Tp53 (rat; UniProt P10361) encodes cellular tumor antigen p53, a conserved p53-family, sequence-specific DNA-binding transcription factor that acts as the central node of the cellular stress response and as a tumor suppressor ("guardian of the genome"). p53 has a modular architecture (N-terminal transactivation domains, proline-rich region, central sequence-specific DNA-binding domain, and an oligomerization/tetramerization domain); the active protein assembles into homotetramers that bind p53 response elements in target gene promoters/enhancers. In response to diverse stresses (notably DNA damage, but also oxidative stress, hypoxia, ribosomal/nucleolar stress and oncogene activation), p53 is stabilized β chiefly by escape from MDM2/MDM4-mediated ubiquitination β and drives transcriptional programs governing cell-cycle arrest (via CDKN1A/p21), apoptosis (via PUMA, BAX, NOXA), DNA repair and senescence. p53 also induces MDM2, forming an autoregulatory negative-feedback loop. It functions predominantly as a nuclear transcription factor but also has transcription-independent cytoplasmic/mitochondrial pro-apoptotic actions. The core, conserved function captured here is sequence-specific DNA-binding transcription factor activity coupled to the DNA-damage/stress response; the vast catalog of downstream tissue- and stimulus-specific responses in the GOA set reflects p53's pleiotropy rather than additional distinct molecular functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core, defining molecular function of p53. As a sequence-specific DNA-binding transcription factor, p53 binds p53 response elements and modulates RNA polymerase II transcription of stress-response target genes. Phylogenetic (IBA) inference is sound and corroborated by the deep research. Reason: Core molecular function of p53, universally applicable across p53-family orthologs and strongly supported by literature. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Tp53 encodes p53, a sequence-specific DNA-binding transcription factor** that acts as a central stress-response node and tumor suppressor file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IBA GO_REF:0000033 | ACCEPT | Summary: p53 is the canonical mediator of the intrinsic (mitochondrial) apoptotic pathway following DNA damage, transactivating PUMA, BAX and NOXA. This is a core p53 process and is the most specific GO term capturing p53-dependent DNA-damage apoptosis. Reason: Core, p53-specific biological process; well-supported phylogenetic inference. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042981 regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: p53 regulates apoptosis, but this generic term is subsumed by the far more specific and informative p53-mediated intrinsic apoptosis terms (GO:0042771, GO:0072332, GO:2001242). Retained as non-core because it is correct but not the most informative representation. Reason: Correct but generic; the p53-specific apoptosis terms better capture the core function. |
| GO:1990841 promoter-specific chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: p53 binds promoter/enhancer chromatin at response elements as part of its transcription factor function. Consistent with the core DNA-binding activity. Reason: Supports the core sequence-specific DNA/chromatin-binding function. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: p53 functions predominantly as a nuclear transcription factor where stabilized tetramers bind DNA response elements. This is the core site of action. Reason: Core localization for the transcription factor function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Nuclear:** stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: p53 transactivates target genes (e.g. CDKN1A/p21, MDM2, pro-apoptotic genes) via RNA polymerase II, a core aspect of its transcriptional activator function. Reason: Core function; p53 is a sequence-specific transcriptional activator. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: p53 is located at chromatin where it binds response elements. Consistent with its DNA-binding transcription factor role. Reason: Core localization for the DNA-binding function. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: p53 binds sequence-specific cis-regulatory regions (p53 response elements) of Pol II target genes. This is a precise statement of the core DNA-binding activity. Reason: Core molecular function; precise DNA-binding specificity term. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic parent of the more specific GO:0000978 sequence-specific cis-regulatory binding already annotated. Correct but redundant/less informative. Reason: Correct but generic; superseded by the more specific DNA-binding terms. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic DNA binding; subsumed by the specific sequence-specific DNA binding (GO:0043565) and cis-regulatory binding terms that capture p53's actual specificity. Reason: Correct but uninformatively generic; more specific terms preferred. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Parent of the Pol II-specific term GO:0000981 already annotated as core. Correct but the Pol II-specific child is more informative. Reason: Generic parent of the core MF term GO:0000981. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant nucleus annotation (also asserted by IBA). Core localization. Reason: Core localization; duplicate of the IBA nucleus annotation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: p53 is also present in the cytoplasm, where a stress-stabilized pool can engage mitochondria for transcription-independent apoptosis. Non-core relative to the primary nuclear TF function. Reason: Real but secondary localization; the core function is nuclear. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | MODIFY | Summary: p53's transcription-independent apoptotic action occurs at the outer mitochondrial membrane/cytosolic interface with BCL-2 family proteins, not in the matrix. Matrix localization is not well supported and likely over-annotated from a generic subcellular-location mapping. Reason: Mitochondrial p53 acts at the OMM with BCL-2 proteins, not in the matrix; IEA subcellular-location mapping is too imprecise. [2026-08 SL project sweep] Upgraded from MARK_AS_OVER_ANNOTATED to MODIFY. The prior review named the correct destination in its own text - the outer mitochondrial membrane - but recorded no replacement, leaving the annotation flagged with nowhere to go. GO:0005741 exists and the gene does not currently carry it, so the mis-assignment can be corrected rather than merely noted. This is a wrong-sub-compartment call, not an under-specification one - the SL term is precise and points at the wrong part of the organelle. Proposed replacements: mitochondrial outer membrane |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: ER localization is not a recognized site of p53 function; this IEA subcellular-location mapping likely reflects transient/contextual detection rather than a functional compartment for p53. Reason: Not a recognized functional compartment for p53; imprecise IEA mapping. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosomal p53 has been reported in the context of centrosome-duplication surveillance, but it is a peripheral, non-core localization relative to the nuclear TF function. Reason: Peripheral localization linked to centrosome surveillance; not core. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic transcription regulation; subsumed by the specific Pol II positive/negative regulation terms already annotated. Reason: Correct but generic parent of the more specific Pol II regulation terms. |
| GO:0006915 apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: p53 is a master regulator/inducer of apoptosis. As a bare process term it is generic; the regulatory and p53-specific intrinsic-apoptosis terms are more informative, but apoptosis is genuinely central to p53 biology. Reason: Generic; the p53-mediated intrinsic apoptosis terms capture the core role. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 is activated by and responds to oxidative stress as part of its stress-sensing function. A genuine but downstream/contextual stress response. Reason: One of many specific stress stimuli that activate the core stress response. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: A specific stimulus that can activate p53; downstream/contextual rather than a core molecular function. Reason: Specific stress stimulus; non-core. |
| GO:0009411 response to UV | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: UV is a classic DNA-damaging stimulus that activates p53. A specific instance of the DNA-damage response; non-core as a standalone term. Reason: Specific DNA-damage stimulus; subsumed by the core DNA-damage response. |
| GO:0010165 response to X-ray | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Ionizing radiation (X-ray) activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0016605 PML body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: p53 localizes to PML nuclear bodies, which modulate its acetylation and activation. A real but specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization relevant to p53 regulation; non-core. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 binds the E3 ubiquitin ligase MDM2 (and others), central to its regulation. A meaningful interaction underlying the MDM2 feedback loop, but not the core molecular activity. Reason: Captures MDM2/E3 ligase interaction central to p53 turnover; regulatory, not the core MF. |
| GO:0051053 negative regulation of DNA metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very generic; p53 can negatively regulate DNA replication/synthesis under stress, but this term is uninformative relative to specific checkpoint/repair terms. Reason: Overly generic ARBA-derived term; more specific checkpoint terms preferred. |
| GO:0051262 protein tetramerization | IEA GO_REF:0000002 | ACCEPT | Summary: Active p53 assembles into homotetramers via its oligomerization domain; tetramerization is required for efficient DNA binding and full transactivation. A genuine, mechanistically important molecular feature. Reason: Tetramerization is an experimentally established, functionally required property of p53. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md activated p53 forms tetramers; tetramerization is required for efficient DNA binding and full transactivation |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Hypoxia is one of the stresses that activates p53. A specific stimulus response; non-core. Reason: Specific stress stimulus; non-core. |
| GO:0097190 apoptotic signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Generic apoptotic signaling; subsumed by the p53-specific intrinsic apoptosis terms. Correct but not most informative. Reason: Generic; p53-specific intrinsic apoptosis terms are more informative. |
| GO:0097371 MDM2/MDM4 family protein binding | IEA GO_REF:0000117 | ACCEPT | Summary: p53 binds MDM2/MDM4, the principal negative regulators that control its stability and the autoregulatory feedback loop. A core regulatory interaction of the pathway. Reason: Direct, well-established interaction central to p53 regulation. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md MDM2 ubiquitinylates p53, inhibiting transactivation and promoting nuclear export and degradation; stress disrupts this interaction, stabilizing p53 |
| GO:2001242 regulation of intrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 regulates the intrinsic apoptotic pathway. Consistent with core p53 apoptosis function, though the positive-regulation child term is more specific. Reason: Correct; subsumed by the more specific positive-regulation term GO:2001244. |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Reflects p53 self-association into homo-oligomers/tetramers. Captured more precisely by protein tetramerization (GO:0051262). Generic binding term. Reason: Generic restatement of homotetramerization; protein tetramerization is preferred. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: p53 acts in the nucleoplasm as a transcription factor. Consistent with the core nuclear localization. Reason: Core localization consistent with nuclear TF function. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cytosolic p53 pool exists and contributes to transcription-independent apoptosis. Non-core relative to nuclear function. Reason: Secondary cytosolic localization; non-core. |
| GO:1990841 promoter-specific chromatin binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the IBA promoter-specific chromatin binding annotation. Supports the core DNA-binding function. Reason: Supports core DNA/chromatin-binding function; duplicate of IBA call. |
| GO:0010628 positive regulation of gene expression | IGI PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | MARK AS OVER ANNOTATED | Summary: Very generic positive regulation of gene expression. p53 does activate gene expression, but the specific Pol II transactivation terms are far more informative. The cited paper concerns clusterin/Dickkopf-1/Wnt in amyloid toxicity, a peripheral context. Reason: Generic; subsumed by specific Pol II transactivation terms. |
| GO:0001223 transcription coactivator binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 binds transcriptional coactivators (e.g. p300/CBP) to drive transactivation. A genuine MF supporting the core transcriptional activator function. Reason: Supports transactivation via coactivator recruitment; ancillary to the core DNA-binding MF. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) nucleus annotation. Core localization. Reason: Core localization; duplicate. |
| GO:0140693 molecular condensate scaffold activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: p53 has been reported to undergo phase separation in vitro, but condensate scaffold activity as a physiological function for rat p53 is not well established; ISS transfer is speculative. Reason: Speculative; condensate scaffolding is not an established core function. |
| GO:0140693 molecular condensate scaffold activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the speculative condensate scaffold activity annotation. Reason: Speculative; not an established core function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human TP53 condensate-scaffold annotations are recent IDAs from in vitro phase-separation studies (e.g. PMID:35618207, PMID:36634798); too speculative to transfer as a rat function. |
| GO:0032211 negative regulation of telomere maintenance via telomerase | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 can repress TERT and limit telomerase, linked to senescence. A specific downstream transcriptional-repression output; non-core. Reason: Specific downstream repression output; non-core. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core positive-regulation-of-Pol-II-transcription annotation. Reason: Core function; duplicate of IBA call. |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 transactivates specific miRNAs (e.g. miR-34 family). A specific downstream transcriptional output; non-core. Reason: Specific transcriptional output; non-core. |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the generic DNA-binding TF activity; parent of the core Pol II-specific term. Reason: Generic parent of core MF term GO:0000981. |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent of the specific positive/negative Pol II regulation terms already annotated. Reason: Generic parent term; non-core. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core sequence-specific cis-regulatory DNA-binding annotation. Reason: Core DNA-binding specificity; duplicate of IBA call. |
| GO:0097190 apoptotic signaling pathway | IMP PMID:17998337 p53 initiates apoptosis by transcriptionally targeting the a... | KEEP AS NON CORE | Summary: Experimental (IMP) support that p53 initiates apoptotic signaling by transactivating a target (ARC). Genuine, though the generic term is subsumed by p53-specific intrinsic apoptosis terms. Reason: Generic apoptotic signaling; p53-specific intrinsic apoptosis terms preferred. |
| GO:0005515 protein binding | IPI PMID:11278372 Stabilization and activation of p53 by the coactivator prote... | MARK AS OVER ANNOTATED | Summary: Uninformative 'protein binding'. The underlying interaction (with the coactivator TAFII31) is better captured by transcription coactivator/coregulator binding terms. Reason: Per curation guidelines, bare protein binding is uninformative; specific coactivator-binding terms are preferred. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic positive regulation of gene expression; subsumed by specific Pol II transactivation terms. Reason: Generic; specific Pol II transactivation terms preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence (IDA/IMP, e.g. PMID:20332243, PMID:19160485) is for specific Pol II transactivation events; the generic parent term adds nothing. |
| GO:0045815 transcription initiation-coupled chromatin remodeling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 recruits chromatin remodelers/coactivators during transactivation. A mechanistic detail of transactivation; non-core. Reason: Mechanistic detail of p53 transactivation; non-core. |
| GO:0016605 PML body | IDA PMID:17289031 Subcellular localization of Daxx determines its opposing fun... | KEEP AS NON CORE | Summary: Direct (IDA) localization to PML nuclear bodies. A real but specialized sub-nuclear localization tied to p53 acetylation/activation; non-core. Reason: Specialized sub-nuclear localization; non-core. |
| GO:0071456 cellular response to hypoxia | IEP PMID:17289031 Subcellular localization of Daxx determines its opposing fun... | KEEP AS NON CORE | Summary: Expression-pattern (IEP) evidence linking p53 to hypoxic/ischemic response. A specific stimulus response; non-core. Reason: Specific stress stimulus; non-core. |
| GO:0044325 transmembrane transporter binding | IPI PMID:27013579 Suppressing activity of tributyrin on hepatocarcinogenesis i... | MARK AS OVER ANNOTATED | Summary: The cited study concerns p53-CRM1 interaction and nucleocytoplasmic compartmentalization; CRM1 (XPO1) is an exportin, not a transmembrane transporter. The mapping to transmembrane transporter binding appears mislabeled. Reason: The GO term is mislabeled for this interaction. CRM1/XPO1 is a soluble nuclear export receptor (karyopherin/exportin), not a transmembrane transporter, so the underlying p53-CRM1 nuclear-export interaction (PMID:27013579) does not map to transmembrane transporter binding. |
| GO:0071401 cellular response to triglyceride | IEP PMID:27013579 Suppressing activity of tributyrin on hepatocarcinogenesis i... | KEEP AS NON CORE | Summary: Highly specific contextual stimulus (tributyrin/triglyceride in a hepatocarcinogenesis model). Peripheral to p53's core function. Reason: Narrow contextual stimulus response; non-core. |
| GO:0000785 chromatin | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) chromatin localization. Consistent with core DNA-binding. Reason: Core localization for DNA-binding function; duplicate. |
| GO:2000774 positive regulation of cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 is a master inducer of cellular senescence (via p21 and other effectors). A genuine core-adjacent output of the p53 stress response. Reason: Senescence induction is a canonical p53 output; retained as non-core (one of the major cell-fate programs, captured at the core level via the stress response). Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 coordinates programs that enforce durable arrest and facilitate genomic maintenance |
| GO:0071889 14-3-3 protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with 14-3-3 proteins, modulating its stability/activity. A specific regulatory interaction; non-core. Reason: Specific regulatory protein interaction; non-core. |
| GO:0140677 molecular function activator activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Very generic 'activator activity' term. p53 activates transcription, but this MF term is uninformative relative to its DNA-binding TF activity. Reason: Generic/uninformative MF; specific TF terms preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor rows (EXP/IPI, e.g. PMID:7559631) describe specific activation events; the root-level activator-activity term is uninformative for the rat gene. |
| GO:0090398 cellular senescence | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular senescence is a canonical p53-controlled cell-fate program. A genuine, important downstream output of the p53 stress response. Reason: Major p53 cell-fate program; captured at the core level via the stress response, retained as non-core. |
| GO:0090398 cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) cellular senescence annotation. Reason: Duplicate; major p53 cell-fate program, non-core. |
| GO:0007283 spermatogenesis | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: A Tp53-knockout rat shows testicular atrophy despite normal spermatogonial proliferation. This is a pleiotropic developmental/tissue phenotype, not a core molecular function of p53. Reason: Pleiotropic tissue-level phenotype; non-core. |
| GO:0010165 response to X-ray | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: Experimental support that p53 mediates the X-ray (ionizing radiation) response in rat tissue. A specific instance of the DNA-damage response; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: Context-dependent anti-apoptotic effect reported in the Tp53-knockout rat testis study. p53 is predominantly pro-apoptotic; this opposite-direction effect is context-specific and non-core. Reason: Context-specific anti-apoptotic effect; non-core (p53's core apoptotic role is pro-apoptotic). |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 regulates the cell cycle via p21-mediated arrest. Core-adjacent; the specific checkpoint terms are more informative but this captures a canonical output. Reason: Generic; specific checkpoint/arrest terms preferred. Canonical p53 output. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: p53 represses a subset of target genes (e.g. via repression of survival/cell-cycle genes). Transcriptional repression is a genuine part of the p53 program. Reason: p53 acts as both activator and repressor of Pol II transcription; this is part of the core transcriptional regulator function. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Closely related to the core sequence-specific cis-regulatory DNA-binding function (GO:0000978). Supports the core DNA-binding activity. Reason: Core DNA-binding specificity. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: p53 has sequence-specific repressor activity for a subset of targets. Part of the core transcription factor function (dual activator/repressor). Reason: Core MF; p53 acts as a sequence-specific repressor for some targets. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Experimental support (CELF1/p53 axis, villus atrophy) that p53 suppresses proliferation. A canonical tumor-suppressive output via cell-cycle arrest. Reason: Canonical antiproliferative output; captured at the core level via cell-cycle arrest/stress response. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0051726 regulation of cell cycle | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Experimental (IMP) support for p53 regulation of the cell cycle. Canonical p53 output; generic term subsumed by specific checkpoint terms. Reason: Generic; canonical output, specific checkpoint terms preferred. |
| GO:1903451 negative regulation of G1 to G0 transition | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Specific cell-cycle/quiescence regulatory term. A downstream detail of p53's cell-cycle control; non-core. Reason: Specific cell-cycle regulatory detail; non-core. |
| GO:1902749 regulation of cell cycle G2/M phase transition | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contributes to the G2/M checkpoint. A specific aspect of cell-cycle arrest; non-core relative to the overall arrest program. Reason: Specific checkpoint detail; non-core. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A stress-stabilized p53 pool relocalizes to mitochondria for transcription-independent apoptosis. Real but secondary localization; non-core. Reason: Secondary localization supporting transcription-independent apoptosis; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0036310 ATP-dependent DNA/DNA annealing activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: An in-vitro reannealing/strand-transfer activity reported for the p53 C-terminus. This is an in-vitro biochemical curiosity, not an established in-vivo function, and ISS transfer is weakly supported. Reason: In-vitro-only activity not established as a physiological function; weak ISS support. |
| GO:0036310 ATP-dependent DNA/DNA annealing activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the in-vitro DNA annealing activity. Reason: In-vitro-only activity; not an established physiological function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single early in vitro biochemical IDA (PMID:8183576) with no established physiological role. |
| GO:0140296 general transcription initiation factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contacts general transcription machinery (e.g. TFIID/TBP) during transactivation. A mechanistic interaction supporting the core TF function. Reason: Mechanistic interaction supporting transactivation; ancillary to core MF. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: The specific sequence-specific transcriptional activator activity of p53 for Pol II targets. Together with the repressor activity, this constitutes the core MF. Reason: Core molecular function; p53 is a sequence-specific Pol II transcriptional activator. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Context-dependent anti-apoptotic role transferred by orthology. p53 is predominantly pro-apoptotic; the opposite-direction effect is context-specific and non-core. Reason: Context-specific; p53's core apoptotic role is pro-apoptotic. |
| GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A mechanistic detail of p53-driven transactivation (promoting PIC assembly). Supports the core activator function; non-core as a standalone term. Reason: Mechanistic transactivation detail; non-core. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 intersects with TNF/death-receptor signaling in some contexts. A peripheral cross-talk; non-core. Reason: Peripheral signaling cross-talk; non-core. |
| GO:0001046 core promoter sequence-specific DNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 binds sequence-specific DNA; whether it specifically binds the core promoter (vs distal/proximal response elements) is debatable. Related to the core DNA-binding function but the specific 'core promoter' qualifier may be over-specific. Reason: Related to core DNA-binding; the core-promoter specificity is uncertain. |
| GO:0005813 centrosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Centrosomal localization linked to centrosome-duplication surveillance. Peripheral; non-core. Reason: Peripheral localization; non-core. |
| GO:0005813 centrosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) centrosome localization. Reason: Peripheral localization; non-core; duplicate. |
| GO:0043065 positive regulation of apoptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: p53 is a master positive regulator of apoptosis, transactivating PUMA, BAX and NOXA. This is a canonical core p53 output. Reason: Canonical, well-established pro-apoptotic role; core p53 output. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:10329733 p53 suppresses the activation of the Bcl-2 promoter by the B... | KEEP AS NON CORE | Summary: Direct interaction (IPI) with another Pol II transcription factor (Brn-3a) to modulate the Bcl-2 promoter. A specific cofactor/TF interaction; non-core. Reason: Specific TF-TF interaction; ancillary to the core MF. |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:10329733 p53 suppresses the activation of the Bcl-2 promoter by the B... | ACCEPT | Summary: p53 is part of Pol II transcription regulator complexes at target promoters. Consistent with the core transcription factor function. Reason: Consistent with core TF function; p53 acts within Pol II regulatory complexes. |
| GO:0002244 hematopoietic progenitor cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic tissue/developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. |
| GO:0060218 hematopoietic stem cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. |
| GO:0048539 bone marrow development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic tissue/developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: p53 positively regulates the intrinsic apoptotic pathway. A core p53 apoptosis term, specific to the p53-driven mitochondrial program. Reason: Core p53 apoptosis output; specific and informative. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | IMP PMID:27031958 Nupr1/Chop signal axis is involved in mitochondrion-related ... | ACCEPT | Summary: Experimental (IMP) support for p53 positively regulating intrinsic apoptosis (Nupr1/Chop axis, mitochondrial endothelial apoptosis). Core p53 apoptosis output. Reason: Core p53 apoptosis output; experimentally supported. Supporting Evidence: PMID:27031958 Nupr1/Chop/P53 axis is involved in classical mitochondrial apoptosis caused by METH in endothelial cells |
| GO:0062100 positive regulation of programmed necrotic cell death | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 has been linked to necroptosis/programmed necrosis in some contexts. A specific, less-canonical cell-death output; non-core. Reason: Less-canonical, context-specific cell-death output; non-core. |
| GO:0005667 transcription regulator complex | ISO GO_REF:0000121 | ACCEPT | Summary: p53 functions within transcription regulator complexes at target genes. Consistent with the core TF function. Reason: Consistent with core TF function. |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the MDM2/E3-ligase-binding annotation central to p53 turnover. Reason: Regulatory interaction (MDM2 etc.); non-core; duplicate. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) of the core sequence-specific cis-regulatory DNA-binding annotation. Reason: Core DNA-binding specificity; duplicate. |
| GO:1905856 negative regulation of pentose-phosphate shunt | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 represses TIGAR/G6PD-related metabolism, influencing the pentose-phosphate pathway. A specific metabolic output of p53; non-core. Reason: Specific metabolic output; non-core. |
| GO:0006974 DNA damage response | ISS GO_REF:0000024 | ACCEPT | Summary: The DNA damage response is the central pathway in which p53 acts, linking genotoxic stress to transcriptional reprogramming. This is a core process for p53. Reason: Core pathway role of p53. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0006974 DNA damage response | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core DNA damage response annotation. Reason: Core pathway role; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:1990841 promoter-specific chromatin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) promoter-specific chromatin binding. Supports the core DNA-binding function. Reason: Supports core DNA/chromatin-binding; duplicate. |
| GO:0001094 TFIID-class transcription factor complex binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contacts the TFIID complex during transactivation. A mechanistic interaction supporting the core TF function. Reason: Mechanistic interaction; ancillary to core MF. |
| GO:0009299 mRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic 'mRNA transcription'; subsumed by the specific Pol II regulation terms. Uninformative as a standalone. Reason: Generic; specific Pol II regulation terms preferred. |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the canonical pro-apoptotic regulation annotation. Reason: Canonical core p53 output; duplicate. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core DNA-binding transcription factor activity annotation. Reason: Core molecular function; duplicate of IBA call. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Tp53 encodes p53, a sequence-specific DNA-binding transcription factor** that acts as a central stress-response node and tumor suppressor |
| GO:0003730 mRNA 3'-UTR binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: A reported non-canonical RNA-binding activity (e.g. p53 binding CDK4 mRNA). An in-vitro/non-canonical activity not central to p53 function; weak support. Reason: Non-canonical RNA-binding activity; not an established core function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single IDA (PMID:16213212) for non-canonical mRNA binding; weak grounding for a gene-level molecular function in rat. |
| GO:0034644 cellular response to UV | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: UV is a DNA-damaging stimulus activating p53. Specific instance of the DNA-damage response; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core p53-mediated DNA-damage intrinsic apoptosis annotation. Reason: Core, p53-specific apoptosis process; duplicate. |
| GO:0071479 cellular response to ionizing radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ionizing radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0071480 cellular response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Gamma radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0072331 signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: This is the defining signaling process for p53 (intracellular signaling induced by p53). A core, p53-specific pathway term. Reason: Core, p53-specific signaling process. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: The p53-mediated intrinsic apoptotic signaling pathway. A core, p53-specific apoptosis process. Reason: Core, p53-specific apoptosis process. |
| GO:0072717 cellular response to actinomycin D | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Actinomycin D (a nucleolar/transcription stressor) activates p53. Highly specific stimulus; non-core. Reason: Narrow specific stimulus; non-core. |
| GO:0002039 p53 binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 self-association (and binding to p53-family members). Reflects homotetramerization; captured more precisely by protein tetramerization. Reason: Self/family-binding; subsumed by tetramerization. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Extremely generic cellular component (any protein complex). Uninformative. Reason: Root-level generic CC; uninformative. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor's complex memberships are documented (IDA/IMP, e.g. PMID:9529249) but by specific complexes; the root-level component term conveys nothing. |
| GO:0097718 disordered domain specific binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Reflects p53's intrinsically disordered regions mediating interactions. A generic binding term; non-core. Reason: Generic binding modality; non-core. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) cytoplasm localization (secondary p53 pool). Reason: Secondary localization; non-core; duplicate. |
| GO:0006914 autophagy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 modulates autophagy (context-dependent, both pro- and anti-autophagic). A specific downstream output; non-core. Reason: Specific, context-dependent downstream output; non-core. |
| GO:0042826 histone deacetylase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with HDACs (e.g. in repressive complexes/Sin3). A specific cofactor interaction; non-core. Reason: Specific cofactor interaction; non-core. |
| GO:0045892 negative regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53-mediated transcriptional repression. Part of the core dual activator/repressor function; the Pol II-specific child (GO:0000122) is more informative. Reason: Generic repression term; Pol II-specific child preferred. |
| GO:0060333 type II interferon-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 cross-talks with interferon signaling in some contexts. Peripheral; non-core. Reason: Peripheral signaling cross-talk; non-core. |
| GO:1905587 positive regulation of outer hair cell apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A highly tissue-specific apoptotic output (cochlear outer hair cells). Far downstream/pleiotropic; non-core. Reason: Highly tissue-specific apoptotic output; non-core. |
| GO:0005515 protein binding | IPI PMID:15872011 Polyamine depletion induces nucleophosmin modulating stabili... | MARK AS OVER ANNOTATED | Summary: Uninformative 'protein binding'. The underlying interaction (nucleophosmin/B23 modulating p53) is better captured by a specific binding term. Reason: Bare protein binding is uninformative per curation guidelines. |
| GO:0045471 response to ethanol | IEP PMID:20961644 Activation of p53 enhances apoptosis and insulin resistance ... | KEEP AS NON CORE | Summary: Specific stimulus (alcohol/ethanol in an alcoholic liver disease model). Peripheral contextual stress response; non-core. Reason: Narrow contextual stimulus; non-core. |
| GO:0034614 cellular response to reactive oxygen species | IMP PMID:24817286 Role of reactive oxygen species in p53 activation during cis... | KEEP AS NON CORE | Summary: Experimental support that ROS activate p53 (cisplatin-induced apoptosis in rat mesangial cells). A specific oxidative-stress instance; non-core. Reason: Specific oxidative-stress stimulus; non-core. |
| GO:0032306 regulation of prostaglandin secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A highly specific secretory/physiological output transferred by orthology. Far downstream; non-core. Reason: Specific downstream physiological output; non-core. |
| GO:0090276 regulation of peptide hormone secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific physiological/secretory output transferred by orthology. Far downstream; non-core. Reason: Specific downstream physiological output; non-core. |
| GO:2000871 negative regulation of progesterone secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A very specific endocrine output transferred by orthology. Far downstream; non-core. Reason: Specific endocrine output; non-core. |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) antiproliferative output; canonical tumor-suppressive effect via cell-cycle arrest. Reason: Canonical output captured at core level via cell-cycle arrest; duplicate. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific stress-triggered branch of intrinsic apoptosis. p53 participates in ER-stress apoptosis in some contexts; specific/non-core. Reason: Specific stress-branch of apoptosis; non-core. |
| GO:1900119 positive regulation of execution phase of apoptosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific apoptosis-execution regulatory term. A downstream detail of p53's pro-apoptotic role; non-core. Reason: Specific apoptosis-execution detail; non-core. |
| GO:0007623 circadian rhythm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 cross-talks with the circadian clock in some contexts. Peripheral/pleiotropic; non-core. Reason: Peripheral cross-talk; non-core. |
| GO:0043153 entrainment of circadian clock by photoperiod | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: A very specific circadian-entrainment role transferred by sequence similarity. Far from p53's core function; weakly supported for rat. Reason: Specific circadian role; weak ISS support, not a core p53 function. |
| GO:0043153 entrainment of circadian clock by photoperiod | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the specific circadian-entrainment annotation. Reason: Specific circadian role; not a core p53 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET The mouse donor support is an IMP from a single circadian study (PMID:24051492); a specialised organismal context rather than a core p53 role. PR:P02340 Β· mouse Trp53 (PRO entity) SUPPORTS SOURCE BUT NOT TARGET PRO entity for the mouse p53 protein listed alongside the MGI donor; it points at the same PMID:24051492 evidence, so it is the same source rather than a second one. |
| GO:0048512 circadian behavior | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: A behavioral/organismal circadian phenotype transferred by similarity. Far downstream/pleiotropic; non-core. Reason: Organismal behavioral phenotype; not a core p53 function. |
| GO:0048512 circadian behavior | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the circadian-behavior annotation. Reason: Organismal behavioral phenotype; not a core p53 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET The mouse donor support is an IMP from the same circadian study (PMID:24051492); an organismal behavioural phenotype, not a p53 molecular role. PR:P02340 Β· mouse Trp53 (PRO entity) SUPPORTS SOURCE BUT NOT TARGET PRO entity for the mouse p53 protein listed alongside the MGI donor; same PMID:24051492 evidence, so no independent support. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) of the core DNA-binding transcription factor activity annotation. Reason: Core molecular function; duplicate. |
| GO:0097371 MDM2/MDM4 family protein binding | IPI PMID:23941874 Caveolin-1/PTRF upregulation constitutes a mechanism for med... | ACCEPT | Summary: Direct (IPI) MDM2/MDM4-family binding evidence. Central regulatory interaction; duplicate of the IEA call. Reason: Direct, well-established interaction central to p53 regulation. |
| GO:0005634 nucleus | IDA PMID:17571083 Mutant ubiquitin found in Alzheimer's disease causes neuriti... | ACCEPT | Summary: Direct (IDA) nuclear localization. Core localization for the TF function. Reason: Core localization; direct evidence. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Nuclear:** stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0046677 response to antibiotic | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific xenobiotic/drug stimulus transferred by orthology. Peripheral; non-core. Reason: Specific drug stimulus; non-core. |
| GO:0071456 cellular response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) hypoxia response. Specific stress stimulus; non-core. Reason: Specific stress stimulus; non-core; duplicate. |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A mechanistic step of p53-driven intrinsic apoptosis (cytochrome c release). Supports the core pro-apoptotic role; specific/non-core as a standalone term. Reason: Mechanistic step of intrinsic apoptosis; non-core. |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core p53 positive-regulation-of-intrinsic-apoptosis annotation. Reason: Core p53 apoptosis output; duplicate. |
| GO:0034605 cellular response to heat | IEP PMID:11295070 Hyperthermia-induced apoptosis in two rat yolk sac tumor cel... | KEEP AS NON CORE | Summary: Hyperthermia-induced apoptosis (rat yolk sac tumor lines) linking p53 to heat stress. Specific stimulus; non-core. Reason: Specific stress stimulus; non-core. |
| GO:0010224 response to UV-B | IEP PMID:22559303 Kinetics of GADD45Ξ±, TP53 and CASP3 gene expression in the r... | KEEP AS NON CORE | Summary: UV-B-induced p53/GADD45/CASP3 response in rat lens. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0001221 transcription coregulator binding | IPI PMID:21792911 Analysis of p53 and NF-ΞΊB signaling in modulating the cardio... | KEEP AS NON CORE | Summary: Direct (IPI) interaction with a transcription coregulator (NF-kB context). Supports the core transactivation function via cofactor recruitment. Reason: Cofactor interaction supporting transactivation; ancillary to core MF. |
| GO:0097252 oligodendrocyte apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A highly cell-type-specific apoptotic output. Far downstream/pleiotropic; non-core. Reason: Cell-type-specific apoptotic output; non-core. |
| GO:0097252 oligodendrocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the oligodendrocyte apoptosis annotation. Reason: Cell-type-specific apoptotic output; non-core; duplicate. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53-mediated transcriptional activation. Part of the core activator function; the Pol II-specific term GO:0045944 is more informative. Reason: Generic activation term; Pol II-specific child preferred. |
| GO:0016605 PML body | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) PML body localization. Specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core; duplicate. |
| GO:0016032 viral process | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic 'viral process' transferred by orthology (p53 is targeted by viral oncoproteins). Uninformative/peripheral; non-core. Reason: Generic viral-process term; uninformative for p53's own function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH ROLE CONFLATION Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence is an IMP (PMID:22574148) in a viral-infection setting; the generic viral-process term conflates being a viral target with a p53 function. |
| GO:0030971 receptor tyrosine kinase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific protein interaction transferred by orthology. Peripheral; non-core. Reason: Specific protein interaction; non-core. |
| GO:0048147 negative regulation of fibroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific antiproliferative output. A specific instance of p53's antiproliferative role; non-core. Reason: Cell-type-specific antiproliferative output; non-core. |
| GO:0042149 cellular response to glucose starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 responds to metabolic/nutrient stress (e.g. via AMPK). Specific stress stimulus; non-core. Reason: Specific metabolic stress stimulus; non-core. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the specific TF-TF binding annotation. Reason: Specific TF-TF interaction; ancillary; duplicate. |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic 'enzyme binding'. Uninformative relative to specific interaction terms (e.g. MDM2, HDAC, kinases). Reason: Generic binding term; uninformative. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor row rests on a single IPI (PMID:17805299); specific interaction terms are far more informative than this generic parent. |
| GO:0071466 cellular response to xenobiotic stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic xenobiotic-stress response transferred by orthology. Specific stimulus class; non-core. Reason: Specific stimulus class; non-core. |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 modulates ROS/redox metabolism (context-dependent, both pro- and anti-oxidant). A specific metabolic output; non-core. Reason: Specific metabolic output; non-core. |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent (ISO) of the specific sequence-specific cis-regulatory binding. Subsumed by GO:0000978. Reason: Generic parent of the more specific DNA-binding term. |
| GO:0008104 intracellular protein localization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Very generic process term transferred by orthology. Uninformative. Reason: Generic/uninformative process; not a core p53 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence is an IDA (PMID:16507995) for a specific localisation event, and the GOA rows also cite isoform P04637-4; the generic parent term conveys no function. |
| GO:0008340 determination of adult lifespan | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: An organismal aging/longevity phenotype transferred by orthology. Far downstream/pleiotropic; non-core. Reason: Organismal aging phenotype; non-core. |
| GO:0070245 positive regulation of thymocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific apoptotic output (thymocytes). A classic p53-dependent apoptosis instance, but cell-type-specific; non-core. Reason: Cell-type-specific apoptotic output; non-core. |
| GO:0097371 MDM2/MDM4 family protein binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) MDM2/MDM4 binding. Central regulatory interaction. Reason: Direct interaction central to p53 regulation; duplicate. |
| GO:0090399 replicative senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific senescence subtype. p53 enforces replicative senescence; a downstream instance of the senescence program; non-core. Reason: Specific senescence subtype; non-core. |
| GO:0090403 oxidative stress-induced premature senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific senescence subtype induced by oxidative stress. Downstream instance of the senescence program; non-core. Reason: Specific senescence subtype; non-core. |
| GO:0006983 ER overload response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific ER-stress response transferred by orthology. Specific stimulus; non-core. Reason: Specific stress response; non-core. |
| GO:0042981 regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the generic apoptosis-regulation annotation; subsumed by p53-specific terms. Reason: Generic; p53-specific apoptosis terms preferred; duplicate. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: The DNA-damage-response signaling specifically mediated by p53. A core, p53-specific pathway term integrating DNA damage with p53 signaling. Reason: Core, p53-specific DNA-damage signaling process. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0002020 protease binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific protein interaction transferred by orthology. Peripheral; non-core. Reason: Specific protein interaction; non-core. |
| GO:0051721 protein phosphatase 2A binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific interaction (PP2A regulating p53 phosphorylation). A regulatory interaction; non-core. Reason: Specific regulatory interaction; non-core. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:16330492 Ubiquitin-dependent degradation of p53 protein despite phosp... | KEEP AS NON CORE | Summary: Direct (IPI) E3 ligase binding (acetaminophen-induced p53 degradation context). Captures the MDM2/E3-ligase interaction underlying p53 turnover; non-core. Reason: Regulatory E3-ligase interaction; non-core. |
| GO:0016604 nuclear body | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent of PML body. p53 localizes to nuclear bodies; specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core. |
| GO:0007265 Ras protein signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A signaling cross-talk transferred by orthology (oncogene-induced p53 activation). Peripheral; non-core. Reason: Peripheral signaling cross-talk; non-core. |
| GO:0005515 protein binding | IPI PMID:8389468 Physical and functional interaction between WT1 and p53 prot... | MARK AS OVER ANNOTATED | Summary: Uninformative 'protein binding'. The underlying WT1-p53 interaction is captured better by a specific TF-binding term; the same paper also supports the negative-regulation-of-transcription annotation below. Reason: Bare protein binding is uninformative per curation guidelines. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:8389468 Physical and functional interaction between WT1 and p53 prot... | KEEP AS NON CORE | Summary: Direct (IDA) evidence that p53 represses transcription (WT1/p53 functional interaction). Supports the core dual activator/repressor function; generic term, Pol II-specific child preferred. Reason: Generic repression term; supports core repressor activity, Pol II-specific child preferred. |
| GO:0010332 response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Gamma radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0031571 mitotic G1 DNA damage checkpoint signaling | ISO GO_REF:0000121 | ACCEPT | Summary: p53 enforces the G1 DNA-damage checkpoint (via p21). A specific, mechanistically central output of the p53 DNA-damage response. Reason: A defining, specific p53-mediated checkpoint output of the DNA-damage response. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11278372 Stabilization and activation of p53 by the coactivator prote... | ACCEPT | Summary: Direct (IDA) evidence of p53-driven Pol II transactivation (TAFII31 coactivator). Core transcriptional activator function. Reason: Core function; direct evidence of Pol II transactivation. |
| GO:0051087 protein-folding chaperone binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with chaperones (e.g. HSP90/HSP70) that regulate its folding/stability. A regulatory interaction; non-core. Reason: Specific regulatory chaperone interaction; non-core. |
| GO:0006979 response to oxidative stress | IEP PMID:17600529 Oxidative stress regulates IGF1R expression in vascular smoo... | KEEP AS NON CORE | Summary: Expression-pattern evidence for p53 in oxidative-stress response (IGF1R/HDAC in VSMCs). Specific stress stimulus; non-core. Reason: Specific stress stimulus; non-core. |
| GO:0010038 response to metal ion | IEP PMID:17466256 Apoptosis and inhibition of gap-junctional intercellular com... | KEEP AS NON CORE | Summary: A specific stimulus (platinum complex). Peripheral contextual stress response; non-core. Reason: Specific drug/metal stimulus; non-core. |
| GO:0031000 response to caffeine | IEP PMID:16544096 Activation of p53 signaling initiates apoptotic death in a c... | KEEP AS NON CORE | Summary: A specific stimulus (caffeine, in a Parkinson's-disease cell model). Peripheral; non-core. Reason: Narrow specific stimulus; non-core. |
| GO:0033552 response to vitamin B3 | IEP PMID:17516866 Niacin deficiency alters p53 expression and impairs etoposid... | KEEP AS NON CORE | Summary: Niacin (vitamin B3) deficiency alters p53 expression in rat bone marrow. A specific nutritional stimulus; non-core. Reason: Specific nutritional stimulus; non-core. |
| GO:0043200 response to amino acid | IEP PMID:17542038 Glutamine supplementation prevents exercise-induced neutroph... | KEEP AS NON CORE | Summary: A specific nutritional stimulus (glutamine). Peripheral; non-core. Reason: Specific nutritional stimulus; non-core. |
| GO:0002687 positive regulation of leukocyte migration | IMP PMID:18317410 Inhibition of p53 by pifithrin-alpha reduces myocyte apoptos... | KEEP AS NON CORE | Summary: A specific physiological output (leukocyte transmigration in aged rat hearts, via pifithrin-alpha p53 inhibition). Far downstream/pleiotropic; non-core. Reason: Specific tissue-level physiological output; non-core. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18336558 Effects of chronic treatment with valproate and oxcarbazepin... | KEEP AS NON CORE | Summary: A specific xenobiotic stimulus (valproate/oxcarbazepine). Peripheral; non-core. Reason: Specific xenobiotic stimulus; non-core. |
| GO:0009411 response to UV | IEP PMID:17724205 p53 expression and apoptosis in the lens after ultraviolet r... | KEEP AS NON CORE | Summary: UV-induced p53 expression/apoptosis in the rat lens. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0010165 response to X-ray | IEP PMID:17699727 A novel animal model to investigate fractionated radiotherap... | KEEP AS NON CORE | Summary: Radiotherapy-induced p53/apoptosis in a rat mucositis model. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. |
| GO:0032526 response to retinoic acid | IEP PMID:17962954 Retinoic acid downregulates microRNAs to induce abnormal dev... | KEEP AS NON CORE | Summary: A specific stimulus (retinoic acid in a spina bifida model). Peripheral; non-core. Reason: Specific stimulus; non-core. |
| GO:0034097 response to cytokine | IEP PMID:17651018 IFN-gamma promotes apoptosis of the uterus and placenta in p... | KEEP AS NON CORE | Summary: IFN-gamma-associated apoptosis in pregnant rat uterus/placenta. Specific cytokine stimulus; non-core. Reason: Specific cytokine stimulus; non-core. |
| GO:0045787 positive regulation of cell cycle | IMP PMID:18026139 Activation of the p53-p21(Cip1) pathway is required for CDK2... | KEEP AS NON CORE | Summary: A context-specific positive cell-cycle effect (p53-p21 required for CDK2/S-phase entry in primary rat hepatocytes). p53 canonically arrests the cell cycle; this opposite-direction effect is context-specific and non-core. Reason: Context-specific positive effect; p53's core cell-cycle role is arrest. |
| GO:0048662 negative regulation of smooth muscle cell proliferation | IMP PMID:17659301 Induction of p53 by GKLF is essential for inhibition of prol... | KEEP AS NON CORE | Summary: A cell-type-specific antiproliferative output (VSMCs, via GKLF-induced p53). A specific instance of p53's antiproliferative role; non-core. Reason: Cell-type-specific antiproliferative output; non-core. |
| GO:0055093 response to hyperoxia | IEP PMID:18337831 Hyperbaric oxygen attenuates apoptosis and decreases inflamm... | KEEP AS NON CORE | Summary: A specific oxidative stimulus (hyperbaric oxygen/ischemic wound). Peripheral; non-core. Reason: Specific oxidative stimulus; non-core. |
| GO:1901423 response to benzene | IEP PMID:18093815 Differentially expressed pro- and anti-apoptogenic genes in ... | KEEP AS NON CORE | Summary: A specific xenobiotic stimulus (benzene exposure, lung epithelia). Peripheral; non-core. Reason: Specific xenobiotic stimulus; non-core. |
| GO:0000785 chromatin | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) chromatin localization (bradykinin B2 receptor promoter). Supports the core DNA-binding function. Reason: Core localization for DNA-binding; direct evidence. |
| GO:0005667 transcription regulator complex | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) evidence that p53 acts within a transcription regulator complex (with CREB, KLF-4, CBP on the B2R promoter). Consistent with the core TF function. Reason: Consistent with core TF function; direct evidence. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) evidence of p53 sequence-specific DNA binding at a target promoter. This is the core DNA-binding molecular function. Reason: Core molecular function; direct experimental evidence of sequence-specific DNA binding. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0003682 chromatin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic chromatin binding; subsumed by the specific sequence-specific and promoter-specific binding terms. Reason: Generic; specific DNA/chromatin binding terms preferred. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidifi... | ACCEPT | Summary: Direct functional (IMP) evidence of p53-dependent apoptosis (benzo[a]pyrene-exposed hepatic cells). Core pro-apoptotic role. Reason: Core pro-apoptotic role; experimentally supported. |
| GO:0051453 regulation of intracellular pH | IMP PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidifi... | KEEP AS NON CORE | Summary: A specific output (p53-dependent acidification in the same benzo[a]pyrene study). An unusual/specific downstream effect; non-core. Reason: Specific, unusual downstream effect; non-core. |
| GO:0046982 protein heterodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 can heterodimerize/hetero-oligomerize with family members (p63/p73) or interact with partners. A binding modality; subsumed by tetramerization for the core homo-oligomer. Reason: Binding modality; non-core relative to homotetramerization. |
| GO:0016363 nuclear matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A sub-nuclear localization transferred by orthology. Specialized; non-core. Reason: Specialized sub-nuclear localization; non-core. |
| GO:0065003 protein-containing complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic complex-assembly term (reflects tetramer/complex formation). Uninformative relative to protein tetramerization. Reason: Generic; tetramerization is the informative term. |
| GO:0005515 protein binding | IPI PMID:12464630 A nucleolar mechanism controlling cell proliferation in stem... | MARK AS OVER ANNOTATED | Summary: Uninformative 'protein binding' (nucleolar/nucleophosmin context). Specific interaction terms preferred. Reason: Bare protein binding is uninformative per curation guidelines. |
| GO:1904584 cellular response to polyamine macromolecule | IEP PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition o... | KEEP AS NON CORE | Summary: A specific stimulus (polyamine depletion stabilizing p53 in intestinal epithelium). Peripheral; non-core. Reason: Specific stimulus; non-core. |
| GO:2000279 negative regulation of DNA biosynthetic process | IMP PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition o... | KEEP AS NON CORE | Summary: p53-dependent inhibition of DNA synthesis/proliferation (polyamine-depletion context). A specific instance of p53's antiproliferative/checkpoint role; non-core. Reason: Specific antiproliferative output; non-core. |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) generic DNA binding; subsumed by the specific sequence-specific DNA-binding terms. Reason: Generic; specific DNA-binding terms preferred; duplicate. |
| GO:0005507 copper ion binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: p53 can bind metal ions (zinc is structurally required in the DBD; copper binding has been reported in vitro). Copper binding is not an established physiological function and ISS support is weak. Reason: Copper binding is not an established p53 function (the structurally required metal is zinc); weak ISS support. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) nucleus localization. Core localization. Reason: Core localization; duplicate. |
| GO:0005730 nucleolus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: p53 localizes to the nucleolus in some contexts (nucleolar stress sensing). A specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) cytoplasm localization (secondary pool). Reason: Secondary localization; non-core; duplicate. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) mitochondrion localization (transcription-independent apoptosis). Secondary; non-core. Reason: Secondary localization; non-core; duplicate. |
| GO:0006289 nucleotide-excision repair | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: p53 facilitates nucleotide-excision repair (e.g. via transactivation of repair genes such as DDB2/XPC). A genuine DNA-repair-supporting role downstream of its TF function; non-core. Reason: DNA-repair-supporting role downstream of the core DNA-damage response; non-core. |
| GO:0030308 negative regulation of cell growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A generic antigrowth term; subsumed by the specific cell-cycle-arrest/antiproliferation terms. Canonical tumor-suppressive output. Reason: Generic; specific arrest/antiproliferation terms preferred. |
| GO:0006289 nucleotide-excision repair | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the NER-supporting role. Reason: DNA-repair-supporting role; non-core; duplicate. |
| GO:0005507 copper ion binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the speculative copper-binding annotation. Reason: Not an established p53 function (zinc is the structural metal); weak support. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single in vitro metal-binding IDA (PMID:7824276); zinc, not copper, is p53's established structural metal. |
| GO:0030308 negative regulation of cell growth | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic antigrowth term. Reason: Generic; specific arrest terms preferred; duplicate. |
| GO:0003677 DNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic DNA binding; subsumed by specific terms. Reason: Generic; specific DNA-binding terms preferred; duplicate. |
| GO:0005730 nucleolus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) nucleolus localization (nucleolar stress sensing). Specialized; non-core. Reason: Specialized sub-nuclear localization; non-core; duplicate. |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic transcription-regulation term; subsumed by the specific Pol II terms. Reason: Generic parent; non-core; duplicate. |
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Download this section (compressed HTML)Q: Which of the many tissue- and stimulus-specific p53 responses annotated by orthology (e.g. progesterone secretion, circadian behavior, outer hair cell apoptosis) reflect direct rat Tp53 functions versus transfer artifacts from other mammals?
Q: Is the reported in-vitro ATP-dependent DNA/DNA annealing and copper-ion-binding activity of p53 physiologically relevant in rat, or are these in-vitro artifacts that should not be annotated?
Experiment: ChIP-seq for endogenous p53 in rat cells before and after a defined genotoxic stress (e.g. doxorubicin or ionizing radiation) to define the direct rat p53 cistrome and distinguish direct transcriptional targets from indirect/pleiotropic responses.
Type: ChIP-seq
Experiment: RNA-seq of rat cells with Tp53 knockout versus wild-type under basal and DNA-damage conditions to define the rat p53-dependent transcriptional program (arrest, apoptosis, senescence) and test which annotated downstream processes are p53-dependent in rat.
Type: RNA-seq
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