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Protein

Beclin-1

Gene

Becn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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 Expressed in 287 organ(s), highest expression level in blood
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 TRIM50 (PubMed:29604308). Interacts with TRIM16 (By similarity). 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 similarityCurated9 Publications
(Microbial infection) Interacts with murine gammaherpesvirus 68 M11; the viral protein binds BECN1 with higher affinity than cellular BCL2.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207843, 11 interactors
ComplexPortaliCPX-75 Phosphatidylinositol 3-kinase complex, class III, ATG14 variant
CPX-76 Phosphatidylinositol 3-kinase complex, class III, UVRAG variant
CORUMiO88597
DIPiDIP-41636N
IntActiO88597, 17 interactors
MINTiO88597
STRINGi10090.ENSMUSP00000119369

Structurei

Secondary structure

1448
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiYIPPARM
OrthoDBiEOG091G0COC
PhylomeDBiO88597
TreeFamiTF314282

Family and domain databases

Gene3Di1.10.418.40, 1 hit
InterProiView protein in InterPro
IPR007243 Atg6/Beclin
IPR038274 Atg6/Beclin_C_sf
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PYD6E9PYD6_MOUSE
Beclin-1
Becn1
277Annotation score:
F7CVL9F7CVL9_MOUSE
Beclin-1
Becn1
125Annotation score:
F7C090F7C090_MOUSE
Beclin-1
Becn1
168Annotation score:
F7DB15F7DB15_MOUSE
Beclin-1
Becn1
110Annotation score:
E9QAM0E9QAM0_MOUSE
Beclin-1
Becn1
105Annotation score:
E9PX06E9PX06_MOUSE
Beclin-1
Becn1
46Annotation score:

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 No translation available.
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

Cross-referencesi

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 No translation available.
BC005770 mRNA Translation: AAH05770.1
CCDSiCCDS25462.1
RefSeqiNP_062530.2, NM_019584.3
UniGeneiMm.178947
Mm.288064

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BL2X-ray2.30C/D106-124[»]
5YR0X-ray1.90A174-223[»]
ProteinModelPortaliO88597
SMRiO88597
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207843, 11 interactors
ComplexPortaliCPX-75 Phosphatidylinositol 3-kinase complex, class III, ATG14 variant
CPX-76 Phosphatidylinositol 3-kinase complex, class III, UVRAG variant
CORUMiO88597
DIPiDIP-41636N
IntActiO88597, 17 interactors
MINTiO88597
STRINGi10090.ENSMUSP00000119369

PTM databases

iPTMnetiO88597
PhosphoSitePlusiO88597

Proteomic databases

EPDiO88597
MaxQBiO88597
PaxDbiO88597
PRIDEiO88597

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8678
MGIiMGI:1891828 Becn1

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiBecn1 mouse
EvolutionaryTraceiO88597
PROiPR:O88597
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035086 Expressed in 287 organ(s), highest expression level in blood
CleanExiMM_BECN1
ExpressionAtlasiO88597 baseline and differential
GenevisibleiO88597 MM

Family and domain databases

Gene3Di1.10.418.40, 1 hit
InterProiView protein in InterPro
IPR007243 Atg6/Beclin
IPR038274 Atg6/Beclin_C_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 163 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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