BECN_CAEEL
ID BECN_CAEEL Reviewed; 375 AA.
AC Q22592; V6CL88;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Beclin homolog {ECO:0000312|WormBase:T19E7.3a};
GN Name=bec-1 {ECO:0000312|WormBase:T19E7.3a};
GN Synonyms=atg-6 {ECO:0000312|WormBase:T19E7.3a};
GN ORFNames=T19E7.3 {ECO:0000312|WormBase:T19E7.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=12958363; DOI=10.1126/science.1087782;
RA Melendez A., Talloczy Z., Seaman M., Eskelinen E.L., Hall D.H., Levine B.;
RT "Autophagy genes are essential for dauer development and life-span
RT extension in C. elegans.";
RL Science 301:1387-1391(2003).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CED-9 AND VPS-34, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16111945; DOI=10.1016/j.cub.2005.07.035;
RA Takacs-Vellai K., Vellai T., Puoti A., Passannante M., Wicky C., Streit A.,
RA Kovacs A.L., Mueller F.;
RT "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in
RT C. elegans.";
RL Curr. Biol. 15:1513-1517(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17204841; DOI=10.4161/auto.3636;
RA Hars E.S., Qi H., Ryazanov A.G., Jin S., Cai L., Hu C., Liu L.F.;
RT "Autophagy regulates ageing in C. elegans.";
RL Autophagy 3:93-95(2007).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=17890369; DOI=10.1534/genetics.107.075762;
RA Aladzsity I., Toth M.L., Sigmond T., Szabo E., Bicsak B., Barna J.,
RA Regos A., Orosz L., Kovacs A.L., Vellai T.;
RT "Autophagy genes unc-51 and bec-1 are required for normal cell size in
RT Caenorhabditis elegans.";
RL Genetics 177:655-660(2007).
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17327275; DOI=10.1242/jcs.03401;
RA Toth M.L., Simon P., Kovacs A.L., Vellai T.;
RT "Influence of autophagy genes on ion-channel-dependent neuronal
RT degeneration in Caenorhabditis elegans.";
RL J. Cell Sci. 120:1134-1141(2007).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19667176; DOI=10.1073/pnas.0813319106;
RA Jia K., Thomas C., Akbar M., Sun Q., Adams-Huet B., Gilpin C., Levine B.;
RT "Autophagy genes protect against Salmonella typhimurium infection and
RT mediate insulin signaling-regulated pathogen resistance.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14564-14569(2009).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=21183797; DOI=10.4161/auto.7.4.14391;
RA Ruck A., Attonito J., Garces K.T., Nunez L., Palmisano N.J., Rubel Z.,
RA Bai Z., Nguyen K.C., Sun L., Grant B.D., Hall D.H., Melendez A.;
RT "The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde
RT transport in addition to autophagy in C. elegans.";
RL Autophagy 7:386-400(2011).
RN [9]
RP FUNCTION, INTERACTION WITH VPS-34; SORF-1 AND SORF-2, AND DISRUPTION
RP PHENOTYPE.
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 [10]
RP ERRATUM OF PUBMED:26783301.
RX PubMed=26975852; DOI=10.1083/jcb.20150608103012016c;
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 "Correction: Negative regulation of phosphatidylinositol 3-phosphate levels
RT in early-to-late endosome conversion.";
RL J. Cell Biol. 212:739-739(2016).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28285998; DOI=10.1016/j.cub.2017.02.015;
RA Ames K., Da Cunha D.S., Gonzalez B., Konta M., Lin F., Shechter G.,
RA Starikov L., Wong S., Buelow H.E., Melendez A.;
RT "A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-
RT Cycle Progression and Stem Cell Proliferation during Germline
RT Development.";
RL Curr. Biol. 27:905-913(2017).
CC -!- FUNCTION: Regulates autophagy (PubMed:12958363). Together with
CC phosphatidyl-3-phosphate kinase vps-34, acts as a core subunit of the
CC PI3K complex that mediates formation of phosphatidylinositol 3-
CC phosphate (PtdIns3P), thereby regulating membrane trafficking
CC (PubMed:16111945, PubMed:21183797, PubMed:26783301). In association
CC with sorf-1 and sorf-2, negatively regulates phosphatidylinositol 3-
CC phosphate in early endosomes to allow for the conversion to late
CC endosomes (PubMed:26783301). Involved in the clearance of engulfed
CC apoptotic cell corpses (PubMed:16111945, PubMed:21183797). Together
CC with ced-9, negatively regulates somatic and germline apoptosis
CC (PubMed:17890369). Plays a role in endosome-to-Golgi retrograde
CC transport of mig-14 (PubMed:21183797). In a daf-18/PTEN- and skn-1/Nrf-
CC dependent manner, promotes germline stem cell proliferation during late
CC and adult stages, probably by ensuring cell survival and cell cycle
CC progression (PubMed:28285998). Required for embryonic development and
CC L3/L4 molting during larval development (PubMed:16111945). Required for
CC normal dauer morphogenesis and lifespan (PubMed:12958363,
CC PubMed:17204841). Plays a role in male tail ray pattern formation
CC (PubMed:17890369). Required for normal survival when exposed to
CC pathogenic bacteria S.typhimurium by promoting autophagic degradation
CC of intracellular S.typhimurium (PubMed:19667176).
CC {ECO:0000269|PubMed:12958363, ECO:0000269|PubMed:16111945,
CC ECO:0000269|PubMed:17204841, ECO:0000269|PubMed:17890369,
CC ECO:0000269|PubMed:19667176, ECO:0000269|PubMed:21183797,
CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28285998}.
CC -!- SUBUNIT: Interacts with ced-9 (PubMed:16111945). Interacts with vps-34
CC (PubMed:16111945, PubMed:26783301). Interacts with sorf-1 and sorf-2
CC (PubMed:26783301). {ECO:0000269|PubMed:16111945,
CC ECO:0000269|PubMed:26783301}.
CC -!- INTERACTION:
CC Q22592; Q23533: sorf-1; NbExp=3; IntAct=EBI-2413500, EBI-13941886;
CC Q22592; Q10122: sorf-2; NbExp=3; IntAct=EBI-2413500, EBI-13941960;
CC Q22592; Q9TXI7: vps-34; NbExp=2; IntAct=EBI-2413500, EBI-21398789;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16111945}.
CC Perikaryon {ECO:0000269|PubMed:17327275}. Cell projection, dendrite
CC {ECO:0000269|PubMed:17327275}. Cell projection, axon
CC {ECO:0000269|PubMed:17327275}. Endosome {ECO:0000269|PubMed:21183797}.
CC Note=Co-localizes with rme-8, a component of the retromer complex, on
CC endosomes. {ECO:0000269|PubMed:21183797}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:T19E7.3a};
CC IsoId=Q22592-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T19E7.3b};
CC IsoId=Q22592-2; Sequence=VSP_058342;
CC -!- TISSUE SPECIFICITY: Expressed in PVM touch receptor neurons, the
CC ventral nerve cord and in the nerve ring.
CC {ECO:0000269|PubMed:17327275}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in embryos and to a lesser extent
CC in larvae (PubMed:16111945). Expressed in pharynx, seam cells and
CC ventral nerve cord neurons at the L1 and L4 larval stages
CC (PubMed:12958363, PubMed:16111945). Expressed in vulva cell precursors
CC and somatic gonad at the L2 larval stage and in vulva at the L4 larval
CC stage (PubMed:12958363). {ECO:0000269|PubMed:12958363,
CC ECO:0000269|PubMed:16111945}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal with few surviving larvae which
CC fail to carry out the L3/L4 molt and few surviving adults which are
CC sterile (PubMed:16111945, PubMed:21183797). At the L3 larval stage,
CC accumulates vacuoles in intestine, hypodermis, pharynx and coelomocytes
CC (PubMed:21183797). Abnormal accumulation of mig-14, lmp-1, and rab-7 on
CC these vacuoles (PubMed:21183797). Mislocalization of several components
CC of the retromer complex, including rme-8, snx-1 and vps-35
CC (PubMed:21183797). Impaired fluid phase endocytosis in coelomocytes
CC (PubMed:21183797). Double knockout with either sorf-1 or sorf-2 results
CC in smaller endosomes and an irregular distribution pattern of PtdIns3P
CC in the cytoplasm (PubMed:26783301). RNAi-mediated knockdown results in
CC reduced stem cell proliferation in the germline during larval
CC development (PubMed:28285998). RNAi-mediated knockdown at the L4 larval
CC stage causes a slight decrease in lifespan and multiple defects in the
CC progeny which fails to produce viable embryos (PubMed:12958363,
CC PubMed:16111945, PubMed:17204841). In addition, causes an increase in
CC the number of apoptotic cell corpses at various embryonic stages and in
CC the gonads (PubMed:16111945, PubMed:21183797). Reduces
CC phosphatidylinositol 3-phosphate levels on intracellular membrane
CC vesicles and impairs endocytosis (PubMed:16111945, PubMed:21183797).
CC Prevents necrotic cell death of CEP and ADE dopamin neurons induced by
CC neurotoxin 6-hydroxidopamine (PubMed:17327275). Impaired survival when
CC exposed to pathogenic bacteria S.typhimurium which is associated with
CC the persistence of intact bacteria-containing vesicles in intestinal
CC cells, the formation of few autophagosomes and autolysosomes followed
CC by a progressive destruction of intestinal cells (PubMed:19667176). In
CC addition, causes a reduction in mig-14 and rme-8 association with
CC puncta structures as well as an increase in mig-14 protein levels
CC (PubMed:21183797). RNAi-mediated knockdown causes abnormalities in
CC constitutive dauer formation in daf-2 e1370 mutant including uneven
CC distribution of hyperpigmented granules in the intestine and a
CC reduction in fat storage and radial constriction elongation of the body
CC and the pharynx (PubMed:12958363). In addition, prevents increase in
CC lifespan and the formation of autophagosomes in lateral hypodermal seam
CC cells in daf-2 e1370 mutant (PubMed:12958363, PubMed:19667176). Reduces
CC the number of vacuolated (dying) touch receptor neurons and restores
CC touch sensitivity in mec-4 u231, deg-1 u506 or deg-3 u662 mutants
CC (PubMed:17327275). {ECO:0000269|PubMed:12958363,
CC ECO:0000269|PubMed:16111945, ECO:0000269|PubMed:17204841,
CC ECO:0000269|PubMed:17327275, ECO:0000269|PubMed:19667176,
CC ECO:0000269|PubMed:21183797, ECO:0000269|PubMed:26783301,
CC ECO:0000269|PubMed:28285998}.
CC -!- SIMILARITY: Belongs to the beclin family. {ECO:0000305}.
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DR EMBL; BX284604; CCD62215.1; -; Genomic_DNA.
DR EMBL; BX284604; CDK13324.1; -; Genomic_DNA.
DR PIR; T29537; T29537.
DR PIR; T29538; T29538.
DR RefSeq; NP_001293684.1; NM_001306755.1.
DR RefSeq; NP_500844.1; NM_068443.3. [Q22592-1]
DR AlphaFoldDB; Q22592; -.
DR SMR; Q22592; -.
DR IntAct; Q22592; 6.
DR STRING; 6239.T19E7.3; -.
DR EPD; Q22592; -.
DR PaxDb; Q22592; -.
DR PeptideAtlas; Q22592; -.
DR EnsemblMetazoa; T19E7.3a.1; T19E7.3a.1; WBGene00000247. [Q22592-1]
DR EnsemblMetazoa; T19E7.3b.1; T19E7.3b.1; WBGene00000247. [Q22592-2]
DR GeneID; 177345; -.
DR KEGG; cel:CELE_T19E7.3; -.
DR UCSC; T19E7.3.1; c. elegans. [Q22592-1]
DR CTD; 177345; -.
DR WormBase; T19E7.3a; CE27592; WBGene00000247; bec-1. [Q22592-1]
DR WormBase; T19E7.3b; CE49136; WBGene00000247; bec-1. [Q22592-2]
DR eggNOG; KOG2751; Eukaryota.
DR GeneTree; ENSGT00390000008164; -.
DR HOGENOM; CLU_706449_0_0_1; -.
DR InParanoid; Q22592; -.
DR OMA; VGWNEIN; -.
DR OrthoDB; 1085752at2759; -.
DR PhylomeDB; Q22592; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR PRO; PR:Q22592; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000247; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:WormBase.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
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:0043277; P:apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IGI:WormBase.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IMP:WormBase.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0036093; P:germ cell proliferation; IMP:UniProtKB.
DR GO; GO:0042078; P:germ-line stem cell division; IMP:UniProtKB.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0048284; P:organelle fusion; IMP:UniProtKB.
DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IGI:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; IGI:WormBase.
DR GO; GO:0030163; P:protein catabolic process; IMP:WormBase.
DR GO; GO:0051036; P:regulation of endosome size; IGI:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IGI:WormBase.
DR Gene3D; 1.10.418.40; -; 2.
DR InterPro; IPR007243; Atg6/Beclin.
DR InterPro; IPR038274; Atg6/Beclin_C_sf.
DR InterPro; IPR041691; Atg6/beclin_CC.
DR InterPro; IPR040455; Atg6_BARA.
DR PANTHER; PTHR12768; PTHR12768; 1.
DR Pfam; PF04111; APG6; 1.
DR Pfam; PF17675; APG6_N; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cell projection; Coiled coil; Cytoplasm;
KW Endocytosis; Endosome; Reference proteome.
FT CHAIN 1..375
FT /note="Beclin homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436304"
FT COILED 71..147
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..257
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058342"
SQ SEQUENCE 375 AA; 42774 MW; 630D0F04EEF324D8 CRC64;
MTTQRSHICL NCQHPLRLDF TQRRPDSADS EKKSETVITE ALTGHSRNLM KLISDAQFPS
DAPVCNDCSD ALRNEMDAQV ATLDDEIKTY QTYINYLKEN HPTTSIPDLK AKLQNVSDEE
KELEQQLKKL LAEEEQLDLD LQTKRRTAEA ASEKSGELWK KYRDNLRQVF EDQDELHSLE
AERQYAEVQH RKLTDTNVLD LCFHIWVDGI VGEINGFRLG YLKDAPVEFT EINAALGQIV
LLLEILLERI GVQHHELMPV AMGSHSYIKL RRNGIDMETY ALYGQGTPLS GSSGIDPGIR
RFLQLLEFLL KELKDRNKNF KPPYQIHADS LVDNGVKYNA VMTLNTDVRW TRAMALMLTD
LKAACAQCDA LRSPI
