BECN1

GeneName

BECN1

Summary

BECN1, also known as Beclin1, Beclin-1, or Beclin 1, is a 52 kDa protein that plays a crucial role in autophagy, a cellular degradation process. It is localised to various cellular compartments, including the cytoplasm, endoplasmic reticulum, mitochondria, and autophagosomes. BECN1 functions as a molecular adaptor and is involved in the assembly and maturation of autophagosomes, facilitating the degradation of cellular components and organelles. It interacts with multiple proteins, including those in the phosphatidylinositol 3-kinase complex, to regulate autophagic processes and cellular responses to stressors such as nutrient deprivation and oxidative stress.

Importance

BECN1 is relevant to: - Autophagy and cellular homeostasis, impacting processes such as cellular defence responses and apoptosis - Neurodegenerative diseases, including Alzheimer’s, through its role in amyloid-beta metabolism and clearance - Cancer biology, as it influences cell proliferation and survival through its regulatory effects on autophagy - Metabolic disorders, given its involvement in responses to nutrient availability and stressors

Top Products

For researchers investigating BECN1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-Beclin 1 antibody (ab62557), which has garnered 342 citations, reflecting its reliability in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). This antibody is a trusted choice for those looking to study BECN1 in various contexts.Additionally, we offer the recombinant antibody, Anti-Beclin 1 antibody [EPR19662] (ab207612), which has been validated in knockout models and is suitable for Western blotting (WB) and immunoprecipitation (IP). With 415 citations, this monoclonal antibody is ideal for researchers seeking the consistency and specificity that recombinant antibodies provide. Together, these products represent a robust toolkit for studying BECN1 effectively. The Recombinant Human Beclin 1 protein ELISA Kit (ab137161), supported by 3 citations, is an excellent option for researchers looking to accurately measure BECN1 levels in their samples.

Abcam Product Citation Summary

The data indicates a strong focus on the role of BECN1 in various contexts related to autophagy, particularly in human cell lines and tissues. Studies have explored its involvement in cancer, hypoxia, and cellular responses to stress, highlighting its significance in both normal physiological processes and pathological conditions. The use of multiple antibodies across different species underscores the importance of BECN1 in research aimed at understanding autophagy mechanisms.

Abcam Product Citation Table

Domain

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.

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 (PubMed:28445460). As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3 (PubMed:28445460).

Function

Plays a central role in autophagy (PubMed:18570871, PubMed:21358617, PubMed:23184933, PubMed:23974797, PubMed:25484083, PubMed:28445460, PubMed:37776275). Acts as a 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 abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123, PubMed:23974797, PubMed:26783301). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). 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.

(Microbial infection) Protects against infection by a neurovirulent strain of Sindbis virus.

Post-translational modifications

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, PubMed:25891078).

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). Ubiquitinated at Lys-437 via 'Lys-63'-linkage by the DCX(AMBRA1) complex, thereby increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (PubMed:23974797). 'Lys-48'-linked ubiquitination by RNF216 leads to proteasomal degradation and autophagy inhibition (PubMed:25484083).

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.

Sequence Similarities

Belongs to the beclin family.

Tissue Specificity

Ubiquitous.

Cellular localization

• Cytoplasm
• Golgi apparatus
• trans-Golgi network membrane
• Peripheral membrane protein
• Endosome membrane
• Peripheral membrane protein
• Endoplasmic reticulum membrane
• Peripheral membrane protein
• Mitochondrion membrane
• Peripheral membrane protein
• Endosome
• Cytoplasmic vesicle
• 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
• Mitochondrion
• Nucleus
• Cytoplasm
• Beclin-1-C 37 kDa
• Mitochondrion

Alternative names

GT197, BECN1, Beclin-1, Coiled-coil myosin-like BCL2-interacting protein, Protein GT197

Database links

swissprot:Q14457 omim:604378 entrezGene:8678

Other research areas

• Neuroscience