BECN2/Beclin 2 is a mammalian Beclin-family autophagy and endolysosomal trafficking regulator. It interacts with class III PI3K complex components including PIK3C3/VPS34 and ATG14/UVRAG-associated partners to support autophagy/autophagosome assembly, and it also mediates GASP1/GPRASP1-dependent lysosomal degradation of GPCRs. Beclin-family PI3KC3/autophagy-complex participation is a shared core role, while GPCR catabolism is a BECN2-specific functional branch.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000423 mitophagy | IBA GO_REF:0000033 | MODIFY | Summary: Mitophagy is too cargo-specific for accessible BECN2 evidence; the supported Beclin-family role is autophagosome assembly/autophagy. Reason: Modify to autophagosome assembly. BECN2 is directly supported in autophagy and ATG14/PI3KC3 complex context, but neither the cached human paper nor UniProt establishes a BECN2-specific mitophagy role. Quiles et al. 2023 (PMID:36719945) directly show that selective mitophagy is impaired by BECN1 loss but not BECN2 loss, while BECN2 still contributes to general autophagosome formation, independently corroborating this reassignment. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy PMID:28218432 ATG14 binding to BECN/Beclin homologs is essential for autophagy file:human/BECN2/BECN2-uniprot.txt GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: BECN2 has a supported adaptor/scaffold role in autophagy and GPCR degradation complexes. Reason: Accept as core molecular function. BECN2 links Beclin-family PI3KC3/autophagy components and GASP1-dependent GPCR degradation machinery. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 file:human/BECN2/BECN2-uniprot.txt acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover |
| GO:0043548 phosphatidylinositol 3-kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phosphatidylinositol 3-kinase binding is supported by BECN2 interaction with PIK3C3/VPS34 and other PI3KC3 complex components. Reason: Accept as core molecular function/context. BECN2 interacts with class III PI3K complex components and UniProt specifically records PIK3C3/VPS34 interaction. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 file:human/BECN2/BECN2-uniprot.txt Interacts with AMBRA1, UVRAG and PIK3C3/VPS34 file:human/BECN2/BECN2-uniprot.txt GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central file:human/BECN2/BECN2-uniprot.txt GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central |
| GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I | IBA GO_REF:0000033 | ACCEPT | Summary: BECN2 is supportable in ATG14-containing class III PI3K complex I/autophagy-initiation context. Reason: Accept as PN-relevant complex membership/context. BECN2 interacts with ATG14 and PIK3C3/VPS34 and is annotated by UniProt/GO Central to PI3KC3-C1. Supporting Evidence: file:human/BECN2/BECN2-uniprot.txt GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central file:human/BECN2/BECN2-uniprot.txt Interacts (via coiled-coil domain) with ATG14 file:human/BECN2/BECN2-uniprot.txt Interacts with AMBRA1, UVRAG and PIK3C3/VPS34 PMID:28218432 the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer |
| GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II | IBA GO_REF:0000033 | ACCEPT | Summary: BECN2 is also supportable in UVRAG-containing class III PI3K complex II/endolysosomal context. Reason: Accept as supported complex membership/context. BECN2 interacts with UVRAG and PIK3C3/VPS34 and has a direct endolysosomal GPCR degradation role. Supporting Evidence: file:human/BECN2/BECN2-uniprot.txt GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central file:human/BECN2/BECN2-uniprot.txt Interacts with AMBRA1, UVRAG and PIK3C3/VPS34 PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 functions in an additional lysosomal degradation pathway |
| GO:0006995 cellular response to nitrogen starvation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nitrogen-starvation response is plausible autophagy context but is not the most informative BECN2 process annotation. Reason: Keep as non-core. Starvation is an autophagy context transferred from evolutionary models; the direct human evidence supports autophagy/autophagosome assembly and GPCR turnover. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy file:human/BECN2/BECN2-uniprot.txt acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover |
| GO:0045324 late endosome to vacuole transport | IBA GO_REF:0000033 | MODIFY | Summary: Late endosome to vacuole transport should be translated to the supported human endosome-to-lysosome/GPCR degradation context. Reason: Modify to endosome to lysosome transport. BECN2 is directly required for ligand-induced endolysosomal degradation of GPCRs, while vacuole wording is yeast-specific transfer. Proposed replacements: endosome to lysosome transport Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 functions in an additional lysosomal degradation pathway file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm is supported as the broad BECN2 cellular location. Reason: Accept as supported location. UniProt places BECN2 in the cytoplasm, consistent with its autophagy and endolysosomal trafficking roles. Supporting Evidence: file:human/BECN2/BECN2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 |
| GO:0006914 autophagy | IEA GO_REF:0000120 | ACCEPT | Summary: Autophagy is a core BECN2 process. Reason: Accept as core process. The primary paper explicitly identifies Beclin 2 as functioning in autophagy and the mouse knockout phenotype includes defective autophagy. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy PMID:23954414 converging regulator of autophagy and GPCR turnover PMID:28218432 ATG14 binding to BECN/Beclin homologs is essential for autophagy |
| GO:0032801 receptor catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Receptor catabolic process is supported by BECN2-dependent GPCR endolysosomal degradation. Reason: Accept as a supported parent process for the more specific GPCR catabolic role. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0005515 protein binding | IPI PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not an informative BECN2 molecular-function annotation. Reason: Mark as over-annotated. The same evidence is better represented as adaptor activity, PI3K binding, ATG14/UVRAG/PIK3C3 complex context, and GASP1-dependent GPCR catabolism. Supporting Evidence: PMID:23954414 through its interaction with GASP1 file:human/BECN2/BECN2-uniprot.txt Interacts (via coiled-coil domain) with ATG14 file:human/BECN2/BECN2-uniprot.txt Interacts with AMBRA1, UVRAG and PIK3C3/VPS34 |
| GO:0008333 endosome to lysosome transport | IEA GO_REF:0000107 | ACCEPT | Summary: Endosome to lysosome transport is a core BECN2 process through GPCR endolysosomal degradation. Reason: Accept as core process. BECN2 is required for ligand-induced endolysosomal degradation of GPCRs through GASP1/GPRASP1 interaction. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 functions in an additional lysosomal degradation pathway file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MODIFY | Summary: Protein-containing complex binding is broadly true but less informative than adaptor activity for BECN2. Reason: Modify to protein-macromolecule adaptor activity. BECN2 uses interactions with PI3KC3/autophagy components and GASP1 to mediate lysosomal degradation pathways. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) file:human/BECN2/BECN2-uniprot.txt acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover |
| GO:1990172 G protein-coupled receptor catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: G protein-coupled receptor catabolic process is a core BECN2-specific process. Reason: Accept as core process. This is the distinctive BECN2 branch not shared with BECN1: BECN2 is required for ligand-induced endolysosomal degradation of GPCRs via GASP1. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 increased levels of brain cannabinoid 1 receptor file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0006914 autophagy | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: Autophagy is a core BECN2 process. Reason: Accept as core process. The primary paper explicitly identifies Beclin 2 as functioning in autophagy and the mouse knockout phenotype includes defective autophagy. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy PMID:23954414 converging regulator of autophagy and GPCR turnover PMID:28218432 ATG14 binding to BECN/Beclin homologs is essential for autophagy |
| GO:0008333 endosome to lysosome transport | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: Endosome to lysosome transport is a core BECN2 process through GPCR endolysosomal degradation. Reason: Accept as core process. BECN2 is required for ligand-induced endolysosomal degradation of GPCRs through GASP1/GPRASP1 interaction. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 functions in an additional lysosomal degradation pathway file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:1990172 G protein-coupled receptor catabolic process | IPI PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: G protein-coupled receptor catabolic process is a core BECN2-specific process. Reason: Accept as core process. This is the distinctive BECN2 branch not shared with BECN1: BECN2 is required for ligand-induced endolysosomal degradation of GPCRs via GASP1. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 increased levels of brain cannabinoid 1 receptor file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0006914 autophagy | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: Autophagy is a core BECN2 process. Reason: Accept as core process. The primary paper explicitly identifies Beclin 2 as functioning in autophagy and the mouse knockout phenotype includes defective autophagy. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy PMID:23954414 converging regulator of autophagy and GPCR turnover PMID:28218432 ATG14 binding to BECN/Beclin homologs is essential for autophagy |
| GO:0008333 endosome to lysosome transport | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: Endosome to lysosome transport is a core BECN2 process through GPCR endolysosomal degradation. Reason: Accept as core process. BECN2 is required for ligand-induced endolysosomal degradation of GPCRs through GASP1/GPRASP1 interaction. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 functions in an additional lysosomal degradation pathway file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:1990172 G protein-coupled receptor catabolic process | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | ACCEPT | Summary: G protein-coupled receptor catabolic process is a core BECN2-specific process. Reason: Accept as core process. This is the distinctive BECN2 branch not shared with BECN1: BECN2 is required for ligand-induced endolysosomal degradation of GPCRs via GASP1. Supporting Evidence: PMID:23954414 required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) PMID:23954414 through its interaction with GASP1 PMID:23954414 increased levels of brain cannabinoid 1 receptor file:human/BECN2/BECN2-uniprot.txt Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1 |
| GO:0000045 autophagosome assembly | IMP PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | NEW | Summary: BECN2 supports autophagosome assembly through ATG14/PI3KC3 autophagy-complex context. Reason: Add as a new PN-relevant process annotation. BECN2 functions in autophagy, interacts with class III PI3K components, and binds ATG14 through its coiled-coil domain; UniProt/GO Central already lists autophagosome assembly for BECN2. Supporting Evidence: PMID:23954414 functions in autophagy and interacts with class III PI3K complex components and Bcl-2 PMID:23954414 heterozygous knockout mice have defective autophagy PMID:28218432 ATG14 binding to BECN/Beclin homologs is essential for autophagy PMID:28218432 the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer file:human/BECN2/BECN2-uniprot.txt GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central |
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Download this section (compressed HTML)Q: Should BECN2 be curated to PI3KC3-C1 and PI3KC3-C2 complex membership as direct human complex membership or retained primarily as Beclin-family/evolutionary inference?
Suggested experts: GO autophagy editors, Reactome autophagy curators, PAINT curators
Q: Should BECN2 mitophagy be removed or generalized to autophagosome assembly/autophagy unless direct cargo-specific mitophagy evidence is found?
Suggested experts: GO autophagy editors, mitophagy domain experts
Q: What is the most specific GO molecular function for the BECN2-GASP1 GPCR degradation role: adaptor activity, protein-containing complex binding, or a future GPCR-degradation adaptor term?
Suggested experts: GO molecular function editors, GPCR trafficking curators
Q: Should BECN2 acquire process annotations for its ATG9A-dependent (LC3/ATG16L1-independent) non-canonical autophagic degradation of inflammasome sensors and of MAP3K7/MAP3K3, and for negative regulation of NF-kB/innate immune signaling (PMID:34152938, PMID:32865519), given these are not represented in the current GOA-seeded annotations?
Suggested experts: GO autophagy editors, GO immunology curators
Experiment: Use BECN2 knockout/rescue with ATG14-binding coiled-coil mutants to measure PI3KC3 complex association, WIPI/LC3 recruitment, autophagosome assembly, and autophagic flux.
Hypothesis: BECN2 supports autophagosome assembly through ATG14/PI3KC3 complex recruitment rather than by a generic Beclin-family label alone.
Type: autophagy complex rescue assay
Experiment: Use BECN2 I80S/GASP1-binding mutants and GPCR ligand stimulation to separate GPCR lysosomal degradation from autophagy phenotypes in the same cellular background.
Hypothesis: BECN2 has separable autophagy and GPCR endolysosomal degradation functions, with GASP1 binding specifically required for GPCR turnover.
Type: separation-of-function GPCR degradation assay
Experiment: In BECN2-deficient macrophages, test whether ATG9A or ULK1 ablation (versus ATG16L1/LC3 loss) is required for accumulation of inflammasome sensors (NLRP3/AIM2/NLRP1/NLRC4) and of MAP3K7/MAP3K3, measuring sensor/kinase half-life and downstream IL1B, NF-kB, and ERK1/2 activation.
Hypothesis: BECN2 restrains innate immune signaling by routing inflammasome sensors and MAP3K kinases to ATG9A-dependent, LC3/ATG16L1-independent lysosomal degradation, distinct from canonical BECN1 autophagy.
Type: non-canonical autophagic degradation assay
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