFICATION IN A COMPLEX WITH PIK3R4; BECN1; UVRAG AND ATG14Functional interaction between autophagy and ciliogenesis.Pampliega O.Orhon I.Patel B.Sridhar S.Diaz-Carretero A.Beau I.Codogno P.Satir B.H.Satir P.Cuervo A.M.doi:10.1038/nature126392013Nature502194-200SUBCELLULAR LOCATIONAutophagic elimination of ribosomes during spermiogenesis provides energy for flagellar motility.Lei Y.Zhang X.Xu Q.Liu S.Li C.Jiang H.Lin H.Kong E.Liu J.Qi S.Li H.Xu W.Lu K.doi:10.1016/j.devcel.2021.07.0152021Dev. Cell562313-2328INTERACTION WITH ARMC321Phosphatidylinositol 3-kinase complex, class III, ATG14 variantPhosphatidylinositol 3-kinase complex, class III, UVRAG variant81035 antibodies from 39 providersmousePik3c3Eukaryota3474PI3K CascadeMacroautophagySynthesis of PIPs at the Golgi membraneSynthesis of PIPs at the early endosome membraneSynthesis of PIPs at the late endosome membraneToll Like Receptor 9 (TLR9) CascadeRHO GTPases Activate NADPH Oxidases33 hits in 80 CRISPR screensmouseProteinExpressed in orbitosphenoid and 288 other cell types or tissuesbaseline and differentialMMC2_PI3K_class_IIIPI3Ka_IIIPI3Kc_IIIC2 domainPhosphatidylinositol 3-/4-kinase, catalytic domainPhosphatidylinositol 3-kinase, accessory domain (PIK)ARM-type_foldC2_domain_sfKinase-like_dom_sfPI3/4_kinase_cat_domPI3/4_kinase_cat_sfPI3/4_kinase_CSPI3K-type_C2_domPI3K_accessory_domPI3K_accessory_sfPI3K_Vps34PI_KinasePHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT TYPE 3PHOSPHATIDYLINOSITOL KINASEPI3_PI4_kinasePI3K_C2PI3KaPI3K_Vps34PI3K_C2PI3KaPI3KcARM repeatC2 domain (Calcium/lipid-binding domain, CaLB)Protein kinase-like (PK-like)C2_PI3KPI3_4_KINASE_1PI3_4_KINASE_2PI3_4_KINASE_3PIK_HELICALPhosphatidylinositol 3-kinase catalytic subunit type 3PI3-kinase type 3PI3K type 3PtdIns-3-kinase type 32.7.1.137Phosphoinositide-3-kinase class 3Pik3c3Vps34Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity).Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (By similarity). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:17589504). PI3KC3-C1 probably associates with PIK3CB (PubMed:21059846). Interacts with RAB7A in the presence of PIK3R4 (By similarity). Interacts with AMBRA1 (PubMed:17589504). Interacts with BECN1P1/BECN2 (By similarity). Interacts with SLAMF1 (PubMed:22493499). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with NCKAP1L (By similarity). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (By similarity). Interacts with YWHAG (By similarity). Interacts with ARMC3 (PubMed:34428398).As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (By similarity). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (PubMed:24089209).Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by UBE3C, promoting its degradation. Deubiquitination by ZRANB1/TRABID promotes its stabilization, leading to autophagosome maturation.Belongs to the PI3/PI4-kinase family.Phosphatidylinositol 3-kinase catalytic subunit type 31014871887C2 PI3K-type35184PIK helical283520PI3K/PI4K catalytic605871Disordered149170Disordered415466G-loop611617Catalytic loop740748Activation loop759780Polar residues418449Phosphothreonine; by AMPK163Phosphoserine; by AMPK165Phosphoserine244Phosphoserine261Phosphoserine282In isoform 2.ISCHRKM842848In isoform 2.849Loss of phosphorylation but no loss of autophagic function; when associated with A-165.ALoss of phosphorylation but no loss of autophagic function; when associated with A-163.A455S470false6false4Becn1Gja12004-07-0511014875ef68ab14f4f25a740dd945f3243894e1MGEAEKFHYIYSCDLDINVQLKIGSLEGKREQKSYKAVLEDPMLKFSGLYQETCSDLYVTCQVFAEGKPLALPVRTSYKAFSTRWNWNEWLKLPVKYPDLPRNAQVALTIWDVYGPGSAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTRTPGRTSSTLSEDQMSRLAKLTKAHRQGHMVKVDWLDRLTFREIEMINESEKRSSNFMYLMVEFRCVKCDDKEYGIVYYEKDGDESSPILTSFELVKVPDPQMSMENLVESKHHKLARSLRSGPSDHDLKPNATTRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKKDSQTSASESLSNSGVSSGDIDSSQIITNPLPPVASPPPASKAKEVSDGENLEQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQALLKGDKSVRVMRSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSETGPYGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQYWRK2MGEAEKFHYIYSCDLDINVQLKIGSLEGKREQKSYKAVLEDPMLKFSGLYQETCSDLYVTCQVFAEGKPLALPVRTSYKAFSTRWNWNEWLKLPVKYPDLPRNAQVALTIWDVYGPGSAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTRTPGRTSSTLSEDQMSRLAKLTKAHRQGHMVKVDWLDRLTFREIEMINESEKRSSNFMYLMVEFRCVKCDDKEYGIVYYEKDGDESSPILTSFELVKVPDPQMSMENLVESKHHKLARSLRSGPSDHDLKPNATTRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKKDSQTSASESLSNSGVSSGDIDSSQIITNPLPPVASPPPASKAKEVSDGENLEQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQALLKGDKSVRVMRSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSETGPYGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVKKISCHRKMtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue