BAK1 encodes a pro-apoptotic multidomain BCL2-family effector that is constitutively anchored in the mitochondrial outer membrane through a C-terminal transmembrane helix. In response to direct activator BH3-only proteins such as BID, or to release from anti-apoptotic guardians such as MCL1 and BCL-XL, BAK changes conformation, dimerizes, and builds higher-order BAK pores that permeabilize the outer membrane, release cytochrome c and other intermembrane-space proteins, and drive intrinsic apoptotic signaling. BAK also has secondary stress-linked roles at the endoplasmic reticulum in calcium and unfolded-protein-response signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001836 release of cytochrome c from mitochondria | IBA GO_REF:0000033 | ACCEPT | Summary: BAK1 is a direct BCL2-family effector of cytochrome-c release from mitochondria. Reason: Active BAK oligomerizes at the mitochondrial outer membrane and releases cytochrome c during MOMP; the IBA/IEA, isolated-mitochondria, and BH3-peptide rows all capture that core effector function. |
| GO:0001836 release of cytochrome c from mitochondria | IDA PMID:16199525 MAP-1 is a mitochondrial effector of Bax. | ACCEPT | Summary: BAK1 is a direct BCL2-family effector of cytochrome-c release from mitochondria. Reason: Active BAK oligomerizes at the mitochondrial outer membrane and releases cytochrome c during MOMP; the IBA/IEA, isolated-mitochondria, and BH3-peptide rows all capture that core effector function. |
| GO:0001836 release of cytochrome c from mitochondria | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | ACCEPT | Summary: BAK1 is a direct BCL2-family effector of cytochrome-c release from mitochondria. Reason: Active BAK oligomerizes at the mitochondrial outer membrane and releases cytochrome c during MOMP; the IBA/IEA, isolated-mitochondria, and BH3-peptide rows all capture that core effector function. |
| GO:0001836 release of cytochrome c from mitochondria | IEA GO_REF:0000120 | ACCEPT | Summary: BAK1 is a direct BCL2-family effector of cytochrome-c release from mitochondria. Reason: Active BAK oligomerizes at the mitochondrial outer membrane and releases cytochrome c during MOMP; the IBA/IEA, isolated-mitochondria, and BH3-peptide rows all capture that core effector function. |
| GO:0001836 release of cytochrome c from mitochondria | IGI PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | ACCEPT | Summary: BAK1 is a direct BCL2-family effector of cytochrome-c release from mitochondria. Reason: Active BAK oligomerizes at the mitochondrial outer membrane and releases cytochrome c during MOMP; the IBA/IEA, isolated-mitochondria, and BH3-peptide rows all capture that core effector function. |
| GO:0005515 protein binding | IPI PMID:10381623 A novel adenovirus E1B19K-binding protein B5 inhibits apopto... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:10950869 tBID, a membrane-targeted death ligand, oligomerizes BAK to ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:11571294 Tumor necrosis factor-alpha induces Bax-Bak interaction and ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:12624108 Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:14596824 High-throughput methods to detect dimerization of Bcl-2 fami... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:16439990 Interaction of F1L with the BH3 domain of Bak is responsible... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:16439990 Interaction of F1L with the BH3 domain of Bak is responsible... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:17097560 Mechanisms of apoptosis sensitivity and resistance to the BH... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:17446862 Functional and physical interaction between Bcl-X(L) and a B... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:17606912 Bak regulates mitochondrial morphology and pathology during ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:18040043 Small molecule obatoclax (GX15-070) antagonizes MCL-1 and ov... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:19968986 Mcl-1(128-350) fragment induces apoptosis through direct int... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:20023629 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cel... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:21036904 Heterodimerization of BAK and MCL-1 activated by detergent m... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:22516262 Chemical genomics identifies small-molecule MCL1 repressors ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:22516262 Chemical genomics identifies small-molecule MCL1 repressors ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:23055042 Human Bop is a novel BH3-only member of the Bcl-2 protein fa... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:23055042 Human Bop is a novel BH3-only member of the Bcl-2 protein fa... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:23604079 BID-induced structural changes in BAK promote apoptosis. | MODIFY | Summary: The BAK-BID interaction row captures activator BH3-helix binding by BAK. Reason: PMID:23604079 supports direct BID/BH3 engagement of the BAK hydrophobic groove; the informative BAK molecular function is BH3 domain binding rather than generic protein binding. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:23680104 The novel BH3 Ξ±-helix mimetic JY-1-106 induces apoptosis in ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:23680104 The novel BH3 Ξ±-helix mimetic JY-1-106 induces apoptosis in ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:23782464 BAK multimerization for apoptosis, but not bid binding, is i... | MODIFY | Summary: The BAK-BID interaction row captures activator BH3-helix binding by BAK. Reason: PMID:23782464 supports direct BID/BH3 engagement of the BAK hydrophobic groove; the informative BAK molecular function is BH3 domain binding rather than generic protein binding. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:26004684 Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:9027312 Interaction of CED-4 with CED-3 and CED-9: a molecular frame... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:9111042 A common binding site mediates heterodimerization and homodi... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:9463381 The conserved N-terminal BH4 domain of Bcl-2 homologues is e... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005515 protein binding | IPI PMID:9843949 Bax interacts with the permeability transition pore to induc... | REMOVE | Summary: This imported interaction row asserts only generic BAK1 protein binding. Reason: GO:0005515 is uninformative for BAK1 and should not duplicate curated BAK homodimerization, BCL2-family-complex, BH3-domain-binding, or heterodimerization rows. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | TOO GENERAL | Summary: True but broad: entailed by endoplasmic reticulum, mitochondrial membrane and mitochondrial outer membrane and others, kept in this review. Reason: GO's cytoplasm covers everything inside the plasma membrane except the nucleus, organelles and secretory compartments included, so endoplasmic reticulum, mitochondrial membrane and mitochondrial outer membrane and others, kept in this review, entail this term and the claim is true. TOO_GENERAL rather than REMOVE. The objection is a reason not to annotate a narrower term such as cytosol, not to remove this one. Objection recorded at removal: BAK is a C-terminally anchored outer-mitochondrial-membrane effector; unlike BAX, it is not primarily a soluble cytosolic protein that translocates to mitochondria after activation. Summary at removal: Cytoplasm/cytosol is not the functional site of human BAK1. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: BAK1 is a mitochondrial BCL2-family effector. Reason: Mitochondrion is broader than the exact outer-membrane location, but it is true for this resident mitochondrial effector and is supported by localization evidence and ortholog transfer. |
| GO:0005739 mitochondrion | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | ACCEPT | Summary: BAK1 is a mitochondrial BCL2-family effector. Reason: Mitochondrion is broader than the exact outer-membrane location, but it is true for this resident mitochondrial effector and is supported by localization evidence and ortholog transfer. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: BAK1 is a mitochondrial BCL2-family effector. Reason: Mitochondrion is broader than the exact outer-membrane location, but it is true for this resident mitochondrial effector and is supported by localization evidence and ortholog transfer. |
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:22006182 Active Bax and Bak are functional holins. | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:29531808 PLEKHN1 promotes apoptosis by enhancing Bax-Bak hetro-oligom... | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:32929280 BAK core dimers bind lipids and can be bridged by them. | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-114263 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-139895 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-168848 | ACCEPT | Summary: The mitochondrial outer membrane is BAK1's principal site of pore-forming apoptotic activity. Reason: BAK is inserted in the mitochondrial outer membrane before and during apoptotic activation, and the Reactome rows describe the BID-to-BAK activation and BAK oligomerization steps at that membrane. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ER localization captures a secondary BAK/BAX regulatory context. Reason: BAK has reported endoplasmic-reticulum stress and calcium-homeostasis connections, but its core curated role is mitochondrial outer-membrane permeabilization. ORGANELLES check (2026-11-04, ER batch 1). This is an Ensembl projection from mouse Bak (O08734), whose own ER annotation is an MGI IDA from Zong et al. 2003 (PMID:12847083). That paper fractionated untransfected cells and mouse liver: endogenous Bak was in the calnexin-positive light-membrane (ER/microsome) fraction, and that fraction was free of the mitochondrial markers COX IV and Tom40; the fraction is still microsomal (Golgi and plasma membrane were not excluded), but the ER marker was checked and the paper's ER-specific functional data point the same way. An ER-targeted Bak (cb5 tail) depleted ER Ca2+ in Bax/Bak-null cells, a function only the ER pool performs. The organelle claim therefore holds for the ortholog and is expected to hold for human BAK1, which has the same C-terminal tail anchor; the ER pool is minor relative to the mitochondrial outer membrane, so the row stays KEEP_AS_NON_CORE. Supporting Evidence: PMID:12847083 Bax and Bak can also localize to the ER. PMID:12847083 both Bax and Bak were found in the ER/microsome fraction PMID:12847083 However, the S-100 and LM fractions were not contaminated by mitochondria, as indicated by the absence of the mitochondrial inner membrane protein COX IV or mitochondrial outer membrane Tom40 |
| GO:0005789 endoplasmic reticulum membrane | IC PMID:12847083 Bax and Bak can localize to the endoplasmic reticulum to ini... | NEW | Summary: Proposed sub-compartment. The ER pool of BAK is held by its C-terminal tail anchor, so it is an ER-membrane pool; the existing annotations stop at the organelle. Reason: ORGANELLES rule 4 (2026-11-04, ER batch 1). Lines that agree on the membrane rather than the lumen. (1) Topology - BAK1 has a single C-terminal helical TM segment (188-205) and no signal peptide, the tail-anchor arrangement of BCL-2-family effectors, so it cannot enter the ER lumen and any ER pool is membrane-inserted with the BH domains on the cytosolic face. (2) Fractionation - endogenous mouse Bak sits in the calnexin-positive, mitochondria-free light-membrane fraction (PMID:12847083). (3) Function, supportive only - Bak artificially anchored to the ER by a cb5 tail depletes ER Ca2+ stores, an activity at the cytosolic face of the ER membrane; this shows what Bak does if placed at the ER, not that endogenous Bak is there, so line 2 carries the localization. There is no human assay of BAK1 at the ER. GO already places the paralogs BAX and BCL2 in GO:0005789 by direct assay. IC rather than IDA because the TM is predicted and the fractionation is on the mouse ortholog; no carbonate extraction of the ER pool was done. The ER pool is not core, so core_functions are unchanged and the MAM is not asserted. Supporting Evidence: file:human/BAK1/BAK1-uniprot.txt FT TRANSMEM 188..205 FT /note="Helical" PMID:12847083 both Bax and Bak were found in the ER/microsome fraction PMID:12847083 Antibodies against Bax, Bak, calnexin, and Cox IV were used for immunoblotting |
| GO:0005829 cytosol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cytoplasm/cytosol is not the functional site of human BAK1. Reason: The row is transferred from mouse Bak1, where cytosol is annotated from a direct assay (IDA, PMID:12847083), so it is not a baseless projection. BAK is, however, constitutively anchored in the mitochondrial outer membrane by its C-terminal transmembrane helix and, unlike BAX, is not a soluble cytosolic protein that translocates on activation; any soluble pool is minor. The cytosol term therefore over-states where BAK resides rather than being refuted. |
| GO:0006915 apoptotic process | IDA PMID:23028632 The identification of a novel gene, MAPO2, that is involved ... | MODIFY | Summary: The top-level apoptotic-process assertion is mechanistically underspecified for BAK1. Reason: BAK does not merely participate in generic apoptosis; it executes the mitochondrial outer membrane permeabilization step that commits intrinsic apoptotic signaling to cytochrome-c release. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0006915 apoptotic process | NAS PMID:7715731 Modulation of apoptosis by the widely distributed Bcl-2 homo... | MODIFY | Summary: The top-level apoptotic-process assertion is mechanistically underspecified for BAK1. Reason: BAK does not merely participate in generic apoptosis; it executes the mitochondrial outer membrane permeabilization step that commits intrinsic apoptotic signaling to cytochrome-c release. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The row is transferred from rat Bak1, which is annotated from a mutant phenotype (IMP, PMID:18349538), so the claim has experimental support in the ortholog. A reduction in cell number when BAK is active is, however, the downstream outcome of BAK-driven mitochondrial outer membrane permeabilization and cell death, not a separate anti-proliferative activity of the protein. The term is therefore an over-annotation of the apoptotic effector role rather than a wrong mapping. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DNA-damage intrinsic apoptotic signaling is a stimulus-specific use of BAK-mediated MOMP. Reason: BAK can execute MOMP downstream of DNA-damage and p53/BH3-only inputs, but the stimulus qualifier is contextual rather than the core molecular role of the protein. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0010225 response to UV-C | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0010248 establishment or maintenance of transmembrane electrochemical gradient | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | MODIFY | Summary: The permeability-transition-era annotation points at loss of mitochondrial potential after BAK activation. Reason: The 1998 isolated-mitochondria model used permeability-transition language; current BAK curation should represent this outcome as negative regulation of mitochondrial membrane potential during BAK-driven MOMP. Proposed replacements: negative regulation of mitochondrial membrane potential |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0015267 channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: BAK has membrane channel activity after apoptotic activation. Reason: The PAINT channel-activity row lands at the right BAX/BAK-family effector node for proteins that build the MOMP pore. |
| GO:0015288 porin activity | IDA PMID:22006182 Active Bax and Bak are functional holins. | MODIFY | Summary: Activated BAK forms the membrane-permeabilizing MOMP pore, but channel activity is a better term for this holin-like lesion than porin activity. Reason: PMID:22006182 describes active Bax/Bak as displaying holin behavior rather than beta-barrel porin behavior. GO:0015267 captures the membrane channel activity of the apoptotic BAX/BAK-family effector pore without implying a porin mechanism. Proposed replacements: channel activity |
| GO:0031018 endocrine pancreas development | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0031072 heat shock protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chaperone binding is a peripheral BAK1 regulatory context. Reason: The HSP70/BAG-family regulatory projection is not BAK's core pore-forming activity, but it is plausible as non-core stress regulation of a BCL2-family effector. |
| GO:0031100 animal organ regeneration | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:9111042 A common binding site mediates heterodimerization and homodi... | KEEP AS NON CORE | Summary: Generic complex-assembly regulation from an early study of BCL2-family dimerization; only the abstract is available. Reason: The cited study analysed the binding site that mediates hetero- and homodimerization of BCL2-family proteins, including the effect of BH3-derived peptides of Bax and Bak on these associations; only its abstract is available, so the curator's direct-assay annotation cannot be checked against the full text and is not overruled. The term is generic: it does not identify the apoptotic BAK oligomer or the membrane-permeabilization step, which are captured by more specific annotations, so it is kept as non-core rather than as a description of BAK's function. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Mitochondrial membrane is a true but broad BAK1 location. Reason: The Ensembl projection is broader than mitochondrial outer membrane, but it is consistent with the resident OMM localization of BAK. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:0034620 cellular response to unfolded protein | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:0034644 cellular response to UV | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: UV signaling is a stimulus-specific context for BAK activation. Reason: The Willis et al. study directly used UV-induced MEF killing to study BAK control by MCL1 and BCL-XL; the UV term is contextual and non-core but not biologically implausible. |
| GO:0034644 cellular response to UV | IMP PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | KEEP AS NON CORE | Summary: UV signaling is a stimulus-specific context for BAK activation. Reason: The Willis et al. study directly used UV-induced MEF killing to study BAK control by MCL1 and BCL-XL; the UV term is contextual and non-core but not biologically implausible. |
| GO:0034644 cellular response to UV | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UV signaling is a stimulus-specific context for BAK activation. Reason: The Willis et al. study directly used UV-induced MEF killing to study BAK control by MCL1 and BCL-XL; the UV term is contextual and non-core but not biologically implausible. |
| GO:0042542 response to hydrogen peroxide | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0042802 identical protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:10950869 tBID, a membrane-targeted death ligand, oligomerizes BAK to ... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:16439990 Interaction of F1L with the BH3 domain of Bak is responsible... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:17024184 Differential contribution of Puma and Noxa in dual regulatio... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:17446862 Functional and physical interaction between Bcl-X(L) and a B... | ACCEPT | Summary: True: entailed by protein homodimerization activity, kept in this review. Reason: The claim is true: protein homodimerization activity, kept in this review, entails this term. Other rows for this term are ACCEPTed. This row's reference does not establish it; that is recorded in source_defects, not grounds for REMOVE, which judges the claim. |
| GO:0042802 identical protein binding | IPI PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042802 identical protein binding | IPI PMID:23782464 BAK multimerization for apoptosis, but not bid binding, is i... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042803 protein homodimerization activity | IDA PMID:23028632 The identification of a novel gene, MAPO2, that is involved ... | ACCEPT | Summary: BAK self-association is the molecular assembly event that creates the BAK pore. Reason: Activated BAK forms BH3/groove dimers and higher-order oligomers, so the identical-protein-binding and homodimerization rows capture a core pore-assembly activity. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MODIFY | Summary: Generic apoptotic-process regulation should be tightened to the direct MOMP step. Reason: BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: Generic apoptotic-process regulation should be tightened to the direct MOMP step. Reason: BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000135648 SUPPORTS SOURCE BUT NOT TARGET The PAINT row captures a true pro-apoptotic BCL2-family effector function, but BAK itself directly permeabilizes the mitochondrial outer membrane rather than generically regulating apoptosis. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000117 | MODIFY | Summary: Generic apoptotic-process regulation should be tightened to the direct MOMP step. Reason: BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | MODIFY | Summary: Generic apoptotic-process regulation should be tightened to the direct MOMP step. Reason: BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0043065 positive regulation of apoptotic process | ISS GO_REF:0000024 | MODIFY | Summary: Generic apoptotic-process regulation should be tightened to the direct MOMP step. Reason: BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | REMOVE | Summary: This PAINT row crossed the pro- and anti-apoptotic split in the BCL2 family. Reason: BAK is a pro-apoptotic MOMP effector; negative regulation of apoptotic process is appropriate for pro-survival BCL2-family members, not for BAK. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000135648 SUPPORTS SOURCE BUT NOT TARGET This BCL2-family node includes anti-apoptotic family members, but BAK is on the pro-apoptotic effector side of the family split. |
| GO:0044325 transmembrane transporter binding | IPI PMID:25296756 Plasminogen kringle 5 induces endothelial cell apoptosis by ... | UNDECIDED | Summary: The VDAC1 interaction row is not verifiable from the cached abstract. Reason: PMID:25296756 is abstract-only in the local cache and the abstract centers on the K5-VDAC1 feedback loop without exposing the BAK1-specific VDAC1 evidence, so this IPI row should be left for full-text review. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Generic binding term transferred from rat Bak1, where it rests on a physical interaction (PMID:9356461). Reason: The row is transferred from rat Bak1, where it rests on a physical interaction (IPI, PMID:9356461), so it has experimental support in the ortholog and nothing contradicts it: BAK does bind multi-protein assemblies, including pro-survival BCL2-family complexes. The term is generic and says little about BAK's function, which is described by BH3 domain binding and the oligomeric pore, so it is kept as non-core. Supporting Evidence: PMID:9356461 the ability of other pro-apoptotic members (Bax, Bak, and Bik) to interact with all of the anti-apoptotic proteins |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | REMOVE | Summary: This propagated broad phenotype is not a direct BAK1 function. Reason: The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. |
| GO:0045862 positive regulation of proteolysis | IDA PMID:18387192 A pathway sensor for genome-wide screens of intracellular pr... | KEEP AS NON CORE | Summary: The proteolysis row comes from a downstream caspase-reporter readout. Reason: In the cited genome-wide screen BAK scored as an inducer of a DEVD-based caspase cleavage reporter, alongside other known apoptosis inducers (PMID:18387192). The result is real and is what the term states: expressing BAK increases caspase-mediated proteolysis. It is, however, the downstream consequence of BAK-driven mitochondrial outer membrane permeabilization rather than a direct activity of BAK on a protease, so it is kept as non-core. Supporting Evidence: PMID:18387192 The candidates found include known inducers of apoptosis, such as BAK, FADD, BAD and caspase 8, in partial validation of the approach to identify regulators of caspase activation. |
| GO:0046902 regulation of mitochondrial membrane permeability | IDA PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | MODIFY | Summary: Regulation of mitochondrial permeability is too broad for the BAK effector step. Reason: BAK specifically drives apoptotic mitochondrial outer membrane permeabilization rather than a generic mitochondrial permeability process. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0046902 regulation of mitochondrial membrane permeability | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | MODIFY | Summary: Regulation of mitochondrial permeability is too broad for the BAK effector step. Reason: BAK specifically drives apoptotic mitochondrial outer membrane permeabilization rather than a generic mitochondrial permeability process. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0046930 pore complex | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | MODIFY | Summary: The generic pore-complex row should be represented as BAK complex. Reason: BAK does not place in the historical mitochondrial permeability-transition-pore complex; apoptotic pore assembly is better captured by the BAK complex component term. Proposed replacements: BAK complex |
| GO:0046982 protein heterodimerization activity | IPI PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | ACCEPT | Summary: BAK heterodimerizes with the anti-apoptotic BCL2-family protein MCL1. Reason: Although the original PMID:10837489 cache is abstract-only, BAK-MCL1 heterodimerization is a well-supported BCL2-family regulatory interaction captured directly by the MCL1/BCL-XL sequestration model. |
| GO:0051049 regulation of transport | IEA GO_REF:0000117 | TOO GENERAL | Summary: Broad machine-generated term, entailed by the accepted annotation to positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Reason: Regulation of transport is entailed by the accepted annotation to positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway, so the broad term is true of BAK1 but adds nothing to that specific statement. On its own the machine-generated term would not identify what BAK does. |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chaperone binding is a peripheral BAK1 regulatory context. Reason: The HSP70/BAG-family regulatory projection is not BAK's core pore-forming activity, but it is plausible as non-core stress regulation of a BCL2-family effector. |
| GO:0051246 regulation of protein metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: Broad machine-generated term, entailed by the positive regulation of proteolysis annotation kept in this review. Reason: Regulation of protein metabolic process is entailed by the positive regulation of proteolysis annotation kept in this review (BAK activity leads to caspase activation), so the broad term is true of BAK1 but adds nothing. On its own the machine-generated term would not identify what BAK does. |
| GO:0051400 BH domain binding | IEA GO_REF:0000107 | MODIFY | Summary: The broad BH-domain-binding row should be narrowed to BH3-domain binding. Reason: BAK's relevant activation and inhibitory BCL2-family interactions use BH3 helices binding the BAK canonical groove or anti-apoptotic grooves, so GO:0051434 is the more informative molecular-function term. Proposed replacements: BH3 domain binding |
| GO:0051881 regulation of mitochondrial membrane potential | IDA PMID:9843949 Bax interacts with the permeability transition pore to induc... | MODIFY | Summary: The membrane-potential row should state the polarity of activated BAK. Reason: BAK activation leads to loss of mitochondrial membrane potential downstream of outer-membrane permeabilization; the replacement records the negative effect on membrane potential. Proposed replacements: negative regulation of mitochondrial membrane potential |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | TAS PMID:22934019 The endoplasmic reticulum stress response in aging and age-r... | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | REMOVE | Summary: The mechanical-stimulus source does not establish a BAK1 function. Reason: The cached full text of PMID:19593445 is about BAD-dependent prostate-cancer growth and does not provide BAK1-specific evidence for cellular response to mechanical stimulus. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IEA GO_REF:0000107 | MODIFY | Summary: Positive regulation of cytochrome-c release should be captured as direct cytochrome-c release. Reason: Activated BAK forms the pore that releases cytochrome c from mitochondria, so the execution step itself is more direct than a positive-regulation parent. Proposed replacements: release of cytochrome c from mitochondria |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | NAS PMID:32929280 BAK core dimers bind lipids and can be bridged by them. | MODIFY | Summary: Positive regulation of cytochrome-c release should be captured as direct cytochrome-c release. Reason: Activated BAK forms the pore that releases cytochrome c from mitochondria, so the execution step itself is more direct than a positive-regulation parent. Proposed replacements: release of cytochrome c from mitochondria |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | IDA PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: BAK is the restrained target, not the negative regulator, in this anti-apoptotic complex. Reason: MCL1 and BCL-XL sequester BAK to restrain cytochrome-c release; BAK itself does not execute negative regulation of cytochrome-c release in that complex. |
| GO:0097136 Bcl-2 family protein complex | IDA PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | ACCEPT | Summary: BAK forms heteromeric BCL2-family complexes with BH3-binding guardians or peptides. Reason: BAK complexes with anti-apoptotic BCL2-family proteins or their BH3-binding grooves are part of direct BCL2-family control of MOMP. |
| GO:0097136 Bcl-2 family protein complex | IPI PMID:22515821 NMR solution structure of a photoswitchable apoptosis activa... | ACCEPT | Summary: A BAK BH3 helix can form a BCL2-family complex with BCL-XL. Reason: The original structure used a BAK-derived BH3 peptide bound to BCL-XL, and the native BAK/BCL-XL sequestration complex is a direct BCL2-family regulatory assembly. |
| GO:0097145 BAK complex | IDA PMID:10950869 tBID, a membrane-targeted death ligand, oligomerizes BAK to ... | ACCEPT | Summary: BAK is part of the activated BAK complex. Reason: Activated BAK dimerizes and oligomerizes into the BAK complex that constitutes the apoptotic outer-membrane pore. |
| GO:0097145 BAK complex | IDA PMID:17024184 Differential contribution of Puma and Noxa in dual regulatio... | ACCEPT | Summary: BAK is part of the activated BAK complex. Reason: Activated BAK dimerizes and oligomerizes into the BAK complex that constitutes the apoptotic outer-membrane pore. |
| GO:0097145 BAK complex | IDA PMID:23028632 The identification of a novel gene, MAPO2, that is involved ... | ACCEPT | Summary: BAK is part of the activated BAK complex. Reason: Activated BAK dimerizes and oligomerizes into the BAK complex that constitutes the apoptotic outer-membrane pore. |
| GO:0097145 BAK complex | IEA GO_REF:0000120 | ACCEPT | Summary: BAK is part of the activated BAK complex. Reason: Activated BAK dimerizes and oligomerizes into the BAK complex that constitutes the apoptotic outer-membrane pore. |
| GO:0097145 BAK complex | IPI PMID:32929280 BAK core dimers bind lipids and can be bridged by them. | ACCEPT | Summary: BAK is part of the activated BAK complex. Reason: Activated BAK dimerizes and oligomerizes into the BAK complex that constitutes the apoptotic outer-membrane pore. |
| GO:0097190 apoptotic signaling pathway | IMP PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | MODIFY | Summary: The apoptotic-signaling row should be tightened to MOMP. Reason: BAK executes the mitochondrial permeabilization step in apoptotic signaling rather than a generic upstream apoptotic signal. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IBA GO_REF:0000033 | MODIFY | Summary: This PAINT row maps an upstream BCL2-family context onto the BAK effector. Reason: BAK executes mitochondrial outer membrane permeabilization downstream of BH3-only and death-receptor signals; it is not specific to ligand-independent extrinsic apoptotic signaling. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000135648 SUPPORTS SOURCE BUT NOT TARGET The BCL2-family PAINT node combines upstream BH3-only regulators with downstream BAK/BAX effectors; BAK supports MOMP, not this ligand-independent extrinsic branch term. Proposed replacements: mitochondrial outer membrane permeabilization |
| GO:0097193 intrinsic apoptotic signaling pathway | IDA PMID:22006182 Active Bax and Bak are functional holins. | ACCEPT | Summary: BAK pore-forming activity is part of intrinsic apoptotic signaling. Reason: The GO-CAM-backed holin/porin annotation places BAK porin activity at the mitochondrial outer membrane as an intrinsic-apoptosis step. |
| GO:1901029 negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway | IDA PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | REMOVE | Summary: BAK is the restrained target, not the inhibitor, of MOMP in this complex. Reason: MCL1 and BCL-XL prevent BAK-driven MOMP by binding BAK; the captured complex should not make BAK itself a negative regulator of mitochondrial outer membrane permeabilization. |
| GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway | NAS PMID:32929280 BAK core dimers bind lipids and can be bridged by them. | ACCEPT | Summary: BAK directly promotes apoptotic MOMP. Reason: Positive regulation of MOMP is less direct than MOMP itself, but it is a correct ComplexPortal summary of BAK as a pore-forming BCL2-family effector. |
| GO:1902531 regulation of intracellular signal transduction | IEA GO_REF:0000117 | TOO GENERAL | Summary: Broad machine-generated term, entailed by the positive regulation of IRE1-mediated unfolded protein response annotation kept in this review. Reason: Regulation of intracellular signal transduction is entailed by the more specific positive regulation of IRE1-mediated unfolded protein response annotation kept in this review, so the broad term is true of BAK1 but adds nothing. On its own the machine-generated term would not identify what BAK does. |
| GO:1903896 positive regulation of IRE1-mediated unfolded protein response | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | KEEP AS NON CORE | Summary: ER calcium and unfolded-protein-response terms capture secondary BAK/BAX stress biology. Reason: BAK is reported in ER calcium and IRE1/UPR stress contexts, but those rows are peripheral to its core mitochondrial pore-forming apoptotic function. |
| GO:2001233 regulation of apoptotic signaling pathway | IEA GO_REF:0000117 | MODIFY | Summary: Broad apoptotic-signaling regulation should be tightened to MOMP. Reason: The ARBA row captures the correct apoptosis branch only generically; BAK directly permeabilizes the mitochondrial outer membrane. Proposed replacements: mitochondrial outer membrane permeabilization |
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Download this section (compressed HTML)Q: Should GO add a BAK/BAX-specific molecular function term for BH3-triggered mitochondrial outer-membrane permeabilizing pore assembly, instead of using the broader channel or porin activity terms?
Q: Should legacy BAK annotations to mitochondrial permeability-transition-pore terms be systematically retired in favor of BAK complex and mitochondrial outer membrane permeabilization terms?
Experiment: For peripheral BAK contexts such as ER calcium control, UPR signaling, and chaperone binding, reconstitute BAK-defined cells and measure BAK conformational activation, BAK oligomerization, MOMP, cytochrome-c release, and the proposed non-mitochondrial readout in parallel.
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