BECN1

UniProt ID: Q14457
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

Beclin-1 is the central scaffold subunit of class III phosphatidylinositol 3-kinase (PI3KC3/VPS34) complexes that generate phosphatidylinositol 3-phosphate (PI3P) for autophagosome biogenesis and endocytic trafficking. BECN1 forms two mutually exclusive complexes: PI3KC3-C1 (with ATG14L) for autophagosome nucleation, and PI3KC3-C2 (with UVRAG) for endosome maturation and endocytic trafficking. The protein contains an N-terminal BH3 domain (aa 108-127) that binds BCL2/BCL-XL to regulate autophagy, a coiled-coil domain (CCD; aa 144-269) for dimerization and partner binding, and a C-terminal BARA/ECD membrane-binding domain. BECN1 is a haploinsufficient tumor suppressor and is essential for autophagy initiation through its adapter function in assembling PI3KC3 complex components.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000045 autophagosome assembly
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 is essential for autophagosome assembly as the scaffold subunit of PI3KC3-C1 complex. This is a core function supported by extensive literature showing BECN1 with ATG14L, VPS34, and VPS15 generates PI3P required for phagophore nucleation (PMID:25891078, PMID:23878393).
Reason: This is a core function of BECN1. The protein is the central scaffold of the PI3KC3-C1 complex that initiates autophagosome formation. The IBA annotation is based on phylogenetic inference including yeast Atg6/Vps30 and is strongly supported by direct experimental evidence.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly thus governing the formation of autophagy initiation complexes.
PMID:23878393
Human beclin-1 and its yeast homologue, Atg6/Vps30, are scaffold proteins bound in a lipid kinase complex with multiple cellular functions, including autophagy.
file:human/BECN1/BECN1-deep-research-falcon.md
model: Edison Scientific Literature
GO:0000423 mitophagy
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 is specifically required for efficient mitophagy. Recent work shows Beclin-1 uniquely supports mitophagy by localizing to mitochondria-ER contact sites (MAMs) upon ULK1-Ser15 phosphorylation. Beclin-2 cannot substitute for this function (PMID:quiles2023, deep research).
Reason: Core function. BECN1 is required for selective mitophagy through its localization to MAMs during mitochondrial depolarization. This is a specific autophagy-related function.
Supporting Evidence:
PMID:23878393
We identified a unique domain in beclin-1, conserved in the yeast homologue Atg6, which is involved in membrane association
GO:0030674 protein-macromolecule adaptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 functions as an adapter/scaffold to assemble the PI3KC3 complexes. It bridges VPS34/VPS15 with ATG14L or UVRAG to form functional lipid kinase complexes. This is its primary molecular function.
Reason: Core molecular function. BECN1 is definitionally an adapter protein that scaffolds multiple components of the autophagy initiation machinery. The deep research confirms this is its primary molecular function.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly thus governing the formation of autophagy initiation complexes.
GO:0043548 phosphatidylinositol 3-kinase binding
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 directly binds VPS34 (PIK3C3), the catalytic subunit of the class III PI3K, through its coiled-coil and BARA domains. This interaction is essential for PI3KC3 complex function.
Reason: Core molecular function. BECN1 binding to VPS34 is fundamental to its role in forming PI3KC3 complexes for autophagy and endocytic trafficking.
Supporting Evidence:
PMID:23878393
Human beclin-1 and its yeast homologue, Atg6/Vps30, are scaffold proteins bound in a lipid kinase complex
GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 is a defining subunit of PI3KC3-C1, the autophagy-specific complex containing BECN1-VPS34-VPS15-ATG14L. This complex generates PI3P for autophagosome nucleation.
Reason: Core localization. BECN1 is an obligate component of PI3KC3-C1, the autophagy initiation complex.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly
GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 is a defining subunit of PI3KC3-C2, the endocytic trafficking complex containing BECN1-VPS34-VPS15-UVRAG. This complex is involved in endosome maturation and receptor trafficking.
Reason: Core localization. BECN1 is an obligate component of PI3KC3-C2. The deep research confirms PI3KC3-C2 (UVRAG-containing) is involved in endosome maturation and receptor sorting.
GO:0000407 phagophore assembly site
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 localizes to the phagophore assembly site (PAS) as part of the PI3KC3-C1 complex to initiate autophagosome formation. This is consistent with its function in autophagy initiation.
Reason: Core localization for autophagy function. The PI3KC3-C1 complex localizes to PAS.
GO:0006995 cellular response to nitrogen starvation
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 is activated during nitrogen/amino acid starvation to induce autophagy. This is conserved from yeast (Atg6/Vps30) through humans.
Reason: Core function. Autophagy induction in response to nutrient starvation is a fundamental BECN1 function.
GO:0045324 late endosome to vacuole transport
IBA
GO_REF:0000033
ACCEPT
Summary: BECN1 in the PI3KC3-C2 complex (with UVRAG) regulates endosome maturation including early-to-late endosome transport and late endosome-lysosome fusion.
Reason: Represents the endocytic trafficking function of BECN1 via PI3KC3-C2 complex. This is distinct from but related to autophagy.
GO:0005634 nucleus
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: BECN1 has been detected in the nucleus in some studies. UniProt annotation based on subcellular location vocabulary mapping.
Reason: Not a primary localization. BECN1 may transit through nucleus but its functional localization is cytoplasmic/membrane-associated.
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: BECN1 localizes to the cytoplasm where it assembles PI3KC3 complexes. This is consistent with experimental data.
Reason: Core localization. The cytoplasm is where BECN1 assembles with VPS34 and other components.
GO:0005739 mitochondrion
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 localizes to mitochondria-ER contact sites (MAMs) during mitophagy, where it promotes selective degradation of damaged mitochondria.
Reason: Supports mitophagy function. BECN1 relocates to MAMs during mitochondrial depolarization.
GO:0005768 endosome
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 localizes to endosomes as part of PI3KC3-C2 complex function in endocytic trafficking.
Reason: Consistent with PI3KC3-C2 function in endosome maturation.
GO:0005776 autophagosome
IEA
GO_REF:0000120
ACCEPT
Summary: BECN1 localizes to autophagosomes during their formation as part of PI3KC3-C1.
Reason: Core localization for autophagy function.
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 associates with ER membrane where autophagosome nucleation occurs. The ER is a major membrane source for autophagosome formation.
Reason: Consistent with autophagosome nucleation occurring at ER membranes.
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 localizes to Golgi/TGN membranes, particularly the PI3KC3-C2 complex which functions in TGN-proximal trafficking.
Reason: Consistent with PI3KC3-C2 function in membrane trafficking.
GO:0006897 endocytosis
IEA
GO_REF:0000043
ACCEPT
Summary: BECN1 in PI3KC3-C2 complex regulates endocytic trafficking, including receptor sorting and endosome maturation. This is a non-autophagy function.
Reason: Represents PI3KC3-C2 function. Not over-annotation - BECN1 has demonstrated roles in endocytic trafficking independent of autophagy.
GO:0006914 autophagy
IEA
GO_REF:0000120
ACCEPT
Summary: BECN1 is a central regulator of autophagy as the scaffold of PI3KC3-C1 complex.
Reason: Core function. Autophagy is the primary biological process for BECN1.
GO:0006915 apoptotic process
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: This annotation derives from UniProt keyword mapping. While BECN1 interacts with BCL2 family members via its BH3 domain, this interaction serves to REGULATE AUTOPHAGY, not apoptosis. BCL2/BCL-XL sequester BECN1 to inhibit autophagy; competitive displacement releases BECN1 for autophagy induction. The BH3 domain of BECN1 is atypical and has been "designed to induce autophagy by disrupting the Bcl-2-Beclin1 complex without inducing cell death" (PMID:19273585). BECN1 is not an apoptosis effector.
Reason: OVER-ANNOTATION. The BCL2 interaction is for autophagy regulation, not apoptosis. BECN1 contains a BH3-like domain but this domain functions in autophagy regulation by allowing BCL2 to sequester BECN1. When BH3-only proteins compete for BCL2 binding, BECN1 is released to activate autophagy - this is NOT an apoptotic function. The deep research clearly states BECN1's core function is autophagy/PI3KC3 scaffold, and the BCL2 binding is regulatory crosstalk.
Supporting Evidence:
PMID:19273585
we propose a model in which the atypical BH3 domains of hypoxia-induced BNIP3/BNIP3L have been designed to induce autophagy by disrupting the Bcl-2-Beclin1 complex without inducing cell death
PMID:17446862
The anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind and inhibit Beclin-1, an essential mediator of autophagy... BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-X(L).
GO:0010008 endosome membrane
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 localizes to endosome membranes as part of PI3KC3-C2 function.
Reason: Consistent with endocytic trafficking function.
GO:0031410 cytoplasmic vesicle
IEA
GO_REF:0000120
ACCEPT
Summary: BECN1 associates with various cytoplasmic vesicles including autophagosomes and endosomes.
Reason: General but accurate. BECN1 functions on multiple vesicle types.
GO:0031966 mitochondrial membrane
IEA
GO_REF:0000044
ACCEPT
Summary: BECN1 localizes to mitochondrial membranes, particularly MAMs during mitophagy.
Reason: Supports mitophagy function.
GO:0032801 receptor catabolic process
IEA
GO_REF:0000117
ACCEPT
Summary: BECN1 in PI3KC3-C2 complex is involved in receptor trafficking including EGFR sorting. The deep research mentions "receptor sorting (e.g., EGFR, TFR1)".
Reason: Consistent with PI3KC3-C2 function in endocytic trafficking and receptor turnover.
GO:0051301 cell division
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: BECN1 has been implicated in cytokinesis regulation through PI3KC3-C2 function. This represents a non-autophagy function.
Reason: Secondary function. BECN1 has been shown to regulate cytokinesis (PMID:20208530, PMID:20643123) but this is not its primary function.
GO:0051607 defense response to virus
IEA
GO_REF:0000043
ACCEPT
Summary: BECN1 was originally discovered as protective against Sindbis virus encephalitis (PMID:9765397). Autophagy plays a role in antiviral defense, and many viruses target BECN1 to evade autophagy.
Reason: Legitimate function. BECN1 plays a role in antiviral autophagy (xenophagy), and the original discovery paper demonstrated its protective role against viral infection.
Supporting Evidence:
PMID:9765397
These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.
GO:0005515 protein binding
IPI
PMID:17446862
Functional and physical interaction between Bcl-X(L) and a B...
REMOVE
Summary: This paper demonstrated physical interaction between BECN1 BH3 domain and BCL2/BCL-XL using multiple methods. The interaction regulates autophagy - BCL-XL inhibits BECN1-dependent autophagy through this binding.
Reason: Generic protein binding is uninformative. The specific binding activity (BCL2/BCL-XL binding) is captured in other more specific annotations. Should be annotated to a more specific MF term if appropriate.
Supporting Evidence:
PMID:17446862
The anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind and inhibit Beclin-1, an essential mediator of autophagy
GO:0005515 protein binding
IPI
PMID:19050071
Identification of Barkor as a mammalian autophagy-specific f...
REMOVE
Summary: This paper identified ATG14 (Barkor) as a BECN1-binding protein that directs BECN1/VPS34 to autophagosome formation sites. Core autophagy complex formation.
Reason: Generic protein binding is uninformative. The functional significance (autophagy complex formation) is captured in other annotations.
Supporting Evidence:
PMID:19050071
Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase.
GO:0005515 protein binding
IPI
PMID:19180116
DAP-kinase-mediated phosphorylation on the BH3 domain of bec...
REMOVE
Summary: This paper showed DAPK1 phosphorylates BECN1 at Thr119 in the BH3 domain to promote dissociation from BCL-XL and induce autophagy.
Reason: Generic protein binding is uninformative. The interaction with DAPK1 is functionally relevant to autophagy regulation.
Supporting Evidence:
PMID:19180116
DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy.
GO:0005515 protein binding
IPI
PMID:19959994
The IKK complex contributes to the induction of autophagy.
REMOVE
Summary: IKK complex interaction study. Protein binding annotation is too generic.
Reason: Generic protein binding term is uninformative for understanding gene function.
Supporting Evidence:
PMID:19959994
The IKK complex contributes to the induction of autophagy.
GO:0005515 protein binding
IPI
PMID:20562859
Network organization of the human autophagy system.
REMOVE
Summary: Network analysis of human autophagy system interactions.
Reason: Generic protein binding term is uninformative for understanding gene function.
Supporting Evidence:
PMID:20562859
Network organization of the human autophagy system.
GO:0005515 protein binding
IPI
PMID:20638385
Interaction of Beclin 1 with survivin regulates sensitivity ...
REMOVE
Summary: This paper studied BECN1-survivin interaction in glioma cells regarding TRAIL-induced apoptosis.
Reason: Generic protein binding. Also relates to apoptosis context which is not core BECN1 function.
Supporting Evidence:
PMID:20638385
Epub 2010 Jul 16. Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis.
GO:0005515 protein binding
IPI
PMID:20819940
Endogenous HMGB1 regulates autophagy.
REMOVE
Summary: HMGB1-BECN1 interaction study showing HMGB1 regulates autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:20819940
Endogenous HMGB1 regulates autophagy.
GO:0005515 protein binding
IPI
PMID:21062745
The RUN domain of rubicon is important for hVps34 binding, l...
REMOVE
Summary: Rubicon RUN domain interaction with VPS34 and BECN1 complex regulation.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:21062745
Nov 9. The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression.
GO:0005515 protein binding
IPI
PMID:21139567
MCL-1 is a stress sensor that regulates autophagy in a devel...
REMOVE
Summary: MCL-1 interaction with BECN1 to regulate autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:21139567
MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner.
GO:0005515 protein binding
IPI
PMID:21241894
RalB and the exocyst mediate the cellular starvation respons...
REMOVE
Summary: RalB and exocyst complex mediate autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:21241894
RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly.
GO:0005515 protein binding
IPI
PMID:21358617
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
REMOVE
Summary: Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy through BECN1 interaction. This paper demonstrates BCL2-BECN1 interaction at mitochondria regulates autophagy.
Reason: Generic protein binding. The BCL2 interaction is for autophagy regulation.
Supporting Evidence:
PMID:21358617
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
GO:0005515 protein binding
IPI
PMID:21597469
UV irradiation resistance-associated gene suppresses apoptos...
REMOVE
Summary: UVRAG suppresses apoptosis by interfering with BAX activation.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:21597469
UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation.
GO:0005515 protein binding
IPI
PMID:22028648
An integrated approach to elucidate the intra-viral and vira...
REMOVE
Summary: Gamma-herpesvirus protein interactome study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:22028648
2011 Oct 20. An integrated approach to elucidate the intra-viral and viral-cellular protein interaction networks of a gamma-herpesvirus.
GO:0005515 protein binding
IPI
PMID:22081109
Inhibition of autophagy by TAB2 and TAB3.
REMOVE
Summary: TAB2/TAB3 inhibit autophagy through BECN1 interaction.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:22081109
Inhibition of autophagy by TAB2 and TAB3.
GO:0005515 protein binding
IPI
PMID:22493499
Receptor signaling lymphocyte-activation molecule family 1 (...
REMOVE
Summary: SLAMF1 recruits BECN1-VPS34-UVRAG complex for NOX2 regulation.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:22493499
2012 Apr 9. Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex.
GO:0005515 protein binding
IPI
PMID:23112296
Akt-mediated regulation of autophagy and tumorigenesis throu...
REMOVE
Summary: Akt-mediated phosphorylation of BECN1 regulates autophagy and tumorigenesis.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23112296
Oct 25. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation.
GO:0005515 protein binding
IPI
PMID:23197835
Autophagosomes induced by a bacterial Beclin 1 binding prote...
REMOVE
Summary: Bacterial Beclin 1 binding protein study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23197835
Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection.
GO:0005515 protein binding
IPI
PMID:23316280
The VMP1-Beclin 1 interaction regulates autophagy induction.
REMOVE
Summary: VMP1-BECN1 interaction regulates autophagy induction.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23316280
The VMP1-Beclin 1 interaction regulates autophagy induction.
GO:0005515 protein binding
IPI
PMID:23332761
Differential regulation of distinct Vps34 complexes by AMPK ...
REMOVE
Summary: Differential regulation of VPS34 complexes by AMPK.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23332761
Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.
GO:0005515 protein binding
IPI
PMID:23364696
Identification of a candidate therapeutic autophagy-inducing...
REMOVE
Summary: Identification of autophagy-inducing peptide derived from BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23364696
Identification of a candidate therapeutic autophagy-inducing peptide.
GO:0005515 protein binding
IPI
PMID:23478334
Beclin-1 is required for chromosome congression and proper o...
REMOVE
Summary: BECN1 is required for chromosome congression and kinetochore assembly. This is a non-autophagy function.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23478334
Beclin-1 is required for chromosome congression and proper outer kinetochore assembly.
GO:0005515 protein binding
IPI
PMID:23541952
Control of autophagic cell death by caspase-10 in multiple m...
REMOVE
Summary: Control of autophagic cell death by caspase-10 in multiple myeloma.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23541952
2013 Mar 28. Control of autophagic cell death by caspase-10 in multiple myeloma.
GO:0005515 protein binding
IPI
PMID:23954414
Beclin 2 functions in autophagy, degradation of G protein-co...
REMOVE
Summary: Beclin 2 functions study - comparison with BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23954414
Aug 15. Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.
GO:0005515 protein binding
IPI
PMID:23974797
WASH inhibits autophagy through suppression of Beclin 1 ubiq...
REMOVE
Summary: WASH inhibits autophagy through suppression of BECN1 ubiquitination.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23974797
WASH inhibits autophagy through suppression of Beclin 1 ubiquitination.
GO:0005515 protein binding
IPI
PMID:24034250
EGFR-mediated Beclin 1 phosphorylation in autophagy suppress...
REMOVE
Summary: EGFR-mediated BECN1 phosphorylation suppresses autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24034250
EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance.
GO:0005515 protein binding
IPI
PMID:24056303
PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A...
REMOVE
Summary: UVRAG coordinates Golgi-ER retrograde transport with BECN1 complex.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24056303
PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex.
GO:0005515 protein binding
IPI
PMID:24349490
Rab39a interacts with phosphatidylinositol 3-kinase and nega...
REMOVE
Summary: Rab39a negatively regulates autophagy through BECN1 interaction.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24349490
eCollection 2013. Rab39a interacts with phosphatidylinositol 3-kinase and negatively regulates autophagy induced by lipopolysaccharide stimulation in macrophages.
GO:0005515 protein binding
IPI
PMID:24443581
Targeting Ξ³-herpesvirus 68 Bcl-2-mediated down-regulation of...
REMOVE
Summary: Gamma-herpesvirus BCL-2 targeting of autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24443581
2014 Jan 17. Targeting Ξ³-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.
GO:0005515 protein binding
IPI
PMID:24472739
Decorin activates AMPK, an energy sensor kinase, to induce a...
REMOVE
Summary: Decorin activates AMPK to induce autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24472739
Jan 26. Decorin activates AMPK, an energy sensor kinase, to induce autophagy in endothelial cells.
GO:0005515 protein binding
IPI
PMID:24785657
NRBF2 regulates macroautophagy as a component of Vps34 Compl...
REMOVE
Summary: NRBF2 regulates macroautophagy as component of VPS34 complex I.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24785657
NRBF2 regulates macroautophagy as a component of Vps34 Complex I.
GO:0005515 protein binding
IPI
PMID:25311841
Coronavirus membrane-associated papain-like proteases induce...
REMOVE
Summary: Coronavirus papain-like proteases interact with BECN1 to regulate autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:25311841
Oct 15. Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity.
GO:0005515 protein binding
IPI
PMID:25438055
AMBRA1 links autophagy to cell proliferation and tumorigenes...
REMOVE
Summary: AMBRA1 links autophagy to cell proliferation through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:25438055
AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation.
GO:0005515 protein binding
IPI
PMID:25490155
Architecture and dynamics of the autophagic phosphatidylinos...
REMOVE
Summary: Architecture of autophagic PI3K complex - structural study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:25490155
Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex.
GO:0005515 protein binding
IPI
PMID:25594178
A kinase-independent role for EGF receptor in autophagy init...
REMOVE
Summary: Kinase-independent role for EGFR in autophagy initiation.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:25594178
A kinase-independent role for EGF receptor in autophagy initiation.
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
REMOVE
Summary: Human interactome study - high-throughput.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:26496610
Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
GO:0005515 protein binding
IPI
PMID:26783301
Negative regulation of phosphatidylinositol 3-phosphate leve...
REMOVE
Summary: PI3P regulation in endosome conversion involving BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:26783301
Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion.
GO:0005515 protein binding
IPI
PMID:28445460
Polyglutamine tracts regulate beclin 1-dependent autophagy.
REMOVE
Summary: Polyglutamine tracts regulate BECN1-dependent autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:28445460
Polyglutamine tracts regulate beclin 1-dependent autophagy.
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
REMOVE
Summary: Architecture of human interactome - high-throughput study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding
IPI
PMID:29849149
Disruption of the beclin 1-BCL2 autophagy regulatory complex...
REMOVE
Summary: Disruption of BECN1-BCL2 complex promotes longevity in mice. Key study showing BCL2-BECN1 interaction regulates autophagy and lifespan.
Reason: Generic protein binding term is uninformative. The BCL2 interaction is for autophagy regulation.
Supporting Evidence:
PMID:29849149
May 30. Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Reference map of human binary protein interactome.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:32296183
Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Interactome mapping in neurodegenerative disease proteins.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding
IPI
PMID:33422265
ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-m...
REMOVE
Summary: SARS-CoV-2 ORF3a blocks autophagosome-lysosome fusion.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:33422265
Epub 2020 Dec 16. ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Dual proteome-scale networks study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:33961781
2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding
IPI
PMID:34386498
ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute...
REMOVE
Summary: SARS-CoV-2 ORF3a-mediated incomplete autophagy study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:34386498
eCollection 2021. ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication.
GO:0005515 protein binding
IPI
PMID:34524948
Global Proximity Interactome of the Human Macroautophagy Pat...
REMOVE
Summary: Global proximity interactome of human macroautophagy pathway.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:34524948
2021 Sep 15. Global Proximity Interactome of the Human Macroautophagy Pathway.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
REMOVE
Summary: OpenCell endogenous tagging study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:35271311
2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0005515 protein binding
IPI
PMID:35512704
Systematic discovery of mutation-directed neo-protein-protei...
REMOVE
Summary: Mutation-directed neo-protein-protein interactions in cancer.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:35512704
2022 May 4. Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
GO:0005515 protein binding
IPI
PMID:38182563
GRB2 is a BECN1 interacting protein that regulates autophagy...
REMOVE
Summary: GRB2 is a BECN1 interacting protein that regulates autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:38182563
GRB2 is a BECN1 interacting protein that regulates autophagy.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
REMOVE
Summary: Multimodal cell maps study.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:40205054
Apr 9. Multimodal cell maps as a foundation for structural and functional genomics.
GO:0000045 autophagosome assembly
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate of IBA annotation. Core autophagy function.
Reason: Core function - duplicates IBA annotation.
GO:0001666 response to hypoxia
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Autophagy is induced during hypoxia, and BECN1 participates in this response. BNIP3/BNIP3L displace BCL2 from BECN1 to activate autophagy under hypoxia.
Reason: Secondary function. BECN1 participates in hypoxia-induced autophagy through the BNIP3/BNIP3L-BCL2-BECN1 pathway (PMID:19273585).
Supporting Evidence:
PMID:19273585
we propose a model in which the atypical BH3 domains of hypoxia-induced BNIP3/BNIP3L have been designed to induce autophagy by disrupting the Bcl-2-Beclin1 complex
GO:0005802 trans-Golgi network
IEA
GO_REF:0000120
ACCEPT
Summary: BECN1 localizes to TGN as part of PI3KC3-C2 function.
Reason: Consistent with endocytic trafficking function.
GO:0007254 JNK cascade
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: JNK phosphorylates BCL2 to release BECN1 for autophagy activation. This represents regulatory input to BECN1.
Reason: BECN1 is downstream of JNK signaling through BCL2 phosphorylation. Not direct JNK cascade component.
GO:0007623 circadian rhythm
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Autophagy is regulated by circadian rhythm; this annotation likely reflects circadian regulation of autophagy genes including BECN1.
Reason: Secondary/regulatory. BECN1 expression may be circadian-regulated but circadian rhythm is not its core function.
GO:0009410 response to xenobiotic stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Autophagy responds to xenobiotic stress; BECN1 participates in this.
Reason: Secondary. Autophagy is a general stress response mechanism.
GO:0010040 response to iron(II) ion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Iron can regulate autophagy; this is likely through general stress response.
Reason: Secondary stress response annotation.
GO:0010288 response to lead ion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Heavy metal stress induces autophagy.
Reason: Secondary stress response annotation.
GO:0010508 positive regulation of autophagy
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1 is a positive regulator of autophagy as scaffold of PI3KC3-C1.
Reason: Core function. BECN1 positively regulates autophagy initiation.
GO:0016236 macroautophagy
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1 is essential for macroautophagy as scaffold of PI3KC3-C1.
Reason: Core function. Macroautophagy is the primary type of autophagy BECN1 regulates.
GO:0030425 dendrite
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: BECN1 may localize to dendrites in neurons. Neuronal autophagy is important for synaptic function.
Reason: Cell type-specific localization. Not core function.
GO:0030674 protein-macromolecule adaptor activity
IEA
GO_REF:0000107
ACCEPT
Summary: Duplicate annotation - BECN1 has adapter/scaffold function.
Reason: Core molecular function - duplicates IBA annotation.
GO:0031625 ubiquitin protein ligase binding
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1 is regulated by ubiquitination and binds E3 ligases like NEDD4.
Reason: Regulatory interaction. BECN1 is ubiquitinated by multiple E3 ligases to regulate its stability and activity.
GO:0031667 response to nutrient levels
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1-dependent autophagy is activated in response to nutrient deprivation.
Reason: Core function. Nutrient starvation is a primary trigger for BECN1-dependent autophagy.
GO:0032991 protein-containing complex
IEA
GO_REF:0000107
MODIFY
Summary: BECN1 is part of PI3KC3 complexes. Too generic.
Reason: Should be more specific - annotated to PI3KC3 complex terms instead.
GO:0033197 response to vitamin E
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Vitamin E can affect autophagy. Indirect effect.
Reason: Secondary/indirect effect.
GO:0034198 cellular response to amino acid starvation
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1-dependent autophagy is induced by amino acid starvation.
Reason: Core function. Amino acid starvation is a primary trigger for autophagy.
GO:0035032 phosphatidylinositol 3-kinase complex, class III
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1 is a core component of PI3KC3 complexes.
Reason: Core localization. BECN1 is an obligate subunit of PI3KC3.
GO:0038066 p38MAPK cascade
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: p38 MAPK can regulate autophagy; BECN1 may be downstream.
Reason: Secondary regulatory input to autophagy.
GO:0042149 cellular response to glucose starvation
IEA
GO_REF:0000107
ACCEPT
Summary: Glucose starvation induces autophagy through AMPK-BECN1 pathway.
Reason: Core function. Metabolic stress triggers autophagy.
GO:0042802 identical protein binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: BECN1 can homodimerize through its coiled-coil domain. However, functional complexes involve heterodimerization with ATG14L or UVRAG.
Reason: The coiled-coil domain can mediate homodimerization, but this is less functionally relevant than heterodimerization.
GO:0043066 negative regulation of apoptotic process
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: This annotation likely reflects that autophagy can be anti-apoptotic by removing damaged mitochondria. However, this is an indirect effect through autophagy, not direct anti-apoptotic activity.
Reason: OVER-ANNOTATION. BECN1 is an autophagy protein, not an apoptosis regulator. Any anti-apoptotic effect is secondary to its autophagy function. The BCL2 binding is for autophagy regulation, not apoptosis regulation.
GO:0043652 engulfment of apoptotic cell
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: LC3-associated phagocytosis (LAP) involves BECN1 complexes for clearance of apoptotic cells. This is a non-canonical autophagy function.
Reason: Secondary function. LAP uses autophagy machinery for phagocytic clearance.
GO:0045335 phagocytic vesicle
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: BECN1 participates in LC3-associated phagocytosis.
Reason: Secondary function related to LAP.
GO:0060395 SMAD protein signal transduction
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Connection to SMAD signaling is likely indirect through autophagy-TGFbeta crosstalk.
Reason: Indirect/secondary effect.
GO:0062029 positive regulation of stress granule assembly
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Stress granules and autophagy are connected processes.
Reason: Secondary/indirect connection.
GO:0070301 cellular response to hydrogen peroxide
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Oxidative stress induces autophagy.
Reason: Secondary stress response.
GO:0071275 cellular response to aluminum ion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Heavy metal stress can induce autophagy.
Reason: Secondary stress response.
GO:0071280 cellular response to copper ion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Metal ion stress and autophagy.
Reason: Secondary stress response.
GO:0071364 cellular response to epidermal growth factor stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: EGFR phosphorylates BECN1 to suppress autophagy. This is a regulatory input.
Reason: Regulatory input. EGFR-mediated phosphorylation suppresses BECN1 activity.
GO:0090650 cellular response to oxygen-glucose deprivation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Metabolic stress induces autophagy.
Reason: Secondary stress response function.
GO:1905672 negative regulation of lysosome organization
IEA
GO_REF:0000107
UNDECIDED
Summary: BECN1 affects lysosome function through autophagy pathway.
Reason: Unclear annotation - need more evidence for this specific function.
GO:2000786 positive regulation of autophagosome assembly
IEA
GO_REF:0000107
ACCEPT
Summary: BECN1 positively regulates autophagosome assembly as scaffold of PI3KC3-C1.
Reason: Core function.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: This annotation is problematic. BECN1's connection to apoptosis is through its interaction with BCL2 family, but this interaction REGULATES AUTOPHAGY, not apoptosis. BECN1 is NOT a positive regulator of apoptosis.
Reason: OVER-ANNOTATION. BECN1 is NOT an apoptosis regulator. The BCL2 binding domain functions in autophagy regulation. Any effect on apoptosis is indirect through autophagy-apoptosis crosstalk, not direct regulation of apoptotic pathways.
GO:0005829 cytosol
IDA
GO_REF:0000052
ACCEPT
Summary: BECN1 localizes to cytosol based on immunofluorescence.
Reason: Core localization.
GO:0016604 nuclear body
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: BECN1 detected in nuclear bodies by immunofluorescence.
Reason: Not a primary localization. May represent minor pool.
GO:0016236 macroautophagy
NAS
PMID:40442316
Structure and activation of the human autophagy-initiating U...
ACCEPT
Summary: Recent structural study of ULK1C:PI3KC3-C1 supercomplex confirms BECN1 role in macroautophagy.
Reason: Core function confirmed by structural studies.
Supporting Evidence:
PMID:40442316
Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex.
GO:0006622 protein targeting to lysosome
NAS
PMID:16467569
Regulation of membrane traffic by phosphoinositide 3-kinases...
KEEP AS NON CORE
Summary: BECN1 in PI3KC3-C2 regulates trafficking to lysosome.
Reason: Related to PI3KC3-C2 endocytic trafficking function.
Supporting Evidence:
PMID:16467569
Regulation of membrane traffic by phosphoinositide 3-kinases.
GO:0010506 regulation of autophagy
IDA
PMID:16799551
Autophagic and tumour suppressor activity of a novel Beclin1...
ACCEPT
Summary: This paper identified UVRAG as BECN1-binding protein that regulates autophagy. Demonstrates BECN1's role in autophagy regulation.
Reason: Core function.
Supporting Evidence:
PMID:16799551
UVRAG, a tumour suppressor candidate... associates with the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex, where UVRAG and Beclin1 interdependently induce autophagy
GO:0016241 regulation of macroautophagy
IDA
PMID:10625637
Distinct classes of phosphatidylinositol 3'-kinases are invo...
ACCEPT
Summary: Foundational paper showing class III PI3K (VPS34) is required for macroautophagy. BECN1 as VPS34 scaffold regulates this process.
Reason: Core function.
Supporting Evidence:
PMID:10625637
an increase in the class III PI3K product (phosphatidylinositol 3-phosphate)... stimulates macroautophagy
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
IDA
PMID:8999962
Characterization of p150, an adaptor protein for the human p...
ACCEPT
Summary: BECN1 as scaffold of VPS34 complex enables PI3P synthesis. VPS34 is the lipid kinase; BECN1 is the adapter.
Reason: Core function. BECN1 enables PI3P synthesis by scaffolding VPS34 complex.
Supporting Evidence:
PMID:8999962
Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase.
GO:0045022 early endosome to late endosome transport
IDA
PMID:14617358
Human VPS34 and p150 are Rab7 interacting partners.
ACCEPT
Summary: VPS34 and BECN1 interact with Rab7 for endosome maturation.
Reason: Related to PI3KC3-C2 endocytic trafficking function.
Supporting Evidence:
PMID:14617358
Human VPS34 and p150 are Rab7 interacting partners.
GO:0097352 autophagosome maturation
IDA
PMID:10625637
Distinct classes of phosphatidylinositol 3'-kinases are invo...
ACCEPT
Summary: PI3KC3 regulates autophagosome maturation in addition to initiation.
Reason: Core autophagy function.
Supporting Evidence:
PMID:10625637
Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9837231
ACCEPT
Summary: Reactome annotation for ISGylation of BECN1 in cytosol.
Reason: Core localization.
GO:0000423 mitophagy
IMP
PMID:25215947
AMBRA1 is able to induce mitophagy via LC3 binding, regardle...
ACCEPT
Summary: AMBRA1 can induce mitophagy via LC3 binding - involves BECN1 complex.
Reason: Core function - mitophagy.
Supporting Evidence:
PMID:25215947
Sep 12. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1.
GO:0000045 autophagosome assembly
IDA
PMID:25891078
IRGM governs the core autophagy machinery to conduct antimic...
ACCEPT
Summary: IRGM governs autophagy machinery by assembling ULK1 and BECN1 complexes.
Reason: Core function.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly thus governing the formation of autophagy initiation complexes
GO:0030674 protein-macromolecule adaptor activity
IDA
PMID:25891078
IRGM governs the core autophagy machinery to conduct antimic...
ACCEPT
Summary: Direct demonstration of BECN1's adapter function in assembling autophagy complexes.
Reason: Core molecular function.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
IDA
PMID:34796041
Hepatitis B virus X Protein Promotes Liver Cancer Progressio...
KEEP AS NON CORE
Summary: BECN1 links TLR4 signaling to autophagy in liver cancer context.
Reason: Represents autophagy response to PRR signaling. Not core function.
Supporting Evidence:
PMID:34796041
2021 Oct. Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation.
GO:0060090 molecular adaptor activity
IDA
PMID:34796041
Hepatitis B virus X Protein Promotes Liver Cancer Progressio...
ACCEPT
Summary: BECN1 has molecular adapter activity - core function.
Reason: Core molecular function.
Supporting Evidence:
PMID:34796041
2021 Oct. Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation.
GO:0043069 negative regulation of programmed cell death
IMP
PMID:19273585
Hypoxia-induced autophagy is mediated through hypoxia-induci...
MARK AS OVER ANNOTATED
Summary: This paper showed that ablation of BECN1 enhances cell death under hypoxia, suggesting autophagy provides survival. However, this is through autophagy function, not direct cell death regulation.
Reason: OVER-ANNOTATION. The paper states "The ablation of Beclin1, a major actor of autophagy, enhances cell death under hypoxic conditions" - this shows BECN1 promotes survival through AUTOPHAGY, not direct anti-apoptotic activity. The anti-death effect is secondary to autophagy function.
Supporting Evidence:
PMID:19273585
The ablation of Beclin1, a major actor of autophagy, enhances cell death under hypoxic conditions
GO:0032473 cytoplasmic side of mitochondrial outer membrane
IDA
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 associates with mitochondrial outer membrane, particularly MAMs.
Reason: Supports mitophagy function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0005776 autophagosome
ISS
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
ACCEPT
Summary: BECN1 localizes to autophagosomes.
Reason: Core localization.
Supporting Evidence:
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
GO:0006914 autophagy
IDA
PMID:25891078
IRGM governs the core autophagy machinery to conduct antimic...
ACCEPT
Summary: Direct demonstration of BECN1 in autophagy through IRGM interaction study.
Reason: Core function.
Supporting Evidence:
PMID:25891078
2015 Apr 16. IRGM governs the core autophagy machinery to conduct antimicrobial defense.
GO:0065003 protein-containing complex assembly
IDA
PMID:25891078
IRGM governs the core autophagy machinery to conduct antimic...
ACCEPT
Summary: BECN1 assembles into PI3KC3 complexes.
Reason: Core function of BECN1 as scaffold.
Supporting Evidence:
PMID:25891078
2015 Apr 16. IRGM governs the core autophagy machinery to conduct antimicrobial defense.
GO:0005515 protein binding
IPI
PMID:17659302
Molecular basis of Bcl-xL's target recognition versatility r...
REMOVE
Summary: Structural study of BCL-XL in complex with BECN1 BH3 domain.
Reason: Generic protein binding. The specific BCL-XL binding is relevant for autophagy regulation.
Supporting Evidence:
PMID:17659302
2007 Jun 30. Molecular basis of Bcl-xL's target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1.
GO:0005515 protein binding
IPI
PMID:18797192
Molecular basis of the regulation of Beclin 1-dependent auto...
REMOVE
Summary: Gamma-herpesvirus BCL-2 homolog M11 regulation of BECN1-dependent autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:18797192
Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.
GO:0005515 protein binding
IPI
PMID:24115198
Intrinsically disordered regions in autophagy proteins.
REMOVE
Summary: Intrinsically disordered regions in autophagy proteins including BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24115198
Intrinsically disordered regions in autophagy proteins.
GO:0005515 protein binding
IPI
PMID:27046249
The BECN1 N-terminal domain is intrinsically disordered.
REMOVE
Summary: BECN1 N-terminal domain is intrinsically disordered.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:27046249
The BECN1 N-terminal domain is intrinsically disordered.
GO:0005515 protein binding
IPI
PMID:30626284
Structural insights into BCL2 pro-survival protein interacti...
REMOVE
Summary: Structural study of BCL2-BECN1 interaction after STK4/MST1 phosphorylation.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:30626284
2019 Jan 9. Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1.
GO:0005515 protein binding
IPI
PMID:30767700
Members of the autophagy class III phosphatidylinositol 3-ki...
REMOVE
Summary: PI3KC3 complex members interact with GABARAP/GABARAPL1 via LIR motifs.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:30767700
2019 Mar 4. Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs.
GO:0010506 regulation of autophagy
IDA
PMID:18797192
Molecular basis of the regulation of Beclin 1-dependent auto...
ACCEPT
Summary: Gamma-herpesvirus BCL-2 regulates BECN1-dependent autophagy.
Reason: Core function.
Supporting Evidence:
PMID:18797192
Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.
GO:0005515 protein binding
IPI
PMID:22498477
The anti-apoptotic Bcl-B protein inhibits BECN1-dependent au...
REMOVE
Summary: BCL-B inhibits BECN1-dependent autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:22498477
The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death.
GO:0005737 cytoplasm
IDA
PMID:22498477
The anti-apoptotic Bcl-B protein inhibits BECN1-dependent au...
ACCEPT
Summary: BECN1 localized to cytoplasm.
Reason: Core localization.
Supporting Evidence:
PMID:22498477
The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death.
GO:0010508 positive regulation of autophagy
IDA
PMID:21358617
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
ACCEPT
Summary: Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy through BECN1. Releasing BECN1 from BCL-2 promotes autophagy.
Reason: Core function.
Supporting Evidence:
PMID:21358617
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
GO:0006914 autophagy
IMP
PMID:28747345
ORMDL3 Facilitates the Survival of Splenic B Cells via an AT...
ACCEPT
Summary: ORMDL3 regulates autophagy through ATF6alpha-ER stress-BECN1 pathway.
Reason: Core function.
Supporting Evidence:
PMID:28747345
2017 Jul 26. ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6Ξ±-Endoplasmic Reticulum Stress-Beclin1 Autophagy Regulatory Pathway.
GO:0005515 protein binding
IPI
PMID:31806350
The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulat...
REMOVE
Summary: TMEM39A regulates autophagy through SAC1 trafficking affecting BECN1 complex.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:31806350
2019 Dec 2. The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Sequence similarity transfer annotation for apoptosis - problematic.
Reason: OVER-ANNOTATION. BECN1 is not an apoptosis regulator.
GO:0005515 protein binding
IPI
PMID:27031958
Nupr1/Chop signal axis is involved in mitochondrion-related ...
REMOVE
Summary: This paper studies methamphetamine-induced endothelial cell apoptosis and proposes BECN1 involvement. However, the context is non-physiological drug toxicity, and the claims about BECN1 promoting apoptosis are not well-supported.
Reason: Generic protein binding. The paper's claims about BECN1 in apoptosis are questionable given known BECN1 function.
Supporting Evidence:
PMID:27031958
Nupr1/Chop signal axis is involved in mitochondrion-related endothelial cell apoptosis induced by methamphetamine.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
IMP
PMID:27031958
Nupr1/Chop signal axis is involved in mitochondrion-related ...
MARK AS OVER ANNOTATED
Summary: This paper claims BECN1 promotes apoptosis through Nupr1/Chop pathway in methamphetamine-exposed endothelial cells. However, this is a specific toxicological context and does not reflect core BECN1 function. The paper states BECN1 binds BCL2 and releases it for apoptosis, but this misinterprets the BECN1-BCL2 interaction which regulates autophagy.
Reason: OVER-ANNOTATION. This paper misinterprets BECN1 function. BECN1 is an autophagy protein. Its interaction with BCL2 regulates autophagy, not apoptosis. The context (drug toxicity) does not reflect physiological BECN1 function.
Supporting Evidence:
PMID:27031958
Nupr1/Chop signal axis is involved in mitochondrion-related endothelial cell apoptosis induced by methamphetamine.
GO:0032465 regulation of cytokinesis
IMP
PMID:20208530
PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...
KEEP AS NON CORE
Summary: PI3KC3 complex generates PI3P at midbody for cytokinesis regulation. This is a non-autophagy function of BECN1.
Reason: Secondary function. BECN1 in PI3KC3-C2 regulates cytokinesis through PI3P.
Supporting Evidence:
PMID:20208530
PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody.
GO:0019901 protein kinase binding
IPI
PMID:27853422
ROCK1 Is Associated with Alzheimer's Disease-Specific Plaque...
ACCEPT
Summary: ROCK1 interacts with BECN1 and affects autophagosome formation.
Reason: BECN1 is phosphorylated by multiple kinases that regulate its activity.
Supporting Evidence:
PMID:27853422
eCollection 2016. ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic AΞ² Clearance.
GO:0005515 protein binding
IPI
PMID:28479384
Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in ...
REMOVE
Summary: BECN1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:28479384
Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells.
GO:0045022 early endosome to late endosome transport
IMP
PMID:26783301
Negative regulation of phosphatidylinositol 3-phosphate leve...
ACCEPT
Summary: BECN1 in PI3KC3-C2 regulates PI3P levels in endosome conversion.
Reason: Related to PI3KC3-C2 endocytic trafficking function.
Supporting Evidence:
PMID:26783301
Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion.
GO:0051020 GTPase binding
IPI
PMID:25891078
IRGM governs the core autophagy machinery to conduct antimic...
ACCEPT
Summary: IRGM is a GTPase that binds BECN1 to regulate autophagy.
Reason: BECN1 interacts with small GTPases like Rab proteins and IRGM.
Supporting Evidence:
PMID:25891078
IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly
GO:0006914 autophagy
IMP
PMID:23184933
XBP1 mRNA splicing triggers an autophagic response in endoth...
ACCEPT
Summary: XBP1 splicing triggers autophagy through BECN1 transcriptional activation.
Reason: Core function.
Supporting Evidence:
PMID:23184933
2012 Nov 26. XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation.
GO:0000423 mitophagy
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 membrane association and ATG14-dependent phosphorylation regulate BECN1-mediated autophagy including mitophagy.
Reason: Core function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0098780 response to mitochondrial depolarisation
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 responds to mitochondrial depolarization by localizing to mitochondria for mitophagy.
Reason: Relates to mitophagy function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0005515 protein binding
IPI
PMID:22095288
PKD is a kinase of Vps34 that mediates ROS-induced autophagy...
REMOVE
Summary: PKD phosphorylates VPS34 downstream of DAPK to mediate autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:22095288
Nov 18. PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk.
GO:0006914 autophagy
IDA
PMID:23629966
Deacetylation of p53 induces autophagy by suppressing Bmf ex...
ACCEPT
Summary: Deacetylation of p53 induces autophagy through BECN1.
Reason: Core function.
Supporting Evidence:
PMID:23629966
Deacetylation of p53 induces autophagy by suppressing Bmf expression.
GO:0005515 protein binding
IPI
PMID:24113155
Placental autophagy regulation by the BOK-MCL1 rheostat.
REMOVE
Summary: BOK-MCL1 rheostat regulates placental autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24113155
Placental autophagy regulation by the BOK-MCL1 rheostat.
GO:0005829 cytosol
TAS
Reactome:R-HSA-6781779
ACCEPT
Summary: USP13 deubiquitinates BECN1 in cytosol.
Reason: Core localization.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
NAS
PMID:25215947
AMBRA1 is able to induce mitophagy via LC3 binding, regardle...
UNDECIDED
Summary: AMBRA1 can induce mitophagy via LC3 binding regardless of PARKIN. Connection to PI3K/AKT signaling may be indirect.
Reason: Need more evidence for direct BECN1 role in PI3K/AKT signaling.
Supporting Evidence:
PMID:25215947
Sep 12. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1.
GO:0005515 protein binding
IPI
PMID:26347139
TRIM-mediated precision autophagy targets cytoplasmic regula...
REMOVE
Summary: TRIM-mediated precision autophagy targeting cytoplasmic innate immunity regulators.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:26347139
TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.
GO:0031625 ubiquitin protein ligase binding
IPI
PMID:25127057
TRIM proteins regulate autophagy and can target autophagic s...
ACCEPT
Summary: TRIM proteins regulate autophagy by direct recognition and can target autophagic substrates including through BECN1 interaction.
Reason: BECN1 interacts with multiple E3 ligases for regulation.
Supporting Evidence:
PMID:25127057
2014 Aug 7. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
GO:0005515 protein binding
IPI
PMID:25127057
TRIM proteins regulate autophagy and can target autophagic s...
REMOVE
Summary: TRIM5 interacts with BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:25127057
2014 Aug 7. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
GO:0032465 regulation of cytokinesis
IMP
PMID:20643123
A phosphatidylinositol 3-kinase class III sub-complex contai...
KEEP AS NON CORE
Summary: PI3KC3 sub-complex with VPS15, VPS34, BECN1, UVRAG, BIF-1 regulates cytokinesis.
Reason: Secondary function through PI3KC3-C2.
Supporting Evidence:
PMID:20643123
Epub 2010 Jul 17. A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic.
GO:0032801 receptor catabolic process
IMP
PMID:20643123
A phosphatidylinositol 3-kinase class III sub-complex contai...
ACCEPT
Summary: PI3KC3 regulates degradative endocytic traffic including receptor degradation.
Reason: PI3KC3-C2 function in receptor trafficking.
Supporting Evidence:
PMID:20643123
Epub 2010 Jul 17. A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5672012
ACCEPT
Summary: Beclin-1 complex phosphorylates PtdIns in cytosol.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5679205
ACCEPT
Summary: ULK1 phosphorylates Beclin-1 in cytosol.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5682385
ACCEPT
Summary: Phagophore extends from PI3P-enriched structure.
Reason: Core localization.
GO:0005739 mitochondrion
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 localizes to mitochondria for mitophagy function.
Reason: Supports mitophagy function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0000045 autophagosome assembly
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence similarity annotation - consistent with core function.
Reason: Core function.
GO:0016236 macroautophagy
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence similarity annotation - consistent with core function.
Reason: Core function.
GO:0035032 phosphatidylinositol 3-kinase complex, class III
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence similarity annotation - BECN1 is obligate component of PI3KC3.
Reason: Core localization.
GO:0042149 cellular response to glucose starvation
ISS
GO_REF:0000024
ACCEPT
Summary: Autophagy is induced by glucose starvation.
Reason: Core function - metabolic stress triggers autophagy.
GO:0005515 protein binding
IPI
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
REMOVE
Summary: Membrane association and ATG14-dependent phosphorylation of BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0005768 endosome
IDA
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 localizes to endosomes.
Reason: Related to PI3KC3-C2 function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0005783 endoplasmic reticulum
IDA
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 localizes to ER, particularly for autophagosome nucleation.
Reason: Core localization for autophagy initiation.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0043548 phosphatidylinositol 3-kinase binding
IPI
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
ACCEPT
Summary: BECN1 directly binds VPS34 (PI3KC3).
Reason: Core molecular function.
Supporting Evidence:
PMID:23878393
Jul 22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
GO:0005515 protein binding
IPI
PMID:24056301
The deubiquitylase USP33 discriminates between RALB function...
REMOVE
Summary: USP33 deubiquitylase discriminates RALB functions in autophagy.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:24056301
The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response.
GO:0005515 protein binding
IPI
PMID:23182941
A novel ER-localized transmembrane protein, EMC6, interacts ...
REMOVE
Summary: EMC6 interacts with RAB5A and regulates autophagy through BECN1.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:23182941
A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy.
GO:0006914 autophagy
IMP
PMID:24056303
PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A...
ACCEPT
Summary: UVRAG coordinates Golgi-ER retrograde transport with BECN1 complex.
Reason: Core function.
Supporting Evidence:
PMID:24056303
PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex.
GO:0007080 mitotic metaphase chromosome alignment
IMP
PMID:23478334
Beclin-1 is required for chromosome congression and proper o...
KEEP AS NON CORE
Summary: BECN1 is required for proper chromosome congression and kinetochore assembly. Non-autophagy function.
Reason: Secondary/non-autophagy function.
Supporting Evidence:
PMID:23478334
Beclin-1 is required for chromosome congression and proper outer kinetochore assembly.
GO:1902425 positive regulation of attachment of mitotic spindle microtubules to kinetochore
IMP
PMID:23478334
Beclin-1 is required for chromosome congression and proper o...
KEEP AS NON CORE
Summary: BECN1 affects kinetochore-microtubule attachment. Non-autophagy function.
Reason: Secondary/non-autophagy function.
Supporting Evidence:
PMID:23478334
Beclin-1 is required for chromosome congression and proper outer kinetochore assembly.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1169406
ACCEPT
Summary: ISGylation of host proteins in cytosol.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1632857
ACCEPT
Summary: ULK1 phosphorylates AMBRA1:BECN1 complex.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1678841
ACCEPT
Summary: ISG15 deconjugating enzyme USP18 regulation.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5678313
ACCEPT
Summary: AMBRA1:DYNLL binds BECN1 complex.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5678315
ACCEPT
Summary: BECN1 complex dissociates from DYNLL.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5679266
ACCEPT
Summary: Beclin-1 complex translocates to ER.
Reason: Core localization.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755359
ACCEPT
Summary: SARS-CoV-2 ORF8:class I MHC binds BECN1.
Reason: Core localization.
GO:0005515 protein binding
IPI
PMID:17724469
Reduced expression of vacuole membrane protein 1 affects the...
REMOVE
Summary: VMP1 affects invasion capacity through BECN1 interaction.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:17724469
Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells.
GO:0005515 protein binding
IPI
PMID:19270696
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca...
REMOVE
Summary: ATG14L and Rubicon reciprocally regulate autophagy through BECN1 binding.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:19270696
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages.
GO:0005515 protein binding
IPI
PMID:21962518
Beclin1 controls the levels of p53 by regulating the deubiqu...
REMOVE
Summary: BECN1 controls p53 levels through USP10/USP13 deubiquitination activity.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:21962518
Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13.
GO:0005515 protein binding
IPI
PMID:16417406
Hem-1 complexes are essential for Rac activation, actin poly...
REMOVE
Summary: Hem-1 complexes study - BECN1 interaction in neutrophil chemotaxis.
Reason: Generic protein binding term is uninformative.
Supporting Evidence:
PMID:16417406
Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.
GO:0006968 cellular defense response
TAS
PMID:9765397
Protection against fatal Sindbis virus encephalitis by becli...
ACCEPT
Summary: Original paper discovering BECN1 showing it protects against viral encephalitis.
Reason: BECN1 participates in xenophagy/antiviral autophagy.
Supporting Evidence:
PMID:9765397
These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.
GO:0043066 negative regulation of apoptotic process
TAS
PMID:9765397
Protection against fatal Sindbis virus encephalitis by becli...
MARK AS OVER ANNOTATED
Summary: The original BECN1 paper showed it protected against virus-induced neuronal death. However, this was likely through autophagy-mediated viral clearance, not direct anti-apoptotic activity. The paper focused on BECN1's BCL2 interaction but the functional significance was later shown to be autophagy regulation.
Reason: OVER-ANNOTATION. The original paper interpreted BECN1 as anti-apoptotic due to BCL2 interaction. Later work established that this interaction regulates autophagy, and the protective effect is through autophagy-mediated viral clearance, not direct anti-apoptotic activity.
Supporting Evidence:
PMID:9765397
These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.

Core Functions

BECN1 is the central scaffold/adapter of PI3KC3 complexes, assembling VPS34, VPS15, and complex-specific subunits (ATG14L or UVRAG) into functional lipid kinase complexes that generate PI3P for autophagy and endocytic trafficking. As scaffold of PI3KC3-C1 (ATG14L-containing complex), BECN1 is essential for autophagosome nucleation.

BECN1 directly binds VPS34 (PIK3C3), the catalytic subunit of class III PI3K, through its coiled-coil and BARA domains. This binding is essential for PI3KC3 complex formation and function.

References

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Suggested Questions for Experts

Q: What is the precise mechanism by which BECN1 membrane association regulates autophagosome size versus number? The PMID:23878393 study identified a membrane-association domain but the molecular mechanism remains unclear.

Q: Are there isoform-specific or cell type-specific differences in BECN1 function between autophagy and endocytic trafficking? BECN1 participates in both PI3KC3-C1 (autophagy) and PI3KC3-C2 (trafficking) but the determinants of which complex forms are not fully understood.

Deep Research

Falcon

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