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Protein

Beclin-1

Gene

Becn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a central role in autophagy (PubMed:10604474, PubMed:12372286, PubMed:19270693, PubMed:28445460). Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis (PubMed:19270693, PubMed:25275521). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (By similarity). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms (PubMed:25275521). Involved in endocytosis including endosome formation in neuronal cells (PubMed:25275521). May play a role in antiviral host defense (By similarity).By similarity5 Publications
Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors (By similarity).By similarity

Miscellaneous

Expanded poly-Gln tracts inhibit ATXN3-BECN1 interaction, decrease BECN1 levels and impair starvation-induced autophagy (PubMed:28445460).1 Publication

GO - Molecular functioni

GO - Biological processi

  • aging Source: Ensembl
  • amyloid-beta metabolic process Source: MGI
  • angiogenesis Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • autophagosome assembly Source: UniProtKB
  • autophagy Source: CACAO
  • autophagy of mitochondrion Source: ParkinsonsUK-UCL
  • autophagy of nucleus Source: GO_Central
  • cellular response to aluminum ion Source: Ensembl
  • cellular response to amino acid starvation Source: Ensembl
  • cellular response to copper ion Source: Ensembl
  • cellular response to epidermal growth factor stimulus Source: Ensembl
  • cellular response to glucose starvation Source: UniProtKB
  • cellular response to hydrogen peroxide Source: Ensembl
  • cellular response to nitrogen starvation Source: GO_Central
  • cytokinesis Source: UniProtKB
  • defense response to virus Source: UniProtKB-KW
  • early endosome to late endosome transport Source: UniProtKB
  • engulfment of apoptotic cell Source: CACAO
  • late endosome to vacuole transport Source: GO_Central
  • lysosome organization Source: MGI
  • macroautophagy Source: UniProtKB
  • mitophagy Source: MGI
  • mitotic metaphase plate congression Source: MGI
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of cell death Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of lysosome organization Source: Ensembl
  • negative regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • neuron development Source: MGI
  • positive regulation of attachment of mitotic spindle microtubules to kinetochore Source: MGI
  • positive regulation of autophagosome assembly Source: Ensembl
  • receptor catabolic process Source: MGI
  • regulation of catalytic activity Source: MGI
  • regulation of cytokinesis Source: MGI
  • response to drug Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to iron(II) ion Source: Ensembl
  • response to lead ion Source: Ensembl
  • response to mitochondrial depolarisation Source: MGI
  • response to other organism Source: MGI
  • response to vitamin E Source: Ensembl

Keywordsi

Biological processAntiviral defense, Apoptosis, Autophagy, Cell cycle, Cell division, Endocytosis

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.
R-MMU-5689880. Ub-specific processing proteases.

Names & Taxonomyi

Protein namesi
Recommended name:
Beclin-1
Alternative name(s):
Coiled-coil myosin-like BCL2-interacting protein
Cleaved into the following 2 chains:
Beclin-1-C 35 kDa1 Publication
Beclin-1-C 37 kDa1 Publication
Gene namesi
Name:Becn1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1891828. Becn1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Death early in embryogenesis. Embryos show a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal( PubMed:14657337). Accelerated neurodegeneration (conditional knockout in cerebellar Purkinje cells).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91S → A: Complete loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-94. 1 Publication1
Mutagenesisi94S → A: Partial loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-91. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002185561 – 448Beclin-1Add BLAST448
ChainiPRO_0000435038132 – 448Beclin-1-C 37 kDa1 PublicationAdd BLAST317
ChainiPRO_0000435039148 – 448Beclin-1-C 35 kDa1 PublicationAdd BLAST301

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei29PhosphoserineBy similarity1
Modified residuei88Phosphoserine; by AMPKBy similarity1
Modified residuei91Phosphoserine; by AMPK1 Publication1
Modified residuei94Phosphoserine; by AMPK1 Publication1
Modified residuei117Phosphothreonine; by DAPK1By similarity1
Cross-linki400Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Phosphorylation at Thr-117 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy (By similarity). In response to autophagic stimuli, phosphorylated at serine residues by AMPK in an ATG14-dependent manner, and this phosphorylation is critical for maximally efficient autophagy.By similarity1 Publication
Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'-linkages (By similarity). 'Lys-11'-linked poyubiquitination leads to degradation and is enhanced when the stabilizing interaction partner VPS34 is depleted (By similarity). Deubiquitinated by USP10 and USP13, leading to stabilize the PIK3C3/VPS34-containing complexes (By similarity). Polyubiquitinated at Lys-400 with 'Lys-48'-linkages (PubMed:28445460). 'Lys-48'-linked poyubiquitination of Lys-400 leads to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to stabilization (PubMed:28445460).By similarity1 Publication
Proteolytically processed by caspases including CASP8 and CASP3; the C-terminal fragments lack autophagy-inducing capacity and are proposed to induce apoptosis. Thus the cleavage is proposed to be an determinant to switch from autophagy to apoptosis pathways affecting cellular homeostasis including viral infections and survival of tumor cells.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO88597.
MaxQBiO88597.
PaxDbiO88597.
PRIDEiO88597.

PTM databases

iPTMnetiO88597.
PhosphoSitePlusiO88597.

Expressioni

Gene expression databases

BgeeiENSMUSG00000035086.
CleanExiMM_BECN1.
ExpressionAtlasiO88597. baseline and differential.
GenevisibleiO88597. MM.

Interactioni

Subunit structurei

A homodimeric form is proposed to exist; this metastable form readily transits to ATG14- or UVRAG-containing complexes with BECN1:UVRAG being more stable than BECN1:ATG14 (By similarity). Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex whose core is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1, and associates with additional regulatory/auxilliary subunits to form alternative complex forms. Accepted alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG (PubMed:19270693, PubMed:23332761). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (By similarity). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:19270693). PI3KC3-C1 probably associates with PIK3CB (PubMed:21059846.) Interacts with AMBRA1, GOPC, GRID2 and PIK3CB (PubMed:12372286, PubMed:17589504). Interacts with BCL2 and BCL2L1 isoform Bcl-X(L); the interaction inhibits BECN1 function in promoting autophagy by interfering with the formation of the PI3K complex (By similarity). Interacts with cytosolic HMGB1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with USP10, USP13, VMP1, DAPK1 (By similarity). Interacts with the poly-Gln domain of ATXN3; the interaction causes deubiquitination at Lys-400 and stabilizes BECN1 (PubMed:28445460). Interacts with SLAMF1 (PubMed:22493499). Interacts with TRIM5; the interaction causes activation of BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (By similarity). Interacts with active ULK1 (phosphorylated on 'Ser-317') and MEFV simultaneously (By similarity). Interacts with murine gammaherpesvirus 68 M11; the viral protein binds BECN1 with higher affinity than cellular BCL2 (PubMed:18248095). Interacts with WDR81 and WDR91; negatively regulates the PI3 kinase/PI3K activity associated with endosomal membranes (By similarity). Interacts with LAPTM4B; competes with EGFR for LAPTM4B binding; regulates EGFR activity (By similarity).By similarityCurated8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207843. 12 interactors.
CORUMiO88597.
DIPiDIP-41636N.
IntActiO88597. 17 interactors.
MINTiMINT-1791911.
STRINGi10090.ENSMUSP00000119369.

Structurei

Secondary structure

1448
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi107 – 121Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BL2X-ray2.30C/D106-124[»]
ProteinModelPortaliO88597.
SMRiO88597.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO88597.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni110 – 157Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)By similarityAdd BLAST48
Regioni243 – 448Evolutionary conserved domain (ECD)1 PublicationAdd BLAST206
Regioni423 – 448Required for membrane-associationBy similarityAdd BLAST26

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili140 – 268Sequence analysisAdd BLAST129

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi106 – 125BH3By similarityAdd BLAST20

Domaini

The coiled coil domain can form antiparallel homodimers and mediates dimerization with the coiled coil domains of ATG14 or UVRAG involved in the formation of PI3K complexes.By similarity
The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD. As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3.1 Publication

Sequence similaritiesi

Belongs to the beclin family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2751. Eukaryota.
ENOG410XQ85. LUCA.
GeneTreeiENSGT00390000008164.
HOGENOMiHOG000158093.
HOVERGENiHBG003181.
InParanoidiO88597.
KOiK08334.
OMAiMRYAQMQ.
OrthoDBiEOG091G0COC.
PhylomeDBiO88597.
TreeFamiTF314282.

Family and domain databases

InterProiView protein in InterPro
IPR007243. Atg6/Beclin.
IPR032913. BECN1.
IPR029318. BH3_dom.
PANTHERiPTHR12768. PTHR12768. 1 hit.
PTHR12768:SF6. PTHR12768:SF6. 1 hit.
PfamiView protein in Pfam
PF04111. APG6. 1 hit.
PF15285. BH3. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O88597-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGSKASSST MQVSFVCQRC SQPLKLDTSF KILDRVTIQE LTAPLLTTAQ
60 70 80 90 100
AKPGETQEEE ANSGEEPFIE TRQDGVSRRF IPPARMMSTE SANSFTLIGE
110 120 130 140 150
ASDGGTMENL SRRLKVTGDL FDIMSGQTDV DHPLCEECTD TLLDQLDTQL
160 170 180 190 200
NVTENECQNY KRCLEILEQM NEDDSEQLQR ELKELALEEE RLIQELEDVE
210 220 230 240 250
KNRKVVAENL EKVQAEAERL DQEEAQYQRE YSEFKRQQLE LDDELKSVEN
260 270 280 290 300
QVRYAQIQLD KLKKTNVFNA TFHIWHSGQF GTINNFRLGR LPSVPVEWNE
310 320 330 340 350
INAAWGQTVL LLHALANKMG LKFQRYRLVP YGNHSYLESL TDKSKELPLY
360 370 380 390 400
CSGGLRFFWD NKFDHAMVAF LDCVQQFKEE VEKGETRFCL PYRMDVEKGK
410 420 430 440
IEDTGGSGGS YSIKTQFNSE EQWTKALKFM LTNLKWGLAW VSSQFYNK
Length:448
Mass (Da):51,589
Last modified:July 27, 2011 - v3
Checksum:i14623BA002E1AAEE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37T → A in AAC68654 (PubMed:9765397).Curated1
Sequence conflicti228Q → H in AAC68654 (PubMed:9765397).Curated1
Sequence conflicti268F → L in AAC68654 (PubMed:9765397).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077302 mRNA. Translation: AAC68654.2.
AK032176 mRNA. Translation: BAC27745.1.
AK050329 mRNA. Translation: BAC34192.1.
AK083800 mRNA. Translation: BAC39021.1.
AL590969 Genomic DNA. Translation: CAM19559.1.
BC005770 mRNA. Translation: AAH05770.1.
CCDSiCCDS25462.1.
RefSeqiNP_062530.2. NM_019584.3.
UniGeneiMm.178947.
Mm.288064.

Genome annotation databases

EnsembliENSMUST00000130916; ENSMUSP00000119369; ENSMUSG00000035086.
GeneIDi56208.
KEGGimmu:56208.
UCSCiuc007loj.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiBECN1_MOUSE
AccessioniPrimary (citable) accession number: O88597
Secondary accession number(s): Q99J03
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: July 27, 2011
Last modified: October 25, 2017
This is version 153 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families