id: Q14457
gene_symbol: BECN1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
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:
# ============================================================================
# IBA ANNOTATIONS - Core autophagy functions, highly reliable
# ============================================================================
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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).
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly thus governing the formation of autophagy initiation complexes."
        - reference_id: PMID:23878393
          supporting_text: "Human beclin-1 and its yeast homologue, Atg6/Vps30, are
            scaffold proteins bound in a lipid kinase complex with multiple cellular
            functions, including autophagy."

        - reference_id: file:human/BECN1/BECN1-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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).
      action: ACCEPT
      reason: >-
        Core function. BECN1 is required for selective mitophagy through its localization
        to MAMs
        during mitochondrial depolarization. This is a specific autophagy-related
        function.
      supported_by:
        - reference_id: PMID:23878393
          supporting_text: "We identified a unique domain in beclin-1, conserved in
            the yeast homologue Atg6, which is involved in membrane association"

  - term:
      id: GO:0030674
      label: protein-macromolecule adaptor activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly thus governing the formation of autophagy initiation complexes."

  - term:
      id: GO:0043548
      label: phosphatidylinositol 3-kinase binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Core molecular function. BECN1 binding to VPS34 is fundamental to its role
        in forming
        PI3KC3 complexes for autophagy and endocytic trafficking.
      supported_by:
        - reference_id: PMID:23878393
          supporting_text: "Human beclin-1 and its yeast homologue, Atg6/Vps30, are
            scaffold proteins bound in a lipid kinase complex"

  - term:
      id: GO:0034271
      label: phosphatidylinositol 3-kinase complex, class III, type I
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Core localization. BECN1 is an obligate component of PI3KC3-C1, the autophagy
        initiation complex.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly"

  - term:
      id: GO:0034272
      label: phosphatidylinositol 3-kinase complex, class III, type II
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.

  - term:
      id: GO:0000407
      label: phagophore assembly site
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Core localization for autophagy function. The PI3KC3-C1 complex localizes
        to PAS.

  - term:
      id: GO:0006995
      label: cellular response to nitrogen starvation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        BECN1 is activated during nitrogen/amino acid starvation to induce autophagy.
        This is
        conserved from yeast (Atg6/Vps30) through humans.
      action: ACCEPT
      reason: >-
        Core function. Autophagy induction in response to nutrient starvation is a
        fundamental
        BECN1 function.

  - term:
      id: GO:0045324
      label: late endosome to vacuole transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        BECN1 in the PI3KC3-C2 complex (with UVRAG) regulates endosome maturation
        including
        early-to-late endosome transport and late endosome-lysosome fusion.
      action: ACCEPT
      reason: >-
        Represents the endocytic trafficking function of BECN1 via PI3KC3-C2 complex.
        This is
        distinct from but related to autophagy.

# ============================================================================
# IEA LOCALIZATION ANNOTATIONS - Generally acceptable
# ============================================================================
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 has been detected in the nucleus in some studies. UniProt annotation
        based on
        subcellular location vocabulary mapping.
      action: KEEP_AS_NON_CORE
      reason: >-
        Not a primary localization. BECN1 may transit through nucleus but its functional
        localization is cytoplasmic/membrane-associated.

  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        BECN1 localizes to the cytoplasm where it assembles PI3KC3 complexes. This
        is consistent
        with experimental data.
      action: ACCEPT
      reason: >-
        Core localization. The cytoplasm is where BECN1 assembles with VPS34 and other
        components.

  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 localizes to mitochondria-ER contact sites (MAMs) during mitophagy,
        where it
        promotes selective degradation of damaged mitochondria.
      action: ACCEPT
      reason: >-
        Supports mitophagy function. BECN1 relocates to MAMs during mitochondrial
        depolarization.

  - term:
      id: GO:0005768
      label: endosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 localizes to endosomes as part of PI3KC3-C2 complex function in endocytic
        trafficking.
      action: ACCEPT
      reason: >-
        Consistent with PI3KC3-C2 function in endosome maturation.

  - term:
      id: GO:0005776
      label: autophagosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        BECN1 localizes to autophagosomes during their formation as part of PI3KC3-C1.
      action: ACCEPT
      reason: >-
        Core localization for autophagy function.

  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 associates with ER membrane where autophagosome nucleation occurs. The
        ER is
        a major membrane source for autophagosome formation.
      action: ACCEPT
      reason: >-
        Consistent with autophagosome nucleation occurring at ER membranes.

  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 localizes to Golgi/TGN membranes, particularly the PI3KC3-C2 complex
        which
        functions in TGN-proximal trafficking.
      action: ACCEPT
      reason: >-
        Consistent with PI3KC3-C2 function in membrane trafficking.

  - term:
      id: GO:0006897
      label: endocytosis
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        BECN1 in PI3KC3-C2 complex regulates endocytic trafficking, including receptor
        sorting and endosome maturation. This is a non-autophagy function.
      action: ACCEPT
      reason: >-
        Represents PI3KC3-C2 function. Not over-annotation - BECN1 has demonstrated
        roles
        in endocytic trafficking independent of autophagy.

  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        BECN1 is a central regulator of autophagy as the scaffold of PI3KC3-C1 complex.
      action: ACCEPT
      reason: >-
        Core function. Autophagy is the primary biological process for BECN1.

# ============================================================================
# APOPTOSIS ANNOTATIONS - OVER-ANNOTATION as per SPKW project guidance
# ============================================================================
  - term:
      id: GO:0006915
      label: apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:19273585
          supporting_text: "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"
        - reference_id: PMID:17446862
          supporting_text: "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)."

  - term:
      id: GO:0010008
      label: endosome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 localizes to endosome membranes as part of PI3KC3-C2 function.
      action: ACCEPT
      reason: >-
        Consistent with endocytic trafficking function.

  - term:
      id: GO:0031410
      label: cytoplasmic vesicle
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        BECN1 associates with various cytoplasmic vesicles including autophagosomes
        and endosomes.
      action: ACCEPT
      reason: >-
        General but accurate. BECN1 functions on multiple vesicle types.

  - term:
      id: GO:0031966
      label: mitochondrial membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        BECN1 localizes to mitochondrial membranes, particularly MAMs during mitophagy.
      action: ACCEPT
      reason: >-
        Supports mitophagy function.

  - term:
      id: GO:0032801
      label: receptor catabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        BECN1 in PI3KC3-C2 complex is involved in receptor trafficking including EGFR
        sorting.
        The deep research mentions "receptor sorting (e.g., EGFR, TFR1)".
      action: ACCEPT
      reason: >-
        Consistent with PI3KC3-C2 function in endocytic trafficking and receptor turnover.

  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        BECN1 has been implicated in cytokinesis regulation through PI3KC3-C2 function.
        This represents a non-autophagy function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function. BECN1 has been shown to regulate cytokinesis (PMID:20208530,
        PMID:20643123)
        but this is not its primary function.

  - term:
      id: GO:0051607
      label: defense response to virus
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      reason: >-
        Legitimate function. BECN1 plays a role in antiviral autophagy (xenophagy),
        and the original
        discovery paper demonstrated its protective role against viral infection.
      supported_by:
        - reference_id: PMID:9765397
          supporting_text: "These findings demonstrate that Beclin is a novel Bcl-2-interacting
            cellular protein that may play a role in antiviral host defense."

# ============================================================================
# IPI PROTEIN BINDING ANNOTATIONS - Review systematically
# ============================================================================
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17446862
    review:
      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.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:17446862
          supporting_text: "The anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind and
            inhibit Beclin-1, an essential mediator of autophagy"

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19050071
    review:
      summary: >-
        This paper identified ATG14 (Barkor) as a BECN1-binding protein that directs
        BECN1/VPS34
        to autophagosome formation sites. Core autophagy complex formation.
      action: REMOVE
      reason: >-
        Generic protein binding is uninformative. The functional significance (autophagy
        complex
        formation) is captured in other annotations.

      supported_by:
        - reference_id: PMID:19050071
          supporting_text: Identification of Barkor as a mammalian 
            autophagy-specific factor for Beclin 1 and class III 
            phosphatidylinositol 3-kinase.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19180116
    review:
      summary: >-
        This paper showed DAPK1 phosphorylates BECN1 at Thr119 in the BH3 domain to
        promote
        dissociation from BCL-XL and induce autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding is uninformative. The interaction with DAPK1 is functionally
        relevant to autophagy regulation.

      supported_by:
        - reference_id: PMID:19180116
          supporting_text: DAP-kinase-mediated phosphorylation on the BH3 domain
            of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and 
            induction of autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19959994
    review:
      summary: >-
        IKK complex interaction study. Protein binding annotation is too generic.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative for understanding gene function.

      supported_by:
        - reference_id: PMID:19959994
          supporting_text: The IKK complex contributes to the induction of 
            autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20562859
    review:
      summary: >-
        Network analysis of human autophagy system interactions.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative for understanding gene function.

      supported_by:
        - reference_id: PMID:20562859
          supporting_text: Network organization of the human autophagy system.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20638385
    review:
      summary: >-
        This paper studied BECN1-survivin interaction in glioma cells regarding TRAIL-induced
        apoptosis.
      action: REMOVE
      reason: >-
        Generic protein binding. Also relates to apoptosis context which is not core
        BECN1 function.

      supported_by:
        - reference_id: PMID:20638385
          supporting_text: Epub 2010 Jul 16. Interaction of Beclin 1 with 
            survivin regulates sensitivity of human glioma cells to 
            TRAIL-induced apoptosis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20819940
    review:
      summary: >-
        HMGB1-BECN1 interaction study showing HMGB1 regulates autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:20819940
          supporting_text: Endogenous HMGB1 regulates autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21062745
    review:
      summary: >-
        Rubicon RUN domain interaction with VPS34 and BECN1 complex regulation.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:21062745
          supporting_text: Nov 9. The RUN domain of rubicon is important for 
            hVps34 binding, lipid kinase inhibition, and autophagy suppression.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21139567
    review:
      summary: >-
        MCL-1 interaction with BECN1 to regulate autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:21139567
          supporting_text: MCL-1 is a stress sensor that regulates autophagy in 
            a developmentally regulated manner.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21241894
    review:
      summary: >-
        RalB and exocyst complex mediate autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:21241894
          supporting_text: RalB and the exocyst mediate the cellular starvation 
            response by direct activation of autophagosome assembly.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21358617
    review:
      summary: >-
        Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy through BECN1 interaction.
        This paper demonstrates BCL2-BECN1 interaction at mitochondria regulates autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding. The BCL2 interaction is for autophagy regulation.

      supported_by:
        - reference_id: PMID:21358617
          supporting_text: Mitochondrial BCL-2 inhibits AMBRA1-induced 
            autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21597469
    review:
      summary: >-
        UVRAG suppresses apoptosis by interfering with BAX activation.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:21597469
          supporting_text: UV irradiation resistance-associated gene suppresses 
            apoptosis by interfering with BAX activation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22028648
    review:
      summary: >-
        Gamma-herpesvirus protein interactome study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:22028648
          supporting_text: 2011 Oct 20. An integrated approach to elucidate the 
            intra-viral and viral-cellular protein interaction networks of a 
            gamma-herpesvirus.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22081109
    review:
      summary: >-
        TAB2/TAB3 inhibit autophagy through BECN1 interaction.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:22081109
          supporting_text: Inhibition of autophagy by TAB2 and TAB3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22493499
    review:
      summary: >-
        SLAMF1 recruits BECN1-VPS34-UVRAG complex for NOX2 regulation.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:22493499
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23112296
    review:
      summary: >-
        Akt-mediated phosphorylation of BECN1 regulates autophagy and tumorigenesis.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23112296
          supporting_text: Oct 25. Akt-mediated regulation of autophagy and 
            tumorigenesis through Beclin 1 phosphorylation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23197835
    review:
      summary: >-
        Bacterial Beclin 1 binding protein study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23197835
          supporting_text: Autophagosomes induced by a bacterial Beclin 1 
            binding protein facilitate obligatory intracellular infection.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23316280
    review:
      summary: >-
        VMP1-BECN1 interaction regulates autophagy induction.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23316280
          supporting_text: The VMP1-Beclin 1 interaction regulates autophagy 
            induction.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23332761
    review:
      summary: >-
        Differential regulation of VPS34 complexes by AMPK.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23332761
          supporting_text: Differential regulation of distinct Vps34 complexes 
            by AMPK in nutrient stress and autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23364696
    review:
      summary: >-
        Identification of autophagy-inducing peptide derived from BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23364696
          supporting_text: Identification of a candidate therapeutic 
            autophagy-inducing peptide.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23478334
    review:
      summary: >-
        BECN1 is required for chromosome congression and kinetochore assembly.
        This is a non-autophagy function.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23478334
          supporting_text: Beclin-1 is required for chromosome congression and 
            proper outer kinetochore assembly.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23541952
    review:
      summary: >-
        Control of autophagic cell death by caspase-10 in multiple myeloma.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23541952
          supporting_text: 2013 Mar 28. Control of autophagic cell death by 
            caspase-10 in multiple myeloma.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23954414
    review:
      summary: >-
        Beclin 2 functions study - comparison with BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23954414
          supporting_text: Aug 15. Beclin 2 functions in autophagy, degradation 
            of G protein-coupled receptors, and metabolism.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23974797
    review:
      summary: >-
        WASH inhibits autophagy through suppression of BECN1 ubiquitination.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23974797
          supporting_text: WASH inhibits autophagy through suppression of Beclin
            1 ubiquitination.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24034250
    review:
      summary: >-
        EGFR-mediated BECN1 phosphorylation suppresses autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24034250
          supporting_text: EGFR-mediated Beclin 1 phosphorylation in autophagy 
            suppression, tumor progression, and tumor chemoresistance.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24056303
    review:
      summary: >-
        UVRAG coordinates Golgi-ER retrograde transport with BECN1 complex.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24056303
          supporting_text: PtdIns(3)P-bound UVRAG coordinates Golgi-ER 
            retrograde and Atg9 transport by differential interactions with the 
            ER tether and the beclin 1 complex.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24349490
    review:
      summary: >-
        Rab39a negatively regulates autophagy through BECN1 interaction.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24349490
          supporting_text: eCollection 2013. Rab39a interacts with 
            phosphatidylinositol 3-kinase and negatively regulates autophagy 
            induced by lipopolysaccharide stimulation in macrophages.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24443581
    review:
      summary: >-
        Gamma-herpesvirus BCL-2 targeting of autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24443581
          supporting_text: 2014 Jan 17. Targeting γ-herpesvirus 68 
            Bcl-2-mediated down-regulation of autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24472739
    review:
      summary: >-
        Decorin activates AMPK to induce autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24472739
          supporting_text: Jan 26. Decorin activates AMPK, an energy sensor 
            kinase, to induce autophagy in endothelial cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24785657
    review:
      summary: >-
        NRBF2 regulates macroautophagy as component of VPS34 complex I.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24785657
          supporting_text: NRBF2 regulates macroautophagy as a component of 
            Vps34 Complex I.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25311841
    review:
      summary: >-
        Coronavirus papain-like proteases interact with BECN1 to regulate autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:25311841
          supporting_text: Oct 15. Coronavirus membrane-associated papain-like 
            proteases induce autophagy through interacting with Beclin1 to 
            negatively regulate antiviral innate immunity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25438055
    review:
      summary: >-
        AMBRA1 links autophagy to cell proliferation through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:25438055
          supporting_text: AMBRA1 links autophagy to cell proliferation and 
            tumorigenesis by promoting c-Myc dephosphorylation and degradation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25490155
    review:
      summary: >-
        Architecture of autophagic PI3K complex - structural study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:25490155
          supporting_text: Architecture and dynamics of the autophagic 
            phosphatidylinositol 3-kinase complex.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25594178
    review:
      summary: >-
        Kinase-independent role for EGFR in autophagy initiation.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:25594178
          supporting_text: A kinase-independent role for EGF receptor in 
            autophagy initiation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26496610
    review:
      summary: >-
        Human interactome study - high-throughput.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:26496610
          supporting_text: Oct 22. A human interactome in three quantitative 
            dimensions organized by stoichiometries and abundances.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26783301
    review:
      summary: >-
        PI3P regulation in endosome conversion involving BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:26783301
          supporting_text: Negative regulation of phosphatidylinositol 
            3-phosphate levels in early-to-late endosome conversion.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28445460
    review:
      summary: >-
        Polyglutamine tracts regulate BECN1-dependent autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:28445460
          supporting_text: Polyglutamine tracts regulate beclin 1-dependent 
            autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        Architecture of human interactome - high-throughput study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein
            communities and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29849149
    review:
      summary: >-
        Disruption of BECN1-BCL2 complex promotes longevity in mice.
        Key study showing BCL2-BECN1 interaction regulates autophagy and lifespan.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative. The BCL2 interaction is for
        autophagy regulation.

      supported_by:
        - reference_id: PMID:29849149
          supporting_text: May 30. Disruption of the beclin 1-BCL2 autophagy 
            regulatory complex promotes longevity in mice.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: >-
        Reference map of human binary protein interactome.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein 
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: >-
        Interactome mapping in neurodegenerative disease proteins.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:32814053
          supporting_text: Interactome Mapping Provides a Network of 
            Neurodegenerative Disease Proteins and Uncovers Widespread Protein 
            Aggregation in Affected Brains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33422265
    review:
      summary: >-
        SARS-CoV-2 ORF3a blocks autophagosome-lysosome fusion.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:33422265
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        Dual proteome-scale networks study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34386498
    review:
      summary: >-
        SARS-CoV-2 ORF3a-mediated incomplete autophagy study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:34386498
          supporting_text: eCollection 2021. ORF3a-Mediated Incomplete Autophagy
            Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 
            Replication.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34524948
    review:
      summary: >-
        Global proximity interactome of human macroautophagy pathway.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:34524948
          supporting_text: 2021 Sep 15. Global Proximity Interactome of the 
            Human Macroautophagy Pathway.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35271311
    review:
      summary: >-
        OpenCell endogenous tagging study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:35271311
          supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
            of human cellular organization.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35512704
    review:
      summary: >-
        Mutation-directed neo-protein-protein interactions in cancer.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:35512704
          supporting_text: 2022 May 4. Systematic discovery of mutation-directed
            neo-protein-protein interactions in cancer.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:38182563
    review:
      summary: >-
        GRB2 is a BECN1 interacting protein that regulates autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:38182563
          supporting_text: GRB2 is a BECN1 interacting protein that regulates 
            autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:40205054
    review:
      summary: >-
        Multimodal cell maps study.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

# ============================================================================
# Additional IEA annotations
# ============================================================================
      supported_by:
        - reference_id: PMID:40205054
          supporting_text: Apr 9. Multimodal cell maps as a foundation for 
            structural and functional genomics.
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        Duplicate of IBA annotation. Core autophagy function.
      action: ACCEPT
      reason: >-
        Core function - duplicates IBA annotation.

  - term:
      id: GO:0001666
      label: response to hypoxia
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Autophagy is induced during hypoxia, and BECN1 participates in this response.
        BNIP3/BNIP3L displace BCL2 from BECN1 to activate autophagy under hypoxia.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function. BECN1 participates in hypoxia-induced autophagy through
        the BNIP3/BNIP3L-BCL2-BECN1 pathway (PMID:19273585).
      supported_by:
        - reference_id: PMID:19273585
          supporting_text: "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"

  - term:
      id: GO:0005802
      label: trans-Golgi network
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        BECN1 localizes to TGN as part of PI3KC3-C2 function.
      action: ACCEPT
      reason: >-
        Consistent with endocytic trafficking function.

  - term:
      id: GO:0007254
      label: JNK cascade
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        JNK phosphorylates BCL2 to release BECN1 for autophagy activation.
        This represents regulatory input to BECN1.
      action: KEEP_AS_NON_CORE
      reason: >-
        BECN1 is downstream of JNK signaling through BCL2 phosphorylation.
        Not direct JNK cascade component.

  - term:
      id: GO:0007623
      label: circadian rhythm
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Autophagy is regulated by circadian rhythm; this annotation likely reflects
        circadian regulation of autophagy genes including BECN1.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary/regulatory. BECN1 expression may be circadian-regulated but
        circadian rhythm is not its core function.

  - term:
      id: GO:0009410
      label: response to xenobiotic stimulus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Autophagy responds to xenobiotic stress; BECN1 participates in this.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary. Autophagy is a general stress response mechanism.

  - term:
      id: GO:0010040
      label: response to iron(II) ion
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Iron can regulate autophagy; this is likely through general stress response.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response annotation.

  - term:
      id: GO:0010288
      label: response to lead ion
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Heavy metal stress induces autophagy.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response annotation.

  - term:
      id: GO:0010508
      label: positive regulation of autophagy
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 is a positive regulator of autophagy as scaffold of PI3KC3-C1.
      action: ACCEPT
      reason: >-
        Core function. BECN1 positively regulates autophagy initiation.

  - term:
      id: GO:0016236
      label: macroautophagy
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 is essential for macroautophagy as scaffold of PI3KC3-C1.
      action: ACCEPT
      reason: >-
        Core function. Macroautophagy is the primary type of autophagy BECN1 regulates.

  - term:
      id: GO:0030425
      label: dendrite
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 may localize to dendrites in neurons. Neuronal autophagy is important
        for synaptic function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cell type-specific localization. Not core function.

  - term:
      id: GO:0030674
      label: protein-macromolecule adaptor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Duplicate annotation - BECN1 has adapter/scaffold function.
      action: ACCEPT
      reason: >-
        Core molecular function - duplicates IBA annotation.

  - term:
      id: GO:0031625
      label: ubiquitin protein ligase binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 is regulated by ubiquitination and binds E3 ligases like NEDD4.
      action: ACCEPT
      reason: >-
        Regulatory interaction. BECN1 is ubiquitinated by multiple E3 ligases
        to regulate its stability and activity.

  - term:
      id: GO:0031667
      label: response to nutrient levels
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1-dependent autophagy is activated in response to nutrient deprivation.
      action: ACCEPT
      reason: >-
        Core function. Nutrient starvation is a primary trigger for BECN1-dependent
        autophagy.

  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 is part of PI3KC3 complexes. Too generic.
      action: MODIFY
      reason: >-
        Should be more specific - annotated to PI3KC3 complex terms instead.
      proposed_replacement_terms:
        - id: GO:0035032
          label: phosphatidylinositol 3-kinase complex, class III

  - term:
      id: GO:0033197
      label: response to vitamin E
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Vitamin E can affect autophagy. Indirect effect.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary/indirect effect.

  - term:
      id: GO:0034198
      label: cellular response to amino acid starvation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1-dependent autophagy is induced by amino acid starvation.
      action: ACCEPT
      reason: >-
        Core function. Amino acid starvation is a primary trigger for autophagy.

  - term:
      id: GO:0035032
      label: phosphatidylinositol 3-kinase complex, class III
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 is a core component of PI3KC3 complexes.
      action: ACCEPT
      reason: >-
        Core localization. BECN1 is an obligate subunit of PI3KC3.

  - term:
      id: GO:0038066
      label: p38MAPK cascade
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        p38 MAPK can regulate autophagy; BECN1 may be downstream.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary regulatory input to autophagy.

  - term:
      id: GO:0042149
      label: cellular response to glucose starvation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Glucose starvation induces autophagy through AMPK-BECN1 pathway.
      action: ACCEPT
      reason: >-
        Core function. Metabolic stress triggers autophagy.

  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 can homodimerize through its coiled-coil domain. However, functional
        complexes involve heterodimerization with ATG14L or UVRAG.
      action: KEEP_AS_NON_CORE
      reason: >-
        The coiled-coil domain can mediate homodimerization, but this is less
        functionally relevant than heterodimerization.

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.

  - term:
      id: GO:0043652
      label: engulfment of apoptotic cell
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        LC3-associated phagocytosis (LAP) involves BECN1 complexes for clearance
        of apoptotic cells. This is a non-canonical autophagy function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function. LAP uses autophagy machinery for phagocytic clearance.

  - term:
      id: GO:0045335
      label: phagocytic vesicle
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 participates in LC3-associated phagocytosis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function related to LAP.

  - term:
      id: GO:0060395
      label: SMAD protein signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Connection to SMAD signaling is likely indirect through autophagy-TGFbeta
        crosstalk.
      action: KEEP_AS_NON_CORE
      reason: >-
        Indirect/secondary effect.

  - term:
      id: GO:0062029
      label: positive regulation of stress granule assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Stress granules and autophagy are connected processes.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary/indirect connection.

  - term:
      id: GO:0070301
      label: cellular response to hydrogen peroxide
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Oxidative stress induces autophagy.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response.

  - term:
      id: GO:0071275
      label: cellular response to aluminum ion
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Heavy metal stress can induce autophagy.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response.

  - term:
      id: GO:0071280
      label: cellular response to copper ion
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Metal ion stress and autophagy.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response.

  - term:
      id: GO:0071364
      label: cellular response to epidermal growth factor stimulus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        EGFR phosphorylates BECN1 to suppress autophagy. This is a regulatory input.
      action: KEEP_AS_NON_CORE
      reason: >-
        Regulatory input. EGFR-mediated phosphorylation suppresses BECN1 activity.

  - term:
      id: GO:0090650
      label: cellular response to oxygen-glucose deprivation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Metabolic stress induces autophagy.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary stress response function.

  - term:
      id: GO:1905672
      label: negative regulation of lysosome organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 affects lysosome function through autophagy pathway.
      action: UNDECIDED
      reason: >-
        Unclear annotation - need more evidence for this specific function.

  - term:
      id: GO:2000786
      label: positive regulation of autophagosome assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        BECN1 positively regulates autophagosome assembly as scaffold of PI3KC3-C1.
      action: ACCEPT
      reason: >-
        Core function.

  - term:
      id: GO:2001244
      label: positive regulation of intrinsic apoptotic signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.

# ============================================================================
# IDA/IMP/TAS EXPERIMENTAL ANNOTATIONS
# ============================================================================
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        BECN1 localizes to cytosol based on immunofluorescence.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0016604
      label: nuclear body
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        BECN1 detected in nuclear bodies by immunofluorescence.
      action: KEEP_AS_NON_CORE
      reason: >-
        Not a primary localization. May represent minor pool.

  - term:
      id: GO:0016236
      label: macroautophagy
    evidence_type: NAS
    original_reference_id: PMID:40442316
    review:
      summary: >-
        Recent structural study of ULK1C:PI3KC3-C1 supercomplex confirms BECN1 role
        in macroautophagy.
      action: ACCEPT
      reason: >-
        Core function confirmed by structural studies.

      supported_by:
        - reference_id: PMID:40442316
          supporting_text: Structure and activation of the human 
            autophagy-initiating ULK1C:PI3KC3-C1 supercomplex.
  - term:
      id: GO:0006622
      label: protein targeting to lysosome
    evidence_type: NAS
    original_reference_id: PMID:16467569
    review:
      summary: >-
        BECN1 in PI3KC3-C2 regulates trafficking to lysosome.
      action: KEEP_AS_NON_CORE
      reason: >-
        Related to PI3KC3-C2 endocytic trafficking function.

      supported_by:
        - reference_id: PMID:16467569
          supporting_text: Regulation of membrane traffic by phosphoinositide 
            3-kinases.
  - term:
      id: GO:0010506
      label: regulation of autophagy
    evidence_type: IDA
    original_reference_id: PMID:16799551
    review:
      summary: >-
        This paper identified UVRAG as BECN1-binding protein that regulates autophagy.
        Demonstrates BECN1's role in autophagy regulation.
      action: ACCEPT
      reason: >-
        Core function.
      supported_by:
        - reference_id: PMID:16799551
          supporting_text: "UVRAG, a tumour suppressor candidate... associates with
            the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex, where UVRAG and Beclin1
            interdependently induce autophagy"

  - term:
      id: GO:0016241
      label: regulation of macroautophagy
    evidence_type: IDA
    original_reference_id: PMID:10625637
    review:
      summary: >-
        Foundational paper showing class III PI3K (VPS34) is required for macroautophagy.
        BECN1 as VPS34 scaffold regulates this process.
      action: ACCEPT
      reason: >-
        Core function.
      supported_by:
        - reference_id: PMID:10625637
          supporting_text: "an increase in the class III PI3K product (phosphatidylinositol
            3-phosphate)... stimulates macroautophagy"

  - term:
      id: GO:0036092
      label: phosphatidylinositol-3-phosphate biosynthetic process
    evidence_type: IDA
    original_reference_id: PMID:8999962
    review:
      summary: >-
        BECN1 as scaffold of VPS34 complex enables PI3P synthesis. VPS34 is the
        lipid kinase; BECN1 is the adapter.
      action: ACCEPT
      reason: >-
        Core function. BECN1 enables PI3P synthesis by scaffolding VPS34 complex.

      supported_by:
        - reference_id: PMID:8999962
          supporting_text: Characterization of p150, an adaptor protein for the 
            human phosphatidylinositol (PtdIns) 3-kinase.
  - term:
      id: GO:0045022
      label: early endosome to late endosome transport
    evidence_type: IDA
    original_reference_id: PMID:14617358
    review:
      summary: >-
        VPS34 and BECN1 interact with Rab7 for endosome maturation.
      action: ACCEPT
      reason: >-
        Related to PI3KC3-C2 endocytic trafficking function.

      supported_by:
        - reference_id: PMID:14617358
          supporting_text: Human VPS34 and p150 are Rab7 interacting partners.
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IDA
    original_reference_id: PMID:10625637
    review:
      summary: >-
        PI3KC3 regulates autophagosome maturation in addition to initiation.
      action: ACCEPT
      reason: >-
        Core autophagy function.

      supported_by:
        - reference_id: PMID:10625637
          supporting_text: Distinct classes of phosphatidylinositol 3'-kinases 
            are involved in signaling pathways that control macroautophagy in 
            HT-29 cells.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9837231
    review:
      summary: >-
        Reactome annotation for ISGylation of BECN1 in cytosol.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IMP
    original_reference_id: PMID:25215947
    review:
      summary: >-
        AMBRA1 can induce mitophagy via LC3 binding - involves BECN1 complex.
      action: ACCEPT
      reason: >-
        Core function - mitophagy.

      supported_by:
        - reference_id: PMID:25215947
          supporting_text: Sep 12. AMBRA1 is able to induce mitophagy via LC3 
            binding, regardless of PARKIN and p62/SQSTM1.
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: IDA
    original_reference_id: PMID:25891078
    review:
      summary: >-
        IRGM governs autophagy machinery by assembling ULK1 and BECN1 complexes.
      action: ACCEPT
      reason: >-
        Core function.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly thus governing the formation of autophagy initiation complexes"

  - term:
      id: GO:0030674
      label: protein-macromolecule adaptor activity
    evidence_type: IDA
    original_reference_id: PMID:25891078
    review:
      summary: >-
        Direct demonstration of BECN1's adapter function in assembling autophagy complexes.
      action: ACCEPT
      reason: >-
        Core molecular function.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly"

  - term:
      id: GO:0002753
      label: cytoplasmic pattern recognition receptor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:34796041
    review:
      summary: >-
        BECN1 links TLR4 signaling to autophagy in liver cancer context.
      action: KEEP_AS_NON_CORE
      reason: >-
        Represents autophagy response to PRR signaling. Not core function.

      supported_by:
        - reference_id: PMID:34796041
          supporting_text: 2021 Oct. Hepatitis B virus X Protein Promotes Liver 
            Cancer Progression through Autophagy Induction in Response to TLR4 
            Stimulation.
  - term:
      id: GO:0060090
      label: molecular adaptor activity
    evidence_type: IDA
    original_reference_id: PMID:34796041
    review:
      summary: >-
        BECN1 has molecular adapter activity - core function.
      action: ACCEPT
      reason: >-
        Core molecular function.

      supported_by:
        - reference_id: PMID:34796041
          supporting_text: 2021 Oct. Hepatitis B virus X Protein Promotes Liver 
            Cancer Progression through Autophagy Induction in Response to TLR4 
            Stimulation.
  - term:
      id: GO:0043069
      label: negative regulation of programmed cell death
    evidence_type: IMP
    original_reference_id: PMID:19273585
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:19273585
          supporting_text: "The ablation of Beclin1, a major actor of autophagy, enhances
            cell death under hypoxic conditions"

  - term:
      id: GO:0032473
      label: cytoplasmic side of mitochondrial outer membrane
    evidence_type: IDA
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 associates with mitochondrial outer membrane, particularly MAMs.
      action: ACCEPT
      reason: >-
        Supports mitophagy function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0005776
      label: autophagosome
    evidence_type: ISS
    original_reference_id: PMID:23798385
    review:
      summary: >-
        BECN1 localizes to autophagosomes.
      action: ACCEPT
      reason: >-
        Core localization.

      supported_by:
        - reference_id: PMID:23798385
          supporting_text: Decorin causes autophagy in endothelial cells via 
            Peg3.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IDA
    original_reference_id: PMID:25891078
    review:
      summary: >-
        Direct demonstration of BECN1 in autophagy through IRGM interaction study.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:25891078
          supporting_text: 2015 Apr 16. IRGM governs the core autophagy 
            machinery to conduct antimicrobial defense.
  - term:
      id: GO:0065003
      label: protein-containing complex assembly
    evidence_type: IDA
    original_reference_id: PMID:25891078
    review:
      summary: >-
        BECN1 assembles into PI3KC3 complexes.
      action: ACCEPT
      reason: >-
        Core function of BECN1 as scaffold.

      supported_by:
        - reference_id: PMID:25891078
          supporting_text: 2015 Apr 16. IRGM governs the core autophagy 
            machinery to conduct antimicrobial defense.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17659302
    review:
      summary: >-
        Structural study of BCL-XL in complex with BECN1 BH3 domain.
      action: REMOVE
      reason: >-
        Generic protein binding. The specific BCL-XL binding is relevant for autophagy
        regulation.

      supported_by:
        - reference_id: PMID:17659302
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18797192
    review:
      summary: >-
        Gamma-herpesvirus BCL-2 homolog M11 regulation of BECN1-dependent autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:18797192
          supporting_text: Molecular basis of the regulation of Beclin 
            1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24115198
    review:
      summary: >-
        Intrinsically disordered regions in autophagy proteins including BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24115198
          supporting_text: Intrinsically disordered regions in autophagy 
            proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:27046249
    review:
      summary: >-
        BECN1 N-terminal domain is intrinsically disordered.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:27046249
          supporting_text: The BECN1 N-terminal domain is intrinsically 
            disordered.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:30626284
    review:
      summary: >-
        Structural study of BCL2-BECN1 interaction after STK4/MST1 phosphorylation.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:30626284
          supporting_text: 2019 Jan 9. Structural insights into BCL2 
            pro-survival protein interactions with the key autophagy regulator 
            BECN1 following phosphorylation by STK4/MST1.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:30767700
    review:
      summary: >-
        PI3KC3 complex members interact with GABARAP/GABARAPL1 via LIR motifs.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:30767700
          supporting_text: 2019 Mar 4. Members of the autophagy class III 
            phosphatidylinositol 3-kinase complex I interact with GABARAP and 
            GABARAPL1 via LIR motifs.
  - term:
      id: GO:0010506
      label: regulation of autophagy
    evidence_type: IDA
    original_reference_id: PMID:18797192
    review:
      summary: >-
        Gamma-herpesvirus BCL-2 regulates BECN1-dependent autophagy.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:18797192
          supporting_text: Molecular basis of the regulation of Beclin 
            1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22498477
    review:
      summary: >-
        BCL-B inhibits BECN1-dependent autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:22498477
          supporting_text: The anti-apoptotic Bcl-B protein inhibits 
            BECN1-dependent autophagic cell death.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:22498477
    review:
      summary: >-
        BECN1 localized to cytoplasm.
      action: ACCEPT
      reason: >-
        Core localization.

      supported_by:
        - reference_id: PMID:22498477
          supporting_text: The anti-apoptotic Bcl-B protein inhibits 
            BECN1-dependent autophagic cell death.
  - term:
      id: GO:0010508
      label: positive regulation of autophagy
    evidence_type: IDA
    original_reference_id: PMID:21358617
    review:
      summary: >-
        Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy through BECN1.
        Releasing BECN1 from BCL-2 promotes autophagy.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:21358617
          supporting_text: Mitochondrial BCL-2 inhibits AMBRA1-induced 
            autophagy.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:28747345
    review:
      summary: >-
        ORMDL3 regulates autophagy through ATF6alpha-ER stress-BECN1 pathway.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:28747345
          supporting_text: 2017 Jul 26. ORMDL3 Facilitates the Survival of 
            Splenic B Cells via an ATF6α-Endoplasmic Reticulum Stress-Beclin1 
            Autophagy Regulatory Pathway.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31806350
    review:
      summary: >-
        TMEM39A regulates autophagy through SAC1 trafficking affecting BECN1 complex.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:31806350
          supporting_text: 2019 Dec 2. The ER-Localized Transmembrane Protein 
            TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of 
            the PtdIns(4)P Phosphatase SAC1.
  - term:
      id: GO:2001244
      label: positive regulation of intrinsic apoptotic signaling pathway
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Sequence similarity transfer annotation for apoptosis - problematic.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        OVER-ANNOTATION. BECN1 is not an apoptosis regulator.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:27031958
    review:
      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.
      action: REMOVE
      reason: >-
        Generic protein binding. The paper's claims about BECN1 in apoptosis are
        questionable given known BECN1 function.

      supported_by:
        - reference_id: PMID:27031958
          supporting_text: Nupr1/Chop signal axis is involved in 
            mitochondrion-related endothelial cell apoptosis induced by 
            methamphetamine.
  - term:
      id: GO:2001244
      label: positive regulation of intrinsic apoptotic signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:27031958
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.

      supported_by:
        - reference_id: PMID:27031958
          supporting_text: Nupr1/Chop signal axis is involved in 
            mitochondrion-related endothelial cell apoptosis induced by 
            methamphetamine.
  - term:
      id: GO:0032465
      label: regulation of cytokinesis
    evidence_type: IMP
    original_reference_id: PMID:20208530
    review:
      summary: >-
        PI3KC3 complex generates PI3P at midbody for cytokinesis regulation.
        This is a non-autophagy function of BECN1.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function. BECN1 in PI3KC3-C2 regulates cytokinesis through PI3P.

      supported_by:
        - reference_id: PMID:20208530
          supporting_text: PtdIns(3)P controls cytokinesis through 
            KIF13A-mediated recruitment of FYVE-CENT to the midbody.
  - term:
      id: GO:0019901
      label: protein kinase binding
    evidence_type: IPI
    original_reference_id: PMID:27853422
    review:
      summary: >-
        ROCK1 interacts with BECN1 and affects autophagosome formation.
      action: ACCEPT
      reason: >-
        BECN1 is phosphorylated by multiple kinases that regulate its activity.

      supported_by:
        - reference_id: PMID:27853422
          supporting_text: eCollection 2016. ROCK1 Is Associated with 
            Alzheimer's Disease-Specific Plaques, as well as Enhances 
            Autophagosome Formation But not Autophagic Aβ Clearance.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28479384
    review:
      summary: >-
        BECN1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:28479384
          supporting_text: Beclin1 antagonizes LAPTM4B-mediated EGFR 
            overactivation in gastric cancer cells.
  - term:
      id: GO:0045022
      label: early endosome to late endosome transport
    evidence_type: IMP
    original_reference_id: PMID:26783301
    review:
      summary: >-
        BECN1 in PI3KC3-C2 regulates PI3P levels in endosome conversion.
      action: ACCEPT
      reason: >-
        Related to PI3KC3-C2 endocytic trafficking function.

      supported_by:
        - reference_id: PMID:26783301
          supporting_text: Negative regulation of phosphatidylinositol 
            3-phosphate levels in early-to-late endosome conversion.
  - term:
      id: GO:0051020
      label: GTPase binding
    evidence_type: IPI
    original_reference_id: PMID:25891078
    review:
      summary: >-
        IRGM is a GTPase that binds BECN1 to regulate autophagy.
      action: ACCEPT
      reason: >-
        BECN1 interacts with small GTPases like Rab proteins and IRGM.
      supported_by:
        - reference_id: PMID:25891078
          supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
            co-assembly"

  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:23184933
    review:
      summary: >-
        XBP1 splicing triggers autophagy through BECN1 transcriptional activation.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:23184933
          supporting_text: 2012 Nov 26. XBP1 mRNA splicing triggers an 
            autophagic response in endothelial cells through BECLIN-1 
            transcriptional activation.
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IMP
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 membrane association and ATG14-dependent phosphorylation regulate
        BECN1-mediated autophagy including mitophagy.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0098780
      label: response to mitochondrial depolarisation
    evidence_type: IMP
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 responds to mitochondrial depolarization by localizing to mitochondria
        for mitophagy.
      action: ACCEPT
      reason: >-
        Relates to mitophagy function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22095288
    review:
      summary: >-
        PKD phosphorylates VPS34 downstream of DAPK to mediate autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:22095288
          supporting_text: Nov 18. PKD is a kinase of Vps34 that mediates 
            ROS-induced autophagy downstream of DAPk.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IDA
    original_reference_id: PMID:23629966
    review:
      summary: >-
        Deacetylation of p53 induces autophagy through BECN1.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:23629966
          supporting_text: Deacetylation of p53 induces autophagy by suppressing
            Bmf expression.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24113155
    review:
      summary: >-
        BOK-MCL1 rheostat regulates placental autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24113155
          supporting_text: Placental autophagy regulation by the BOK-MCL1 
            rheostat.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6781779
    review:
      summary: >-
        USP13 deubiquitinates BECN1 in cytosol.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0051897
      label: positive regulation of phosphatidylinositol 3-kinase/protein kinase
        B signal transduction
    evidence_type: NAS
    original_reference_id: PMID:25215947
    review:
      summary: >-
        AMBRA1 can induce mitophagy via LC3 binding regardless of PARKIN.
        Connection to PI3K/AKT signaling may be indirect.
      action: UNDECIDED
      reason: >-
        Need more evidence for direct BECN1 role in PI3K/AKT signaling.

      supported_by:
        - reference_id: PMID:25215947
          supporting_text: Sep 12. AMBRA1 is able to induce mitophagy via LC3 
            binding, regardless of PARKIN and p62/SQSTM1.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26347139
    review:
      summary: >-
        TRIM-mediated precision autophagy targeting cytoplasmic innate immunity regulators.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:26347139
          supporting_text: TRIM-mediated precision autophagy targets cytoplasmic
            regulators of innate immunity.
  - term:
      id: GO:0031625
      label: ubiquitin protein ligase binding
    evidence_type: IPI
    original_reference_id: PMID:25127057
    review:
      summary: >-
        TRIM proteins regulate autophagy by direct recognition and can target
        autophagic substrates including through BECN1 interaction.
      action: ACCEPT
      reason: >-
        BECN1 interacts with multiple E3 ligases for regulation.

      supported_by:
        - reference_id: PMID:25127057
          supporting_text: 2014 Aug 7. TRIM proteins regulate autophagy and can 
            target autophagic substrates by direct recognition.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25127057
    review:
      summary: >-
        TRIM5 interacts with BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:25127057
          supporting_text: 2014 Aug 7. TRIM proteins regulate autophagy and can 
            target autophagic substrates by direct recognition.
  - term:
      id: GO:0032465
      label: regulation of cytokinesis
    evidence_type: IMP
    original_reference_id: PMID:20643123
    review:
      summary: >-
        PI3KC3 sub-complex with VPS15, VPS34, BECN1, UVRAG, BIF-1 regulates cytokinesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function through PI3KC3-C2.

      supported_by:
        - reference_id: PMID:20643123
          supporting_text: 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.
  - term:
      id: GO:0032801
      label: receptor catabolic process
    evidence_type: IMP
    original_reference_id: PMID:20643123
    review:
      summary: >-
        PI3KC3 regulates degradative endocytic traffic including receptor degradation.
      action: ACCEPT
      reason: >-
        PI3KC3-C2 function in receptor trafficking.

      supported_by:
        - reference_id: PMID:20643123
          supporting_text: 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.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5672012
    review:
      summary: >-
        Beclin-1 complex phosphorylates PtdIns in cytosol.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5679205
    review:
      summary: >-
        ULK1 phosphorylates Beclin-1 in cytosol.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5682385
    review:
      summary: >-
        Phagophore extends from PI3P-enriched structure.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IMP
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 localizes to mitochondria for mitophagy function.
      action: ACCEPT
      reason: >-
        Supports mitophagy function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Sequence similarity annotation - consistent with core function.
      action: ACCEPT
      reason: >-
        Core function.

  - term:
      id: GO:0016236
      label: macroautophagy
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Sequence similarity annotation - consistent with core function.
      action: ACCEPT
      reason: >-
        Core function.

  - term:
      id: GO:0035032
      label: phosphatidylinositol 3-kinase complex, class III
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Sequence similarity annotation - BECN1 is obligate component of PI3KC3.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0042149
      label: cellular response to glucose starvation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Autophagy is induced by glucose starvation.
      action: ACCEPT
      reason: >-
        Core function - metabolic stress triggers autophagy.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23878393
    review:
      summary: >-
        Membrane association and ATG14-dependent phosphorylation of BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0005768
      label: endosome
    evidence_type: IDA
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 localizes to endosomes.
      action: ACCEPT
      reason: >-
        Related to PI3KC3-C2 function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 localizes to ER, particularly for autophagosome nucleation.
      action: ACCEPT
      reason: >-
        Core localization for autophagy initiation.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0043548
      label: phosphatidylinositol 3-kinase binding
    evidence_type: IPI
    original_reference_id: PMID:23878393
    review:
      summary: >-
        BECN1 directly binds VPS34 (PI3KC3).
      action: ACCEPT
      reason: >-
        Core molecular function.

      supported_by:
        - reference_id: PMID:23878393
          supporting_text: Jul 22. Role of membrane association and 
            Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24056301
    review:
      summary: >-
        USP33 deubiquitylase discriminates RALB functions in autophagy.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:24056301
          supporting_text: The deubiquitylase USP33 discriminates between RALB 
            functions in autophagy and innate immune response.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23182941
    review:
      summary: >-
        EMC6 interacts with RAB5A and regulates autophagy through BECN1.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:23182941
          supporting_text: A novel ER-localized transmembrane protein, EMC6, 
            interacts with RAB5A and regulates cell autophagy.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:24056303
    review:
      summary: >-
        UVRAG coordinates Golgi-ER retrograde transport with BECN1 complex.
      action: ACCEPT
      reason: >-
        Core function.

      supported_by:
        - reference_id: PMID:24056303
          supporting_text: PtdIns(3)P-bound UVRAG coordinates Golgi-ER 
            retrograde and Atg9 transport by differential interactions with the 
            ER tether and the beclin 1 complex.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IMP
    original_reference_id: PMID:23478334
    review:
      summary: >-
        BECN1 is required for proper chromosome congression and kinetochore assembly.
        Non-autophagy function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary/non-autophagy function.

      supported_by:
        - reference_id: PMID:23478334
          supporting_text: Beclin-1 is required for chromosome congression and 
            proper outer kinetochore assembly.
  - term:
      id: GO:1902425
      label: positive regulation of attachment of mitotic spindle microtubules 
        to kinetochore
    evidence_type: IMP
    original_reference_id: PMID:23478334
    review:
      summary: >-
        BECN1 affects kinetochore-microtubule attachment. Non-autophagy function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary/non-autophagy function.

      supported_by:
        - reference_id: PMID:23478334
          supporting_text: Beclin-1 is required for chromosome congression and 
            proper outer kinetochore assembly.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1169406
    review:
      summary: >-
        ISGylation of host proteins in cytosol.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1632857
    review:
      summary: >-
        ULK1 phosphorylates AMBRA1:BECN1 complex.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1678841
    review:
      summary: >-
        ISG15 deconjugating enzyme USP18 regulation.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5678313
    review:
      summary: >-
        AMBRA1:DYNLL binds BECN1 complex.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5678315
    review:
      summary: >-
        BECN1 complex dissociates from DYNLL.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5679266
    review:
      summary: >-
        Beclin-1 complex translocates to ER.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9755359
    review:
      summary: >-
        SARS-CoV-2 ORF8:class I MHC binds BECN1.
      action: ACCEPT
      reason: >-
        Core localization.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17724469
    review:
      summary: >-
        VMP1 affects invasion capacity through BECN1 interaction.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:17724469
          supporting_text: Reduced expression of vacuole membrane protein 1 
            affects the invasion capacity of tumor cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19270696
    review:
      summary: >-
        ATG14L and Rubicon reciprocally regulate autophagy through BECN1 binding.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:19270696
          supporting_text: Two Beclin 1-binding proteins, Atg14L and Rubicon, 
            reciprocally regulate autophagy at different stages.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21962518
    review:
      summary: >-
        BECN1 controls p53 levels through USP10/USP13 deubiquitination activity.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:21962518
          supporting_text: Beclin1 controls the levels of p53 by regulating the 
            deubiquitination activity of USP10 and USP13.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16417406
    review:
      summary: >-
        Hem-1 complexes study - BECN1 interaction in neutrophil chemotaxis.
      action: REMOVE
      reason: >-
        Generic protein binding term is uninformative.

      supported_by:
        - reference_id: PMID:16417406
          supporting_text: Hem-1 complexes are essential for Rac activation, 
            actin polymerization, and myosin regulation during neutrophil 
            chemotaxis.
  - term:
      id: GO:0006968
      label: cellular defense response
    evidence_type: TAS
    original_reference_id: PMID:9765397
    review:
      summary: >-
        Original paper discovering BECN1 showing it protects against viral encephalitis.
      action: ACCEPT
      reason: >-
        BECN1 participates in xenophagy/antiviral autophagy.
      supported_by:
        - reference_id: PMID:9765397
          supporting_text: "These findings demonstrate that Beclin is a novel Bcl-2-interacting
            cellular protein that may play a role in antiviral host defense."

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: TAS
    original_reference_id: PMID:9765397
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:9765397
          supporting_text: "These findings demonstrate that Beclin is a novel Bcl-2-interacting
            cellular protein that may play a role in antiviral host defense."

references:
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data 
      to orthologs by curator judgment of sequence similarity
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation 
      data to orthologs using Ensembl Compara
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:9765397
    title: Protection against fatal Sindbis virus encephalitis by beclin, a 
      novel Bcl-2-interacting protein.
    findings:
      - statement: Original discovery paper identifying BECN1 as 
          BCL2-interacting protein with antiviral activity
        supporting_text: "These findings demonstrate that Beclin is a novel Bcl-2-interacting
          cellular protein that may play a role in antiviral host defense."
  - id: PMID:10625637
    title: Distinct classes of phosphatidylinositol 3'-kinases are involved in 
      signaling pathways that control macroautophagy in HT-29 cells.
    findings:
      - statement: Class III PI3K (VPS34) stimulates macroautophagy through PI3P
          production
        supporting_text: "an increase in the class III PI3K product (phosphatidylinositol
          3-phosphate)... stimulates macroautophagy"
  - id: PMID:16799551
    title: Autophagic and tumour suppressor activity of a novel Beclin1-binding 
      protein UVRAG.
    findings:
      - statement: UVRAG identified as BECN1-binding protein that regulates 
          autophagy
        supporting_text: "UVRAG, a tumour suppressor candidate... associates with
          the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex, where UVRAG and Beclin1
          interdependently induce autophagy"
  - id: PMID:17446862
    title: Functional and physical interaction between Bcl-X(L) and a BH3-like 
      domain in Beclin-1.
    findings:
      - statement: BCL2/BCL-XL bind BECN1 BH3 domain to inhibit autophagy, not 
          regulate apoptosis
        supporting_text: "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)."
  - id: PMID:19273585
    title: Hypoxia-induced autophagy is mediated through hypoxia-inducible 
      factor induction of BNIP3 and BNIP3L via their BH3 domains.
    findings:
      - statement: BNIP3/BNIP3L BH3 domains induce autophagy by disrupting 
          BCL2-BECN1 complex WITHOUT inducing cell death
        supporting_text: "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"
  - id: PMID:23878393
    title: Role of membrane association and Atg14-dependent phosphorylation in 
      beclin-1-mediated autophagy.
    findings:
      - statement: ATG14-dependent phosphorylation at Ser90/93 is required for 
          maximal autophagy
        supporting_text: "We map these novel phosphorylation sites to serines 90 and
          93 and demonstrate that phosphorylation at these sites is necessary for
          maximal autophagy."
      - statement: BECN1 membrane association controls autophagosome size and 
          number
        supporting_text: "We identified a unique domain in beclin-1, conserved in
          the yeast homologue Atg6, which is involved in membrane association and,
          unexpectedly, controls autophagosome size and number in yeast."
  - id: PMID:25891078
    title: IRGM governs the core autophagy machinery to conduct antimicrobial 
      defense.
    findings:
      - statement: IRGM assembles ULK1 and BECN1 to form autophagy initiation 
          complexes
        supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
          co-assembly thus governing the formation of autophagy initiation complexes."
      - statement: BECN1 phosphorylation at Ser93/96 by AMPK activates autophagy
        supporting_text: "IRGM interacts with ULK1 and Beclin 1 and promotes their
          co-assembly"
# Additional references from GOA annotations (stub entries)
  - id: PMID:8999962
    title: Characterization of p150, an adaptor protein for the human 
      phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by 
      phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex.
    findings: []
  - id: PMID:14617358
    title: Human VPS34 and p150 are Rab7 interacting partners.
    findings: []
  - id: PMID:16417406
    title: Hem-1 complexes are essential for Rac activation, actin 
      polymerization, and myosin regulation during neutrophil chemotaxis.
    findings: []
  - id: PMID:16467569
    title: Regulation of membrane traffic by phosphoinositide 3-kinases.
    findings: []
  - id: PMID:17659302
    title: 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.
    findings: []
  - id: PMID:17724469
    title: Reduced expression of vacuole membrane protein 1 affects the invasion
      capacity of tumor cells.
    findings: []
  - id: PMID:18797192
    title: Molecular basis of the regulation of Beclin 1-dependent autophagy by 
      the gamma-herpesvirus 68 Bcl-2 homolog M11.
    findings: []
  - id: PMID:19050071
    title: Identification of Barkor as a mammalian autophagy-specific factor for
      Beclin 1 and class III phosphatidylinositol 3-kinase.
    findings: []
  - id: PMID:19180116
    title: DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 
      promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy.
    findings: []
  - id: PMID:19270696
    title: Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally 
      regulate autophagy at different stages.
    findings: []
  - id: PMID:19959994
    title: The IKK complex contributes to the induction of autophagy.
    findings: []
  - id: PMID:20208530
    title: PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment 
      of FYVE-CENT to the midbody.
    findings: []
  - id: PMID:20562859
    title: Network organization of the human autophagy system.
    findings: []
  - id: PMID:20638385
    title: Interaction of Beclin 1 with survivin regulates sensitivity of human 
      glioma cells to TRAIL-induced apoptosis.
    findings: []
  - id: PMID:20643123
    title: A phosphatidylinositol 3-kinase class III sub-complex containing 
      VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and 
      degradative endocytic traffic.
    findings: []
  - id: PMID:20819940
    title: Endogenous HMGB1 regulates autophagy.
    findings: []
  - id: PMID:21062745
    title: The RUN domain of rubicon is important for hVps34 binding, lipid 
      kinase inhibition, and autophagy suppression.
    findings: []
  - id: PMID:21139567
    title: MCL-1 is a stress sensor that regulates autophagy in a 
      developmentally regulated manner.
    findings: []
  - id: PMID:21241894
    title: RalB and the exocyst mediate the cellular starvation response by 
      direct activation of autophagosome assembly.
    findings: []
  - id: PMID:21358617
    title: Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
    findings: []
  - id: PMID:21597469
    title: UV irradiation resistance-associated gene suppresses apoptosis by 
      interfering with BAX activation.
    findings: []
  - id: PMID:21962518
    title: Beclin1 controls the levels of p53 by regulating the deubiquitination
      activity of USP10 and USP13.
    findings: []
  - id: PMID:22028648
    title: An integrated approach to elucidate the intra-viral and 
      viral-cellular protein interaction networks of a gamma-herpesvirus.
    findings: []
  - id: PMID:22081109
    title: Inhibition of autophagy by TAB2 and TAB3.
    findings: []
  - id: PMID:22095288
    title: PKD is a kinase of Vps34 that mediates ROS-induced autophagy 
      downstream of DAPk.
    findings: []
  - id: PMID:22493499
    title: 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.
    findings: []
  - id: PMID:22498477
    title: The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic 
      cell death.
    findings: []
  - id: PMID:23112296
    title: Akt-mediated regulation of autophagy and tumorigenesis through Beclin
      1 phosphorylation.
    findings: []
  - id: PMID:23182941
    title: A novel ER-localized transmembrane protein, EMC6, interacts with 
      RAB5A and regulates cell autophagy.
    findings: []
  - id: PMID:23184933
    title: XBP1 mRNA splicing triggers an autophagic response in endothelial 
      cells through BECLIN-1 transcriptional activation.
    findings: []
  - id: PMID:23197835
    title: Bacterial Beclin 1 binding protein.
    findings: []
  - id: PMID:23316280
    title: The VMP1-Beclin 1 interaction regulates autophagy induction.
    findings: []
  - id: PMID:23332761
    title: Differential regulation of distinct Vps34 complexes by AMPK in 
      nutrient stress and autophagy.
    findings: []
  - id: PMID:23364696
    title: Identification of a candidate therapeutic autophagy-inducing peptide.
    findings: []
  - id: PMID:23478334
    title: Beclin-1 is required for chromosome congression and proper outer 
      kinetochore assembly.
    findings: []
  - id: PMID:23541952
    title: Control of autophagic cell death by caspase-10 in multiple myeloma.
    findings: []
  - id: PMID:23629966
    title: Deacetylation of p53 induces autophagy by suppressing Bmf expression.
    findings: []
  - id: PMID:23798385
    title: Decorin causes autophagy in endothelial cells via Peg3.
    findings: []
  - id: PMID:23954414
    title: Beclin 2 functions in autophagy, degradation of G protein-coupled 
      receptors, and metabolism.
    findings: []
  - id: PMID:23974797
    title: WASH inhibits autophagy through suppression of Beclin 1 
      ubiquitination.
    findings: []
  - id: PMID:24034250
    title: EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, 
      tumor progression, and tumor chemoresistance.
    findings: []
  - id: PMID:24056301
    title: The deubiquitylase USP33 discriminates between RALB functions in 
      autophagy and innate immune response.
    findings: []
  - id: PMID:24056303
    title: PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 
      transport by differential interactions with the ER tether and the beclin 1
      complex.
    findings: []
  - id: PMID:24113155
    title: Placental autophagy regulation by the BOK-MCL1 rheostat.
    findings: []
  - id: PMID:24115198
    title: Intrinsically disordered regions in autophagy proteins.
    findings: []
  - id: PMID:24349490
    title: Rab39a interacts with phosphatidylinositol 3-kinase and negatively 
      regulates autophagy induced by lipopolysaccharide stimulation in 
      macrophages.
    findings: []
  - id: PMID:24443581
    title: Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of 
      autophagy.
    findings: []
  - id: PMID:24472739
    title: Decorin activates AMPK, an energy sensor kinase, to induce autophagy 
      in endothelial cells.
    findings: []
  - id: PMID:24785657
    title: NRBF2 regulates macroautophagy.
    findings: []
  - id: PMID:25127057
    title: TRIM proteins regulate autophagy.
    findings: []
  - id: PMID:25215947
    title: AMBRA1 is able to induce mitophagy via LC3 binding, regardless of 
      PARKIN and p62/SQSTM1.
    findings: []
  - id: PMID:25311841
    title: Coronavirus membrane-associated papain-like proteases induce 
      autophagy through interacting with Beclin1 to negatively regulate 
      antiviral innate immunity.
    findings: []
  - id: PMID:25438055
    title: AMBRA1 links autophagy to cell proliferation.
    findings: []
  - id: PMID:25490155
    title: Architecture and dynamics of the autophagic phosphatidylinositol 
      3-kinase complex.
    findings: []
  - id: PMID:25594178
    title: A kinase-independent role for EGF receptor in autophagy initiation.
    findings: []
  - id: PMID:26347139
    title: TRIM-mediated precision autophagy.
    findings: []
  - id: PMID:26496610
    title: A human interactome in three quantitative dimensions organized by 
      stoichiometries and abundances.
    findings: []
  - id: PMID:26783301
    title: Negative regulation of phosphatidylinositol 3-phosphate levels in 
      early-to-late endosome conversion.
    findings: []
  - id: PMID:27031958
    title: Nupr1/Chop signal axis is involved in mitochondrion-related 
      endothelial cell apoptosis induced by methamphetamine.
    findings: []
  - id: PMID:27046249
    title: The BECN1 N-terminal domain is intrinsically disordered.
    findings: []
  - id: PMID:27853422
    title: ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as 
      well as Enhances Autophagosome Formation But not Autophagic Aβ Clearance.
    findings: []
  - id: PMID:28445460
    title: Polyglutamine tracts regulate beclin 1-dependent autophagy.
    findings: []
  - id: PMID:28479384
    title: Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric 
      cancer cells.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and
      disease networks.
    findings: []
  - id: PMID:28747345
    title: ORMDL3 Facilitates the Survival of Splenic B Cells via an 
      ATF6α-Endoplasmic Reticulum Stress-Beclin1 Autophagy Regulatory Pathway.
    findings: []
  - id: PMID:29849149
    title: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes
      longevity in mice.
    findings: []
  - id: PMID:30626284
    title: Structural insights into BCL2 pro-survival protein interactions with 
      the key autophagy regulator BECN1 following phosphorylation by STK4/MST1.
    findings: []
  - id: PMID:30767700
    title: Members of the autophagy class III phosphatidylinositol 3-kinase 
      complex I interact with GABARAP and GABARAPL1 via LIR motifs.
    findings: []
  - id: PMID:31806350
    title: The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates 
      Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase 
      SAC1.
    findings: []
  - id: PMID:32296183
    title: Human binary protein interactome.
    findings: []
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease 
      Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings: []
  - id: PMID:33422265
    title: ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated 
      assembly of the SNARE complex required for autolysosome formation.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks.
    findings: []
  - id: PMID:34386498
    title: ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute 
      Respiratory Syndrome Coronavirus-2 Replication.
    findings: []
  - id: PMID:34524948
    title: Global Proximity Interactome of the Human Macroautophagy Pathway.
    findings: []
  - id: PMID:34796041
    title: Hepatitis B virus X Protein Promotes Liver Cancer Progression through
      Autophagy Induction in Response to TLR4 Stimulation.
    findings: []
  - id: PMID:35271311
    title: OpenCell endogenous tagging.
    findings: []
  - id: PMID:35512704
    title: Neo-protein-protein interactions in cancer.
    findings: []
  - id: PMID:38182563
    title: GRB2 is a BECN1 interacting protein.
    findings: []
  - id: PMID:40205054
    title: Multimodal cell maps.
    findings: []
  - id: PMID:40442316
    title: Structure and activation of the human autophagy-initiating 
      ULK1C:PI3KC3-C1 supercomplex.
    findings: []
# Reactome references
  - id: Reactome:R-HSA-1169406
    title: ISGylation of host proteins
    findings: []
  - id: Reactome:R-HSA-1632857
    title: ULK1 phosphorylates AMBRA1:BECN1 complex
    findings: []
  - id: Reactome:R-HSA-1678841
    title: USP18 regulation
    findings: []
  - id: Reactome:R-HSA-5672012
    title: Beclin-1 complex phosphorylates PtdIns
    findings: []
  - id: Reactome:R-HSA-5678313
    title: AMBRA1:DYNLL binds BECN1 complex
    findings: []
  - id: Reactome:R-HSA-5678315
    title: BECN1 complex dissociates from DYNLL
    findings: []
  - id: Reactome:R-HSA-5679205
    title: ULK1 phosphorylates Beclin-1
    findings: []
  - id: Reactome:R-HSA-5679266
    title: Beclin-1 complex translocates to ER
    findings: []
  - id: Reactome:R-HSA-5682385
    title: Phagophore extends from PI3P-enriched structure
    findings: []
  - id: Reactome:R-HSA-6781779
    title: USP13 deubiquitinates BECN1
    findings: []
  - id: Reactome:R-HSA-9755359
    title: SARS-CoV-2 ORF8 binds BECN1
    findings: []
  - id: Reactome:R-HSA-9837231
    title: ISGylation of BECN1
    findings: []
  - id: file:human/BECN1/BECN1-deep-research-falcon.md
    title: Deep research report on BECN1
    findings: []

core_functions:
  - molecular_function:
      id: GO:0030674
      label: protein-macromolecule adaptor activity
    directly_involved_in:
      - id: GO:0000045
        label: autophagosome assembly
      - id: GO:0016236
        label: macroautophagy
    in_complex:
      id: GO:0035032
      label: phosphatidylinositol 3-kinase complex, class III
    description: >-
      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.
  - molecular_function:
      id: GO:0043548
      label: phosphatidylinositol 3-kinase binding
    description: >-
      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.

proposed_new_terms: []

suggested_questions:
  - question: >-
      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.
  - question: >-
      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.

suggested_experiments: []