Beclin 2, a mammal-specific homolog of Beclin 1 with unique functional similarities and differences

Wed, 07/15/2015 - 15:57

Beclin 2 (BECN2) is also called Beclin-1-like protein 1/ BECN1P1 and it was recently identified by He et al 2013 as a mammal-specific homolog of the evolutionarily conserved protein Beclin 1 which is well established for its role in the regulation of autophagy and oncogenic suppression (1). He et al 2013 documented that human Beclin 2 is 57% similar to Beclin 1, and they confirmed its presence in several tissues including brain, placenta, thymus, uterus and skeletal muscles. Further studies from various labs established Beclin-2’s critical role in two distinct lysosomal degradation pathways: as a regulator of autophagy and as a regulator of G-protein coupled receptors/GPCRs turnover. Like Beclin 1, Beclin 2 was also found to regulate autophagy and its effects were demonstrated in basal or starvation-induced autophagy experiments involving bafilomycin A1 and cultured mammalian cells wherein it distinctly reduced the degradation of autophagic substrate p62, the aggregation of a fluorescent form of LC3 into cytoplasmic dots and the lipidation of endogenous LC3 (1, 2). Beclin 2 physically interact with several proteins namely VPS34, ATG14, AMBRA1, BCL2 and UVRAG but not with RUBICON/ KIAA0226, a known BECN1-binding partner and a negative regulator of autophagy, suggesting that Beclin 2 -mediated autophagy is independent of Beclin 1 or RUBICON (2). In an interesting observation, Wei’s lab employed Beclin 2 antibody (NB110- 60984) in WB application on lysates of HeLa cells subjected or not to knockout of BECN1 followed by exogenous expression of BECN1, and demonstrated that the loss of Beclin 1 does not have any effect on Beclin 2 expression (3)

Beclin 2 Antibody [NB110-60984] - Simple Western lane view shows a specific band for Beclin 2 in 0.5 mg/ml of HeLa lysate. This experiment was performed under reducing conditions using the 12-230 kDa separation system.

Unlike Beclin 1, Beclin 2 specifically interacts/binds with GPCR -associated sorting protein 1 (GASP1 or GPRASP1) and this direct interaction was found to be essential for the agonist-induced lysosomal degradation of GPCRs such as DOR/opioid receptor delta 1 and CB1R/ cannabinoid receptor 1 (1). Beclin 2 has been revealed as a novel regulator of metabolism, obesity and diabetes, and haploinsufficiency of Beclin 2 was observed to lead to increased food intake, obesity and aggravated insulin resistance, which was suggested to be related to enhanced​ CB1R signaling rather than decreased autophagic activity (1, 4).

Beclin 2 is unique for its mammal-specific presence and its differential roles vs Beclin 1, and it would be exciting to further delineate its functional protein-protein interactions under physiological as well as  stress conditions in experiments involving autophagy signaling and mammalian-specific biological functions.

Novus Biologicals offers a variety of Beclin 2 products for your research needs including: Beclin 2 Primary Antibodies Beclin 1/ATG6 Peptides and Proteins


  • PMID 23954414
  • PMID: 24018378
  • PMID: 25955014
  • PMID: 24991830
  By: Subhash Gangar

Blog Topics