BECN1

This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants.

Beclin 1

Beclin 1; Coiled-Coil Myosin-Like BCL2-Interacting Protein; Beclin 1, Autophagy Related; Beclin 1 (Coiled-Coil, Moesin-Like BCL2 Interacting Protein); Beclin 1 (Coiled-Coil, Moesin-Like BCL2-Interacting Protein); ATG6 Autophagy Related 6 Homolog (S. Cerevisiae); Testis Secretory Sperm-Binding Protein Li 215e; ATG6 Autophagy Related 6 Homolog;

Plays a central role in autophagy (PubMed:23184933, PubMed:28445460).
Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms 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. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530, PubMed:26783301).
Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521).
Protects against infection by a neurovirulent strain of Sindbis virus (PubMed:9765397).
May play a role in antiviral host defense.
Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors.

Aging Source: Ensembl
Amyloid-beta metabolic process Source: Ensembl
Apoptotic process Source: UniProtKB-KW
Autophagosome assembly Source: UniProtKB
Autophagy Source: CAFA
Autophagy of mitochondrion Source: ParkinsonsUK-UCL
Cell division Source: UniProtKB-KW
Cellular defense response Source: ProtInc
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
Defense response to virus Source: UniProtKB-KW
Early endosome to late endosome transport Source: UniProtKB
Engulfment of apoptotic cell Source: Ensembl
Late endosome to vacuole transport Source: GO_Central
Lysosome organization Source: Ensembl
Macroautophagy Source: UniProtKB
Mitophagy Source: ParkinsonsUK-UCL
Mitotic metaphase plate congression Source: CACAO
Negative regulation of apoptotic process Source: ProtInc
Negative regulation of autophagosome assembly Source: Ensembl
Negative regulation of cell death Source: MGI
Negative regulation of cell population proliferation Source: Ensembl
Negative regulation of lysosome organization Source: Ensembl
Negative regulation of reactive oxygen species metabolic process Source: Ensembl
Neuron development Source: Ensembl
Positive regulation of attachment of mitotic spindle microtubules to kinetochore Source: CACAO
Positive regulation of autophagosome assembly Source: Ensembl
Positive regulation of cardiac muscle hypertrophy Source: Ensembl
Positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signaling Source: ParkinsonsUK-UCL
Protein deubiquitination Source: Reactome
Receptor catabolic process Source: UniProtKB
Regulation of catalytic activity Source: Ensembl
Regulation of cytokinesis Source: UniProtKB
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: BHF-UCL
Response to vitamin E Source: Ensembl
Viral process Source: UniProtKB-KW

Cytoplasm; Endoplasmic reticulum membrane; Mitochondrion membrane; Trans-Golgi network membrane; Endosome membrane; Endosome; Autophagosome. Interaction with ATG14 promotes translocation to autophagosomes. Expressed in dendrites and cell bodies of cerebellar Purkinje cells (By similarity).
Beclin-1-C 35 kDa: Cytoplasm; Mitochondrion; Nucleus
Beclin-1-C 37 kDa: Mitochondrion

Phosphorylation at Thr-119 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy (PubMed:19180116). 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 (PubMed:23878393).
Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'-linkages (PubMed:21936852). 'Lys-11'-linked polyubiquitination leads to degradation and is enhanced when the stabilizing interaction partner VPS34 is depleted (PubMed:21936852). Deubiquitinated by USP10 and USP13, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). Polyubiquitinated at Lys-402 with 'Lys-48'-linkages (PubMed:28445460). 'Lys-48'-linked polyubiquitination of Lys-402 leads to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to stabilization (PubMed:28445460).
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.