BECN1_DANRE
ID BECN1_DANRE Reviewed; 447 AA.
AC F1RCP1; A2A135; Q6P4P7;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 3.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Beclin-1;
GN Name=becn1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yabu T., Yamashita M.;
RT "Cloning of zebrafish beclin1 gene.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INDUCTION.
RX PubMed=23195281; DOI=10.1071/rd12187;
RA Gioacchini G., Dalla Valle L., Benato F., Fimia G.M., Nardacci R.,
RA Ciccosanti F., Piacentini M., Borini A., Carnevali O.;
RT "Interplay between autophagy and apoptosis in the development of Danio
RT rerio follicles and the effects of a probiotic.";
RL Reprod. Fertil. Dev. 25:1115-1125(2013).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24441423; DOI=10.4161/auto.27649;
RA Lee E., Koo Y., Ng A., Wei Y., Luby-Phelps K., Juraszek A., Xavier R.J.,
RA Cleaver O., Levine B., Amatruda J.F.;
RT "Autophagy is essential for cardiac morphogenesis during vertebrate
RT development.";
RL Autophagy 10:572-587(2014).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27467399; DOI=10.1080/15548627.2016.1207015;
RA Saera-Vila A., Kish P.E., Louie K.W., Grzegorski S.J., Klionsky D.J.,
RA Kahana A.;
RT "Autophagy regulates cytoplasmic remodeling during cell reprogramming in a
RT zebrafish model of muscle regeneration.";
RL Autophagy 12:1864-1875(2016).
RN [7]
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).
CC -!- FUNCTION: Plays a central role in autophagy (PubMed:24441423,
CC PubMed:27467399, PubMed:28445460). Acts as core subunit of different
CC PI3K complex forms that mediate formation of phosphatidylinositol 3-
CC phosphate and are believed to play a role in multiple membrane
CC trafficking pathways: PI3KC3-C1 is involved in initiation of
CC autophagosomes and PI3KC3-C2 in maturation of autophagosomes and
CC endocytosis (By similarity). Involved in regulation of degradative
CC endocytic trafficking and required for the abcission step in
CC cytokinesis, probably in the context of PI3KC3-C2 (By similarity).
CC Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex
CC forms (By similarity). Involved in endocytosis including endosome
CC formation in neuronal cells (By similarity).
CC {ECO:0000250|UniProtKB:Q14457, ECO:0000269|PubMed:24441423,
CC ECO:0000269|PubMed:27467399, ECO:0000305|PubMed:28445460}.
CC -!- SUBUNIT: Component of the PI3K (PI3KC3/PI3K-III/class III
CC phosphatidylinositol 3-kinase) complex (By similarity). Interacts with
CC the poly-Gln domain of ATXN3; the interaction causes deubiquitination
CC at Lys-399 and stabilizes BECN1 (PubMed:28445460).
CC {ECO:0000250|UniProtKB:Q14457, ECO:0000250|UniProtKB:Q91XJ1,
CC ECO:0000305|PubMed:28445460}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14457}. 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
CC {ECO:0000250|UniProtKB:Q14457}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000305}.
CC -!- INDUCTION: Expressed during follicle development in the ovary
CC (PubMed:23195281). {ECO:0000269|PubMed:23195281}.
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: Polyubiquitinated at Lys-399 with 'Lys-48'-linkages
CC (PubMed:28445460). 'Lys-48'-linked polyubiquitination of Lys-399 leads
CC to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to
CC stabilization (PubMed:28445460). {ECO:0000305|PubMed:28445460}.
CC -!- DISRUPTION PHENOTYPE: Results in defects in morphogenesis, increased
CC numbers of dead cells, abnormal heart structure, and reduced organismal
CC survival (PubMed:24441423). Reduces the regenerative response to muscle
CC injury with accumulation of sarcomeric and nuclear debris
CC (PubMed:27467399). {ECO:0000269|PubMed:24441423,
CC ECO:0000269|PubMed:27467399}.
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; AB266448; BAF45347.1; -; mRNA.
DR EMBL; CABZ01056306; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU565519; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU607073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO704673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO704675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063319; AAH63319.1; -; mRNA.
DR RefSeq; NP_957166.1; NM_200872.1.
DR AlphaFoldDB; F1RCP1; -.
DR SMR; F1RCP1; -.
DR STRING; 7955.ENSDARP00000100986; -.
DR PaxDb; F1RCP1; -.
DR Ensembl; ENSDART00000115237; ENSDARP00000100986; ENSDARG00000079128.
DR GeneID; 393846; -.
DR KEGG; dre:393846; -.
DR CTD; 8678; -.
DR ZFIN; ZDB-GENE-040426-1666; becn1.
DR eggNOG; KOG2751; Eukaryota.
DR GeneTree; ENSGT00390000008164; -.
DR InParanoid; F1RCP1; -.
DR OMA; DTFCIGH; -.
DR OrthoDB; 1085752at2759; -.
DR TreeFam; TF314282; -.
DR Reactome; R-DRE-1632852; Macroautophagy.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR PRO; PR:F1RCP1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 12.
DR Bgee; ENSDARG00000079128; Expressed in brain and 23 other tissues.
DR ExpressionAtlas; F1RCP1; baseline.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; 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:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IMP:ZFIN.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0090398; P:cellular senescence; IGI:ZFIN.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:InterPro.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IEA:InterPro.
DR GO; GO:0043416; P:regulation of skeletal muscle tissue regeneration; IMP:ZFIN.
DR Gene3D; 1.10.418.40; -; 1.
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 2: Evidence at transcript level;
KW Autophagy; Cell cycle; Cell division; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Golgi apparatus;
KW Isopeptide bond; Membrane; Mitochondrion; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..447
FT /note="Beclin-1"
FT /id="PRO_0000441635"
FT REGION 109..156
FT /note="Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT REGION 242..447
FT /note="Evolutionary conserved domain (ECD)"
FT /evidence="ECO:0000305|PubMed:28445460"
FT REGION 422..447
FT /note="Required for membrane-association"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT COILED 140..214
FT /evidence="ECO:0000255"
FT MOTIF 105..124
FT /note="BH3"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CONFLICT 254
FT /note="C -> R (in Ref. 1; BAF45347)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 51410 MW; A37454F2EA3FFF42 CRC64;
METLRFSSNT MQVSFVCQRC NQPLKLDTSF NVLDRMTIHE LTAPLVMVTA NKQQDSGESS
SFPEETFLEN KQDGVARKFI PPARMMSAES TNSFTLIGEA SDGGTMENLS RRLKVTSNLF
DIMSGQTDID HPLCEECTDT LLDHLDTQLN ITENECQNYK SCLELLSQLP EEEEASLLNA
LQQLKQEEES LIQELESIET KREAVAKELD EGRNHSQLMD TEELRYQKEY CEFKRQQLEL
DDDLKSVDNQ MRYCQIQLDK LKKTNVFNAT FHIWHSGQFG TINNFRLGRL PSVPVEWNEI
NAAWGQTVLL LHALASKMGL CFQRYQLVPY GNHSYLESLS DKSKELPLYC SGGLRFFWDN
KFDHAMVAFL DCVQQFKEEV EKDDTGFCLP YRMDVDKGKI EDTGGSGGSY SIKTQFNSEE
QWTKALKFML TNLKWGLAWV SSQFYNR
