ID BECN1_HUMAN Reviewed; 450 AA. AC Q14457; B2R6N7; O75595; Q9UNA8; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 2. DT 27-MAR-2024, entry version 217. DE RecName: Full=Beclin-1; DE AltName: Full=Coiled-coil myosin-like BCL2-interacting protein; DE AltName: Full=Protein GT197; DE Contains: DE RecName: Full=Beclin-1-C 35 kDa {ECO:0000303|PubMed:21364619}; DE Contains: DE RecName: Full=Beclin-1-C 37 kDa {ECO:0000303|PubMed:21364619}; GN Name=BECN1; Synonyms=GT197; 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], AND INTERACTION WITH BCL-2. RC TISSUE=Brain; RX PubMed=9765397; DOI=10.1128/jvi.72.11.8586-8596.1998; RA Liang X.H., Kleeman L.K., Jiang H.H., Gordon G., Goldman J.E., Berry G., RA Herman B., Levine B.; RT "Protection against fatal Sindbis virus encephalitis by beclin, a novel RT Bcl-2-interacting protein."; RL J. Virol. 72:8586-8596(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10395800; DOI=10.1006/geno.1999.5851; RA Aita V.M., Liang X.H., Murty V.V.V.S., Pincus D.L., Yu W., Cayanis E., RA Kalachikov S., Gilliam T.C., Levine B.; RT "Cloning and genomic organization of beclin 1, a candidate tumor suppressor RT gene on chromosome 17q21."; RL Genomics 59:59-65(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 150-450. RC TISSUE=Mammary gland; RX PubMed=7490091; DOI=10.1006/geno.1995.1185; RA Rommens J.M., Durocher F., McArthur J., Tonin P., Leblanc J.-F., Allen T., RA Samson C., Ferri L., Narod S., Morgan K., Simard J.; RT "Generation of a transcription map at the HSD17B locus centromeric to BRCA1 RT at 17q21."; RL Genomics 28:530-542(1995). RN [6] RP INTERACTION WITH BCL2, AND MUTAGENESIS OF PHE-123. RX PubMed=16179260; DOI=10.1016/j.cell.2005.07.002; RA Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., RA Packer M., Schneider M.D., Levine B.; RT "Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy."; RL Cell 122:927-939(2005). RN [7] RP INTERACTION WITH BCL2L1, AND MUTAGENESIS OF LEU-116 AND PHE-123. RX PubMed=17446862; DOI=10.1038/sj.emboj.7601689; RA Maiuri M.C., Le Toumelin G., Criollo A., Rain J.C., Gautier F., Juin P., RA Tasdemir E., Pierron G., Troulinaki K., Tavernarakis N., Hickman J.A., RA Geneste O., Kroemer G.; RT "Functional and physical interaction between Bcl-X(L) and a BH3-like domain RT in Beclin-1."; RL EMBO J. 26:2527-2539(2007). RN [8] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP34.5 (MICROBIAL RP INFECTION). RX PubMed=18005679; DOI=10.1016/j.chom.2006.12.001; RA Orvedahl A., Alexander D., Talloczy Z., Sun Q., Wei Y., Zhang W., Burns D., RA Leib D.A., Levine B.; RT "HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy RT protein."; RL Cell Host Microbe 1:23-35(2007). RN [9] RP INTERACTION WITH ATG14; PIK3C3; PIK3R4 AND UVRAG. RX PubMed=18843052; DOI=10.1091/mbc.e08-01-0080; RA Itakura E., Kishi C., Inoue K., Mizushima N.; RT "Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with RT mammalian Atg14 and UVRAG."; RL Mol. Biol. Cell 19:5360-5372(2008). RN [10] RP FUNCTION, AND INTERACTION WITH BCL2. RX PubMed=18570871; DOI=10.1016/j.molcel.2008.06.001; RA Wei Y., Pattingre S., Sinha S., Bassik M., Levine B.; RT "JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced RT autophagy."; RL Mol. Cell 30:678-688(2008). RN [11] RP IDENTIFICATION BY 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 [12] RP INTERACTION WITH VMP1. RX PubMed=17724469; DOI=10.1038/sj.onc.1210743; RA Sauermann M., Sahin O., Sultmann H., Hahne F., Blaszkiewicz S., Majety M., RA Zatloukal K., Fuzesi L., Poustka A., Wiemann S., Arlt D.; RT "Reduced expression of vacuole membrane protein 1 affects the invasion RT capacity of tumor cells."; RL Oncogene 27:1320-1326(2008). RN [13] RP INTERACTION WITH ATG14; PIK3C3 AND UVRAG, AND SUBCELLULAR LOCATION. RX PubMed=19050071; DOI=10.1073/pnas.0810452105; RA Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.; RT "Identification of Barkor as a mammalian autophagy-specific factor for RT Beclin 1 and class III phosphatidylinositol 3-kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008). RN [14] RP PHOSPHORYLATION AT THR-119, AND INTERACTION WITH DAPK1. RX PubMed=19180116; DOI=10.1038/embor.2008.246; RA Zalckvar E., Berissi H., Mizrachy L., Idelchuk Y., Koren I., Eisenstein M., RA Sabanay H., Pinkas-Kramarski R., Kimchi A.; RT "DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes RT dissociation of beclin 1 from Bcl-XL and induction of autophagy."; RL EMBO Rep. 10:285-292(2009). RN [15] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP34.5 (MICROBIAL RP INFECTION). RX PubMed=19759141; DOI=10.1128/jvi.01676-09; RA Leib D.A., Alexander D.E., Cox D., Yin J., Ferguson T.A.; RT "Interaction of ICP34.5 with Beclin 1 modulates herpes simplex virus type 1 RT pathogenesis through control of CD4+ T-cell responses."; RL J. Virol. 83:12164-12171(2009). RN [16] 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 [17] 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 [18] RP INTERACTION WITH ATG14; RUBCN; PIK3C3; PIK3R4 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 [19] RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF RP ASP-149. RX PubMed=19713971; DOI=10.1038/cdd.2009.121; RA Luo S., Rubinsztein D.C.; RT "Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect RT rescued by Bcl-xL."; RL Cell Death Differ. 17:268-277(2010). RN [20] RP FUNCTION, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-133 AND ASP-149. RX PubMed=21364619; DOI=10.1038/cddis.2009.16; RA Wirawan E., Vande Walle L., Kersse K., Cornelis S., Claerhout S., RA Vanoverberghe I., Roelandt R., De Rycke R., Verspurten J., Declercq W., RA Agostinis P., Vanden Berghe T., Lippens S., Vandenabeele P.; RT "Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced RT autophagy and enhances apoptosis by promoting the release of proapoptotic RT factors from mitochondria."; RL Cell Death Dis. 1:E18-E18(2010). RN [21] RP INTERACTION WITH HMGB1. RX PubMed=20819940; DOI=10.1083/jcb.200911078; RA Tang D., Kang R., Livesey K.M., Cheh C.W., Farkas A., Loughran P., RA Hoppe G., Bianchi M.E., Tracey K.J., Zeh H.J. III, Lotze M.T.; RT "Endogenous HMGB1 regulates autophagy."; RL J. Cell Biol. 190:881-892(2010). RN [22] RP FUNCTION. RX PubMed=20208530; DOI=10.1038/ncb2036; RA Sagona A.P., Nezis I.P., Pedersen N.M., Liestol K., Poulton J., RA Rusten T.E., Skotheim R.I., Raiborg C., Stenmark H.; RT "PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of RT FYVE-CENT to the midbody."; RL Nat. Cell Biol. 12:362-371(2010). RN [23] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-133 AND ASP-146. RX PubMed=21444671; DOI=10.1158/0008-5472.can-10-4475; RA Li H., Wang P., Sun Q., Ding W.X., Yin X.M., Sobol R.W., Stolz D.B., Yu J., RA Zhang L.; RT "Following cytochrome c release, autophagy is inhibited during RT chemotherapy-induced apoptosis by caspase 8-mediated cleavage of Beclin RT 1."; RL Cancer Res. 71:3625-3634(2011). RN [24] RP UBIQUITINATION, AND INTERACTION WITH USP10 AND USP13. RX PubMed=21962518; DOI=10.1016/j.cell.2011.08.037; RA Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V., RA Zhang T., Furuya T., Jin M., Zhu Z., Wang H., Yu J., Li Y., Hao Y., RA Choi A., Ke H., Ma D., Yuan J.; RT "Beclin1 controls the levels of p53 by regulating the deubiquitination RT activity of USP10 and USP13."; RL Cell 147:223-234(2011). RN [25] RP FUNCTION, AND INTERACTION WITH BCL2 AND AMBRA1. RX PubMed=21358617; DOI=10.1038/emboj.2011.49; RA Strappazzon F., Vietri-Rudan M., Campello S., Nazio F., Florenzano F., RA Fimia G.M., Piacentini M., Levine B., Cecconi F.; RT "Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy."; RL EMBO J. 30:1195-1208(2011). RN [26] RP INTERACTION WITH BCL2L10 AND BCL2L1, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF PHE-123. RX PubMed=22498477; DOI=10.4161/auto.19084; RA Robert G., Gastaldi C., Puissant A., Hamouda A., Jacquel A., Dufies M., RA Belhacene N., Colosetti P., Reed J.C., Auberger P., Luciano F.; RT "The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell RT death."; RL Autophagy 8:637-649(2012). RN [27] RP UBIQUITINATION BY NEDD4, AND MUTAGENESIS OF TYR-352. RX PubMed=21936852; DOI=10.1042/bj20111424; RA Platta H.W., Abrahamsen H., Thoresen S.B., Stenmark H.; RT "Nedd4-dependent lysine-11-linked polyubiquitination of the tumour RT suppressor Beclin 1."; RL Biochem. J. 441:399-406(2012). RN [28] RP INTERACTION WITH SLAMF1. RX PubMed=22493499; DOI=10.1074/jbc.m112.367060; RA Ma C., Wang N., Detre C., Wang G., O'Keeffe M., Terhorst C.; RT "Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) RT regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting RT a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) RT complex."; RL J. Biol. Chem. 287:18359-18365(2012). RN [29] RP INTERACTION WITH HHV-5 PROTEIN TRS1 (MICROBIAL INFECTION). RX PubMed=22205736; DOI=10.1128/jvi.05746-11; RA Chaumorcel M., Lussignol M., Mouna L., Cavignac Y., Fahie K., RA Cotte-Laffitte J., Geballe A., Brune W., Beau I., Codogno P., Esclatine A.; RT "The human cytomegalovirus protein TRS1 inhibits autophagy via its RT interaction with Beclin 1."; RL J. Virol. 86:2571-2584(2012). RN [30] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [31] RP FUNCTION, INTERACTION WITH WASHC1, UBIQUITINATION AT LYS-437, AND RP MUTAGENESIS OF LYS-117 AND LYS-437. RX PubMed=23974797; DOI=10.1038/emboj.2013.189; RA Xia P., Wang S., Du Y., Zhao Z., Shi L., Sun L., Huang G., Ye B., Li C., RA Dai Z., Hou N., Cheng X., Sun Q., Li L., Yang X., Fan Z.; RT "WASH inhibits autophagy through suppression of Beclin 1 ubiquitination."; RL EMBO J. 32:2685-2696(2013). RN [32] RP FUNCTION. RX PubMed=23184933; DOI=10.1074/jbc.m112.412783; RA Margariti A., Li H., Chen T., Martin D., Vizcay-Barrena G., Alam S., RA Karamariti E., Xiao Q., Zampetaki A., Zhang Z., Wang W., Jiang Z., Gao C., RA Ma B., Chen Y.G., Cockerill G., Hu Y., Xu Q., Zeng L.; RT "XBP1 mRNA splicing triggers an autophagic response in endothelial cells RT through BECLIN-1 transcriptional activation."; RL J. Biol. Chem. 288:859-872(2013). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, 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 [34] RP PHOSPHORYLATION AT SER-90 AND SER-93, MUTAGENESIS OF SER-90; SER-93 AND RP TRP-425, SUBCELLULAR LOCATION, MEMBRANE-SPANNING REGION, AND INTERACTION RP WITH PIK3C3; PIK3R4; UVRAG AND ATG14. 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 [35] RP INTERACTION WITH RAB39A. RX PubMed=24349490; DOI=10.1371/journal.pone.0083324; RA Seto S., Sugaya K., Tsujimura K., Nagata T., Horii T., Koide Y.; RT "Rab39a interacts with phosphatidylinositol 3-kinase and negatively RT regulates autophagy induced by lipopolysaccharide stimulation in RT macrophages."; RL PLoS ONE 8:E83324-E83324(2013). RN [36] RP INTERACTION WITH TRIM5. RX PubMed=25127057; DOI=10.1016/j.devcel.2014.06.013; RA Mandell M.A., Jain A., Arko-Mensah J., Chauhan S., Kimura T., Dinkins C., RA Silvestri G., Munch J., Kirchhoff F., Simonsen A., Wei Y., Levine B., RA Johansen T., Deretic V.; RT "TRIM proteins regulate autophagy and can target autophagic substrates by RT direct recognition."; RL Dev. Cell 30:394-409(2014). RN [37] RP FUNCTION. RX PubMed=25275521; DOI=10.1371/journal.pgen.1004626; RA McKnight N.C., Zhong Y., Wold M.S., Gong S., Phillips G.R., Dou Z., RA Zhao Y., Heintz N., Zong W.X., Yue Z.; RT "Beclin 1 is required for neuron viability and regulates endosome pathways RT via the UVRAG-VPS34 complex."; RL PLoS Genet. 10:E1004626-E1004626(2014). RN [38] RP FUNCTION, AND UBIQUITINATION BY RNF216. RX PubMed=25484083; DOI=10.4161/15548627.2014.981792; RA Xu C., Feng K., Zhao X., Huang S., Cheng Y., Qian L., Wang Y., Sun H., RA Jin M., Chuang T.H., Zhang Y.; RT "Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 RT ubiquitination."; RL Autophagy 10:2239-2250(2014). RN [39] 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 [40] RP INTERACTION WITH PPP2CA AND AMBRA1. RX PubMed=25803737; DOI=10.1080/15384101.2015.1021526; RA Cianfanelli V., D'Orazio M., Cecconi F.; RT "AMBRA1 and BECLIN 1 interplay in the crosstalk between autophagy and cell RT proliferation."; RL Cell Cycle 14:959-963(2015). RN [41] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-133 AND ASP-149. RX PubMed=26263979; DOI=10.3390/ijms160817611; RA Siddiqui M.A., Mukherjee S., Manivannan P., Malathi K.; RT "RNase L cleavage products promote switch from autophagy to apoptosis by RT caspase-mediated cleavage of beclin-1."; RL Int. J. Mol. Sci. 16:17611-17636(2015). RN [42] RP INTERACTION WITH MEFV; TRIM21 AND ULK1. RX PubMed=26347139; DOI=10.1083/jcb.201503023; RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T., RA Deretic V.; RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate RT immunity."; RL J. Cell Biol. 210:973-989(2015). RN [43] RP INTERACTION WITH IRGM, AND PHOSPHORYLATION AT SER-93 AND SER-96. RX PubMed=25891078; DOI=10.1016/j.molcel.2015.03.020; RA Chauhan S., Mandell M.A., Deretic V.; RT "IRGM governs the core autophagy machinery to conduct antimicrobial RT defense."; RL Mol. Cell 58:507-521(2015). RN [44] RP INTERACTION WITH TRIM16. RX PubMed=27693506; DOI=10.1016/j.devcel.2016.08.003; RA Chauhan S., Kumar S., Jain A., Ponpuak M., Mudd M.H., Kimura T., Choi S.W., RA Peters R., Mandell M., Bruun J.A., Johansen T., Deretic V.; RT "TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct RT Autophagy in Endomembrane Damage Homeostasis."; RL Dev. Cell 39:13-27(2016). RN [45] RP FUNCTION, AND INTERACTION WITH WDR81 AND WDR91. RX PubMed=26783301; DOI=10.1083/jcb.201506081; RA Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J., RA Jing Y., Mitani S., He S., Yang C.; RT "Negative regulation of phosphatidylinositol 3-phosphate levels in early- RT to-late endosome conversion."; RL J. Cell Biol. 212:181-198(2016). RN [46] RP INTERACTION WITH TRIM17. RX PubMed=27562068; DOI=10.1242/jcs.190017; RA Mandell M.A., Jain A., Kumar S., Castleman M.J., Anwar T., Eskelinen E.L., RA Johansen T., Prekeris R., Deretic V.; RT "TRIM17 contributes to autophagy of midbodies while actively sparing other RT targets from degradation."; RL J. Cell Sci. 129:3562-3573(2016). RN [47] RP INTERACTION WITH LAPTM4B. RX PubMed=28479384; DOI=10.1016/j.gene.2017.05.006; RA Tian M., Chen Y., Tian D., Qiao X., Ma Z., Li J.; RT "Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer RT cells."; RL Gene 626:48-53(2017). RN [48] RP INTERACTION WITH ATXN3, UBIQUITINATION AT LYS-402, DEUBIQUITINATION BY RP ATXN3, MUTAGENESIS OF LYS-402, DOMAIN, AND FUNCTION. RX PubMed=28445460; DOI=10.1038/nature22078; RA Ashkenazi A., Bento C.F., Ricketts T., Vicinanza M., Siddiqi F., Pavel M., RA Squitieri F., Hardenberg M.C., Imarisio S., Menzies F.M., Rubinsztein D.C.; RT "Polyglutamine tracts regulate beclin 1-dependent autophagy."; RL Nature 545:108-111(2017). RN [49] RP INTERACTION WITH TRIM50. RX PubMed=29604308; DOI=10.1016/j.bbamcr.2018.03.011; RA Fusco C., Mandriani B., Di Rienzo M., Micale L., Malerba N., RA Cocciadiferro D., Sjoettem E., Augello B., Squeo G.M., Pellico M.T., RA Jain A., Johansen T., Fimia G.M., Merla G.; RT "TRIM50 regulates Beclin 1 proautophagic activity."; RL Biochim. Biophys. Acta 1865:908-919(2018). RN [50] RP INTERACTION WITH ATG14. RX PubMed=31806350; DOI=10.1016/j.molcel.2019.10.035; RA Miao G., Zhang Y., Chen D., Zhang H.; RT "The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy RT by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1."; RL Mol. Cell 0:0-0(2019). RN [51] RP PHOSPHORYLATION AT SER-15. RX PubMed=31123703; DOI=10.1126/sciadv.aau8857; RA Di Rienzo M., Antonioli M., Fusco C., Liu Y., Mari M., Orhon I., Refolo G., RA Germani F., Corazzari M., Romagnoli A., Ciccosanti F., Mandriani B., RA Pellico M.T., De La Torre R., Ding H., Dentice M., Neri M., Ferlini A., RA Reggiori F., Kulesz-Martin M., Piacentini M., Merla G., Fimia G.M.; RT "Autophagy induction in atrophic muscle cells requires ULK1 activation by RT TRIM32 through unanchored K63-linked polyubiquitin chains."; RL Sci. Adv. 5:eaau8857-eaau8857(2019). RN [52] RP INTERACTION WITH SH3BGRL. RX PubMed=34870550; DOI=10.1080/15548627.2021.2002108; RA Zhang S., Liu X., Abdulmomen Ali Mohammed S., Li H., Cai W., Guan W., RA Liu D., Wei Y., Rong D., Fang Y., Haider F., Lv H., Jin Z., Chen X., Mo Z., RA Li L., Yang S., Wang H.; RT "Adaptor SH3BGRL drives autophagy-mediated chemoresistance through RT promoting PIK3C3 translation and ATG12 stability in breast cancers."; RL Autophagy 18:1-19(2021). RN [53] RP FUNCTION, AND INTERACTION WITH EPSTEIN-BARR VIRUS PROTEIN BHRF1 (MICROBIAL RP INFECTION). RX PubMed=37776275; DOI=10.1021/acs.biochem.3c00225; RA Wyatt S., Glover K., Dasanna S., Lewison M., Gonzalez-Garcia M., RA Colbert C.L., Sinha S.C.; RT "Epstein-Barr Virus Encoded BCL2, BHRF1, Downregulates Autophagy by RT Noncanonical Binding of BECN1."; RL Biochemistry 62:2934-2951(2023). RN [54] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 107-135 IN COMPLEX WITH BCL2L1, RP AND DOMAIN BH3 MOTIF. RX PubMed=17337444; DOI=10.1074/jbc.m700492200; RA Oberstein A., Jeffrey P.D., Shi Y.; RT "Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a RT novel BH3-only protein."; RL J. Biol. Chem. 282:13123-13132(2007). RN [55] RP STRUCTURE BY NMR OF 106-128 IN COMPLEX WITH BCL2L1. RX PubMed=17659302; DOI=10.1016/j.jmb.2007.06.069; RA Feng W., Huang S., Wu H., Zhang M.; RT "Molecular basis of Bcl-xL's target recognition versatility revealed by the RT structure of Bcl-xL in complex with the BH3 domain of beclin-1."; RL J. Mol. Biol. 372:223-235(2007). RN [56] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 105-130 IN COMPLEX WITH MUHV-4 M11 RP (MICROBIAL INFECTION), AND MUTAGENESIS OF LEU-112; LEU-116; GLY-120; RP ASP-121 AND PHE-123. RX PubMed=18797192; DOI=10.4161/auto.6803; RA Sinha S., Colbert C.L., Becker N., Wei Y., Levine B.; RT "Molecular basis of the regulation of Beclin 1-dependent autophagy by the RT gamma-herpesvirus 68 Bcl-2 homolog M11."; RL Autophagy 4:989-997(2008). RN [57] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 107-130 IN COMPLEX WITH MUHV-4 M11 RP (MICROBIAL INFECTION), AND MUTAGENESIS OF LEU-112; LEU-116; LYS-117; RP GLY-120; ASP-121 AND PHE-123. RX PubMed=24443581; DOI=10.1074/jbc.m113.515361; RA Su M., Mei Y., Sanishvili R., Levine B., Colbert C.L., Sinha S.; RT "Targeting gamma-herpesvirus 68 Bcl-2-mediated down-regulation of RT autophagy."; RL J. Biol. Chem. 289:8029-8040(2014). CC -!- FUNCTION: Plays a central role in autophagy (PubMed:18570871, CC PubMed:21358617, PubMed:23184933, PubMed:23974797, PubMed:28445460, CC PubMed:25484083, PubMed:37776275). Acts as a core subunit of the PI3K CC complex that mediates formation of phosphatidylinositol 3-phosphate; CC different complex forms are believed to play a role in multiple CC membrane trafficking pathways: PI3KC3-C1 is involved in initiation of CC autophagosomes and PI3KC3-C2 in maturation of autophagosomes and CC endocytosis. Involved in regulation of degradative endocytic CC trafficking and required for the abcission step in cytokinesis, CC probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530, CC PubMed:23974797, PubMed:26783301). Essential for the formation of CC PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis CC (PubMed:25275521). Protects against infection by a neurovirulent strain CC of Sindbis virus (PubMed:9765397). May play a role in antiviral host CC defense. {ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20208530, CC ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:21358617, CC ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23974797, CC ECO:0000269|PubMed:25275521, ECO:0000269|PubMed:25484083, CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460, CC ECO:0000269|PubMed:37776275, ECO:0000269|PubMed:9765397}. CC -!- FUNCTION: Beclin-1-C 35 kDa localized to mitochondria can promote CC apoptosis; it induces the mitochondrial translocation of BAX and the CC release of proapoptotic factors. {ECO:0000269|PubMed:21364619, CC ECO:0000269|PubMed:26263979}. CC -!- SUBUNIT: A homodimeric form is proposed to exist; this metastable form CC readily transits to ATG14- or UVRAG-containing complexes with CC BECN1:UVRAG being more stable than BECN1:ATG14 (By similarity). CC Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol CC 3-kinase) complex the core of which is composed of the catalytic CC subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating CC with additional regulatory/auxilliary subunits to form alternative CC complex forms. Alternative complex forms containing a forth regulatory CC subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) CC containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG. CC PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a CC bridge between PIK3C3 and the ATG14:BECN1 subcomplex (PubMed:18843052, CC PubMed:19050071, PubMed:19270696, PubMed:23878393, PubMed:25490155). CC Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory CC subunits, such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:20643123, CC PubMed:19270696). PI3KC3-C1 probably associates with PIK3CB (By CC similarity). Interacts with AMBRA1, GOPC, GRID2 (PubMed:21358617). CC Forms a complex with PPP2CA and AMBRA1; AMBRA1 and BECN1 components of CC the complex regulate MYC stability via different pathways CC (PubMed:25803737). Interacts with BCL2 and BCL2L1 isoform Bcl-X(L); the CC interaction inhibits BECN1 function in promoting autophagy by CC interfering with the formation of the PI3K complex (PubMed:9765397, CC PubMed:16179260, PubMed:17446862, PubMed:18570871, PubMed:21358617, CC PubMed:22498477, PubMed:17337444, PubMed:17659302). Interacts with CC cytosolic HMGB1; inhibits the interaction of BECN1 and BCL2 leading to CC promotion of autophagy (PubMed:20819940). Interacts with USP10, USP13, CC VMP1, DAPK1, RAB39A (PubMed:19180116, PubMed:17724469, PubMed:17337444, CC PubMed:21962518, PubMed:24349490). Interacts with the poly-Gln domain CC of ATXN3; the interaction causes deubiquitination at Lys-402 and CC stabilizes BECN1 (PubMed:28445460). Interacts with SLAMF1 CC (PubMed:22493499). Interacts with TRIM5; the interaction causes CC activation of BECN1 by causing its dissociation from its inhibitors CC BCL2 and TAB2 (PubMed:25127057). Interacts with active ULK1 CC (phosphorylated on 'Ser-317') and MEFV simultaneously CC (PubMed:26347139). Interacts with WDR81 and WDR91; negatively regulates CC the PI3 kinase/PI3K activity associated with endosomal membranes CC (PubMed:26783301). Interacts with LAPTM4B; competes with EGFR for CC LAPTM4B binding; regulates EGFR activity (PubMed:28479384). Interacts CC with TRIM50 (PubMed:29604308). Interacts with TRIM16. Interacts with CC ATG14; this interaction is increased in the absence of TMEM39A CC (PubMed:31806350). Interacts with WASHC1; preventing interaction with CC AMBRA1 and the DCX(AMBRA1) complex and subsequent ubiquitination CC (PubMed:23974797). Interacts with TRIM17 (PubMed:27562068). Interacts CC with BCL2L10/BCL-B (via BH1 domain) (PubMed:22498477). Interacts with CC SH3BGRL (PubMed:34870550). Interacts with IRGM; enhancing BECN1- CC interacting partners and influencing the composition of the BECN1 CC complex (PubMed:25891078). Interacts with ARMC3 (By similarity). CC {ECO:0000250|UniProtKB:O88597, ECO:0000250|UniProtKB:Q91XJ1, CC ECO:0000269|PubMed:16179260, ECO:0000269|PubMed:17337444, CC ECO:0000269|PubMed:17446862, ECO:0000269|PubMed:17659302, CC ECO:0000269|PubMed:17724469, ECO:0000269|PubMed:18570871, CC ECO:0000269|PubMed:18797192, ECO:0000269|PubMed:18843052, CC ECO:0000269|PubMed:19050071, ECO:0000269|PubMed:19180116, CC ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20643123, CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21358617, CC ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22493499, CC ECO:0000269|PubMed:22498477, ECO:0000269|PubMed:23878393, CC ECO:0000269|PubMed:24349490, ECO:0000269|PubMed:24443581, CC ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:25490155, CC ECO:0000269|PubMed:25803737, ECO:0000269|PubMed:25891078, CC ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:26783301, CC ECO:0000269|PubMed:27562068, ECO:0000269|PubMed:27693506, CC ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:28479384, CC ECO:0000269|PubMed:29604308, ECO:0000269|PubMed:31806350, CC ECO:0000269|PubMed:34870550, ECO:0000269|PubMed:9765397, ECO:0000305}. CC -!- SUBUNIT: (Microbial infection) Interacts with human CC cytomegalovirus/HHV-5 protein TRS1. {ECO:0000269|PubMed:22205736}. CC -!- SUBUNIT: (Microbial infection) Interacts with murine gammaherpesvirus CC 68 M11. {ECO:0000269|PubMed:18797192, ECO:0000269|PubMed:24443581}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC (HHV-1) protein ICP34.5; this interaction antagonizes the host CC autophagy response. {ECO:0000269|PubMed:18005679, CC ECO:0000269|PubMed:19759141}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus CC protein BHRF1; this interaction inhibits BECN1-mediated autophagy CC induction. {ECO:0000269|PubMed:37776275}. CC -!- INTERACTION: CC Q14457; Q9C0C7: AMBRA1; NbExp=9; IntAct=EBI-949378, EBI-2512975; CC Q14457; Q6ZNE5: ATG14; NbExp=47; IntAct=EBI-949378, EBI-2690371; CC Q14457; P54253: ATXN1; NbExp=6; IntAct=EBI-949378, EBI-930964; CC Q14457; P54252-1: ATXN3; NbExp=10; IntAct=EBI-949378, EBI-946068; CC Q14457; P46379-2: BAG6; NbExp=3; IntAct=EBI-949378, EBI-10988864; CC Q14457; P10415: BCL2; NbExp=18; IntAct=EBI-949378, EBI-77694; CC Q14457; Q07817-1: BCL2L1; NbExp=5; IntAct=EBI-949378, EBI-287195; CC Q14457; O15392: BIRC5; NbExp=3; IntAct=EBI-949378, EBI-518823; CC Q14457; P38398-6: BRCA1; NbExp=3; IntAct=EBI-949378, EBI-25833510; CC Q14457; P48643: CCT5; NbExp=3; IntAct=EBI-949378, EBI-355710; CC Q14457; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-949378, EBI-21553822; CC Q14457; P53355: DAPK1; NbExp=4; IntAct=EBI-949378, EBI-358616; CC Q14457; O75190-2: DNAJB6; NbExp=3; IntAct=EBI-949378, EBI-12593112; CC Q14457; O14645: DNALI1; NbExp=3; IntAct=EBI-949378, EBI-395638; CC Q14457; P00533: EGFR; NbExp=7; IntAct=EBI-949378, EBI-297353; CC Q14457; Q8IYI6: EXOC8; NbExp=4; IntAct=EBI-949378, EBI-742102; CC Q14457; P15311: EZR; NbExp=3; IntAct=EBI-949378, EBI-1056902; CC Q14457; P21333-2: FLNA; NbExp=3; IntAct=EBI-949378, EBI-9641086; CC Q14457; P01100: FOS; NbExp=3; IntAct=EBI-949378, EBI-852851; CC Q14457; P50440: GATM; NbExp=3; IntAct=EBI-949378, EBI-2552594; CC Q14457; P62993: GRB2; NbExp=3; IntAct=EBI-949378, EBI-401755; CC Q14457; P42261: GRIA1; NbExp=3; IntAct=EBI-949378, EBI-6980805; CC Q14457; P28799: GRN; NbExp=3; IntAct=EBI-949378, EBI-747754; CC Q14457; P09429: HMGB1; NbExp=2; IntAct=EBI-949378, EBI-389432; CC Q14457; P04792: HSPB1; NbExp=3; IntAct=EBI-949378, EBI-352682; CC Q14457; P42858: HTT; NbExp=14; IntAct=EBI-949378, EBI-466029; CC Q14457; O60333-2: KIF1B; NbExp=3; IntAct=EBI-949378, EBI-10975473; CC Q14457; O14901: KLF11; NbExp=3; IntAct=EBI-949378, EBI-948266; CC Q14457; P05783: KRT18; NbExp=2; IntAct=EBI-949378, EBI-297888; CC Q14457; Q13449: LSAMP; NbExp=3; IntAct=EBI-949378, EBI-4314821; CC Q14457; Q07820: MCL1; NbExp=2; IntAct=EBI-949378, EBI-1003422; CC Q14457; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-949378, EBI-398874; CC Q14457; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-949378, EBI-473160; CC Q14457; Q8NEB9: PIK3C3; NbExp=39; IntAct=EBI-949378, EBI-1056470; CC Q14457; Q16512: PKN1; NbExp=3; IntAct=EBI-949378, EBI-602382; CC Q14457; P60891: PRPS1; NbExp=3; IntAct=EBI-949378, EBI-749195; CC Q14457; Q14964: RAB39A; NbExp=2; IntAct=EBI-949378, EBI-3048577; CC Q14457; P63000: RAC1; NbExp=3; IntAct=EBI-949378, EBI-413628; CC Q14457; P10276-2: RARA; NbExp=3; IntAct=EBI-949378, EBI-10197061; CC Q14457; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-949378, EBI-396669; CC Q14457; Q92622: RUBCN; NbExp=15; IntAct=EBI-949378, EBI-2952709; CC Q14457; Q9H714-3: RUBCNL; NbExp=3; IntAct=EBI-949378, EBI-9088146; CC Q14457; Q96ES7: SGF29; NbExp=3; IntAct=EBI-949378, EBI-743117; CC Q14457; P14678-2: SNRPB; NbExp=3; IntAct=EBI-949378, EBI-372475; CC Q14457; P12931: SRC; NbExp=3; IntAct=EBI-949378, EBI-621482; CC Q14457; Q9NYJ8: TAB2; NbExp=11; IntAct=EBI-949378, EBI-358708; CC Q14457; Q8N5C8: TAB3; NbExp=9; IntAct=EBI-949378, EBI-359964; CC Q14457; P17752: TPH1; NbExp=3; IntAct=EBI-949378, EBI-3956833; CC Q14457; Q13885: TUBB2A; NbExp=3; IntAct=EBI-949378, EBI-711595; CC Q14457; P14679-2: TYR; NbExp=3; IntAct=EBI-949378, EBI-25894402; CC Q14457; P14927: UQCRB; NbExp=3; IntAct=EBI-949378, EBI-743128; CC Q14457; P31930: UQCRC1; NbExp=3; IntAct=EBI-949378, EBI-1052596; CC Q14457; Q9P2Y5: UVRAG; NbExp=45; IntAct=EBI-949378, EBI-2952704; CC Q14457; P61758: VBP1; NbExp=3; IntAct=EBI-949378, EBI-357430; CC Q14457; P08670: VIM; NbExp=3; IntAct=EBI-949378, EBI-353844; CC Q14457; Q96GC9: VMP1; NbExp=3; IntAct=EBI-949378, EBI-2800296; CC Q14457; A8K0Z3: WASHC1; NbExp=3; IntAct=EBI-949378, EBI-6160405; CC Q14457; O76024: WFS1; NbExp=3; IntAct=EBI-949378, EBI-720609; CC Q14457; O95229: ZWINT; NbExp=6; IntAct=EBI-949378, EBI-1001132; CC Q14457; Q2GJL5: ats-1; Xeno; NbExp=4; IntAct=EBI-949378, EBI-16025394; CC Q14457; P03407: nef; Xeno; NbExp=2; IntAct=EBI-949378, EBI-7355020; CC Q14457; PRO_0000283876 [P0C6X5]: rep; Xeno; NbExp=3; IntAct=EBI-949378, EBI-25622115; CC Q14457; Q9QUM4: Slamf1; Xeno; NbExp=8; IntAct=EBI-949378, EBI-7910086; CC Q14457; P89884: vBCL2; Xeno; NbExp=4; IntAct=EBI-949378, EBI-8849581; CC Q14457; Q91ZQ0: Vmp1; Xeno; NbExp=6; IntAct=EBI-949378, EBI-11163586; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19713971, CC ECO:0000269|PubMed:21364619, ECO:0000269|PubMed:22498477, CC ECO:0000269|PubMed:25484083}. Golgi apparatus, trans-Golgi network CC membrane {ECO:0000269|PubMed:19050071}; Peripheral membrane protein CC {ECO:0000269|PubMed:19050071}. Endosome membrane CC {ECO:0000269|PubMed:23878393}; Peripheral membrane protein CC {ECO:0000269|PubMed:23878393}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:23878393}; Peripheral membrane protein CC {ECO:0000269|PubMed:23878393}. Mitochondrion membrane CC {ECO:0000269|PubMed:23878393}; Peripheral membrane protein CC {ECO:0000269|PubMed:23878393}. Endosome {ECO:0000250|UniProtKB:O88597}. CC Cytoplasmic vesicle, autophagosome {ECO:0000305}. Note=Interaction with CC ATG14 promotes translocation to autophagosomes. Expressed in dendrites CC and cell bodies of cerebellar Purkinje cells (By similarity). CC {ECO:0000250|UniProtKB:O88597, ECO:0000269|PubMed:19050071}. CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 35 kDa]: Mitochondrion CC {ECO:0000269|PubMed:21364619, ECO:0000269|PubMed:26263979}. Nucleus CC {ECO:0000269|PubMed:19713971}. Cytoplasm {ECO:0000269|PubMed:19713971}. CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 37 kDa]: Mitochondrion CC {ECO:0000250|UniProtKB:O88597}. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DOMAIN: The coiled coil domain can form antiparallel homodimers and CC mediates dimerization with the coiled coil domains of ATG14 or UVRAG CC involved in the formation of PI3K complexes. CC {ECO:0000250|UniProtKB:Q91XJ1}. CC -!- DOMAIN: The C-terminal evolutionary conserved domain (ECD) contains CC poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent CC with structural docking models revealing two highly scored poly-Gln- CC binding pockets in the ECD (PubMed:28445460). As some binding is CC observed with BECN1 lacking the ECD, other domains of BECN1 may also CC interact with ATXN3 (PubMed:28445460). {ECO:0000269|PubMed:28445460}. CC -!- PTM: Phosphorylation at Thr-119 by DAPK1 reduces its interaction with CC BCL2 and BCL2L1 and promotes induction of autophagy (PubMed:19180116). CC In response to autophagic stimuli, phosphorylated at serine residues by CC AMPK in an ATG14-dependent manner, and this phosphorylation is critical CC for maximally efficient autophagy (PubMed:23878393, PubMed:25891078). CC {ECO:0000269|PubMed:19180116, ECO:0000269|PubMed:23878393, CC ECO:0000269|PubMed:25891078}. CC -!- PTM: Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'- CC linkages (PubMed:21936852). 'Lys-11'-linked polyubiquitination leads to CC degradation and is enhanced when the stabilizing interaction partner CC VPS34 is depleted (PubMed:21936852). Deubiquitinated by USP10 and CC USP13, leading to stabilize the PIK3C3/VPS34-containing complexes CC (PubMed:21962518). Polyubiquitinated at Lys-402 with 'Lys-48'-linkages CC (PubMed:28445460). 'Lys-48'-linked polyubiquitination of Lys-402 leads CC to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to CC stabilization (PubMed:28445460). Ubiquitinated at Lys-437 via 'Lys-63'- CC linkage by the DCX(AMBRA1) complex, thereby increasing the association CC between BECN1 and PIK3C3 to promote PIK3C3 activity (PubMed:23974797). CC 'Lys-48'-linked ubiquitination by RNF216 leads to proteasomal CC degradation and autophagy inhibition (PubMed:25484083). CC {ECO:0000269|PubMed:21936852, ECO:0000269|PubMed:21962518, CC ECO:0000269|PubMed:23974797, ECO:0000269|PubMed:25484083, CC ECO:0000269|PubMed:28445460}. CC -!- PTM: Proteolytically processed by caspases including CASP8 and CASP3; CC the C-terminal fragments lack autophagy-inducing capacity and are CC proposed to induce apoptosis. Thus the cleavage is proposed to be an CC determinant to switch from autophagy to apoptosis pathways affecting CC cellular homeostasis including viral infections and survival of tumor CC cells. {ECO:0000305|PubMed:19713971, ECO:0000305|PubMed:21364619}. CC -!- MISCELLANEOUS: Expanded poly-Gln tracts inhibit ATXN3-BECN1 CC interaction, decrease BECN1 levels and impair starvation-induced CC autophagy (PubMed:28445460). {ECO:0000269|PubMed:28445460}. CC -!- SIMILARITY: Belongs to the beclin family. {ECO:0000305}. 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; AF077301; AAC68653.1; -; mRNA. DR EMBL; AF139131; AAD27650.1; -; mRNA. DR EMBL; AK312651; BAG35534.1; -; mRNA. DR EMBL; BC010276; AAH10276.1; -; mRNA. DR EMBL; L38932; AAB59573.1; -; mRNA. DR CCDS; CCDS11441.1; -. DR PIR; I54209; I54209. DR RefSeq; NP_001300927.1; NM_001313998.1. DR RefSeq; NP_001300928.1; NM_001313999.1. DR RefSeq; NP_001300929.1; NM_001314000.1. DR RefSeq; NP_003757.1; NM_003766.4. DR PDB; 2P1L; X-ray; 2.50 A; B/D/F/H=107-135. DR PDB; 2PON; NMR; -; A=106-128. DR PDB; 3DVU; X-ray; 2.50 A; C/D=105-130. DR PDB; 4DDP; X-ray; 1.55 A; A=241-450. DR PDB; 4MI8; X-ray; 2.10 A; C/D=107-130. DR PDB; 5EFM; X-ray; 1.95 A; A=141-171. DR PDB; 5HHE; X-ray; 1.46 A; A/D=175-265. DR PDB; 5VAU; X-ray; 1.75 A; E/F/G/H=105-130. DR PDB; 5VAX; X-ray; 2.00 A; E/F/G/H=105-130. DR PDB; 5VAY; X-ray; 1.80 A; E/F/G/H=105-130. DR PDB; 6DCN; X-ray; 2.44 A; C/D=105-130. DR PDB; 6DCO; X-ray; 2.20 A; C/D=105-130. DR PDB; 6HOI; X-ray; 1.14 A; F/G=93-102. DR PDB; 6HOJ; X-ray; 1.51 A; A/B/C=93-105. DR PDB; 6HOK; X-ray; 1.61 A; A=93-105. DR PDB; 7BL1; EM; 9.80 A; EEE=1-450. DR PDB; 8SOR; EM; 3.96 A; D=1-450. DR PDB; 8SRQ; EM; 6.20 A; Z=149-449. DR PDBsum; 2P1L; -. DR PDBsum; 2PON; -. DR PDBsum; 3DVU; -. DR PDBsum; 4DDP; -. DR PDBsum; 4MI8; -. DR PDBsum; 5EFM; -. DR PDBsum; 5HHE; -. DR PDBsum; 5VAU; -. DR PDBsum; 5VAX; -. DR PDBsum; 5VAY; -. DR PDBsum; 6DCN; -. DR PDBsum; 6DCO; -. DR PDBsum; 6HOI; -. DR PDBsum; 6HOJ; -. DR PDBsum; 6HOK; -. DR PDBsum; 7BL1; -. DR PDBsum; 8SOR; -. DR PDBsum; 8SRQ; -. DR AlphaFoldDB; Q14457; -. DR EMDB; EMD-12214; -. DR EMDB; EMD-12237; -. DR EMDB; EMD-12238; -. DR EMDB; EMD-2846; -. DR EMDB; EMD-40669; -. DR EMDB; EMD-40738; -. DR SASBDB; Q14457; -. DR SMR; Q14457; -. DR BioGRID; 114226; 205. 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; Q14457; -. DR DIP; DIP-44611N; -. DR ELM; Q14457; -. DR IntAct; Q14457; 154. DR MINT; Q14457; -. DR STRING; 9606.ENSP00000355231; -. DR BindingDB; Q14457; -. DR ChEMBL; CHEMBL4296010; -. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB13952; Estradiol acetate. DR DrugBank; DB13953; Estradiol benzoate. DR DrugBank; DB13954; Estradiol cypionate. DR DrugBank; DB13955; Estradiol dienanthate. DR DrugBank; DB13956; Estradiol valerate. DR MoonDB; Q14457; Predicted. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR GlyGen; Q14457; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14457; -. DR PhosphoSitePlus; Q14457; -. DR BioMuta; BECN1; -. DR DMDM; 13124704; -. DR EPD; Q14457; -. DR jPOST; Q14457; -. DR MassIVE; Q14457; -. DR MaxQB; Q14457; -. DR PaxDb; 9606-ENSP00000355231; -. DR PeptideAtlas; Q14457; -. DR ProteomicsDB; 59999; -. DR Pumba; Q14457; -. DR Antibodypedia; 4116; 1882 antibodies from 47 providers. DR DNASU; 8678; -. DR Ensembl; ENST00000361523.8; ENSP00000355231.3; ENSG00000126581.13. DR Ensembl; ENST00000590099.6; ENSP00000465364.1; ENSG00000126581.13. DR GeneID; 8678; -. DR KEGG; hsa:8678; -. DR MANE-Select; ENST00000590099.6; ENSP00000465364.1; NM_001313998.2; NP_001300927.1. DR UCSC; uc002ibn.3; human. DR AGR; HGNC:1034; -. DR CTD; 8678; -. DR DisGeNET; 8678; -. DR GeneCards; BECN1; -. DR HGNC; HGNC:1034; BECN1. DR HPA; ENSG00000126581; Low tissue specificity. DR MIM; 604378; gene. DR neXtProt; NX_Q14457; -. DR OpenTargets; ENSG00000126581; -. DR PharmGKB; PA25337; -. DR VEuPathDB; HostDB:ENSG00000126581; -. DR eggNOG; KOG2751; Eukaryota. DR GeneTree; ENSGT00390000008164; -. DR HOGENOM; CLU_024219_4_1_1; -. DR InParanoid; Q14457; -. DR OMA; EWDVYKA; -. DR OrthoDB; 11439at2759; -. DR PhylomeDB; Q14457; -. DR TreeFam; TF314282; -. DR PathwayCommons; Q14457; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. 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; Q14457; -. DR SIGNOR; Q14457; -. DR BioGRID-ORCS; 8678; 88 hits in 1172 CRISPR screens. DR ChiTaRS; BECN1; human. DR EvolutionaryTrace; Q14457; -. DR GeneWiki; BECN1; -. DR GenomeRNAi; 8678; -. DR Pharos; Q14457; Tbio. DR PRO; PR:Q14457; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q14457; Protein. DR Bgee; ENSG00000126581; Expressed in rectum and 208 other cell types or tissues. DR ExpressionAtlas; Q14457; baseline and differential. DR GO; GO:0005776; C:autophagosome; ISS:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:ParkinsonsUK-UCL. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl. DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central. 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:0005802; C:trans-Golgi network; IEA:Ensembl. DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProt. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0050435; P:amyloid-beta metabolic process; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProt. DR GO; GO:0097352; P:autophagosome maturation; IDA:ComplexPortal. DR GO; GO:0006914; P:autophagy; IDA:CAFA. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0071275; P:cellular response to aluminum ion; IEA:Ensembl. DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl. DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl. DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central. DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEA:Ensembl. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProt. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0045022; P:early endosome to late endosome transport; IDA:ComplexPortal. DR GO; GO:0043652; P:engulfment of apoptotic cell; IEA:Ensembl. DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl. DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central. DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl. DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB. DR GO; GO:0000423; P:mitophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0007080; P:mitotic metaphase chromosome alignment; IMP:CACAO. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc. DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:1905672; P:negative regulation of lysosome organization; IEA:Ensembl. DR GO; GO:0043069; P:negative regulation of programmed cell death; IMP:MGI. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0038066; P:p38MAPK cascade; IEA:Ensembl. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:ComplexPortal. DR GO; GO:1902425; P:positive regulation of attachment of mitotic spindle microtubules to kinetochore; IMP:CACAO. DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IEA:Ensembl. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IEA:Ensembl. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; NAS:ParkinsonsUK-UCL. DR GO; GO:0006622; P:protein targeting to lysosome; NAS:ComplexPortal. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProt. 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 GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl. DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl. DR GO; GO:0098780; P:response to mitochondrial depolarisation; IMP:BHF-UCL. DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl. DR GO; GO:0039521; P:suppression by virus of host autophagy; IDA:DisProt. DR DisProt; DP01149; -. DR Gene3D; 6.10.250.3110; -; 1. DR Gene3D; 1.10.418.40; Autophagy protein 6/Beclin 1; 1. DR IDEAL; IID00669; -. DR InterPro; IPR007243; Atg6/Beclin. DR InterPro; IPR038274; Atg6/Beclin_C_sf. DR InterPro; IPR041691; Atg6/beclin_CC. DR InterPro; IPR040455; Atg6_BARA. DR InterPro; IPR029318; BH3_dom. DR PANTHER; PTHR12768; BECLIN 1; 1. DR PANTHER; PTHR12768:SF6; BECLIN-1; 1. DR Pfam; PF04111; APG6; 1. DR Pfam; PF17675; APG6_N; 1. DR Pfam; PF15285; BH3; 1. DR Genevisible; Q14457; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antiviral defense; Apoptosis; Autophagy; KW Cell cycle; Cell division; Coiled coil; Cytoplasm; Cytoplasmic vesicle; KW Endocytosis; Endoplasmic reticulum; Endosome; Golgi apparatus; KW Host-virus interaction; Isopeptide bond; Membrane; Mitochondrion; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..450 FT /note="Beclin-1" FT /id="PRO_0000218555" FT CHAIN 134..450 FT /note="Beclin-1-C 37 kDa" FT /evidence="ECO:0000305|PubMed:21364619" FT /id="PRO_0000435036" FT CHAIN 150..450 FT /note="Beclin-1-C 35 kDa" FT /evidence="ECO:0000305|PubMed:21364619, FT ECO:0000305|PubMed:26263979" FT /id="PRO_0000435037" FT REGION 48..72 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 112..159 FT /note="Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)" FT /evidence="ECO:0000269|PubMed:17446862" FT REGION 245..450 FT /note="Evolutionary conserved domain (ECD)" FT /evidence="ECO:0000305|PubMed:28445460" FT REGION 425..450 FT /note="Required for membrane-association" FT /evidence="ECO:0000269|PubMed:23878393" FT COILED 142..270 FT /evidence="ECO:0000255" FT MOTIF 108..127 FT /note="BH3" FT /evidence="ECO:0000269|PubMed:17337444" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 15 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31123703" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 90 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:23878393" FT MOD_RES 93 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:23878393, FT ECO:0000269|PubMed:25891078" FT MOD_RES 96 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:25891078" FT MOD_RES 119 FT /note="Phosphothreonine; by DAPK1" FT /evidence="ECO:0000269|PubMed:19180116" FT CROSSLNK 402 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:28445460" FT CROSSLNK 437 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:23974797" FT VARIANT 103 FT /note="A -> V" FT /id="VAR_010384" FT VARIANT 403 FT /note="I -> T" FT /id="VAR_005236" FT MUTAGEN 90 FT /note="S->A: Complete loss of phosphorylation. Complete FT loss of phosphorylation and defective autophagic function; FT when associated with Ala-93." FT /evidence="ECO:0000269|PubMed:23878393" FT MUTAGEN 93 FT /note="S->A: Partial loss of phosphorylation. Complete loss FT of phosphorylation and defective autophagic function; when FT associated with Ala-90." FT /evidence="ECO:0000269|PubMed:23878393" FT MUTAGEN 112 FT /note="L->A: Weakly decreases interaction with MUHV-4 M11, FT greatly decreases interaction with BCL2L1 isoform FT Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:18797192, FT ECO:0000269|PubMed:24443581" FT MUTAGEN 116 FT /note="L->A: Decreases interaction with BCL2L1 isoform FT Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:17446862, FT ECO:0000269|PubMed:18797192, ECO:0000269|PubMed:24443581" FT MUTAGEN 117 FT /note="K->A: Weakly decreases interaction with MUHV-4 M11, FT greatly decreases interaction with BCL2L1 isoform FT Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:24443581" FT MUTAGEN 117 FT /note="K->R: Does not affect ubiquitination by the FT DCX(AMBRA1) complex." FT /evidence="ECO:0000269|PubMed:23974797" FT MUTAGEN 120..121 FT /note="GD->EA: Weakly decreases interaction with MUHV-4 FT M11, disrupts interaction with BCL2L1 isoform Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:24443581" FT MUTAGEN 120 FT /note="G->E: Decreases interaction with MUHV-4 M11, FT disrupts interaction with BCL2L1 isoform Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:24443581" FT MUTAGEN 121 FT /note="D->A: No effect on interaction with MUHV-4 M11, FT disrupts interaction with BCL2L1 isoform Bcl-X(L)." FT /evidence="ECO:0000269|PubMed:24443581" FT MUTAGEN 123 FT /note="F->A: Weakly decreases interaction with MUHV-4 M11, FT disrupts interaction with BCL2 and decreases interaction FT with BCL2L1 isoform Bcl-X(L). Reduces interaction with FT BCL2L10." FT /evidence="ECO:0000269|PubMed:16179260, FT ECO:0000269|PubMed:17446862, ECO:0000269|PubMed:18797192, FT ECO:0000269|PubMed:22498477, ECO:0000269|PubMed:24443581" FT MUTAGEN 133 FT /note="D->A: Abolishes in vitro cleavage by CASP3 and FT CASP8; when associated with A-149." FT /evidence="ECO:0000269|PubMed:21364619" FT MUTAGEN 133 FT /note="D->A: Abolishes in vitro cleavage by CASP8; when FT associated with A-146." FT /evidence="ECO:0000269|PubMed:21444671" FT MUTAGEN 146 FT /note="D->A: Abolishes in vitro cleavage by CASP8; when FT associated with A-133." FT /evidence="ECO:0000269|PubMed:21444671" FT MUTAGEN 149 FT /note="D->A: Abolishes in vitro cleavage by CASP3 and FT CASP8; when associated with A-133." FT /evidence="ECO:0000269|PubMed:21364619" FT MUTAGEN 149 FT /note="D->E: Abolishes in vitro cleavage by CASP3." FT /evidence="ECO:0000269|PubMed:19713971" FT MUTAGEN 352 FT /note="Y->A: Significantly reduces ubiquitination." FT /evidence="ECO:0000269|PubMed:21936852" FT MUTAGEN 402 FT /note="K->R: Decreases K48 polyubiquitination and FT stabilizes BECN1." FT /evidence="ECO:0000269|PubMed:28445460" FT MUTAGEN 425 FT /note="W->A: Decrease in membrane-association." FT /evidence="ECO:0000269|PubMed:23878393" FT MUTAGEN 437 FT /note="K->R: Abolished ubiquitination by the DCX(AMBRA1) FT complex." FT /evidence="ECO:0000269|PubMed:23974797" FT CONFLICT 150 FT /note="T -> A (in Ref. 5; AAB59573)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="N -> S (in Ref. 3; BAG35534)" FT /evidence="ECO:0000305" FT CONFLICT 314 FT /note="L -> H (in Ref. 3; BAG35534)" FT /evidence="ECO:0000305" FT HELIX 110..127 FT /evidence="ECO:0007829|PDB:5VAU" FT HELIX 160..169 FT /evidence="ECO:0007829|PDB:5EFM" FT HELIX 176..265 FT /evidence="ECO:0007829|PDB:5HHE" FT STRAND 276..279 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 282..285 FT /evidence="ECO:0007829|PDB:4DDP" FT HELIX 300..321 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 326..331 FT /evidence="ECO:0007829|PDB:4DDP" FT HELIX 334..336 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 338..343 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 349..351 FT /evidence="ECO:0007829|PDB:4DDP" FT HELIX 358..360 FT /evidence="ECO:0007829|PDB:4DDP" FT HELIX 364..384 FT /evidence="ECO:0007829|PDB:4DDP" FT TURN 398..401 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 402..404 FT /evidence="ECO:0007829|PDB:4DDP" FT TURN 406..409 FT /evidence="ECO:0007829|PDB:4DDP" FT STRAND 412..415 FT /evidence="ECO:0007829|PDB:4DDP" FT HELIX 422..446 FT /evidence="ECO:0007829|PDB:4DDP" SQ SEQUENCE 450 AA; 51896 MW; ABF0C2DD7087473C CRC64; MEGSKTSNNS TMQVSFVCQR CSQPLKLDTS FKILDRVTIQ ELTAPLLTTA QAKPGETQEE ETNSGEEPFI ETPRQDGVSR RFIPPARMMS TESANSFTLI GEASDGGTME NLSRRLKVTG DLFDIMSGQT DVDHPLCEEC TDTLLDQLDT QLNVTENECQ NYKRCLEILE QMNEDDSEQL QMELKELALE EERLIQELED VEKNRKIVAE NLEKVQAEAE RLDQEEAQYQ REYSEFKRQQ LELDDELKSV ENQMRYAQTQ LDKLKKTNVF NATFHIWHSG QFGTINNFRL GRLPSVPVEW NEINAAWGQT VLLLHALANK MGLKFQRYRL VPYGNHSYLE SLTDKSKELP LYCSGGLRFF WDNKFDHAMV AFLDCVQQFK EEVEKGETRF CLPYRMDVEK GKIEDTGGSG GSYSIKTQFN SEEQWTKALK FMLTNLKWGL AWVSSQFYNK //