BECN1_MOUSE
ID BECN1_MOUSE Reviewed; 448 AA.
AC O88597; Q99J03;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Beclin-1;
DE AltName: Full=Coiled-coil myosin-like BCL2-interacting protein;
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=10604474; DOI=10.1038/45257;
RA Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H.,
RA Levine B.;
RT "Induction of autophagy and inhibition of tumorigenesis by beclin 1.";
RL Nature 402:672-676(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver, Olfactory bulb, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary tumor;
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 [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH GOPC AND GRID2, AND FUNCTION.
RX PubMed=12372286; DOI=10.1016/s0896-6273(02)00861-9;
RA Yue Z., Horton A., Bravin M., DeJager P.L., Selimi F., Heintz N.;
RT "A novel protein complex linking the delta 2 glutamate receptor and
RT autophagy: implications for neurodegeneration in lurcher mice.";
RL Neuron 35:921-933(2002).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=14657337; DOI=10.1073/pnas.2436255100;
RA Yue Z., Jin S., Yang C., Levine A.J., Heintz N.;
RT "Beclin 1, an autophagy gene essential for early embryonic development, is
RT a haploinsufficient tumor suppressor.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15077-15082(2003).
RN [8]
RP INTERACTION WITH AMBRA1 AND PIK3C3.
RX PubMed=17589504; DOI=10.1038/nature05925;
RA Maria Fimia G., Stoykova A., Romagnoli A., Giunta L., Di Bartolomeo S.,
RA Nardacci R., Corazzari M., Fuoco C., Ucar A., Schwartz P., Gruss P.,
RA Piacentini M., Chowdhury K., Cecconi F.;
RT "Ambra1 regulates autophagy and development of the nervous system.";
RL Nature 447:1121-1125(2007).
RN [9]
RP FUNCTION, AND INTERACTION WITH ATG14; RUBCN; PIK3C3; PIK3R4 AND UVRAG.
RX PubMed=19270693; DOI=10.1038/ncb1854;
RA Zhong Y., Wang Q.J., Li X., Yan Y., Backer J.M., Chait B.T., Heintz N.,
RA Yue Z.;
RT "Distinct regulation of autophagic activity by Atg14L and Rubicon
RT associated with Beclin 1-phosphatidylinositol-3-kinase complex.";
RL Nat. Cell Biol. 11:468-476(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION.
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 [12]
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 [13]
RP INTERACTION WITH PIK3CB.
RX PubMed=21059846; DOI=10.1083/jcb.201006056;
RA Dou Z., Chattopadhyay M., Pan J.-A., Guerriero J.L., Jiang Y.-P.,
RA Ballou L.M., Yue Z., Lin R.Z., Zong W.-X.;
RT "The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive
RT regulator of autophagy.";
RL J. Cell Biol. 191:827-843(2010).
RN [14]
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 [15]
RP PHOSPHORYLATION AT SER-91 AND SER-94, MUTAGENESIS OF SER-91 AND SER-94, AND
RP IDENTIFICATION IN A COMPLEX WITH PIK3C3; PIK3R4; UVRAG AND ATG14.
RX PubMed=23332761; DOI=10.1016/j.cell.2012.12.016;
RA Kim J., Kim Y.C., Fang C., Russell R.C., Kim J.H., Fan W., Liu R.,
RA Zhong Q., Guan K.L.;
RT "Differential regulation of distinct Vps34 complexes by AMPK in nutrient
RT stress and autophagy.";
RL Cell 152:290-303(2013).
RN [16]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
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 [17]
RP 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 [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 106-124 IN COMPLEX WITH MUHV-4 M11
RP (MICROBIAL INFECTION).
RX PubMed=18248095; DOI=10.1371/journal.ppat.0040025;
RA Ku B., Woo J.S., Liang C., Lee K.H., Hong H.S., E X., Kim K.S., Jung J.U.,
RA Oh B.H.;
RT "Structural and biochemical bases for the inhibition of autophagy and
RT apoptosis by viral BCL-2 of murine gamma-herpesvirus 68.";
RL PLoS Pathog. 4:E25-E25(2008).
CC -!- FUNCTION: Plays a central role in autophagy (PubMed:10604474,
CC PubMed:12372286, PubMed:19270693, PubMed:28445460). Acts as core
CC subunit of different PI3K complex forms that mediate formation of
CC phosphatidylinositol 3-phosphate and are believed to play a role in
CC multiple membrane trafficking pathways: PI3KC3-C1 is involved in
CC initiation of autophagosomes and PI3KC3-C2 in maturation of
CC autophagosomes and endocytosis (PubMed:19270693, PubMed:25275521).
CC Involved in regulation of degradative endocytic trafficking and
CC required for the abcission step in cytokinesis, probably in the context
CC of PI3KC3-C2 (By similarity). Essential for the formation of PI3KC3-C2
CC but not PI3KC3-C1 PI3K complex forms (PubMed:25275521). Involved in
CC endocytosis including endosome formation in neuronal cells
CC (PubMed:25275521). May play a role in antiviral host defense (By
CC similarity). {ECO:0000250|UniProtKB:Q14457,
CC ECO:0000269|PubMed:10604474, ECO:0000269|PubMed:12372286,
CC ECO:0000269|PubMed:19270693, ECO:0000269|PubMed:25275521,
CC ECO:0000269|PubMed:28445460}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q14457}.
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 whose core is composed of the catalytic subunit
CC PIK3C3, the regulatory subunit PIK3R4 and BECN1, and associates with
CC additional regulatory/auxilliary subunits to form alternative complex
CC forms. Accepted 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 (PubMed:19270693, PubMed:23332761). PI3KC3-C1 displays a V-shaped
CC architecture with PIK3R4 serving as a bridge between PIK3C3 and the
CC ATG14:BECN1 subcomplex (By similarity). Both, PI3KC3-C1 and PI3KC3-C2,
CC can associate with further regulatory subunits, such as RUBCN,
CC SH3GLB1/Bif-1 and AMBRA1 (PubMed:19270693). PI3KC3-C1 probably
CC associates with PIK3CB (PubMed:21059846.) Interacts with AMBRA1, GOPC,
CC GRID2 and PIK3CB (PubMed:12372286, PubMed:17589504). Forms a complex
CC with PPP2CA and AMBRA1; AMBRA1 and BECN1 components of the complex
CC regulate MYC stability via different pathways (By similarity).
CC Interacts with BCL2 and BCL2L1 isoform Bcl-X(L); the interaction
CC inhibits BECN1 function in promoting autophagy by interfering with the
CC formation of the PI3K complex (By similarity). Interacts with cytosolic
CC HMGB1; inhibits the interaction of BECN1 and BCL2 leading to promotion
CC of autophagy (PubMed:20819940). Interacts with USP10, USP13, VMP1,
CC DAPK1 (By similarity). Interacts with the poly-Gln domain of ATXN3; the
CC interaction causes deubiquitination at Lys-400 and stabilizes BECN1
CC (PubMed:28445460). Interacts with SLAMF1 (PubMed:22493499). Interacts
CC with TRIM5; the interaction causes activation of BECN1 by causing its
CC dissociation from its inhibitors BCL2 and TAB2 (By similarity).
CC Interacts with active ULK1 (phosphorylated on 'Ser-317') and MEFV
CC simultaneously (By similarity). Interacts with TRIM50
CC (PubMed:29604308). Interacts with TRIM16 (By similarity). Interacts
CC with WDR81 and WDR91; negatively regulates the PI3 kinase/PI3K activity
CC associated with endosomal membranes (By similarity). Interacts with
CC LAPTM4B; competes with EGFR for LAPTM4B binding; regulates EGFR
CC activity (By similarity). Interacts with ATG14; this interaction is
CC increased in the absence of TMEM39A (By similarity). Interacts with
CC WASHC1; preventing interaction with AMBRA1 and the DCX(AMBRA1) complex
CC and subsequent ubiquitination (By similarity). Interacts with TRIM17
CC (By similarity). Interacts with BCL2L10/BCL-B (via BH1 domain) (By
CC similarity). {ECO:0000250|UniProtKB:Q14457,
CC ECO:0000250|UniProtKB:Q91XJ1, ECO:0000269|PubMed:12372286,
CC ECO:0000269|PubMed:17589504, ECO:0000269|PubMed:18248095,
CC ECO:0000269|PubMed:19270693, ECO:0000269|PubMed:20819940,
CC ECO:0000269|PubMed:21059846, ECO:0000269|PubMed:22493499,
CC ECO:0000269|PubMed:23332761, ECO:0000269|PubMed:29604308, ECO:0000305,
CC ECO:0000305|PubMed:28445460}.
CC -!- SUBUNIT: (Microbial infection) Interacts with murine gammaherpesvirus
CC 68 M11; the viral protein binds BECN1 with higher affinity than
CC cellular BCL2. {ECO:0000269|PubMed:18248095}.
CC -!- INTERACTION:
CC O88597; P10417: Bcl2; NbExp=11; IntAct=EBI-643716, EBI-526314;
CC O88597; Q8BH60: Gopc; NbExp=5; IntAct=EBI-643716, EBI-296357;
CC O88597; P63158: Hmgb1; NbExp=3; IntAct=EBI-643716, EBI-6665811;
CC O88597; Q8VCQ3: Nrbf2; NbExp=5; IntAct=EBI-643716, EBI-2365563;
CC O88597; Q6PF93: Pik3c3; NbExp=6; IntAct=EBI-643716, EBI-6678149;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12372286}. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q14457};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q14457}. Endosome
CC membrane {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Endosome {ECO:0000269|PubMed:25275521}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000305}. Note=Interaction with
CC ATG14 promotes translocation to autophagosomes (By similarity).
CC Expressed in dendrites and cell bodies of cerebellar Purkinje cells.
CC Localized to endosomes in neurons (PubMed:25275521).
CC {ECO:0000250|UniProtKB:Q14457, ECO:0000269|PubMed:12372286,
CC ECO:0000269|PubMed:25275521}.
CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 35 kDa]: Mitochondrion
CC {ECO:0000269|PubMed:21364619}. Nucleus {ECO:0000250|UniProtKB:Q14457}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q14457}.
CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 37 kDa]: Mitochondrion
CC {ECO:0000269|PubMed:21364619}.
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. As some binding is observed with BECN1
CC lacking the ECD, other domains of BECN1 may also interact with ATXN3.
CC {ECO:0000305|PubMed:28445460}.
CC -!- PTM: Phosphorylation at Thr-117 by DAPK1 reduces its interaction with
CC BCL2 and BCL2L1 and promotes induction of autophagy (By similarity). In
CC 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. {ECO:0000250|UniProtKB:Q14457,
CC ECO:0000269|PubMed:23332761}.
CC -!- PTM: Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'-
CC linkages (By similarity). 'Lys-11'-linked poyubiquitination leads to
CC degradation and is enhanced when the stabilizing interaction partner
CC VPS34 is depleted (By similarity). Deubiquitinated by USP10 and USP13,
CC leading to stabilize the PIK3C3/VPS34-containing complexes (By
CC similarity). Polyubiquitinated at Lys-400 with 'Lys-48'-linkages
CC (PubMed:28445460). 'Lys-48'-linked poyubiquitination of Lys-400 leads
CC to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to
CC stabilization (PubMed:28445460). Ubiquitinated at Lys-435 via 'Lys-63'-
CC linkage by the DCX(AMBRA1) complex, thereby increasing the association
CC between BECN1 and PIK3C3 to promote PIK3C3 activity (By similarity).
CC {ECO:0000250|UniProtKB:Q14457, 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:21364619}.
CC -!- DISRUPTION PHENOTYPE: Death early in embryogenesis. Embryos show a
CC severely altered autophagic response, whereas their apoptotic response
CC to serum withdrawal or UV light is normal (PubMed:14657337).
CC Accelerated neurodegeneration (conditional knockout in cerebellar
CC Purkinje cells). {ECO:0000269|PubMed:14657337,
CC ECO:0000269|PubMed:25275521}.
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}.
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DR EMBL; AF077302; AAC68654.2; -; mRNA.
DR EMBL; AK032176; BAC27745.1; -; mRNA.
DR EMBL; AK050329; BAC34192.1; -; mRNA.
DR EMBL; AK083800; BAC39021.1; -; mRNA.
DR EMBL; AL590969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005770; AAH05770.1; -; mRNA.
DR CCDS; CCDS25462.1; -.
DR RefSeq; NP_062530.2; NM_019584.3.
DR PDB; 3BL2; X-ray; 2.30 A; C/D=106-124.
DR PDB; 5YR0; X-ray; 1.90 A; A=174-223.
DR PDBsum; 3BL2; -.
DR PDBsum; 5YR0; -.
DR AlphaFoldDB; O88597; -.
DR SMR; O88597; -.
DR BioGRID; 207843; 12.
DR ComplexPortal; CPX-75; Phosphatidylinositol 3-kinase complex, class III, ATG14 variant.
DR ComplexPortal; CPX-76; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant.
DR CORUM; O88597; -.
DR DIP; DIP-41636N; -.
DR IntAct; O88597; 17.
DR MINT; O88597; -.
DR STRING; 10090.ENSMUSP00000119369; -.
DR iPTMnet; O88597; -.
DR PhosphoSitePlus; O88597; -.
DR EPD; O88597; -.
DR MaxQB; O88597; -.
DR PaxDb; O88597; -.
DR PRIDE; O88597; -.
DR ProteomicsDB; 273601; -.
DR Antibodypedia; 4116; 1645 antibodies from 47 providers.
DR DNASU; 56208; -.
DR Ensembl; ENSMUST00000130916; ENSMUSP00000119369; ENSMUSG00000035086.
DR GeneID; 56208; -.
DR KEGG; mmu:56208; -.
DR UCSC; uc007loj.1; mouse.
DR CTD; 8678; -.
DR MGI; MGI:1891828; Becn1.
DR VEuPathDB; HostDB:ENSMUSG00000035086; -.
DR eggNOG; KOG2751; Eukaryota.
DR GeneTree; ENSGT00390000008164; -.
DR HOGENOM; CLU_024219_4_1_1; -.
DR InParanoid; O88597; -.
DR OMA; DTFCIGH; -.
DR OrthoDB; 1085752at2759; -.
DR PhylomeDB; O88597; -.
DR TreeFam; TF314282; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 56208; 18 hits in 76 CRISPR screens.
DR ChiTaRS; Becn1; mouse.
DR EvolutionaryTrace; O88597; -.
DR PRO; PR:O88597; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O88597; protein.
DR Bgee; ENSMUSG00000035086; Expressed in renal medulla collecting duct and 253 other tissues.
DR ExpressionAtlas; O88597; baseline and differential.
DR Genevisible; O88597; MM.
DR GO; GO:0005776; C:autophagosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISS:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic component of membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISS:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:MGI.
DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; IDA:UniProtKB.
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:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005802; C:trans-Golgi network; IDA:MGI.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:MGI.
DR GO; GO:0001525; P:angiogenesis; TAS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; ISO:MGI.
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: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; IDA: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; ISS:UniProtKB.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:CACAO.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0007040; P:lysosome organization; IMP:MGI.
DR GO; GO:0016236; P:macroautophagy; IMP:UniProtKB.
DR GO; GO:0000423; P:mitophagy; ISO:MGI.
DR GO; GO:0007080; P:mitotic metaphase plate congression; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:MGI.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:1905672; P:negative regulation of lysosome organization; ISO:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048666; P:neuron development; IMP:MGI.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; ISO:MGI.
DR GO; GO:1902425; P:positive regulation of attachment of mitotic spindle microtubules to kinetochore; ISO:MGI.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0006622; P:protein targeting to lysosome; IC:ComplexPortal.
DR GO; GO:0032801; P:receptor catabolic process; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISO:MGI.
DR GO; GO:0050790; P:regulation of catalytic activity; IMP:MGI.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0051707; P:response to other organism; IDA:MGI.
DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR DisProt; DP01612; -.
DR Gene3D; 1.10.418.40; -; 1.
DR IDEAL; IID50268; -.
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 Isopeptide bond; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..448
FT /note="Beclin-1"
FT /id="PRO_0000218556"
FT CHAIN 132..448
FT /note="Beclin-1-C 37 kDa"
FT /evidence="ECO:0000305|PubMed:21364619"
FT /id="PRO_0000435038"
FT CHAIN 148..448
FT /note="Beclin-1-C 35 kDa"
FT /evidence="ECO:0000305|PubMed:21364619"
FT /id="PRO_0000435039"
FT REGION 47..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 110..157
FT /note="Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT REGION 243..448
FT /note="Evolutionary conserved domain (ECD)"
FT /evidence="ECO:0000305|PubMed:28445460"
FT REGION 423..448
FT /note="Required for membrane-association"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT COILED 140..268
FT /evidence="ECO:0000255"
FT MOTIF 106..125
FT /note="BH3"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 88
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 91
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:23332761"
FT MOD_RES 94
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:23332761"
FT MOD_RES 117
FT /note="Phosphothreonine; by DAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CROSSLNK 400
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MUTAGEN 91
FT /note="S->A: Complete loss of phosphorylation. Complete
FT loss of phosphorylation and defective autophagic function;
FT when associated with Ala-94."
FT /evidence="ECO:0000269|PubMed:23332761"
FT MUTAGEN 94
FT /note="S->A: Partial loss of phosphorylation. Complete loss
FT of phosphorylation and defective autophagic function; when
FT associated with Ala-91."
FT /evidence="ECO:0000269|PubMed:23332761"
FT CONFLICT 37
FT /note="T -> A (in Ref. 2; AAC68654)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="Q -> H (in Ref. 2; AAC68654)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="F -> L (in Ref. 2; AAC68654)"
FT /evidence="ECO:0000305"
FT HELIX 107..121
FT /evidence="ECO:0007829|PDB:3BL2"
FT HELIX 176..221
FT /evidence="ECO:0007829|PDB:5YR0"
SQ SEQUENCE 448 AA; 51589 MW; 14623BA002E1AAEE CRC64;
MEGSKASSST MQVSFVCQRC SQPLKLDTSF KILDRVTIQE LTAPLLTTAQ AKPGETQEEE
ANSGEEPFIE TRQDGVSRRF IPPARMMSTE SANSFTLIGE ASDGGTMENL SRRLKVTGDL
FDIMSGQTDV DHPLCEECTD TLLDQLDTQL NVTENECQNY KRCLEILEQM NEDDSEQLQR
ELKELALEEE RLIQELEDVE KNRKVVAENL EKVQAEAERL DQEEAQYQRE YSEFKRQQLE
LDDELKSVEN QVRYAQIQLD KLKKTNVFNA TFHIWHSGQF GTINNFRLGR LPSVPVEWNE
INAAWGQTVL LLHALANKMG LKFQRYRLVP YGNHSYLESL TDKSKELPLY CSGGLRFFWD
NKFDHAMVAF LDCVQQFKEE VEKGETRFCL PYRMDVEKGK IEDTGGSGGS YSIKTQFNSE
EQWTKALKFM LTNLKWGLAW VSSQFYNK
