ATF3 is a human stress-inducible ATF/CREB-family bZIP transcription factor. Its basic region and leucine zipper support sequence-specific binding to CRE/ATF-like cis-regulatory DNA and homo- or heterodimerization with other bZIP factors. Canonical full-length ATF3 acts primarily as a nuclear RNA polymerase II transcriptional regulator, often repressing ATF-site promoters as a homodimer, while heterodimers and delta-Zip splice isoforms can produce context-dependent transcriptional activation or relief of repression. ATF3 is induced by cellular stress programs including ER stress and integrated stress response signaling and links those inputs to gene-expression outputs in inflammation, apoptosis, antiviral response, and metabolic stress. These pathway effects are important biological contexts, but the conserved core function is partner-dependent transcriptional regulation in the nucleus/chromatin.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
ATF3_FULL_LENGTHATF3_DELTA_ZIP| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: ATF3 is a DNA-binding RNA polymerase II transcription factor. Reason: The bZIP domain, CRE/ATF-site binding, and extensive transcriptional regulation evidence support this as a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of RNA polymerase II transcription is a core ATF3 function for full-length ATF3. Reason: Primary ATF3 studies show that full-length ATF3 represses promoters with ATF sites and that the ATF3 homodimer represses transcription. Supporting Evidence: PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: ATF3 has direct DNA-binding transcription repressor activity. Reason: Full-length ATF3 represses ATF-site promoters and ATF3 homodimers repress transcription, making this a core molecular function of the canonical full-length protein. Supporting Evidence: PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: ATF3 can act as a context-dependent RNA polymerase II transcriptional activator through heterodimers, splice isoforms, and specific target promoters. Reason: Although canonical full-length ATF3 is often a repressor, published evidence and the deep research synthesis support context-dependent activator activity in specific partner, promoter, and isoform contexts, including Jun/ATF3 promoter activation, ATF3-dependent EphA1 promoter activation, and delta-Zip relief of repression. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cell population proliferation is reported in disease and stress contexts but is a broad downstream phenotype. Reason: The deep research and older isoform literature describe ATF3 roles in proliferation and cancer contexts, but this process is an indirect systems-level outcome of transcriptional regulation and should not be treated as core. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: positive regulation of gene expression is directionally consistent with ATF3 biology but is less specific than existing ATF3 transcription-factor annotations. Reason: ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0030968 endoplasmic reticulum unfolded protein response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: endoplasmic reticulum unfolded protein response is a supported stress-response context for ATF3 but not the core molecular function. Reason: ATF3 is induced downstream of ER stress and ISR/ATF4 signaling and regulates stress-response targets. These process terms are useful context, but the conserved core function remains nuclear transcriptional regulation rather than ER-stress sensing itself. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0034198 cellular response to amino acid starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to amino acid starvation is a supported stress-response context for ATF3 but not the core molecular function. Reason: This IEA row is an orthology-transfer context from mouse Atf3, and amino acid starvation is one trigger of the integrated stress response. The reviewed human evidence supports ATF3 as a downstream ISR/eIF2alpha-ATF4 transcriptional effector, but the conserved core function remains nuclear transcriptional regulation rather than amino-acid starvation sensing itself. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara; the GOA row is an amino acid-starvation response annotation transferred from mouse Atf3. file:human/ATF3/ATF3-deep-research-falcon.md Amino acid starvation is interpreted here as an integrated stress response input; recent mechanistic work strengthens a unifying view of ATF3 as a stress-to-transcription coupling factor downstream of ISR/eIF2alpha-ATF4 signaling in multiple contexts. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of RNA polymerase II transcription is supported for specific ATF3 contexts, especially heterodimers and stress-response target promoters. Reason: ATF3 is context-dependent: LRF-1/ATF3 with Jun proteins activates CRE-containing promoters, ATF3 stimulates the EphA1 promoter, and ATF3 supports DR5 transcription during ER-stress/TRAIL sensitization. This is real biology, but it should be interpreted together with ATF3 repressor annotations. Supporting Evidence: PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of the ERK1/ERK2 cascade is not a well-supported direct ATF3 function in the reviewed human evidence. Reason: This IEA transfer may reflect a downstream pathway effect in a specific ortholog/context. The ATF3 review evidence supports transcriptional regulation and stress-response coupling, but not direct negative regulation of ERK signaling as a core annotation. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0005515 protein binding | IPI PMID:10327051 The N-terminal transactivation domain of ATF2 is a target fo... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Same treatment applied to all other GO:0005515 IPI rows in this review. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:18255255 A protein-protein interaction network of transcription facto... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:19164757 ERAD inhibitors integrate ER stress with an epigenetic mecha... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:32911434 A functionally defined high-density NRF2 interactome reveals... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | MARK AS OVER ANNOTATED | Summary: This is a generic protein binding row from interaction data; ATF3 dimerization is real, but this term does not capture the informative function. Reason: ATF3 function depends on bZIP homo- and heterodimerization, and several interaction screens identify ATF3 partners. However, protein binding is too generic for curator use here. Specific dimerization annotations and transcription-factor complex annotations better represent the biologically meaningful interaction function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0042802 identical protein binding | IPI PMID:18255255 A protein-protein interaction network of transcription facto... | MODIFY | Summary: ATF3 homodimerization is well supported, but protein homodimerization activity is the more specific term. Reason: ATF3 forms homodimers that bind ATF/CRE DNA and repress transcription; this dimerization is central to DNA recognition and regulatory output. GO:0042802 is valid but less specific than GO:0042803, which captures the same supported homodimerization activity more directly. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0042802 identical protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: ATF3 homodimerization is well supported, but protein homodimerization activity is the more specific term. Reason: ATF3 forms homodimers that bind ATF/CRE DNA and repress transcription; this dimerization is central to DNA recognition and regulatory output. GO:0042802 is valid but less specific than GO:0042803, which captures the same supported homodimerization activity more directly. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: DNA binding is directionally consistent with ATF3 biology but is less specific than existing ATF3 transcription-factor annotations. Reason: ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: DNA-binding transcription factor activity is directionally consistent with ATF3 biology but is less specific than existing ATF3 transcription-factor annotations. Reason: ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: regulation of DNA-templated transcription is directionally consistent with ATF3 biology but is less specific than existing ATF3 transcription-factor annotations. Reason: ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: sequence-specific double-stranded DNA binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: nucleoplasm localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleolus localization is reported in immunofluorescence data but is not the primary site of ATF3 transcription-factor action. Reason: The core supported localization is nucleus/nucleoplasm/chromatin. Nucleolus may be a detected subnuclear localization, but the reviewed literature does not make it central to ATF3 function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:7515060 ATF3 and ATF3 delta Zip. Transcriptional repression versus a... | ACCEPT | Summary: Negative regulation of RNA polymerase II transcription is a core ATF3 function for full-length ATF3. Reason: Primary ATF3 studies show that full-length ATF3 represses promoters with ATF sites and that the ATF3 homodimer represses transcription. Supporting Evidence: PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0005634 nucleus | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005634 nucleus | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005634 nucleus | NAS PMID:28186491 Combinatorial bZIP dimers display complex DNA-binding specif... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005634 nucleus | IDA PMID:7515060 ATF3 and ATF3 delta Zip. Transcriptional repression versus a... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005634 nucleus | NAS PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:28186491 Combinatorial bZIP dimers display complex DNA-binding specif... | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: ATF3 regulates RNA polymerase II transcription as a nuclear bZIP transcription factor. Reason: This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | NAS PMID:1406655 Interactions among LRF-1, JunB, c-Jun, and c-Fos define a re... | ACCEPT | Summary: Positive regulation of RNA polymerase II transcription is supported for specific ATF3 contexts, especially heterodimers and stress-response target promoters. Reason: ATF3 is context-dependent: LRF-1/ATF3 with Jun proteins activates CRE-containing promoters, ATF3 stimulates the EphA1 promoter, and ATF3 supports DR5 transcription during ER-stress/TRAIL sensitization. This is real biology, but it should be interpreted together with ATF3 repressor annotations. Supporting Evidence: PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0005634 nucleus | EXP PMID:12034827 An alternatively spliced isoform of transcriptional represso... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:24939851 Role of activating transcription factor 3 (ATF3) in endoplas... | KEEP AS NON CORE | Summary: response to endoplasmic reticulum stress is a supported stress-response context for ATF3 but not the core molecular function. Reason: ATF3 is induced downstream of ER stress and ISR/ATF4 signaling and regulates stress-response targets. These process terms are useful context, but the conserved core function remains nuclear transcriptional regulation rather than ER-stress sensing itself. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:24939851 Role of activating transcription factor 3 (ATF3) in endoplas... | ACCEPT | Summary: Positive regulation of RNA polymerase II transcription is supported for specific ATF3 contexts, especially heterodimers and stress-response target promoters. Reason: ATF3 is context-dependent: LRF-1/ATF3 with Jun proteins activates CRE-containing promoters, ATF3 stimulates the EphA1 promoter, and ATF3 supports DR5 transcription during ER-stress/TRAIL sensitization. This is real biology, but it should be interpreted together with ATF3 repressor annotations. Supporting Evidence: PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | REMOVE | Summary: This CHOP/GADD153 review does not directly support the ATF3 annotation. Reason: The cited reference reviews CHOP/GADD153 roles in ER stress and does not provide direct evidence that ATF3 negatively regulates transcription by RNA polymerase II. ATF3 repression is well supported by other primary ATF3 papers, but this specific TAS-supported row should not be retained on this citation. Supporting Evidence: PMID:14685163 we summarize the current understanding of the roles of CHOP/GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0042803 protein homodimerization activity | IPI PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: ATF3 homodimerization/identical protein binding is an expected bZIP transcription-factor property. Reason: ATF3 forms homodimers that bind ATF/CRE DNA and repress transcription; this dimerization is central to DNA recognition and regulatory output. Supporting Evidence: PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISS PMID:18308734 Fibronectin type I repeat is a nonactivating ligand for EphA... | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS PMID:18308734 Fibronectin type I repeat is a nonactivating ligand for EphA... | ACCEPT | Summary: ATF3 can act as a context-dependent RNA polymerase II transcriptional activator through heterodimers, splice isoforms, and specific target promoters. Reason: Although canonical full-length ATF3 is often a repressor, published evidence and the deep research synthesis support context-dependent activator activity in specific partner, promoter, and isoform contexts, including Jun/ATF3 promoter activation, ATF3-dependent EphA1 promoter activation, and delta-Zip relief of repression. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS PMID:18308734 Fibronectin type I repeat is a nonactivating ligand for EphA... | ACCEPT | Summary: Positive regulation of RNA polymerase II transcription is supported for specific ATF3 contexts, especially heterodimers and stress-response target promoters. Reason: ATF3 is context-dependent: LRF-1/ATF3 with Jun proteins activates CRE-containing promoters, ATF3 stimulates the EphA1 promoter, and ATF3 supports DR5 transcription during ER-stress/TRAIL sensitization. This is real biology, but it should be interpreted together with ATF3 repressor annotations. Supporting Evidence: PMID:1406655 LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. PMID:18308734 ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | MODIFY | Summary: ATF3 sequence-specific RNA polymerase II regulatory DNA binding is well supported, but the more specific cis-regulatory-region child term is preferable. Reason: ATF3 contains a basic region/leucine zipper domain and binds ATF/CRE-like cis-regulatory DNA. GO:0000977 is a valid parent, but GO:0000978 captures the same supported activity more specifically and is already represented in the review. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: ATF3 has direct DNA-binding transcription repressor activity. Reason: Full-length ATF3 represses ATF-site promoters and ATF3 homodimers repress transcription, making this a core molecular function of the canonical full-length protein. Supporting Evidence: PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: sequence-specific double-stranded DNA binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:16300731 ATF5 increases cisplatin-induced apoptosis through up-regula... | REMOVE | Summary: This citation is for an ATF5 study, not an ATF3 study. Reason: The original publication title and abstract concern ATF5-mediated Cyclin D3 transcription and cisplatin-induced apoptosis. It does not provide direct evidence for ATF3 enabling transcription activator activity or positively regulating RNA polymerase II transcription. Supporting Evidence: PMID:16300731 ATF5 transcription factor plays an essential role in hematopoietic and glioma cell survival and neuronal cell differentiation |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin localization is consistent with ATF3 promoter/enhancer binding as a transcription factor. Reason: ATF3 binding is analyzed by promoter binding, ChIP, and bZIP DNA-binding studies; chromatin is therefore an appropriate active cellular context. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: ATF3 is a DNA-binding RNA polymerase II transcription factor. Reason: The bZIP domain, CRE/ATF-site binding, and extensive transcriptional regulation evidence support this as a core molecular function. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:24939851 Role of activating transcription factor 3 (ATF3) in endoplas... | ACCEPT | Summary: transcription cis-regulatory region binding is well supported for ATF3 as a bZIP transcription factor that binds ATF/CRE-like cis-regulatory DNA. Reason: ATF3 contains a basic region/leucine zipper domain, binds ATF/CRE-like regulatory DNA, and its in vivo binding specificity is shaped by ATF3-containing homo- and heterodimers. This is a core molecular function, but the PMID:24939851 source row appears to support cis-regulatory involvement mainly by reporter/knockdown evidence rather than a direct binding assay, so its IDA evidence code should be checked at source. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:24939851 A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0003700 DNA-binding transcription factor activity | IGI PMID:24939851 Role of activating transcription factor 3 (ATF3) in endoplas... | MODIFY | Summary: DNA-binding transcription factor activity is directionally consistent with ATF3 biology but is less specific than existing ATF3 transcription-factor annotations. Reason: ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:1903984 positive regulation of TRAIL-activated apoptotic signaling pathway | IMP PMID:24939851 Role of activating transcription factor 3 (ATF3) in endoplas... | KEEP AS NON CORE | Summary: ATF3 promotes TRAIL-mediated apoptosis in a specific ER-stress/cancer-cell context through DR5 induction. Reason: This experimentally supported pathway effect is real, but it is a downstream context-specific consequence of ATF3 transcriptional regulation rather than the conserved core function of the gene product. Supporting Evidence: PMID:24939851 we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells |
| GO:1990622 CHOP-ATF3 complex | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: The CHOP-ATF3 complex annotation is supported by direct ATF3-CHOP/GADD153 interaction evidence. Reason: The cited primary study reports a gadd153/Chop10 heterodimer with ATF3. The complex is biologically informative even though that heterodimer is nonfunctional for ATF/CRE DNA binding and repression. Supporting Evidence: PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: Negative regulation of RNA polymerase II transcription is a core ATF3 function for full-length ATF3. Reason: Primary ATF3 studies show that full-length ATF3 represses promoters with ATF sites and that the ATF3 homodimer represses transcription. Supporting Evidence: PMID:7515060 ATF3 represses rather than activates transcription from promoters with ATF sites PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0005634 nucleus | IDA PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: nucleus localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0046982 protein heterodimerization activity | IPI PMID:8622660 Analysis of ATF3, a transcription factor induced by physiolo... | ACCEPT | Summary: ATF3 heterodimerization is a core property that determines DNA specificity and transcriptional output. Reason: ATF3-containing heterodimers with bZIP partners are repeatedly documented; partner choice changes DNA-binding specificity and can switch regulatory output. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. PMID:8622660 ATF3-interacting protein gadd153/Chop10 forms a nonfunctional heterodimer with ATF3; the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:2516827 Transcription factor ATF cDNA clones: an extensive family of... | MODIFY | Summary: ATF3 sequence-specific RNA polymerase II regulatory DNA binding is well supported, but the more specific cis-regulatory-region child term is preferable. Reason: ATF3 contains a basic region/leucine zipper domain and binds ATF/CRE-like cis-regulatory DNA. GO:0000977 is a valid parent, but GO:0000978 captures the same supported activity more specifically and is already represented in the review. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:2516827 some, but not all, combinations of ATF proteins form heterodimers that efficiently bind to DNA PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16300731 ATF5 increases cisplatin-induced apoptosis through up-regula... | REMOVE | Summary: This citation is for an ATF5 study, not an ATF3 study. Reason: The original publication title and abstract concern ATF5-mediated Cyclin D3 transcription and cisplatin-induced apoptosis. It does not provide direct evidence for ATF3 enabling transcription activator activity or positively regulating RNA polymerase II transcription. Supporting Evidence: PMID:16300731 ATF5 transcription factor plays an essential role in hematopoietic and glioma cell survival and neuronal cell differentiation |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9653893 | ACCEPT | Summary: nucleoplasm localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9909594 | ACCEPT | Summary: nucleoplasm localization is consistent with ATF3 acting as a nuclear transcription factor. Reason: ATF3 is reported as a nuclear protein and experimentally studied as a promoter/chromatin-associated transcription factor. Nucleus and nucleoplasm are appropriate cellular component annotations for the active gene product. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:12034827 ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MARK AS OVER ANNOTATED | Summary: ComplexPortal-derived part_of annotation citing a high-throughput bZIP interaction screen; ATF3 dimerization is real but this row is downstream of a generic PPI dataset and does not specifically demonstrate stable transcription-regulator-complex assembly. Reason: GO:0090575 is intended for multi-subunit RNA polymerase II transcription regulator complexes (e.g., Mediator, SAGA, NuRD). The cited IPI source (a coiled-coil array screen of viral bZIP partners) tests pairwise bZIP-bZIP dimerization, which is already captured at the molecular function level (homodimer/heterodimer DNA-binding TF activity) and through specific bZIP partner annotations. The same PMID is treated as MARK_AS_OVER_ANNOTATED for its GO:0005515 protein binding row in this review, for the same reason. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MARK AS OVER ANNOTATED | Summary: ComplexPortal-derived part_of annotation citing a high-throughput bZIP interaction network; the underlying screen tests pairwise bZIP dimerization rather than complex assembly with the broader Pol II transcription machinery. Reason: GO:0090575 is intended for multi-subunit RNA polymerase II transcription regulator complexes (e.g., Mediator, SAGA, NuRD). The cited IPI source is a billion-year evolutionary bZIP PPI network screen, identifying pairwise bZIP-bZIP partners that are already captured at the MF level (homodimer/heterodimer DNA-binding TF activity). The same PMID is treated as MARK_AS_OVER_ANNOTATED for its GO:0005515 protein binding row in this review, for the same reason. Supporting Evidence: file:human/ATF3/ATF3-deep-research-falcon.md Human ATF3 is best annotated as a stress-inducible nuclear bZIP transcription factor that binds CRE-like motifs and acts via partner-dependent dimerization to remodel transcriptional programs across stress, immunity, metabolism, and cell fate. PMID:28186491 Genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. |
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Download this section (compressed HTML)Q: Should ATF3 delta-Zip isoforms receive isoform-specific GO annotations that distinguish cofactor-sequestration/relief-of-repression activity from canonical full-length DNA-binding transcription factor activity?
Suggested experts: Tsonwin Hai, Shigetaka Kitajima
Q: Can the ATF3 protein-binding rows from high-throughput interaction screens be replaced by specific bZIP dimerization or transcription-factor complex annotations where the partner and mechanism are clear?
Q: Should annotations citing PMID:16300731 and PMID:14685163 be corrected at source because the former is an ATF5 paper and the latter is a CHOP/GADD153 ER-stress review without direct ATF3 evidence?
Q: Should the GOA source row for GO:0000976 citing PMID:24939851 be reviewed for evidence-code accuracy, since the cached abstract supports ATF3-dependent DR5 reporter transcription but not a direct ATF3 binding assay?
Q: Should the GOA rows using ISS with PMID:18308734 be reviewed for evidence-code accuracy, since the publication directly studies ATF3-dependent EphA1 promoter activation rather than inferring function from sequence or structural similarity?
Experiment: Express individual ATF3 isoforms in matched cells and assay ATF/CRE and target-promoter reporters, paired with DNA-binding-defective and leucine-zipper-defective controls.
Hypothesis: Full-length ATF3 and delta-Zip ATF3 isoforms have distinct GO-relevant transcriptional activities.
Type: Isoform-specific reporter assay
Experiment: Profile ATF3 occupancy after perturbing JUN, JUNB, ATF4, DDIT3/CHOP, and selected C/EBP partners, then compare motifs and target gene regulation.
Hypothesis: ATF3 genomic binding specificity depends on its bZIP dimerization partner.
Type: CUT&RUN or ChIP-seq with partner perturbation
Experiment: Validate candidate ATF3 interactors with reciprocal co-immunoprecipitation, DNA-bound complex assays, and reporter readouts to separate specific bZIP dimerization from nonspecific protein-binding evidence.
Hypothesis: Only a subset of high-throughput ATF3 interaction partners represent biologically meaningful transcription-factor dimers.
Type: Focused interaction validation
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