Mouse Bcl2 encodes a BCL-2-family regulator that binds BH3-containing partners and restrains mitochondrial apoptotic signaling. Membrane-associated Bcl2 acts at mitochondria, the endoplasmic reticulum and the nuclear envelope, with additional compartmental pools observed in specific tissues. Bcl2 also directly inhibits autophagy through BECN1 binding; phosphorylation-dependent release of BECN1 couples this interaction to starvation and exercise responses. Its control of cell survival supports lymphocyte homeostasis, neuronal maintenance, renal development and pigmentation. Context-dependent calcium signaling, cell-cycle regulation, neuronal maturation and axon growth extend its functions beyond a uniform antiapoptotic response. Under specific apoptotic signals, conformational conversion can expose a proapoptotic BH3 activity; this conditional capacity coexists with its principal survival function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Bcl2 has a supported conditional proapoptotic regulatory capacity. Reason: The shared report supports conversion of BCL2 but only examined mouse sequence conservation. Independent full PMID:18835031 supplies direct mouse evidence: NuBCP9-induced death occurs in WT MEFs and is lost in Bcl2-knockout MEFs; full PMID:18443228 detects endogenous Bcl2 BH3 exposure in stimulated mouse thymocytes with knockout specificity controls. Human biochemical experiments explain an active contribution: converted BCL2 neutralizes BCLXL through its exposed BH3 region, rather than directly activating BAX. Actual PTHR11256 target leaf PTN000135797 descends from PTN000135648 with no recovered loss. Retain inherited positive regulation as a condition-dependent noncore function, without making conversion the basal survival mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000135648 SUPPORTS TRANSFER Independent current v19 tree verifies the root IBD on the exact mouse lineage. Direct mouse knockout and conformational experiments complement human conversion mechanism; no loss is established. Supporting Evidence: PMID:18835031 NuBCP-9 and D-NuBCP-9 induced apoptosis of MEFs but not Bcl-2β/βMEFs in a dose (Figure 1F) and time (Figure 1G) dependent manner. PMID:18443228 No staining was seen in PMA/ionomycin-stimulated Bcl-2β/β DP thymocytes, confirming the specificity of the antibodies file:human/BCL2/BCL2-hypotheses/conditional-proapoptotic-and-channel-capacities/openscientist.md The proapoptotic capacity is real but proteoform- and context-dependent. |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IBA GO_REF:0000033 | ACCEPT | Summary: Bcl2 directly regulates the apoptotic response to withdrawal of extracellular survival ligands. Reason: GO:0097192 begins with ligand withdrawal from a cell-surface receptor and can proceed through mitochondrial signaling. In murine T cells, Bcl2 binds the IL-2-deprivation-induced BH3 protein ITM2B(s) (PMID:12082633); Bcl2 expression also protects CTLL-2 cells after IL-2 withdrawal (PMID:7751019). Mitochondrial execution therefore does not make the extracellular-withdrawal pathway incorrect. Retain the broad pathway assignment. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 SUPPORTS TRANSFER Mouse Bcl2 itself supplies experimental descendant evidence for the PTN000135648 IBD. Its appearance among the sources is expected and supports the inherited pathway function. Supporting Evidence: PMID:12082633 Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. PMID:7751019 when bcl-2 transfected CTLL-2 cells are deprived of IL-2, they do not undergo apoptosis |
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: mitochondrial outer membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IBA GO_REF:0000033 | ACCEPT | Summary: Bcl2 is a direct control point in DNA-damage-induced intrinsic apoptotic signaling. Reason: Full PMID:15983387 examines the FRAG1βRAD9βBcl2 pathway in mouse embryonic fibroblasts: genotoxic stress changes RAD9βBcl2 association, and Bcl2 expression profoundly inhibits apoptosis. An inhibitory pathway component can carry this unsigned pathway term; it need not be replaced merely to repeat the sign of the more specific negative-regulation annotations. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 SUPPORTS TRANSFER The cached IBD at PTN000135648 includes target experimental grounding, corroborated by full PMID:15983387. No propagation defect is established. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). |
| GO:0015267 channel activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Bcl2 has a conserved, experimentally grounded capacity for membrane conductance. Reason: Purified human BCL2 lacking the C-terminal anchor forms discrete ion-conducting channels in planar bilayers at pH7.4 (PMID:9144199), distinct from acidic-pH-dependent liposome insertion or carboxyfluorescein release. The shared report corroborates channel capacity but does not establish native mouse pore conductance. Actual PAINT root ancestry and direct human ortholog biochemistry support the conserved noncore capacity. Neither inhibition of BAX/IP3R nor predominant antiapoptotic function excludes intrinsic small-ion conduction; physiological substrates and contribution remain uncertain. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000135648 SUPPORTS TRANSFER Current tree independently verifies mouse leaf PTN000135797 below IBD PTN000135648. Human BCL2 is itself an experimentally grounded channel descendant, not a circular donor. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. file:human/BCL2/BCL2-hypotheses/conditional-proapoptotic-and-channel-capacities/openscientist.md Single-channel conductance was 18 Β± 2 pS in 0.5 M KCl at pH 7.4 |
| GO:0001836 release of cytochrome c from mitochondria | IBA GO_REF:0000033 | UNDECIDED | Summary: Cytochrome-c release by conditionally converted Bcl2 needs to be separated from its usual inhibition of release. Reason: Conditional Bcl2 proapoptotic regulation is supported by direct mouse knockout/conformation evidence and human conversion biochemistry. The shared report does not establish whether Bcl2 itself supplies cytochrome-c-permeable structure in mouse: full PMID:18835031 explicitly separates BH3-mediated neutralization of BCLXL from direct BAX activation, and uses dextran as a cytochrome-c surrogate in reconstitution. Actual ancestral PTN000135648 remains on the mouse path. Keep this more specific release-process assertion unresolved rather than substituting the opposite sign merely from basal function. The separate direct PMID:9843949 annotation remains refined according to its inhibitory experiment. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000135648 UNRESOLVED Current exact mouse ancestry verified below the real release-process IBD. Positive apoptosis is supported, while direct release versus regulation of another effector remains mechanistically distinct and unresolved. Supporting Evidence: PMID:18835031 NuBCP-9 and D-NuBCP-9 induced apoptosis of MEFs but not Bcl-2β/βMEFs in a dose (Figure 1F) and time (Figure 1G) dependent manner. PMID:18835031 Thus, NuBCP-9 does not induce Bcl-2 to directly activate Bax. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Bcl2 has a conserved, experimentally grounded capacity for membrane conductance. Reason: Purified human BCL2 lacking the C-terminal anchor forms discrete ion-conducting channels in planar bilayers at pH7.4 (PMID:9144199), distinct from acidic-pH-dependent liposome insertion or carboxyfluorescein release. The shared report corroborates channel capacity but does not establish native mouse pore conductance. Actual PAINT root ancestry and direct human ortholog biochemistry support the conserved noncore capacity. Neither inhibition of BAX/IP3R nor predominant antiapoptotic function excludes intrinsic small-ion conduction; physiological substrates and contribution remain uncertain. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. file:human/BCL2/BCL2-hypotheses/conditional-proapoptotic-and-channel-capacities/openscientist.md Single-channel conductance was 18 Β± 2 pS in 0.5 M KCl at pH 7.4 |
| GO:0001541 ovarian follicle development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ovarian follicle development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002931 response to ischemia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: response to ischemia is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: mitochondrial outer membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: endoplasmic reticulum membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000117 | ACCEPT | Summary: Bcl2 is a direct control point in DNA-damage-induced intrinsic apoptotic signaling. Reason: Full PMID:15983387 examines the FRAG1βRAD9βBcl2 pathway in mouse embryonic fibroblasts: genotoxic stress changes RAD9βBcl2 association, and Bcl2 expression profoundly inhibits apoptosis. An inhibitory pathway component can carry this unsigned pathway term; it need not be replaced merely to repeat the sign of the more specific negative-regulation annotations. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). |
| GO:0008637 apoptotic mitochondrial changes | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Bcl2 directly controls mitochondrial or neuronal apoptotic responses in the annotated context. Reason: Retain the experimentally grounded context-specific pathway annotation. Inhibitory Bcl2 activity is part of the control of these apoptotic responses and does not by itself refute an unsigned pathway term. The cited source concerns this context; broader antiapoptotic activity is represented separately. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: nuclear membrane is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000117 | ACCEPT | Summary: mitochondrial membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: file:mouse/Bcl2/Bcl2-deep-research-falcon.md Mechanistically, BCL-2 binds BH3-containing partners through its groove, thereby preventing downstream **BAX/BAK oligomerization** and **pore formation** in the mitochondrial outer membrane that would otherwise cause **MOMP** and apoptosis. PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: response to glucocorticoid is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: cellular response to hypoxia is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IEA GO_REF:0000117 | ACCEPT | Summary: Bcl2 directly regulates the apoptotic response to withdrawal of extracellular survival ligands. Reason: GO:0097192 begins with ligand withdrawal from a cell-surface receptor and can proceed through mitochondrial signaling. In murine T cells, Bcl2 binds the IL-2-deprivation-induced BH3 protein ITM2B(s) (PMID:12082633); Bcl2 expression also protects CTLL-2 cells after IL-2 withdrawal (PMID:7751019). Mitochondrial execution therefore does not make the extracellular-withdrawal pathway incorrect. Retain the broad pathway assignment. Supporting Evidence: PMID:12082633 Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. PMID:7751019 when bcl-2 transfected CTLL-2 cells are deprived of IL-2, they do not undergo apoptosis |
| GO:0005515 protein binding | IPI PMID:16509771 IAN family critically regulates survival and development of ... | REMOVE | Summary: Generic protein binding is uninformative despite the reported association. Reason: The source supports an association involving Bcl2 (GIMAP proteins, RAD9, or HSP90 beta). This evidence is retained in the references and informs regulation, but does not establish a more specific shared molecular activity for every partner. Removing the generic GO term does not reject the interaction. |
| GO:0005515 protein binding | IPI PMID:16839884 Mitochondrial rhomboid PARL regulates cytochrome c release d... | UNDECIDED | Summary: The exact Bcl2 interaction in the cited experiment remains insufficiently resolved. Reason: The accessible source emphasizes another protein or pathway, and the relevant Bcl2 assay cannot be confidently adjudicated from the material inspected. A title or abstract naming a partner is not evidence of misattribution. Leave the original assertion unchanged and unresolved rather than invent a specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:20621101 Upregulation of Bcl2 inhibits apoptosis-driven BAX insertion... | MODIFY | Summary: The source identifies heteromeric BCL2-family binding. Reason: Bcl2 physically associates with the named BCL2-family partner (BAX or BAD), rather than an unspecified protein. Use protein heterodimerization activity to retain the demonstrated interaction at an informative level. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20621101 a physical interaction between BAX and Bcl2 is necessary for these two effects to occur. |
| GO:0005515 protein binding | IPI PMID:20819940 Endogenous HMGB1 regulates autophagy. | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. |
| GO:0005515 protein binding | IPI PMID:21151042 Cyclic-AMP-dependent protein kinase A regulates apoptosis by... | UNDECIDED | Summary: The exact Bcl2 interaction in the cited experiment remains insufficiently resolved. Reason: The accessible source emphasizes another protein or pathway, and the relevant Bcl2 assay cannot be confidently adjudicated from the material inspected. A title or abstract naming a partner is not evidence of misattribution. Leave the original assertion unchanged and unresolved rather than invent a specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:22258505 Exercise-induced BCL2-regulated autophagy is required for mu... | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. |
| GO:0005515 protein binding | IPI PMID:29849149 Disruption of the beclin 1-BCL2 autophagy regulatory complex... | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. |
| GO:0002020 protease binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: protease binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005741 mitochondrial outer membrane | ISO GO_REF:0000119 | ACCEPT | Summary: mitochondrial outer membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000119 | ACCEPT | Summary: endoplasmic reticulum is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000119 | ACCEPT | Summary: endoplasmic reticulum membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0006974 DNA damage response | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: DNA damage response is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 can enhance proliferation in specific cellular contexts. Reason: PMID:11983915 reports more cycling cardiomyocytes, mitotic spindles, contractile rings, karyokinesis and cytokinesis in Bcl2-transgenic mouse hearts while apoptosis remained low and unchanged. Thus proliferation cannot be dismissed universally as survival-driven cell accumulation. Retain context-specific positive regulation alongside separate studies showing cell-cycle retardation. Supporting Evidence: PMID:11983915 Apoptosis was low at all ages and was not affected by Bcl-2. |
| GO:0009410 response to xenobiotic stimulus | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0009636 response to toxic substance | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0010039 response to iron ion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Iron-associated endothelial survival is a non-core ortholog-supported response. Reason: The human donor study PMID:11264898 reports iron-dependent endothelial survival accompanied by increased BCL2 expression. Retain the established ortholog response annotation with its expression/survival scope, without claiming iron binding or a direct iron-sensing molecular mechanism. Antiapoptotic activity is compatible with participation in this response. Supporting Evidence: PMID:11264898 Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. |
| GO:0010507 negative regulation of autophagy | ISO GO_REF:0000119 | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0015267 channel activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 has a conserved, experimentally grounded capacity for membrane conductance. Reason: Purified human BCL2 lacking the C-terminal anchor forms discrete ion-conducting channels in planar bilayers at pH7.4 (PMID:9144199), distinct from acidic-pH-dependent liposome insertion or carboxyfluorescein release. The shared report corroborates channel capacity but does not establish native mouse pore conductance. Actual PAINT root ancestry and direct human ortholog biochemistry support the conserved noncore capacity. Neither inhibition of BAX/IP3R nor predominant antiapoptotic function excludes intrinsic small-ion conduction; physiological substrates and contribution remain uncertain. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P10415 SUPPORTS TRANSFER Human BCL2 channel reconstitution supports the ortholog inference, with artificial-membrane/construct conditions retained as a scope limitation. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. file:human/BCL2/BCL2-hypotheses/conditional-proapoptotic-and-channel-capacities/openscientist.md Single-channel conductance was 18 Β± 2 pS in 0.5 M KCl at pH 7.4 |
| GO:0016248 channel inhibitor activity | ISO GO_REF:0000119 | ACCEPT | Summary: channel inhibitor activity is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0030061 mitochondrial crista | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat immunogold microscopy supports a context-specific mitochondrial crista pool inherited by mouse Bcl2. Reason: The ISO donor is RGD:2199 (rat Bcl2/P49950); live QuickGO traces its exact GO:0030061 IDA annotation to PMID:9731187. That primary study uses cryosection immunogold labeling and immunoblotting and reports inner-membrane/crista localization in normal rat liver, while acknowledging earlier outer-membrane findings. An additional tissue-dependent compartment is not contradicted by predominant outer-membrane localization. Retain the ortholog inference as non-core, without calling this a direct mouse experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:2199 SUPPORTS TRANSFER Rat Bcl2/P49950 exact GO:0030061 IDA derives from PMID:9731187. Primary immunogold localization supplies a valid donor; mouse-specific loss or exclusive OMM topology has not been established. Supporting Evidence: PMID:9731187 In this study, using a cryo-sectioning immunogold labeling technique and immunoblotting, we carefully determined the subcellular localization of Bcl-2. |
| GO:0030890 positive regulation of B cell proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 supports expansion of IL-7-dependent early B-cell populations. Reason: PMID:1373874 expresses human BCL2 in mouse early pre-B cells and reports a two-fold net proliferative advantage in IL-7-supplemented liquid medium, together with survival after factor withdrawal. The source supports context-dependent population expansion and ortholog transfer; it does not establish Bcl2 as a mitogen or exclude contributions from survival. Supporting Evidence: PMID:1373874 Cells expressing bcl-2 grew at rates similar to those of control (vector only) cells when plated on bone marrow stromal lines, but exhibited a c. two-fold net proliferative advantage when grown in liquid medium supplemented with IL-7 alone. |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ubiquitin protein ligase binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0031965 nuclear membrane | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: nuclear membrane is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032848 negative regulation of cellular pH reduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: negative regulation of cellular pH reduction is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | ACCEPT | Summary: protein-containing complex is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0035094 response to nicotine | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Nicotine-responsive phosphorylation changes Bcl2-dependent survival. Reason: Human donor PMID:12421819 directly compares wild-type and S70A BCL2 in nicotine-stimulated small-cell lung cancer cells. BCL2 participates by altering apoptotic susceptibility; it is not the nicotine receptor. This conditional biochemical response is biologically compatible with mouse ortholog transfer and belongs outside the core. Supporting Evidence: PMID:12421819 nicotine can induce Bcl2 phosphorylation exclusively at the serine 70 site in association with prolonged survival of SCLC H82 cells expressing wild-type but not the phosphorylation-deficient S70A mutant Bcl2 |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: identical protein binding is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000119 | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0046930 pore complex | ISO GO_REF:0000119 | UNDECIDED | Summary: A Bcl2-containing pore complex is plausible but not resolved by conductance alone. Reason: The report and full human reconstitution paper establish ion conduction but do not resolve monomeric versus oligomeric architecture or demonstrate a native mouse Bcl2 pore complex. GO:0046930 specifically names a protein complex providing an opening. Report incorporation leaves this composition question unresolved; it is not rejected because Bcl2 usually suppresses apoptosis. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10415 UNRESOLVED Human ortholog channel evidence is real; complex composition and native mouse assembly remain unresolved. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. |
| GO:0046982 protein heterodimerization activity | ISO GO_REF:0000119 | ACCEPT | Summary: protein heterodimerization activity is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0050853 B cell receptor signaling pathway | ISO GO_REF:0000119 | UNDECIDED | Summary: The specific B-cell receptor signaling assignment requires source-level verification. Reason: The human donor is P10415, whose experimental source PMID:17875758 studies CLL signaling and fludarabine susceptibility. Its abstract alone does not establish the BCL2-specific BCR step. Bcl2 can directly control lymphocyte survival downstream of receptor inputs, so the term is not rejected merely because the protein is antiapoptotic; the precise source claim remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10415 UNRESOLVED Human donor GO:0050853 refers to PMID:17875758. Full source-specific BCL2 receptor-signaling evidence is not yet resolved; antiapoptotic function itself is compatible with the pathway. |
| GO:0051434 BH3 domain binding | ISO GO_REF:0000119 | ACCEPT | Summary: BH3 domain binding is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051607 defense response to virus | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 protects against HIV Vpr-induced mitochondrial injury in the donor experiments. Reason: PMID:10620603 shows that BCL2 blocks mitochondrial and cytotoxic effects of the HIV Vpr protein, including protection in reconstituted membrane systems. This supports a conditional host-protective effect and ortholog transfer. It does not make Bcl2 a universal antiviral restriction factor, especially because Bcl2-mediated survival can also increase productive infection by other viruses. Supporting Evidence: PMID:10620603 Both mitochondrial and cytotoxic Vpr effects are prevented by Bcl-2, an inhibitor of the permeability transition pore complex (PTPC). |
| GO:0060090 molecular adaptor activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Bcl2 has evidence for a conditional adaptor-like function in calcium signaling. Reason: The human ISO citation and the mouse BECN1 study should not be equated with a ternary assembly assay. Independently, PMID:12617961 detects calcineurinβBcl2 complexes in mouse/rat brain and reduced calcineurinβIP3R association in Bcl2-null mice, consistent with targeting calcineurin to substrates. Retain this contextual activity with the limitation that the exact ternary arrangement was not established by the autophagy source. Supporting Evidence: PMID:12617961 These data indicate that during times of cellular stress and damage, Bcl-2 targets activated calcineurin to specific compartments and substrates. |
| GO:0140297 DNA-binding transcription factor binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: DNA-binding transcription factor binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2000811 negative regulation of anoikis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: negative regulation of anoikis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2001234 negative regulation of apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: negative regulation of apoptotic signaling pathway is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: negative regulation of intrinsic apoptotic signaling pathway is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0002020 protease binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: protease binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: endoplasmic reticulum is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0006974 DNA damage response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNA damage response is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bcl2 can enhance proliferation in specific cellular contexts. Reason: PMID:11983915 reports more cycling cardiomyocytes, mitotic spindles, contractile rings, karyokinesis and cytokinesis in Bcl2-transgenic mouse hearts while apoptosis remained low and unchanged. Thus proliferation cannot be dismissed universally as survival-driven cell accumulation. Retain context-specific positive regulation alongside separate studies showing cell-cycle retardation. Supporting Evidence: PMID:11983915 Apoptosis was low at all ages and was not affected by Bcl-2. |
| GO:0009636 response to toxic substance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0010039 response to iron ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Iron-associated endothelial survival is a non-core ortholog-supported response. Reason: The human donor study PMID:11264898 reports iron-dependent endothelial survival accompanied by increased BCL2 expression. Retain the established ortholog response annotation with its expression/survival scope, without claiming iron binding or a direct iron-sensing molecular mechanism. Antiapoptotic activity is compatible with participation in this response. Supporting Evidence: PMID:11264898 Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0015267 channel activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bcl2 has a conserved, experimentally grounded capacity for membrane conductance. Reason: Purified human BCL2 lacking the C-terminal anchor forms discrete ion-conducting channels in planar bilayers at pH7.4 (PMID:9144199), distinct from acidic-pH-dependent liposome insertion or carboxyfluorescein release. The shared report corroborates channel capacity but does not establish native mouse pore conductance. Actual PAINT root ancestry and direct human ortholog biochemistry support the conserved noncore capacity. Neither inhibition of BAX/IP3R nor predominant antiapoptotic function excludes intrinsic small-ion conduction; physiological substrates and contribution remain uncertain. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P10415 SUPPORTS TRANSFER Human BCL2 channel reconstitution supports the ortholog inference, with artificial-membrane/construct conditions retained as a scope limitation. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. file:human/BCL2/BCL2-hypotheses/conditional-proapoptotic-and-channel-capacities/openscientist.md Single-channel conductance was 18 Β± 2 pS in 0.5 M KCl at pH 7.4 |
| GO:0016248 channel inhibitor activity | IEA GO_REF:0000107 | ACCEPT | Summary: channel inhibitor activity is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0030890 positive regulation of B cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bcl2 supports expansion of IL-7-dependent early B-cell populations. Reason: PMID:1373874 expresses human BCL2 in mouse early pre-B cells and reports a two-fold net proliferative advantage in IL-7-supplemented liquid medium, together with survival after factor withdrawal. The source supports context-dependent population expansion and ortholog transfer; it does not establish Bcl2 as a mitogen or exclude contributions from survival. Supporting Evidence: PMID:1373874 Cells expressing bcl-2 grew at rates similar to those of control (vector only) cells when plated on bone marrow stromal lines, but exhibited a c. two-fold net proliferative advantage when grown in liquid medium supplemented with IL-7 alone. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ubiquitin protein ligase binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032848 negative regulation of cellular pH reduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of cellular pH reduction is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: protein-containing complex is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0035094 response to nicotine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nicotine-responsive phosphorylation changes Bcl2-dependent survival. Reason: Human donor PMID:12421819 directly compares wild-type and S70A BCL2 in nicotine-stimulated small-cell lung cancer cells. BCL2 participates by altering apoptotic susceptibility; it is not the nicotine receptor. This conditional biochemical response is biologically compatible with mouse ortholog transfer and belongs outside the core. Supporting Evidence: PMID:12421819 nicotine can induce Bcl2 phosphorylation exclusively at the serine 70 site in association with prolonged survival of SCLC H82 cells expressing wild-type but not the phosphorylation-deficient S70A mutant Bcl2 |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: identical protein binding is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | REMOVE | Summary: The human donor source assays MITF binding to the BCL2 promoter, not BCL2 binding DNA. Reason: Mouse GOA transfers GO:0043565 from human P10415. Full PMID:12086670 Figure 3 identifies MITF by antibody-specific ChIP and EMSA supershift; BCL2 is the regulated promoter/gene. The demonstrated activity is on MITF, making the donor attribution unsuitable for transfer. This conclusion follows the actual assay identity, not an assumption that antiapoptotic proteins lack every possible DNA interaction. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION Sources checked: UniProtKB:P10415 SOURCE BAD The source PMID:12086670 assay measures MITF occupancy of BCL2 DNA. Human BCL2 is the target gene, not the assayed DNA-binding protein. Supporting Evidence: file:mouse/Bcl2/Bcl2-primary-source-checks.md The demonstrated sequence-specific DNA-binding protein is MITF. BCL2 is the regulated gene, not the DNA-binding protein in these assays. |
| GO:0046930 pore complex | IEA GO_REF:0000107 | UNDECIDED | Summary: A Bcl2-containing pore complex is plausible but not resolved by conductance alone. Reason: The report and full human reconstitution paper establish ion conduction but do not resolve monomeric versus oligomeric architecture or demonstrate a native mouse Bcl2 pore complex. GO:0046930 specifically names a protein complex providing an opening. Report incorporation leaves this composition question unresolved; it is not rejected because Bcl2 usually suppresses apoptosis. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10415 UNRESOLVED Human ortholog channel evidence is real; complex composition and native mouse assembly remain unresolved. Supporting Evidence: PMID:9144199 In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. |
| GO:0046982 protein heterodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: protein heterodimerization activity is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0050853 B cell receptor signaling pathway | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific B-cell receptor signaling assignment requires source-level verification. Reason: The human donor is P10415, whose experimental source PMID:17875758 studies CLL signaling and fludarabine susceptibility. Its abstract alone does not establish the BCL2-specific BCR step. Bcl2 can directly control lymphocyte survival downstream of receptor inputs, so the term is not rejected merely because the protein is antiapoptotic; the precise source claim remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10415 UNRESOLVED Human donor GO:0050853 refers to PMID:17875758. Full source-specific BCL2 receptor-signaling evidence is not yet resolved; antiapoptotic function itself is compatible with the pathway. |
| GO:0051434 BH3 domain binding | IEA GO_REF:0000107 | ACCEPT | Summary: BH3 domain binding is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051607 defense response to virus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bcl2 protects against HIV Vpr-induced mitochondrial injury in the donor experiments. Reason: PMID:10620603 shows that BCL2 blocks mitochondrial and cytotoxic effects of the HIV Vpr protein, including protection in reconstituted membrane systems. This supports a conditional host-protective effect and ortholog transfer. It does not make Bcl2 a universal antiviral restriction factor, especially because Bcl2-mediated survival can also increase productive infection by other viruses. Supporting Evidence: PMID:10620603 Both mitochondrial and cytotoxic Vpr effects are prevented by Bcl-2, an inhibitor of the permeability transition pore complex (PTPC). |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNA-binding transcription factor binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2000811 negative regulation of anoikis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of anoikis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2001234 negative regulation of apoptotic signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of apoptotic signaling pathway is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of intrinsic apoptotic signaling pathway is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0097138 BAD-BCL-2 complex | ISO GO_REF:0000119 | ACCEPT | Summary: BAD-BCL-2 complex is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0097148 BCL-2 complex | ISO GO_REF:0000119 | ACCEPT | Summary: BCL-2 complex is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005739 mitochondrion | ISO GO_REF:0000096 | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: negative regulation of cardiac muscle cell apoptotic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000096 | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: protein-containing complex binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0045471 response to ethanol | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: response to ethanol is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048471 perinuclear region of cytoplasm | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0051400 BH domain binding | ISO GO_REF:0000096 | ACCEPT | Summary: BH domain binding is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0000902 cell morphogenesis | IDA PMID:18548006 Osteoclast size is controlled by Fra-2 through LIF/LIF-recep... | KEEP AS NON CORE | Summary: cell morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | IDA PMID:36812915 Exercise-activated hepatic autophagy via the FN1-Ξ±5Ξ²1 integr... | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
| GO:0010507 negative regulation of autophagy | IDA PMID:36812915 Exercise-activated hepatic autophagy via the FN1-Ξ±5Ξ²1 integr... | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0060090 molecular adaptor activity | IDA PMID:36812915 Exercise-activated hepatic autophagy via the FN1-Ξ±5Ξ²1 integr... | MODIFY | Summary: The cited autophagy study supports inhibitory BECN1 binding more directly than a molecular-adaptor activity. Reason: Full PMID:36812915 measures BCL2βBECN1 association, BCL2 phosphorylation, and BECN1 release in mouse liver (Figures 4H and 5D); it does not demonstrate Bcl2 bringing two independent partners together. Refine this source-specific molecular function to BH3-domain binding, supported by the established BECN1 interface in PMID:22258505. This does not deny the independent calcineurin-targeting mechanism. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0009791 post-embryonic development | TAS PMID:10674380 Hair follicle apoptosis and Bcl-2. | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048087 positive regulation of developmental pigmentation | TAS PMID:10674380 Hair follicle apoptosis and Bcl-2. | KEEP AS NON CORE | Summary: positive regulation of developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | IDA PMID:29020630 Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: mitochondrial outer membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: endoplasmic reticulum membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0010507 negative regulation of autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0048873 homeostasis of number of cells within a tissue | IMP PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: homeostasis of number of cells within a tissue is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:10582606 Bax and Bcl-2 interaction in a transgenic mouse model of fam... | MODIFY | Summary: The source identifies heteromeric BCL2-family binding. Reason: Bcl2 physically associates with the named BCL2-family partner (BAX or BAD), rather than an unspecified protein. Use protein heterodimerization activity to retain the demonstrated interaction at an informative level. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20621101 a physical interaction between BAX and Bcl2 is necessary for these two effects to occur. |
| GO:0005515 protein binding | IPI PMID:11226327 Bax ablation prevents dopaminergic neurodegeneration in the ... | UNDECIDED | Summary: The exact Bcl2 interaction in the cited experiment remains insufficiently resolved. Reason: The accessible source emphasizes another protein or pathway, and the relevant Bcl2 assay cannot be confidently adjudicated from the material inspected. A title or abstract naming a partner is not evidence of misattribution. Leave the original assertion unchanged and unresolved rather than invent a specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:7834748 Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces... | MODIFY | Summary: The source identifies heteromeric BCL2-family binding. Reason: Bcl2 physically associates with the named BCL2-family partner (BAX or BAD), rather than an unspecified protein. Use protein heterodimerization activity to retain the demonstrated interaction at an informative level. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:7834748 Bad selectively dimerized with Bcl-xL as well as Bcl-2, but not with Bax, Bcl-xs, Mcl-1, A1, or itself. |
| GO:0005515 protein binding | IPI PMID:8918887 BID: a novel BH3 domain-only death agonist. | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0040008 regulation of growth | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: regulation of growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0040008 regulation of growth | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: regulation of growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:15983387 Frag1, a homolog of alternative replication factor C subunit... | REMOVE | Summary: Generic protein binding is uninformative despite the reported association. Reason: The source supports an association involving Bcl2 (GIMAP proteins, RAD9, or HSP90 beta). This evidence is retained in the references and informs regulation, but does not establish a more specific shared molecular activity for every partner. Removing the generic GO term does not reject the interaction. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IGI PMID:15983387 Frag1, a homolog of alternative replication factor C subunit... | ACCEPT | Summary: Bcl2 is a direct control point in DNA-damage-induced intrinsic apoptotic signaling. Reason: Full PMID:15983387 examines the FRAG1βRAD9βBcl2 pathway in mouse embryonic fibroblasts: genotoxic stress changes RAD9βBcl2 association, and Bcl2 expression profoundly inhibits apoptosis. An inhibitory pathway component can carry this unsigned pathway term; it need not be replaced merely to repeat the sign of the more specific negative-regulation annotations. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:8084613 Antisense oligonucleotides suppress B-cell lymphoma growth i... | UNDECIDED | Summary: The cited lymphoma-growth experiment does not resolve direct mouse Bcl2 regulation of proliferation. Reason: PMID:8084613 explicitly uses a human lymphoma line in SCID mice. Reduced engraftment after antisense treatment supports tumor maintenance but does not by itself separate proliferation from survival or establish which mouse experiment grounded this IMP row. Full text remains unavailable. Keep the source assertion unchanged and use UNDECIDED rather than infer impossibility or misattribution from its title/abstract. Supporting Evidence: PMID:8084613 Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. |
| GO:0030217 T cell differentiation | IGI PMID:9215624 Bcl-2 can rescue T lymphocyte development in interleukin-7 r... | KEEP AS NON CORE | Summary: T cell differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0098609 cell-cell adhesion | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: cell-cell adhesion is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:23629966 Deacetylation of p53 induces autophagy by suppressing Bmf ex... | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. |
| GO:0042981 regulation of apoptotic process | IGI PMID:8918887 BID: a novel BH3 domain-only death agonist. | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0005515 protein binding | IPI PMID:26949185 BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Re... | UNDECIDED | Summary: The exact Bcl2 interaction in the cited experiment remains insufficiently resolved. Reason: The accessible source emphasizes another protein or pathway, and the relevant Bcl2 assay cannot be confidently adjudicated from the material inspected. A title or abstract naming a partner is not evidence of misattribution. Leave the original assertion unchanged and unresolved rather than invent a specific binding mechanism. |
| GO:0005515 protein binding | IPI PMID:17475835 Involvement of heat shock protein (Hsp)90 beta but not Hsp90... | REMOVE | Summary: Generic protein binding is uninformative despite the reported association. Reason: The source supports an association involving Bcl2 (GIMAP proteins, RAD9, or HSP90 beta). This evidence is retained in the references and informs regulation, but does not establish a more specific shared molecular activity for every partner. Removing the generic GO term does not reject the interaction. |
| GO:0006915 apoptotic process | ISO PMID:8022822 Evidence that BCL-2 represses apoptosis by regulating endopl... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0006915 apoptotic process | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0006915 apoptotic process | IMP PMID:8372353 Disappearance of the lymphoid system in Bcl-2 homozygous mut... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0006915 apoptotic process | ISO PMID:8949945 Bcl-2 prevents hippocampal cell death induced by the neurole... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0042149 cellular response to glucose starvation | IDA PMID:7595537 Bcl-2 protects neural cells from cyanide/aglycemia-induced l... | KEEP AS NON CORE | Summary: cellular response to glucose starvation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0071456 cellular response to hypoxia | IDA PMID:7595537 Bcl-2 protects neural cells from cyanide/aglycemia-induced l... | KEEP AS NON CORE | Summary: cellular response to hypoxia is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:11546872 Bmf: a proapoptotic BH3-only protein regulated by interactio... | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:2001234 negative regulation of apoptotic signaling pathway | IDA PMID:11546872 Bmf: a proapoptotic BH3-only protein regulated by interactio... | ACCEPT | Summary: negative regulation of apoptotic signaling pathway is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: negative regulation of extrinsic apoptotic signaling pathway in absence of ligand is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0008637 apoptotic mitochondrial changes | IDA PMID:14707049 TCR-independent and caspase-independent apoptosis of murine ... | KEEP AS NON CORE | Summary: Bcl2 directly controls mitochondrial or neuronal apoptotic responses in the annotated context. Reason: Retain the experimentally grounded context-specific pathway annotation. Inhibitory Bcl2 activity is part of the control of these apoptotic responses and does not by itself refute an unsigned pathway term. The cited source concerns this context; broader antiapoptotic activity is represented separately. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. |
| GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: intrinsic apoptotic signaling pathway in response to oxidative stress is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002931 response to ischemia | IMP PMID:10488913 Targeted disruption of the bcl-2 gene in mice exacerbates fo... | KEEP AS NON CORE | Summary: response to ischemia is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:12082633 Proapoptotic activity of ITM2B(s), a BH3-only protein induce... | MODIFY | Summary: The interaction is best represented as BH3-domain binding. Reason: The cited BCL2 interaction belongs to the BH3-mediated regulatory network. BECN1 BH3 binding is demonstrated in the mouse autophagy studies, while BID/BMF/ITM2B(s) interactions map to their BH3 domains. This specific binding function identifies the mechanism; generic protein binding does not. Proposed replacements: BH3 domain binding Supporting Evidence: PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IGI PMID:12082633 Proapoptotic activity of ITM2B(s), a BH3-only protein induce... | ACCEPT | Summary: Bcl2 directly regulates the apoptotic response to withdrawal of extracellular survival ligands. Reason: GO:0097192 begins with ligand withdrawal from a cell-surface receptor and can proceed through mitochondrial signaling. In murine T cells, Bcl2 binds the IL-2-deprivation-induced BH3 protein ITM2B(s) (PMID:12082633); Bcl2 expression also protects CTLL-2 cells after IL-2 withdrawal (PMID:7751019). Mitochondrial execution therefore does not make the extracellular-withdrawal pathway incorrect. Retain the broad pathway assignment. Supporting Evidence: PMID:12082633 Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. PMID:7751019 when bcl-2 transfected CTLL-2 cells are deprived of IL-2, they do not undergo apoptosis |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | ISO PMID:10597216 Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in p... | KEEP AS NON CORE | Summary: extrinsic apoptotic signaling pathway via death domain receptors is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: negative regulation of G1/S transition of mitotic cell cycle is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IDA PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | KEEP AS NON CORE | Summary: negative regulation of G1/S transition of mitotic cell cycle is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IMP PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | KEEP AS NON CORE | Summary: negative regulation of G1/S transition of mitotic cell cycle is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010506 regulation of autophagy | IMP PMID:22258505 Exercise-induced BCL2-regulated autophagy is required for mu... | ACCEPT | Summary: Bcl2 directly regulates autophagy through inhibitory binding of BECN1. Reason: Mouse Bcl2 AAA knock-in mutations prevent stimulus-induced BCL2βBECN1 dissociation and autophagy activation (PMID:22258505), and the reciprocal Becn1 F121A interface mutation increases autophagic flux (PMID:29849149). Full PMID:36812915 extends this mechanism to exercise-stimulated mouse liver. This is direct regulatory work, not a downstream survival phenotype, and is retained as core autophagy regulation. Supporting Evidence: PMID:22258505 BCL2 is an anti-apoptotic and anti-autophagy protein that inhibits autophagy through a direct interaction with the BH3 domain of the autophagy protein beclin 1 at the endoplasmic reticulum8. PMID:29849149 We observed marked reduction in beclin 1 co-immunoprecipitation with Bcl-2 in tissues of the KI mice (Fig. 1a, b). PMID:36812915 Via co-immunoprecipitation, we found that exercise induces phosphorylation of BCL2 at Ser70 and decreases BECN1-BCL2 binding in the liver of control mice; however, these exercise-induced effects are largely reduced in the liver of FN1Ξmuscle mice (Fig. 4H) |
| GO:0016020 membrane | IDA PMID:8030757 Bcl-2 protein expression during murine development. | ACCEPT | Summary: membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:9560217 Bax directly induces release of cytochrome c from isolated m... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005515 protein binding | IPI PMID:18223655 Dual role of proapoptotic BAD in insulin secretion and beta ... | UNDECIDED | Summary: The exact Bcl2 interaction in the cited experiment remains insufficiently resolved. Reason: The accessible source emphasizes another protein or pathway, and the relevant Bcl2 assay cannot be confidently adjudicated from the material inspected. A title or abstract naming a partner is not evidence of misattribution. Leave the original assertion unchanged and unresolved rather than invent a specific binding mechanism. |
| GO:0072593 reactive oxygen species metabolic process | IMP PMID:10726970 Developmental changes in antioxidant enzymes and oxidative d... | KEEP AS NON CORE | Summary: reactive oxygen species metabolic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0072593 reactive oxygen species metabolic process | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: reactive oxygen species metabolic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0072593 reactive oxygen species metabolic process | IMP PMID:9681465 Enhanced oxidative stress and altered antioxidants in brains... | KEEP AS NON CORE | Summary: reactive oxygen species metabolic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001657 ureteric bud development | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | KEEP AS NON CORE | Summary: ureteric bud development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0019903 protein phosphatase binding | IDA PMID:12617961 Calcium-dependent interaction of calcineurin with Bcl-2 in n... | KEEP AS NON CORE | Summary: protein phosphatase binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0051721 protein phosphatase 2A binding | IDA PMID:16717086 PP2A regulates BCL-2 phosphorylation and proteasome-mediated... | KEEP AS NON CORE | Summary: protein phosphatase 2A binding is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:15613488 Proapoptotic BAX and BAK regulate the type 1 inositol trisph... | MODIFY | Summary: Bcl2 binds the IP3 receptor channel in the ER. Reason: PMID:15613488 explicitly reports BCL2βIP3R-1 physical interaction and altered IP3R phosphorylation/calcium leak in Bax/Bak-deficient cells. Ion-channel binding is more informative than generic protein binding and does not assert that Bcl2 itself catalyzes phosphorylation. Proposed replacements: ion channel binding Supporting Evidence: PMID:15613488 BCL-2 and IP3R-1 physically interact at the ER, and their binding is increased in the absence of BAX and BAK. |
| GO:0030307 positive regulation of cell growth | ISO PMID:8022822 Evidence that BCL-2 represses apoptosis by regulating endopl... | KEEP AS NON CORE | Summary: Bcl2 affects growth/survival under the experimental conditions. Reason: PMID:8022822 establishes altered ER calcium flux and protection from apoptosis in transfected mouse lymphoma cells. Growth effects are retained as a contextual phenotype, without assuming that growth enhancement is impossible for an antiapoptotic protein or that every increase in cell number is cell division. Supporting Evidence: PMID:8022822 BCL-2 also blocked induction of apoptosis by thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump. |
| GO:0000209 protein polyubiquitination | ISO PMID:16717086 PP2A regulates BCL-2 phosphorylation and proteasome-mediated... | REMOVE | Summary: The full source identifies Bcl2 as the modified substrate, not the executor of its modification. Reason: Full PMID:16717086 was recovered from the Harvard manuscript and read. Figure 3G immunoprecipitates human BCL2 from transfected Bcl2-null MEFs under partner-dissociating conditions and detects ubiquitination of BCL2; the PP2A experiments likewise measure dephosphorylation of BCL2. The source establishes binding, phosphoregulation and survival effects, but not a Bcl2 cofactor/catalytic step executing these reactions. Remove this source-specific process attribution; independent calcineurin-targeting evidence is not a demonstration that this PP2A assay measures Bcl2 execution of dephosphorylation. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P10415 SOURCE BAD Human BCL2 is ubiquitinated in the source Figure 3G. The human substrate annotation, rather than ortholog conservation, is the problem. Supporting Evidence: file:mouse/Bcl2/Bcl2-primary-source-checks.md The assay makes BCL2 the modified substrate, not the ubiquitination machinery. The PP2A assay similarly makes BCL2 the phosphatase substrate. |
| GO:0005737 cytoplasm | ISO PMID:7546744 Role of BCL-2 in the survival and function of developing and... | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0016020 membrane | ISO PMID:7896880 The intracellular distribution and pattern of expression of ... | ACCEPT | Summary: membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005739 mitochondrion | HDA PMID:18614015 A mitochondrial protein compendium elucidates complex I dise... | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
| GO:0005634 nucleus | ISO PMID:7546744 Role of BCL-2 in the survival and function of developing and... | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005634 nucleus | ISO PMID:7896880 The intracellular distribution and pattern of expression of ... | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005739 mitochondrion | ISO PMID:7896880 The intracellular distribution and pattern of expression of ... | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0009410 response to xenobiotic stimulus | ISO PMID:8949945 Bcl-2 prevents hippocampal cell death induced by the neurole... | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0009636 response to toxic substance | ISO PMID:16717086 PP2A regulates BCL-2 phosphorylation and proteasome-mediated... | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0034097 response to cytokine | ISO PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by ... | KEEP AS NON CORE | Summary: response to cytokine is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0042100 B cell proliferation | ISO PMID:1373874 Bcl-2 confers growth and survival advantage to interleukin 7... | KEEP AS NON CORE | Summary: Bcl2 supports expansion of IL-7-dependent early B-cell populations. Reason: PMID:1373874 expresses human BCL2 in mouse early pre-B cells and reports a two-fold net proliferative advantage in IL-7-supplemented liquid medium, together with survival after factor withdrawal. The source supports context-dependent population expansion and ortholog transfer; it does not establish Bcl2 as a mitogen or exclude contributions from survival. Supporting Evidence: PMID:1373874 Cells expressing bcl-2 grew at rates similar to those of control (vector only) cells when plated on bone marrow stromal lines, but exhibited a c. two-fold net proliferative advantage when grown in liquid medium supplemented with IL-7 alone. |
| GO:0043066 negative regulation of apoptotic process | ISO PMID:1373874 Bcl-2 confers growth and survival advantage to interleukin 7... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | ISO PMID:7650367 Expression of Bcl-2, Bcl-x, and Bax after T cell activation ... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | ISO PMID:7772249 Evolutionary conservation of function among mammalian, avian... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | ISO PMID:8050499 bcl-2 gene prevents apoptosis of basic fibroblast growth fac... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | ISO PMID:8080725 bcl-2 gene enables rescue from in vitro myelosuppression (bo... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043524 negative regulation of neuron apoptotic process | ISO PMID:7546744 Role of BCL-2 in the survival and function of developing and... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051924 regulation of calcium ion transport | ISO PMID:8022822 Evidence that BCL-2 represses apoptosis by regulating endopl... | KEEP AS NON CORE | Summary: regulation of calcium ion transport is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | ISS PMID:15776018 Proapoptotic BAX and BAK control multiple initiator caspases... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISS PMID:15776018 Proapoptotic BAX and BAK control multiple initiator caspases... | KEEP AS NON CORE | Summary: Bcl2 directly controls mitochondrial or neuronal apoptotic responses in the annotated context. Reason: Retain the experimentally grounded context-specific pathway annotation. Inhibitory Bcl2 activity is part of the control of these apoptotic responses and does not by itself refute an unsigned pathway term. The cited source concerns this context; broader antiapoptotic activity is represented separately. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15613488 Proapoptotic BAX and BAK regulate the type 1 inositol trisph... | ACCEPT | Summary: endoplasmic reticulum membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0010523 negative regulation of calcium ion transport into cytosol | IGI PMID:15613488 Proapoptotic BAX and BAK regulate the type 1 inositol trisph... | KEEP AS NON CORE | Summary: negative regulation of calcium ion transport into cytosol is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IGI PMID:15613488 Proapoptotic BAX and BAK regulate the type 1 inositol trisph... | KEEP AS NON CORE | Summary: endoplasmic reticulum calcium ion homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0033138 positive regulation of peptidyl-serine phosphorylation | IGI PMID:15613488 Proapoptotic BAX and BAK regulate the type 1 inositol trisph... | KEEP AS NON CORE | Summary: positive regulation of peptidyl-serine phosphorylation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005515 protein binding | IPI PMID:16717086 PP2A regulates BCL-2 phosphorylation and proteasome-mediated... | MODIFY | Summary: Bcl2 associates with PP2A at the ER. Reason: PMID:16717086 reports co-immunoprecipitation and microcystin affinity purification of endogenous BCL2 and PP2A. Refine generic protein binding to protein phosphatase 2A binding; binding does not by itself establish execution of dephosphorylation by the substrate. Proposed replacements: protein phosphatase 2A binding Supporting Evidence: PMID:16717086 The association of endogenous PP2A and BCL-2 at the ER was verified by co-immunoprecipitation and microcystin affinity purification. |
| GO:0001658 branching involved in ureteric bud morphogenesis | IGI PMID:16672320 Suppression of ureteric bud apoptosis rescues nephron endowm... | KEEP AS NON CORE | Summary: branching involved in ureteric bud morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IMP PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IGI PMID:16672320 Suppression of ureteric bud apoptosis rescues nephron endowm... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002260 lymphocyte homeostasis | IGI PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: lymphocyte homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0042981 regulation of apoptotic process | IGI PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0043067 regulation of programmed cell death | IGI PMID:16672320 Suppression of ureteric bud apoptosis rescues nephron endowm... | ACCEPT | Summary: Bcl2 directly controls apoptosis through BCL-2-family interactions. Reason: The broad apoptotic-process or regulation term includes Bcl2βs established control of the death machinery. It does not assert that Bcl2 must promote apoptosis. Mouse loss-of-function and interaction evidence supports the existing annotation; the more specific negative-regulation annotations are compatible and do not require replacement of this row. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:8918887 Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. |
| GO:0048070 regulation of developmental pigmentation | IGI PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: regulation of developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048536 spleen development | IMP PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: spleen development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048536 spleen development | IGI PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: spleen development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048538 thymus development | IMP PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: thymus development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048538 thymus development | IGI PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: thymus development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048589 developmental growth | IMP PMID:15818405 Polycystic kidney disease prevented by transgenic RNA interf... | KEEP AS NON CORE | Summary: developmental growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001662 behavioral fear response | IMP PMID:16095731 Increased anxiety-like behaviors and mitochondrial dysfuncti... | KEEP AS NON CORE | Summary: behavioral fear response is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IMP PMID:16282979 Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney dise... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0006470 protein dephosphorylation | IDA PMID:16717086 PP2A regulates BCL-2 phosphorylation and proteasome-mediated... | REMOVE | Summary: The full source identifies Bcl2 as the modified substrate, not the executor of its modification. Reason: Full PMID:16717086 was recovered from the Harvard manuscript and read. Figure 3G immunoprecipitates human BCL2 from transfected Bcl2-null MEFs under partner-dissociating conditions and detects ubiquitination of BCL2; the PP2A experiments likewise measure dephosphorylation of BCL2. The source establishes binding, phosphoregulation and survival effects, but not a Bcl2 cofactor/catalytic step executing these reactions. Remove this source-specific process attribution; independent calcineurin-targeting evidence is not a demonstration that this PP2A assay measures Bcl2 execution of dephosphorylation. Supporting Evidence: file:mouse/Bcl2/Bcl2-primary-source-checks.md The assay makes BCL2 the modified substrate, not the ubiquitination machinery. The PP2A assay similarly makes BCL2 the phosphatase substrate. |
| GO:0010332 response to gamma radiation | IMP PMID:10815637 Effects of deficiency in p53 or bcl-2 on the sensitivity of ... | KEEP AS NON CORE | Summary: response to gamma radiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010332 response to gamma radiation | IMP PMID:17068116 Radiation-induced gastric epithelial apoptosis occurs in the... | KEEP AS NON CORE | Summary: response to gamma radiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010332 response to gamma radiation | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: response to gamma radiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0014911 positive regulation of smooth muscle cell migration | IMP PMID:17382917 c-Myc is essential for urokinase plasminogen activator expre... | KEEP AS NON CORE | Summary: positive regulation of smooth muscle cell migration is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: PMID:17382917 links Bcl2βc-Myc binding to enhanced uPA/MMP-2 activity and hypoxia-induced migration of mouse vascular smooth muscle cells. Retain this context-specific signaling function; it is not merely inferred from general cell survival. Supporting Evidence: PMID:17382917 hypoxia-induced Bcl2 expression and Bcl2 binding to c-Myc led to enhanced c-Myc-mediated uPA and MMP-2 activity in response to hypoxia. |
| GO:0043029 T cell homeostasis | IGI PMID:17591857 Bim/Bcl-2 balance is critical for maintaining naive and memo... | KEEP AS NON CORE | Summary: T cell homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:17068116 Radiation-induced gastric epithelial apoptosis occurs in the... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:17267035 Regulation of the lifespan in dendritic cell subsets. | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:9681465 Enhanced oxidative stress and altered antioxidants in brains... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043085 positive regulation of catalytic activity | IMP PMID:17382917 c-Myc is essential for urokinase plasminogen activator expre... | KEEP AS NON CORE | Summary: Bcl2 enhances MYC-dependent uPA and MMP-2 activity under hypoxia. Reason: The abstract of PMID:17382917 explicitly describes mouse vascular smooth muscle cells, Bcl2 binding to c-Myc, and increased c-Myc-mediated uPA/MMP-2 activity. Positive regulation of catalytic activity does not require Bcl2 itself to be a protease. This is a supported context-specific regulatory function, rather than an unresolved claim based on a paper that merely names c-Myc. Supporting Evidence: PMID:17382917 hypoxia-induced Bcl2 expression and Bcl2 binding to c-Myc led to enhanced c-Myc-mediated uPA and MMP-2 activity in response to hypoxia. |
| GO:0043524 negative regulation of neuron apoptotic process | IMP PMID:9681465 Enhanced oxidative stress and altered antioxidants in brains... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0045636 positive regulation of melanocyte differentiation | IMP PMID:16427619 Indispensable role of Bcl2 in the development of the melanoc... | KEEP AS NON CORE | Summary: positive regulation of melanocyte differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048873 homeostasis of number of cells within a tissue | IMP PMID:16427619 Indispensable role of Bcl2 in the development of the melanoc... | KEEP AS NON CORE | Summary: homeostasis of number of cells within a tissue is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0050790 regulation of catalytic activity | IMP PMID:9681465 Enhanced oxidative stress and altered antioxidants in brains... | KEEP AS NON CORE | Summary: regulation of catalytic activity is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0051402 neuron apoptotic process | IMP PMID:7546744 Role of BCL-2 in the survival and function of developing and... | KEEP AS NON CORE | Summary: Bcl2 directly controls mitochondrial or neuronal apoptotic responses in the annotated context. Reason: Retain the experimentally grounded context-specific pathway annotation. Inhibitory Bcl2 activity is part of the control of these apoptotic responses and does not by itself refute an unsigned pathway term. The cited source concerns this context; broader antiapoptotic activity is represented separately. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. |
| GO:0001952 regulation of cell-matrix adhesion | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: regulation of cell-matrix adhesion is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010468 regulation of gene expression | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: regulation of gene expression is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010559 regulation of glycoprotein biosynthetic process | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: regulation of glycoprotein biosynthetic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030336 negative regulation of cell migration | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: negative regulation of cell migration is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048041 focal adhesion assembly | IMP PMID:15292044 Alterations in cell-adhesive and migratory properties of pro... | KEEP AS NON CORE | Summary: focal adhesion assembly is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | REMOVE | Summary: The full paper studies phosphorylation of Bcl2 as a substrate, not Bcl2 execution of the phosphorylation process. Reason: Full PMID:14660795 methods and results assay murine Bcl2 phosphosite substitutions, survival, cytochrome-c release, cell-cycle entry and turnover. Bcl2 is acted on by protein kinases; the study does not identify Bcl2 as a catalyst, scaffold, or cofactor performing serine/threonine phosphorylation of a substrate. Substrate modification alone is not participation in the modifying reaction. Supporting Evidence: PMID:14660795 This may explain why Bcl2 is the target of multiple such protein kinases, including c-Jun N-terminal kinase 1, protein kinase A, PKC, and mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | REMOVE | Summary: The full paper studies phosphorylation of Bcl2 as a substrate, not Bcl2 execution of the phosphorylation process. Reason: Full PMID:14660795 methods and results assay murine Bcl2 phosphosite substitutions, survival, cytochrome-c release, cell-cycle entry and turnover. Bcl2 is acted on by protein kinases; the study does not identify Bcl2 as a catalyst, scaffold, or cofactor performing serine/threonine phosphorylation of a substrate. Substrate modification alone is not participation in the modifying reaction. Supporting Evidence: PMID:14660795 This may explain why Bcl2 is the target of multiple such protein kinases, including c-Jun N-terminal kinase 1, protein kinase A, PKC, and mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 |
| GO:0031647 regulation of protein stability | IMP PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | REMOVE | Summary: The stability experiment measures Bcl2βs own susceptibility to degradation. Reason: Full PMID:14660795 Figure 6 compares turnover of wild-type and phosphomimetic Bcl2, and digestion of immunoprecipitated Bcl2 with an apoptotic extract. The modified Bcl2 is the stabilized substrate, not an identified regulator executing stabilization of another protein. Preserve the phosphoregulation finding in the reference, without converting it into an activity solely from altered half-life. Supporting Evidence: PMID:14660795 These results indicate that the charge conferred by phosphorylation enhances Bcl2's stability to turnover. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: PMID:14660795 All phosphomimetic Bcl2 mutants containing one or more E-substitution (i.e., at T69, S70, or S87) demonstrate significantly prolonged survival whereas the nonphosphorylatable A-containing mutants have much reduced antiapoptotic activity when compared with WT Bcl2 |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:14660795 Mono- and multisite phosphorylation enhances Bcl2's antiapop... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: PMID:14660795 All phosphomimetic Bcl2 mutants containing one or more E-substitution (i.e., at T69, S70, or S87) demonstrate significantly prolonged survival whereas the nonphosphorylatable A-containing mutants have much reduced antiapoptotic activity when compared with WT Bcl2 |
| GO:0001658 branching involved in ureteric bud morphogenesis | IDA PMID:14699151 Interaction of bcl-2 with Paxillin through its BH4 domain is... | KEEP AS NON CORE | Summary: branching involved in ureteric bud morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: PMID:14699151 maps paxillin interaction to Bcl2 BH4 residues 17β31 and shows inhibition of ureteric-bud branching by the BH4 peptide in embryonic kidney culture. This supports a contextual protein-interaction contribution to morphogenesis beyond an untested assumption of precursor survival. Supporting Evidence: PMID:14699151 In embryonic kidney organ culture, incubation with the bcl-2 BH4 domain resulted in inhibition of ureteric bud branching. |
| GO:0006979 response to oxidative stress | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: response to oxidative stress is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010468 regulation of gene expression | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: regulation of gene expression is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030308 negative regulation of cell growth | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: negative regulation of cell growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0034097 response to cytokine | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: response to cytokine is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0042542 response to hydrogen peroxide | IMP PMID:12855558 Bcl2 retards G1/S cell cycle transition by regulating intrac... | KEEP AS NON CORE | Summary: response to hydrogen peroxide is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001782 B cell homeostasis | IMP PMID:7650488 Bcl-XL and Bcl-2 repress a common pathway of cell death. | KEEP AS NON CORE | Summary: B cell homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001782 B cell homeostasis | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: B cell homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002260 lymphocyte homeostasis | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: lymphocyte homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009887 animal organ morphogenesis | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: animal organ morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030183 B cell differentiation | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: B cell differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030217 T cell differentiation | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: T cell differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030318 melanocyte differentiation | IMP PMID:12086670 Bcl2 regulation by the melanocyte master regulator Mitf modu... | KEEP AS NON CORE | Summary: melanocyte differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030318 melanocyte differentiation | IGI PMID:12086670 Bcl2 regulation by the melanocyte master regulator Mitf modu... | KEEP AS NON CORE | Summary: melanocyte differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0033077 T cell differentiation in thymus | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: T cell differentiation in thymus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043029 T cell homeostasis | IMP PMID:7650488 Bcl-XL and Bcl-2 repress a common pathway of cell death. | KEEP AS NON CORE | Summary: T cell homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043029 T cell homeostasis | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: T cell homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043375 CD8-positive, alpha-beta T cell lineage commitment | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: CD8-positive, alpha-beta T cell lineage commitment is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043583 ear development | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: ear development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048066 developmental pigmentation | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048545 response to steroid hormone | IMP PMID:8170972 Targeted disruption of Bcl-2 alpha beta in mice: occurrence ... | KEEP AS NON CORE | Summary: response to steroid hormone is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IGI PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002260 lymphocyte homeostasis | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: lymphocyte homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002260 lymphocyte homeostasis | IGI PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: lymphocyte homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0006582 melanin metabolic process | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: melanin metabolic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IGI PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030318 melanocyte differentiation | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: melanocyte differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0031966 mitochondrial membrane | IDA PMID:11980919 Intrinsic and extrinsic pathway signaling during neuronal ap... | ACCEPT | Summary: mitochondrial membrane is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. Supporting Evidence: PMID:11980919 BCL-2 was found as an integral membrane protein in the heavy membrane and microsomal fractions, which include mitochondria and ER, respectively, in both NGF-maintained and -deprived sympathetic neurons (Fig. 2; unpublished data). |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: positive regulation of multicellular organism growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043583 ear development | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: ear development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043583 ear development | IGI PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: ear development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048066 developmental pigmentation | IMP PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048066 developmental pigmentation | IGI PMID:11709185 Degenerative disorders caused by Bcl-2 deficiency prevented ... | KEEP AS NON CORE | Summary: developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0021747 cochlear nucleus development | IMP PMID:11027399 Patterns of cell death in mouse anteroventral cochlear nucle... | KEEP AS NON CORE | Summary: cochlear nucleus development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043524 negative regulation of neuron apoptotic process | IMP PMID:11027399 Patterns of cell death in mouse anteroventral cochlear nucle... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0048743 positive regulation of skeletal muscle fiber development | IMP PMID:11146504 Pro- and anti-apoptotic members of the Bcl-2 family in skele... | KEEP AS NON CORE | Summary: positive regulation of skeletal muscle fiber development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0008283 cell population proliferation | IGI PMID:10762311 Differences in bcl-2- and bax-independent function in regula... | KEEP AS NON CORE | Summary: cell population proliferation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0051402 neuron apoptotic process | IGI PMID:10762311 Differences in bcl-2- and bax-independent function in regula... | KEEP AS NON CORE | Summary: Bcl2 directly controls mitochondrial or neuronal apoptotic responses in the annotated context. Reason: Retain the experimentally grounded context-specific pathway annotation. Inhibitory Bcl2 activity is part of the control of these apoptotic responses and does not by itself refute an unsigned pathway term. The cited source concerns this context; broader antiapoptotic activity is represented separately. Supporting Evidence: PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. |
| GO:0043524 negative regulation of neuron apoptotic process | IMP PMID:10762311 Differences in bcl-2- and bax-independent function in regula... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0009636 response to toxic substance | IMP PMID:10602483 Damage-induced apoptosis in intestinal epithelia from bcl-2-... | KEEP AS NON CORE | Summary: Bcl2 contributes to cellular resistance to xenobiotic or toxic stress. Reason: Protection from toxic-agent-induced apoptosis is actual work in the cellular response, although the stimulus is a non-core context. PMID:8949945 shows protection from haloperidol toxicity, and PMID:10602483 shows increased 5-fluorouracil-induced epithelial apoptosis in Bcl2-null mice. The annotation does not imply that Bcl2 chemically detoxifies the compound. Supporting Evidence: PMID:10602483 These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:10602483 Damage-induced apoptosis in intestinal epithelia from bcl-2-... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:10321489 Retinal ganglion cell loss after the period of naturally occ... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0046671 negative regulation of retinal cell programmed cell death | IMP PMID:10321489 Retinal ganglion cell loss after the period of naturally occ... | KEEP AS NON CORE | Summary: negative regulation of retinal cell programmed cell death is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IMP PMID:9950951 Nuclear localization of beta-catenin and loss of apical brus... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0007015 actin filament organization | IMP PMID:9950951 Nuclear localization of beta-catenin and loss of apical brus... | KEEP AS NON CORE | Summary: actin filament organization is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032880 regulation of protein localization | IMP PMID:9950951 Nuclear localization of beta-catenin and loss of apical brus... | KEEP AS NON CORE | Summary: regulation of protein localization is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0010224 response to UV-B | IMP PMID:10200548 Alterations in cell death and cell cycle progression in the ... | KEEP AS NON CORE | Summary: response to UV-B is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:10200548 Alterations in cell death and cell cycle progression in the ... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051726 regulation of cell cycle | IMP PMID:10200548 Alterations in cell death and cell cycle progression in the ... | KEEP AS NON CORE | Summary: regulation of cell cycle is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0000902 cell morphogenesis | IMP PMID:10193316 The bcl-2 knockout mouse exhibits marked changes in osteobla... | KEEP AS NON CORE | Summary: cell morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001503 ossification | IMP PMID:10193316 The bcl-2 knockout mouse exhibits marked changes in osteobla... | KEEP AS NON CORE | Summary: ossification is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0033689 negative regulation of osteoblast proliferation | IMP PMID:10193316 The bcl-2 knockout mouse exhibits marked changes in osteobla... | KEEP AS NON CORE | Summary: negative regulation of osteoblast proliferation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0014042 positive regulation of neuron maturation | IMP PMID:9547242 Bcl-2 accelerates the maturation of early sensory neurons. | KEEP AS NON CORE | Summary: positive regulation of neuron maturation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: PMID:9547242 observes delayed maturation of Bcl2-null early sensory neurons despite similar survival and neuron numbers, supporting a separable contextual maturational function. It remains non-core but is not explained away as selective death. Supporting Evidence: PMID:9547242 The delay was not attributable to the well documented role of Bcl-2 in preventing apoptosis, because Bcl-2-deficient early sensory neurons survived as well as wild-type neurons. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:9374413 Bcl-2 is required for cranial sensory neuron survival at def... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0001822 kidney development | IGI PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0006808 regulation of nitrogen utilization | IGI PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: regulation of nitrogen utilization is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0008584 male gonad development | IGI PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: male gonad development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IGI PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0045930 negative regulation of mitotic cell cycle | IDA PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: negative regulation of mitotic cell cycle is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048087 positive regulation of developmental pigmentation | IGI PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: positive regulation of developmental pigmentation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048538 thymus development | IMP PMID:9241272 Bcl-2 and Bax function independently to regulate cell death. | KEEP AS NON CORE | Summary: thymus development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:9153592 Susceptibility of cerebellar granule neurons derived from Bc... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0033033 negative regulation of myeloid cell apoptotic process | IDA PMID:9202146 Differential involvement of caspases in apoptosis of myeloid... | KEEP AS NON CORE | Summary: negative regulation of myeloid cell apoptotic process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:9098922 Valproic acid-induced changes in gene expression during neur... | KEEP AS NON CORE | Summary: Bcl2 expression responds to valproate exposure in the developing mouse embryo. Reason: PMID:9098922 measures increased bcl-2 expression after teratogenic valproate exposure. Retain this non-core response with an expression-level evidence limitation; it does not establish that Bcl2 metabolizes valproate or alone causes the neural-tube phenotype. Independent toxic-stress experiments establish a functional Bcl2 survival response, so the annotation is not rejected simply for being outside its primary setting. Supporting Evidence: PMID:9098922 There was also a significant over expression of the cell cycle genes p53 and bcl-2 in the LM/Bc embryos in response to the teratogenic insult. |
| GO:0007409 axonogenesis | IMP PMID:9009190 Bcl-2 promotes regeneration of severed axons in mammalian CN... | KEEP AS NON CORE | Summary: Bcl2 promotes retinal axon growth and regeneration in the tested neuronal setting. Reason: PMID:9009190 explicitly distinguishes axon growth/regeneration from survival: the caspase inhibitor ZVAD preserved neuronal survival without promoting regeneration. Retain the neuronal process as non-core, without dismissing it as a secondary consequence of reduced death. Supporting Evidence: PMID:9009190 Another anti-apoptotic drug, ZVAD, supported neuronal survival but did not promote axon regeneration in culture. |
| GO:0031103 axon regeneration | IDA PMID:9009190 Bcl-2 promotes regeneration of severed axons in mammalian CN... | KEEP AS NON CORE | Summary: Bcl2 promotes retinal axon growth and regeneration in the tested neuronal setting. Reason: PMID:9009190 explicitly distinguishes axon growth/regeneration from survival: the caspase inhibitor ZVAD preserved neuronal survival without promoting regeneration. Retain the neuronal process as non-core, without dismissing it as a secondary consequence of reduced death. Supporting Evidence: PMID:9009190 Another anti-apoptotic drug, ZVAD, supported neuronal survival but did not promote axon regeneration in culture. |
| GO:0001776 leukocyte homeostasis | IMP PMID:9028316 Role of bcl-2 in the development of lymphoid cells from the ... | KEEP AS NON CORE | Summary: leukocyte homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002320 lymphoid progenitor cell differentiation | IMP PMID:9028316 Role of bcl-2 in the development of lymphoid cells from the ... | KEEP AS NON CORE | Summary: lymphoid progenitor cell differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030183 B cell differentiation | IMP PMID:9028316 Role of bcl-2 in the development of lymphoid cells from the ... | KEEP AS NON CORE | Summary: B cell differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0033077 T cell differentiation in thymus | IMP PMID:9028316 Role of bcl-2 in the development of lymphoid cells from the ... | KEEP AS NON CORE | Summary: T cell differentiation in thymus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030279 negative regulation of ossification | IMP PMID:9008714 Bcl-2 lies downstream of parathyroid hormone-related peptide... | KEEP AS NON CORE | Summary: negative regulation of ossification is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:7834747 Cloning and functional analysis of BAG-1: a novel Bcl-2-bind... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:7834747 Cloning and functional analysis of BAG-1: a novel Bcl-2-bind... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0001822 kidney development | IMP PMID:8760259 Abnormal postpartum renal development and cystogenesis in th... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0003014 renal system process | IMP PMID:8760259 Abnormal postpartum renal development and cystogenesis in th... | KEEP AS NON CORE | Summary: renal system process is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:8760259 Abnormal postpartum renal development and cystogenesis in th... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0030318 melanocyte differentiation | IMP PMID:8758925 Accelerated disappearance of melanocytes in bcl-2-deficient ... | KEEP AS NON CORE | Summary: melanocyte differentiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048753 pigment granule organization | IMP PMID:8758925 Accelerated disappearance of melanocytes in bcl-2-deficient ... | KEEP AS NON CORE | Summary: pigment granule organization is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001656 metanephros development | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | KEEP AS NON CORE | Summary: metanephros development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IMP PMID:8755480 Inactivation of bcl-2 results in progressive degeneration of... | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0014031 mesenchymal cell development | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | KEEP AS NON CORE | Summary: mesenchymal cell development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0032835 glomerulus development | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | KEEP AS NON CORE | Summary: glomerulus development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0035265 organ growth | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | KEEP AS NON CORE | Summary: organ growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:8623928 Apoptosis during an early stage of nephrogenesis induces ren... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:8663032 Diminished cell proliferation associated with the death-prot... | KEEP AS NON CORE | Summary: negative regulation of cell population proliferation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:8663032 Diminished cell proliferation associated with the death-prot... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0002326 B cell lineage commitment | IMP PMID:8788039 Distinct patterns of Fas cell surface expression during deve... | KEEP AS NON CORE | Summary: B cell lineage commitment is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002360 T cell lineage commitment | IMP PMID:8788039 Distinct patterns of Fas cell surface expression during deve... | KEEP AS NON CORE | Summary: T cell lineage commitment is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:7472523 Bcl-2 overexpression prevents motoneuron cell body loss but ... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005737 cytoplasm | IDA PMID:7675327 Up-regulation of bax and down-regulation of bcl-2 is associa... | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0001541 ovarian follicle development | IMP PMID:7628407 Ablation of bcl-2 gene expression decreases the numbers of o... | KEEP AS NON CORE | Summary: ovarian follicle development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048599 oocyte development | IMP PMID:7628407 Ablation of bcl-2 gene expression decreases the numbers of o... | KEEP AS NON CORE | Summary: oocyte development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | IDA PMID:7563251 Differential regulation of bcl-2, bax, c-fos, junB, and krox... | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0001656 metanephros development | IMP PMID:7840250 Fulminant metanephric apoptosis and abnormal kidney developm... | KEEP AS NON CORE | Summary: metanephros development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0001822 kidney development | IMP PMID:7840250 Fulminant metanephric apoptosis and abnormal kidney developm... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:7840250 Fulminant metanephric apoptosis and abnormal kidney developm... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:7751019 Apoptosis and Bcl-2 expression in cultured murine splenic T ... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0001822 kidney development | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: kidney development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0002520 immune system development | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: immune system development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0009791 post-embryonic development | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: post-embryonic development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0022612 gland morphogenesis | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: gland morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0030097 hemopoiesis | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: hemopoiesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0035265 organ growth | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: organ growth is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0048546 digestive tract morphogenesis | IMP PMID:7812968 bcl-2 deficiency in mice leads to pleiotropic abnormalities:... | KEEP AS NON CORE | Summary: digestive tract morphogenesis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005634 nucleus | IDA PMID:7945396 Bcl-2 overexpression abolishes early calcium waving precedin... | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005739 mitochondrion | IDA PMID:7945396 Bcl-2 overexpression abolishes early calcium waving precedin... | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0006874 intracellular calcium ion homeostasis | IDA PMID:7945396 Bcl-2 overexpression abolishes early calcium waving precedin... | KEEP AS NON CORE | Summary: intracellular calcium ion homeostasis is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005634 nucleus | IDA PMID:7953633 Expression of Bcl-2 protein in murine neural cells in cultur... | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005739 mitochondrion | IDA PMID:7953633 Expression of Bcl-2 protein in murine neural cells in cultur... | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043209 myelin sheath | IDA PMID:7953633 Expression of Bcl-2 protein in murine neural cells in cultur... | UNDECIDED | Summary: The exact myelin-sheath localization remains unverified. Reason: PMID:7953633 directly studies mouse neural cells and detects Bcl2 in neurons, astrocytes and oligodendrocytes. The accessible abstract does not resolve sheath-specific staining, and the detailed localization figures remain unavailable. Glial expression alone does not prove sheath localization, but predominant ER/mitochondrial localization does not refute it either. Supporting Evidence: PMID:7953633 The 26 kDa protein product, Bcl-2, was detected by immunocytochemistry and immunoblotting in cultured neurons, astrocytes and oligodendrocytes |
| GO:0002520 immune system development | IMP PMID:8372353 Disappearance of the lymphoid system in Bcl-2 homozygous mut... | KEEP AS NON CORE | Summary: immune system development is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005634 nucleus | IDA PMID:8030757 Bcl-2 protein expression during murine development. | KEEP AS NON CORE | Summary: nucleus is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005737 cytoplasm | IDA PMID:8030757 Bcl-2 protein expression during murine development. | ACCEPT | Summary: cytoplasm is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005783 endoplasmic reticulum | IDA PMID:8030757 Bcl-2 protein expression during murine development. | ACCEPT | Summary: endoplasmic reticulum is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005829 cytosol | IDA PMID:8030757 Bcl-2 protein expression during murine development. | KEEP AS NON CORE | Summary: A cytosolic Bcl2-containing pool is supported independently of the predominant membrane pools. Reason: The original source-specific localization assay is incompletely available, but PMID:12617961 directly identifies calcineurinβBcl2 complexes in cytosol as well as mitochondrial, nuclear and microsomal fractions of rodent brain. Mouse UniProt also records an alternative beta form lacking the canonical C-terminal membrane anchor. Retain a contextual cytosolic pool without assigning this source row to an unreported isoform or claiming every membrane-associated Bcl2 molecule is soluble. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
| GO:0010332 response to gamma radiation | IMP PMID:8372353 Disappearance of the lymphoid system in Bcl-2 homozygous mut... | KEEP AS NON CORE | Summary: response to gamma radiation is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0031965 nuclear membrane | IDA PMID:8030757 Bcl-2 protein expression during murine development. | KEEP AS NON CORE | Summary: nuclear membrane is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:8313913 Developmental regulation of the Bcl-2 protein and susceptibi... | ACCEPT | Summary: negative regulation of apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051384 response to glucocorticoid | IDA PMID:8313913 Developmental regulation of the Bcl-2 protein and susceptibi... | KEEP AS NON CORE | Summary: response to glucocorticoid is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0051384 response to glucocorticoid | IMP PMID:8372353 Disappearance of the lymphoid system in Bcl-2 homozygous mut... | KEEP AS NON CORE | Summary: response to glucocorticoid is retained as a context-specific Bcl2 phenotype, localization, pathway effect, or stress response rather than the core molecular function. Reason: Bcl2-dependent survival has broad tissue and developmental consequences; these terms are biologically plausible but downstream or peripheral to its core anti-apoptotic mechanism. |
| GO:0005739 mitochondrion | HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity... | ACCEPT | Summary: mitochondrion is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:11983915 bcl-2 overexpression promotes myocyte proliferation. | KEEP AS NON CORE | Summary: Bcl2 can enhance proliferation in specific cellular contexts. Reason: PMID:11983915 reports more cycling cardiomyocytes, mitotic spindles, contractile rings, karyokinesis and cytokinesis in Bcl2-transgenic mouse hearts while apoptosis remained low and unchanged. Thus proliferation cannot be dismissed universally as survival-driven cell accumulation. Retain context-specific positive regulation alongside separate studies showing cell-cycle retardation. Supporting Evidence: PMID:11983915 Apoptosis was low at all ages and was not affected by Bcl-2. |
| GO:0031069 hair follicle morphogenesis | IMP PMID:8402909 Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosi... | KEEP AS NON CORE | Summary: The Bcl2-null hair and pigmentation phenotype is supported mouse biology. Reason: PMID:8402909 reports hypopigmentation beginning with the second hair cycle, and subsequent work (PMID:8758925) documents progressive melanocyte loss. Retain these tissue-specific developmental outcomes as non-core. They do not establish Bcl2 as a melanogenic enzyme, but a survival contribution does not make the existing phenotype annotation false. Supporting Evidence: PMID:8402909 bcl-2-/-mice turn gray with the second hair follicle cycle |
| GO:0043473 pigmentation | IMP PMID:8402909 Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosi... | KEEP AS NON CORE | Summary: The Bcl2-null hair and pigmentation phenotype is supported mouse biology. Reason: PMID:8402909 reports hypopigmentation beginning with the second hair cycle, and subsequent work (PMID:8758925) documents progressive melanocyte loss. Retain these tissue-specific developmental outcomes as non-core. They do not establish Bcl2 as a melanogenic enzyme, but a survival contribution does not make the existing phenotype annotation false. Supporting Evidence: PMID:8402909 bcl-2-/-mice turn gray with the second hair follicle cycle |
| GO:0045069 regulation of viral genome replication | IDA PMID:16950491 Role of Bcl-2 expression for productive herpes simplex virus... | KEEP AS NON CORE | Summary: Bcl2-mediated survival can increase productive HSV-2 infection in the tested cellular context. Reason: PMID:16950491 reports human U937 cells: BCL2 overexpression protects against HSV-2-induced apoptosis and increases productive replication. This supports a contextual virus-replication regulatory effect that can inform the mouse ortholog, with a species limitation. It neither makes Bcl2 a viral replication enzyme nor conflicts with protective effects against other viral insults. Supporting Evidence: PMID:16950491 overexpression of Bcl-2 in U937 cells dramatically increased the capability of these cells to sustain a fully productive infection, while protecting against apoptosis induced by HSV-2. |
| GO:0001836 release of cytochrome c from mitochondria | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | MODIFY | Summary: The reported Bcl2 experiment inhibits Bax-induced cytochrome-c release. Reason: PMID:9843949 explicitly reports inhibition by transgene-derived Bcl2 of Bax-induced mitochondrial potential loss, swelling and cytochrome-c release in isolated mitochondria. Refine this source to negative regulation of release. This source-specific result does not rule out conditional proapoptotic conversion covered by the separate IBA adjudication. Proposed replacements: negative regulation of release of cytochrome c from mitochondria Supporting Evidence: PMID:9843949 Bax-induced mitochondrial changes were inhibited by recombinant Bcl-xL and transgene-derived Bcl-2 |
| GO:0046902 regulation of mitochondrial membrane permeability | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | ACCEPT | Summary: regulation of mitochondrial membrane permeability is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0051881 regulation of mitochondrial membrane potential | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | ACCEPT | Summary: regulation of mitochondrial membrane potential is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:8625820 Bax promotes neuronal survival and antagonises the survival ... | ACCEPT | Summary: negative regulation of neuron apoptotic process is consistent with Bcl2 as an anti-apoptotic BCL-2 family protein that controls mitochondrial membrane permeability and binds BH-domain partners. Reason: The term captures the core anti-apoptotic mechanism, BCL-2 family binding/complex context, or supported mitochondrial/ER membrane localization. |
| GO:0005829 cytosol | IDA PMID:14551195 Targeted disruption of the PDZK1 gene in mice causes tissue-... | KEEP AS NON CORE | Summary: A cytosolic Bcl2-containing pool is supported independently of the predominant membrane pools. Reason: The original source-specific localization assay is incompletely available, but PMID:12617961 directly identifies calcineurinβBcl2 complexes in cytosol as well as mitochondrial, nuclear and microsomal fractions of rodent brain. Mouse UniProt also records an alternative beta form lacking the canonical C-terminal membrane anchor. Retain a contextual cytosolic pool without assigning this source row to an unreported isoform or claiming every membrane-associated Bcl2 molecule is soluble. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:14551195 Targeted disruption of the PDZK1 gene in mice causes tissue-... | ACCEPT | Summary: Negative regulation of apoptosis is an established mouse Bcl2 function. Reason: The specific PMID:14551195 experiment remains unverified from its PDZK1-focused abstract; its omission of Bcl2 is not proof that no Bcl2 control was assayed. Independent mouse genetic evidence (PMID:8372353) and mechanistic evidence (PMID:15983387) establish the biological claim. Accept the function while recording the citation-verification limit separately. Supporting Evidence: PMID:8372353 Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. PMID:15983387 Furthermore, introduction of antiapoptotic Bcl2 into F2 transfectants resulted in profound inhibition of apoptosis (+Bcl2). |
| GO:0005739 mitochondrion | IDA PMID:12420306 Sorting specificity of spermatogenic cell specific region of... | ACCEPT | Summary: Mitochondrial localization of mouse Bcl2 is independently well established. Reason: The detailed Bcl2 control in the hexokinase-s sorting study PMID:12420306 could not be inspected. That does not negate the target localization established in rodent subcellular fractionation (PMID:12617961) and mitochondrial proteomics (PMID:18614015). Accept the biological annotation while keeping the original citation and noting the source-specific limitation. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
| GO:0005829 cytosol | IDA PMID:12050152 A novel transactivating factor that regulates interferon-gam... | KEEP AS NON CORE | Summary: A cytosolic Bcl2-containing pool is supported independently of the predominant membrane pools. Reason: The original source-specific localization assay is incompletely available, but PMID:12617961 directly identifies calcineurinβBcl2 complexes in cytosol as well as mitochondrial, nuclear and microsomal fractions of rodent brain. Mouse UniProt also records an alternative beta form lacking the canonical C-terminal membrane anchor. Retain a contextual cytosolic pool without assigning this source row to an unreported isoform or claiming every membrane-associated Bcl2 molecule is soluble. Supporting Evidence: PMID:12617961 The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. |
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Download this section (compressed HTML)Q: Which physiological mouse contexts engage the conserved proapoptotic conversion and channel-forming capacities of Bcl2, and what native assemblies mediate them?
Q: Can the original mouse myelin-sheath microscopy and source-specific cytosol experiments be recovered to distinguish the observed compartment, construct and isoform?
Experiment: Use Bcl2 BH-domain mutant rescue in mouse primary cells to test which survival and autophagy annotations require canonical BCL-2 family partner binding.
Experiment: Measure mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation in Bcl2 knockout and add-back mouse cells across apoptotic stimuli.
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