BID encodes a BH3-only BCL2-family apoptosis regulator that is held in an inactive, mostly cytosolic full-length form until initiator or executioner caspases expose C-terminal tBID fragments. tBID moves to mitochondrial membranes and uses its BH3 helix to engage BAX and BAK, promoting their oligomeric mitochondrial outer-membrane permeabilization pore, cytochrome-c release, and downstream apoptotic caspase activation. BID therefore links death-receptor signaling, CASP6 feed-forward amplification, and stress-induced mitochondrial apoptosis, while alternative human isoforms and binding to proteins such as ITCH, Humanin, CAV1, and PLEKHN1 tune that pro-apoptotic activity in more restricted contexts.
Definition: Binding to a pro-apoptotic BCL2-family effector such as BAX or BAK to promote the conformational activation and oligomerization that drives apoptotic mitochondrial outer membrane permeabilization.
Justification: BID and other direct activator BH3-only proteins donate a BH3 helix that activates BAX/BAK, but GO:0051434 BH3 domain binding annotates the groove-containing protein that recognizes a BH3 helix. A BID-side molecular-function term would prevent these central interactions from collapsing to GO:0005515 protein binding.
Parent term: molecular function activator activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001836 release of cytochrome c from mitochondria | IDA PMID:17052454 A stapled BID BH3 helix directly binds and activates BAX. | MODIFY | Summary: BID positively regulates cytochrome-c release by activating BAX/BAK rather than itself forming the release pore. Reason: The supported role is tBID-dependent activation of BAX/BAK-dependent MOMP and cytochrome-c release; the release step itself is executed by the BAX/BAK pore. Proposed replacements: positive regulation of release of cytochrome c from mitochondria |
| GO:0001836 release of cytochrome c from mitochondria | IEA GO_REF:0000120 | MODIFY | Summary: BID positively regulates cytochrome-c release by activating BAX/BAK rather than itself forming the release pore. Reason: The supported role is tBID-dependent activation of BAX/BAK-dependent MOMP and cytochrome-c release; the release step itself is executed by the BAX/BAK pore. Proposed replacements: positive regulation of release of cytochrome c from mitochondria |
| GO:0005123 death receptor binding | TAS PMID:8918887 BID: a novel BH3 domain-only death agonist. | REMOVE | Summary: The original cloning paper supports BCL2- and BAX-family binding, not literal death-receptor binding. Reason: PMID:8918887 used receptor language for membrane-bound BAX in a BCL2-family model; BID is cleaved downstream of FAS/CASP8 but is not a receptor ligand for FAS, TNF, or TRAIL death receptors. |
| GO:0005515 protein binding | IPI PMID:12624108 Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:12624108 Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion... | MODIFY | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID acts as a BH3-only direct activator of BAK/BAX-family effectors. GO lacks a directionally correct BID-side molecular-function term, so this BAK row should move to the proposed effector-activator activity instead of remaining generic protein binding. Proposed replacements: pro-apoptotic BCL2 family effector activator activity Supporting Evidence: PMID:12624108 Bcl-2 diminished Bid-induced oligomerization of Bax and Bak |
| GO:0005515 protein binding | IPI PMID:14963330 Direct activation of Bax by p53 mediates mitochondrial membr... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:15694340 Differential targeting of prosurvival Bcl-2 proteins by thei... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:15694340 Differential targeting of prosurvival Bcl-2 proteins by thei... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:15694340 Differential targeting of prosurvival Bcl-2 proteins by thei... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17052454 A stapled BID BH3 helix directly binds and activates BAX. | MODIFY | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID acts as a BH3-only direct activator of BAK/BAX-family effectors. GO lacks a directionally correct BID-side molecular-function term, so this BAX row should move to the proposed effector-activator activity instead of remaining generic protein binding. Proposed replacements: pro-apoptotic BCL2 family effector activator activity Supporting Evidence: PMID:17052454 BID directly engages BAX to trigger mitochondrial apoptosis |
| GO:0005515 protein binding | IPI PMID:17123957 Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bc... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:17485524 Functional and structural studies of the vaccinia virus viru... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:19074266 Mechanism of apoptosis induction by inhibition of the anti-a... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:19074266 Mechanism of apoptosis induction by inhibition of the anti-a... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:19074440 Endophilin B1/Bif-1 stimulates BAX activation independently ... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:20956295 Autophagy protein microtubule-associated protein 1 light cha... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:21036904 Heterodimerization of BAK and MCL-1 activated by detergent m... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:23374347 Bax crystal structures reveal how BH3 domains activate Bax a... | MODIFY | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID acts as a BH3-only direct activator of BAK/BAX-family effectors. GO lacks a directionally correct BID-side molecular-function term, so this BAX row should move to the proposed effector-activator activity instead of remaining generic protein binding. Proposed replacements: pro-apoptotic BCL2 family effector activator activity Supporting Evidence: PMID:23374347 they can activate Bax via its groove |
| GO:0005515 protein binding | IPI PMID:23604079 BID-induced structural changes in BAK promote apoptosis. | MODIFY | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID acts as a BH3-only direct activator of BAK/BAX-family effectors. GO lacks a directionally correct BID-side molecular-function term, so this BAK row should move to the proposed effector-activator activity instead of remaining generic protein binding. Proposed replacements: pro-apoptotic BCL2 family effector activator activity Supporting Evidence: PMID:23604079 BID activates BAK to perform this function |
| GO:0005515 protein binding | IPI PMID:23782464 BAK multimerization for apoptosis, but not bid binding, is i... | MODIFY | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID acts as a BH3-only direct activator of BAK/BAX-family effectors. GO lacks a directionally correct BID-side molecular-function term, so this BAK row should move to the proposed effector-activator activity instead of remaining generic protein binding. Proposed replacements: pro-apoptotic BCL2 family effector activator activity Supporting Evidence: PMID:23782464 the Bid BH3 sequence interacts with the BAK hydrophobic groove |
| GO:0005515 protein binding | IPI PMID:24814347 The DNA-binding domain mediates both nuclear and cytosolic f... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:29531808 PLEKHN1 promotes apoptosis by enhancing Bax-Bak hetro-oligom... | REMOVE | Summary: BID engages this apoptosis-related partner, but the row asserts only generic protein binding. Reason: BID normally contributes its BH3 helix to BCL2-family regulator or effector complexes; GO:0005515 is uninformative and GO:0051434 BH3 domain binding would annotate the partner groove rather than BID itself. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: This large-scale interactome row asserts only generic BID protein binding. Reason: The high-throughput edge is not an informative molecular-function annotation for BID and should not be retained as GO:0005515. |
| GO:0005515 protein binding | IPI PMID:9463381 The conserved N-terminal BH4 domain of Bcl-2 homologues is e... | UNDECIDED | Summary: The IntAct import reports generic BID protein binding, but the exact partner-specific assay is not fully recoverable from the cached source. Reason: Do not reject an experimental IPI row from incomplete evidence; however, GO:0005515 is not precise enough to describe a core BID molecular function and no directionally correct replacement term is currently available. |
| GO:0005737 cytoplasm | EXP PMID:14583606 Three novel Bid proteins generated by alternative splicing o... | ACCEPT | Summary: BID localization to cytoplasm is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: BID localization to cytoplasm is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: BID localization to mitochondrion is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: BID localization to mitochondrion is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: BID localization to mitochondrion is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005739 mitochondrion | TAS PMID:9727491 Bid, a Bcl2 interacting protein, mediates cytochrome c relea... | ACCEPT | Summary: BID localization to mitochondrion is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:29531808 PLEKHN1 promotes apoptosis by enhancing Bax-Bak hetro-oligom... | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-114352 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-139895 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-139897 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-139920 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-168848 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-508162 | ACCEPT | Summary: BID localization to mitochondrial outer membrane is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS PMID:8918887 BID: a novel BH3 domain-only death agonist. | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139893 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139898 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139917 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139920 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141367 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168849 | ACCEPT | Summary: BID localization to cytosol is consistent with cytosolic full-length BID and mitochondrial tBID. Reason: Full-length BID is primarily cytosolic, and proteolytic activation produces tBID fragments that associate with mitochondrial membranes during BAX/BAK activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6791291 | ACCEPT | Summary: The Reactome event describes TP53-dependent BID transcription, not BID protein localization. Reason: Cytosol is the established location of full-length BID and is accepted on the IBA, IDA, IEA and other TAS rows for this term, so the claim stands here as well. The Reactome event behind this row describes TP53-dependent transcription of the BID gene; its product, newly made BID protein, is placed by Reactome in the cytosol, which agrees with the experimental rows. The event is not itself a localization experiment, which limits this row's evidence but not the claim. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | TAS PMID:9727491 Bid, a Bcl2 interacting protein, mediates cytochrome c relea... | ACCEPT | Summary: BID relays death-receptor/caspase-8 signals to the mitochondrial BAX/BAK module. Reason: Caspase-8 cleavage of BID is a direct extrinsic-to-mitochondrial amplification step in FAS and TRAIL signaling. |
| GO:0008637 apoptotic mitochondrial changes | IBA GO_REF:0000033 | MODIFY | Summary: The broad mitochondrial-change term can be replaced by BID-positive regulation of MOMP. Reason: tBID activates BAX and BAK upstream of mitochondrial outer membrane permeabilization; GO:1901030 states that regulated mitochondrial step more precisely than GO:0008637. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002860227 · PTN002860227 SUPPORTS TRANSFER The BID-family PAINT node supports a conserved pro-apoptotic mitochondrial role, but positive regulation of MOMP is more precise than the broad apoptotic mitochondrial changes term. |
| GO:0008637 apoptotic mitochondrial changes | TAS PMID:9727492 Cleavage of BID by caspase 8 mediates the mitochondrial dama... | MODIFY | Summary: The broad mitochondrial-change term can be replaced by BID-positive regulation of MOMP. Reason: tBID activates BAX and BAK upstream of mitochondrial outer membrane permeabilization; GO:1901030 states that regulated mitochondrial step more precisely than GO:0008637. |
| GO:0016020 membrane | IEA GO_REF:0000107 | MODIFY | Summary: The membrane row is too general for BID mitochondrial membrane recruitment. Reason: Activated tBID associates with the mitochondrial outer membrane during apoptotic BAX/BAK activation; the specific mitochondrial outer-membrane location is more informative than generic membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0016020 membrane | TAS PMID:8918887 BID: a novel BH3 domain-only death agonist. | MODIFY | Summary: The membrane row is too general for BID mitochondrial membrane recruitment. Reason: Activated tBID associates with the mitochondrial outer membrane during apoptotic BAX/BAK activation; the specific mitochondrial outer-membrane location is more informative than generic membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:19074440 Endophilin B1/Bif-1 stimulates BAX activation independently ... | MODIFY | Summary: This row represents tBID-dependent BAX/BAK assembly rather than generic complex assembly. Reason: BID promotes assembly of BAX/BAK effector complexes that permeabilize the mitochondrial outer membrane; the more informative process consequence is positive regulation of apoptotic MOMP. |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | MODIFY | Summary: This row represents tBID-dependent BAX/BAK assembly rather than generic complex assembly. Reason: BID promotes assembly of BAX/BAK effector complexes that permeabilize the mitochondrial outer membrane; the more informative process consequence is positive regulation of apoptotic MOMP. |
| GO:0031334 positive regulation of protein-containing complex assembly | IEA GO_REF:0000107 | MODIFY | Summary: This row represents tBID-dependent BAX/BAK assembly rather than generic complex assembly. Reason: BID promotes assembly of BAX/BAK effector complexes that permeabilize the mitochondrial outer membrane; the more informative process consequence is positive regulation of apoptotic MOMP. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The imported row captures ITCH-dependent ubiquitin-ligase binding of cleaved BID. Reason: ITCH binding controls ubiquitination and degradation of tBID, which tunes BID abundance rather than representing the core BAX/BAK activation function. |
| GO:0031966 mitochondrial membrane | EXP PMID:14583606 Three novel Bid proteins generated by alternative splicing o... | MODIFY | Summary: The mitochondrial membrane row should be narrowed to the outer mitochondrial membrane. Reason: BID/tBID functions on the mitochondrial outer membrane with BAX, BAK, and anti-apoptotic BCL2-family partners rather than generically at either mitochondrial membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0031966 mitochondrial membrane | EXP PMID:9727491 Bid, a Bcl2 interacting protein, mediates cytochrome c relea... | MODIFY | Summary: The mitochondrial membrane row should be narrowed to the outer mitochondrial membrane. Reason: BID/tBID functions on the mitochondrial outer membrane with BAX, BAK, and anti-apoptotic BCL2-family partners rather than generically at either mitochondrial membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000120 | MODIFY | Summary: The mitochondrial membrane row should be narrowed to the outer mitochondrial membrane. Reason: BID/tBID functions on the mitochondrial outer membrane with BAX, BAK, and anti-apoptotic BCL2-family partners rather than generically at either mitochondrial membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0031966 mitochondrial membrane | ISS GO_REF:0000024 | MODIFY | Summary: The mitochondrial membrane row should be narrowed to the outer mitochondrial membrane. Reason: BID/tBID functions on the mitochondrial outer membrane with BAX, BAK, and anti-apoptotic BCL2-family partners rather than generically at either mitochondrial membrane. Proposed replacements: mitochondrial outer membrane |
| GO:0033554 cellular response to stress | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This ARBA-derived process parent is too generic for BID. Reason: The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This ARBA-derived process parent is too generic for BID. Reason: The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. |
| GO:0042770 signal transduction in response to DNA damage | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | UNDECIDED | Summary: The cached source is a broad review and does not expose direct primary evidence for a BID DNA-damage signaling function. Reason: Because PMID:18309324 is review/abstract-level support in the cache, leave this row undecided rather than treating DNA-damage signaling as a verified BID activity. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro parent apoptosis-regulation row is too broad for BID. Reason: A BID-family/BH3-domain match supports direct positive regulation of the BAX/BAK MOMP step rather than undirected regulation of apoptosis. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000120 | MODIFY | Summary: BID is a direct positive regulator of apoptotic MOMP rather than a generic positive apoptosis regulator. Reason: The supporting evidence centers on BH3-dependent activation of BAX/BAK and cytochrome-c release; GO:1901030 captures that direct step. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | MODIFY | Summary: BID is a direct positive regulator of apoptotic MOMP rather than a generic positive apoptosis regulator. Reason: The supporting evidence centers on BH3-dependent activation of BAX/BAK and cytochrome-c release; GO:1901030 captures that direct step. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:21525171 Bortezomib primes glioblastoma, including glioblastoma stem ... | MODIFY | Summary: BID supports bortezomib/TRAIL-induced mitochondrial apoptosis in glioblastoma. Reason: The paper places tBID stabilization in a TRAIL death-receptor context, so positive regulation of extrinsic apoptotic signaling is more specific than generic positive regulation of apoptosis. Proposed replacements: positive regulation of extrinsic apoptotic signaling pathway |
| GO:0051402 neuron apoptotic process | TAS PMID:16167175 Inhibition of mitochondrial neural cell death pathways by pr... | UNDECIDED | Summary: The neuron-specific row is only weakly exposed by the cached abstract. Reason: PMID:16167175 is cached as abstract-only and discusses BCL2-family protein transduction in neural protection broadly, without direct BID evidence for a neuron-specific apoptotic step. |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000107 | MODIFY | Summary: The Ensembl row represents BAX/BAK-family assembly in apoptotic MOMP. Reason: Generic protein-containing complex assembly should be narrowed to the apoptotic mitochondrial permeabilization event assembled downstream of BID. |
| GO:0090150 establishment of protein localization to membrane | IDA PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | MODIFY | Summary: BID-dependent protein localization to membrane is a BAX/BAK activation readout. Reason: The supported event is activator BH3-driven BAX/BAK mitochondrial recruitment and assembly during apoptotic MOMP; GO:1901030 captures the BID-regulated MOMP step more directly than a generic localization term. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IBA GO_REF:0000033 | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IDA PMID:32029622 An AMPK-caspase-6 axis controls liver damage in nonalcoholic... | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IEA GO_REF:0000120 | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IGI PMID:21041309 BH3 domains other than Bim and Bid can directly activate Bax... | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IMP PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h... | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IMP PMID:21262771 MK-STYX, a catalytically inactive phosphatase regulating mit... | ACCEPT | Summary: BID positively regulates mitochondrial cytochrome-c release. Reason: Cleaved BID stimulates BAX/BAK-dependent mitochondrial outer membrane permeabilization, increasing cytochrome-c release in death-receptor, intrinsic, and CASP6 feed-forward contexts. |
| GO:0097284 hepatocyte apoptotic process | IDA PMID:32029622 An AMPK-caspase-6 axis controls liver damage in nonalcoholic... | KEEP AS NON CORE | Summary: CASP6-cleaved BID contributes to hepatocyte apoptosis in the NASH feed-forward loop. Reason: The hepatocyte row is supported by the CASP6/NASH model but is a disease-tissue specialization of BID activation rather than the core evolved molecular role. |
| GO:0097435 supramolecular fiber organization | IDA PMID:33106313 Humanin selectively prevents the activation of pro-apoptotic... | MARK AS OVER ANNOTATED | Summary: Humanin sequesters BID into amyloid-like fibers as an inhibitory interaction. Reason: The fiber is induced by Humanin and prevents BID activation; the row is not wholly unrelated but overstates BID as an organizer of a supramolecular-fiber program. |
| GO:1902531 regulation of intracellular signal transduction | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This ARBA-derived process parent is too generic for BID. Reason: The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. |
| GO:2001233 regulation of apoptotic signaling pathway | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA apoptosis-signaling parent can be narrowed to BID activation of intrinsic signaling. Reason: BID acts at the BCL2-family branch point that amplifies intrinsic mitochondrial apoptotic signaling; the signed descendant captures the supported direction. |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: BID positively regulates death-receptor extrinsic apoptosis by linking CASP8 to mitochondrial MOMP. Reason: The supported extrinsic context is specifically FAS/TRAIL death-receptor signaling through CASP8 cleavage of BID, so GO:1902043 is more precise than the broader extrinsic apoptotic signaling term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002860227 · PTN002860227 SUPPORTS TRANSFER The BID-family PAINT node supports conserved positive regulation of death-receptor-driven apoptosis, but the death-domain-receptor descendant captures BID's CASP8-to-MOMP relay more precisely. Proposed replacements: positive regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IMP PMID:21459798 Bortezomib primes neuroblastoma cells for TRAIL-induced apop... | MODIFY | Summary: BID positively regulates death-receptor extrinsic apoptosis by linking CASP8 to mitochondrial MOMP. Reason: The supported extrinsic context is specifically FAS/TRAIL death-receptor signaling through CASP8 cleavage of BID, so GO:1902043 is more precise than the broader extrinsic apoptotic signaling term. Proposed replacements: positive regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: BID activates the mitochondrial MOMP arm of intrinsic apoptotic signaling. Reason: The direct BID-regulated step is BAX/BAK mitochondrial outer membrane permeabilization, so GO:1901030 is more precise than the broader intrinsic apoptotic signaling term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002860227 · PTN002860227 SUPPORTS TRANSFER The BID-family PAINT node supports a conserved pro-apoptotic mitochondrial role, but positive regulation of MOMP is more precise than the broader intrinsic apoptotic signaling term. |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | IMP PMID:21262771 MK-STYX, a catalytically inactive phosphatase regulating mit... | MODIFY | Summary: BID activates the mitochondrial MOMP arm of intrinsic apoptotic signaling. Reason: The direct BID-regulated step is BAX/BAK mitochondrial outer membrane permeabilization, so GO:1901030 is more precise than the broader intrinsic apoptotic signaling term. |
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Download this section (compressed HTML)Q: Should GO add a molecular-function term for direct activator BH3-only proteins such as tBID and BIM, distinct from GO:0051434 BH3 domain binding, which describes the BAX/BAK or pro-survival BCL2-family groove that recognizes a BH3 helix?
Q: Should BID isoforms be curated separately when a source assays BID(EL), BID(S), or BID(ES), given that BID(S) lacks the BH3 domain and antagonizes tBID while BID(ES) has mixed pro- and anti-apoptotic behavior?
Experiment: For contextual BID interactors such as CAV1, PLEKHN1, and large interactome hits, map whether the partner binds full-length BID or tBID, test whether the interaction changes caspase cleavage, membrane recruitment, or BAX/BAK activation directly, and separate those proximal readouts from final viability or caspase-3 cleavage.
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