BECN1_HUMAN
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 03-AUG-2022, entry version 208.
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 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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 Acts as core subunit of the PI3K complex that mediates formation of
CC phosphatidylinositol 3-phosphate; different complex forms are believed
CC to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is
CC involved in initiation of autophagosomes and PI3KC3-C2 in maturation of
CC autophagosomes and endocytosis. Involved in regulation of degradative
CC endocytic trafficking and required for the abcission step in
CC cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123,
CC PubMed:20208530, PubMed:23974797, PubMed:26783301). Essential for the
CC formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved
CC in endocytosis (PubMed:25275521). Protects against infection by a
CC neurovirulent strain of Sindbis virus (PubMed:9765397). May play a role
CC in antiviral host defense. {ECO:0000269|PubMed:18570871,
CC ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123,
CC ECO:0000269|PubMed:21358617, ECO:0000269|PubMed:23184933,
CC ECO:0000269|PubMed:23974797, ECO:0000269|PubMed:25275521,
CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460,
CC ECO:0000269|PubMed:9765397, ECO:0000305}.
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).
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:26347139,
CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27562068,
CC ECO:0000269|PubMed:27693506, ECO:0000269|PubMed:28445460,
CC ECO:0000269|PubMed:28479384, ECO:0000269|PubMed:29604308,
CC ECO:0000269|PubMed:31806350, 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 -!- 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}. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:19050071};
CC Peripheral membrane protein {ECO:0000269|PubMed:19050071}. Endosome
CC membrane {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).
CC {ECO:0000269|PubMed:19180116, ECO:0000269|PubMed:23878393}.
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 {ECO:0000269|PubMed:21936852, ECO:0000269|PubMed:21962518,
CC ECO:0000269|PubMed:23974797, 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 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 AlphaFoldDB; Q14457; -.
DR SMR; Q14457; -.
DR BioGRID; 114226; 191.
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 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; Q14457; -.
DR PeptideAtlas; Q14457; -.
DR PRIDE; Q14457; -.
DR ProteomicsDB; 59999; -.
DR Antibodypedia; 4116; 1645 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 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; DTFCIGH; -.
DR OrthoDB; 1085752at2759; -.
DR PhylomeDB; Q14457; -.
DR TreeFam; TF314282; -.
DR PathwayCommons; Q14457; -.
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; 77 hits in 1092 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 206 other tissues.
DR ExpressionAtlas; Q14457; baseline and differential.
DR Genevisible; Q14457; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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:0019898; C:extrinsic component of membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031966; C:mitochondrial 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:0043548; F:phosphatidylinositol 3-kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
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; ISS:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IDA:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IDA:CAFA.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
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: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: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 plate congression; 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:0060548; P:negative regulation of cell death; IMP:MGI.
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:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; 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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; NAS:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0006622; P:protein targeting to lysosome; IC:ComplexPortal.
DR GO; GO:0032801; P:receptor catabolic process; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:ComplexPortal.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:Ensembl.
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 DisProt; DP01149; -.
DR Gene3D; 1.10.418.40; -; 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; IPR032913; BECN1.
DR InterPro; IPR029318; BH3_dom.
DR PANTHER; PTHR12768; PTHR12768; 1.
DR PANTHER; PTHR12768:SF6; PTHR12768:SF6; 1.
DR Pfam; PF04111; APG6; 1.
DR Pfam; PF17675; APG6_N; 1.
DR Pfam; PF15285; BH3; 1.
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 MOD_RES 96
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:O88597"
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 Bcl-
FT 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 Bcl-
FT 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 Bcl-
FT 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
