{"gene":"NAB1","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":1995,"finding":"NAB1 was identified as a transcriptional corepressor that physically interacts with the inhibitory domain of NGFI-A (Egr-1) and Krox20, repressing their transcriptional activity, but does not affect Egr3 or NGFI-G, thus providing differential regulation within the Egr family.","method":"Yeast two-hybrid interaction screen, transcriptional repression assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — original discovery paper with direct protein-protein interaction assay and functional transcriptional repression assay, highly cited and replicated","pmids":["7624335"],"is_preprint":false},{"year":1998,"finding":"NAB1 represses transcription through an active repression mechanism localized to the conserved NCD2 domain in its C-terminus; it does not block DNA binding or nuclear localization of NGFI-A, and its repression is not activator-specific. A bipartite-like nuclear localization sequence was identified. Replacement mutagenesis of residues conserved with corepressors Dr1 and E1b 55-kDa protein within NCD2 interfered with NAB1 repression.","method":"Domain deletion/replacement mutagenesis, tethered repression assays, nuclear localization analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple mutagenesis experiments with functional readouts, mechanistic dissection with controls, highly cited","pmids":["9418898"],"is_preprint":false},{"year":2000,"finding":"The inhibitory domain of Egr-1 serves as a docking site for NAB1 via protein-protein interaction, bringing NAB1 into proximity of the transcription unit to repress transcription; a GAL4-NAB1 fusion protein represses transcription from both proximal and distal positions, demonstrating intrinsic repressor activity independent of position.","method":"Fusion protein transcriptional repression assays, co-expression overexpression studies, GAL4-tethered repression","journal":"Biochimica et biophysica acta","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal functional assays in human cell lines, consistent with prior foundational work","pmids":["11018254"],"is_preprint":false},{"year":2001,"finding":"Aspirin-triggered lipoxin A4 analog (ATLa) rapidly upregulates NAB1 gene expression in human neutrophils via a G protein-coupled receptor pathway, as demonstrated by pertussis toxin blockade of ATLa-induced NAB1 upregulation.","method":"Differential display RT-PCR, pertussis toxin inhibition assay, in vivo murine lung model","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 — functional pathway placement via pharmacological inhibitor, but single lab study","pmids":["11687510"],"is_preprint":false},{"year":2011,"finding":"Valproic acid suppresses IL-1β-induced mPGES-1 expression in chondrocytes by inducing NAB1 expression and its recruitment to the mPGES-1 promoter; NAB1 silencing with siRNA blocked this suppressive effect, placing NAB1 as a mediator of Egr-1 inhibition at the mPGES-1 promoter.","method":"Chromatin immunoprecipitation, siRNA knockdown, Western blotting, promoter-reporter assays","journal":"The Journal of rheumatology","confidence":"Medium","confidence_rationale":"Tier 2 — ChIP and siRNA knockdown with defined promoter-level readout, single lab","pmids":["21239760"],"is_preprint":false},{"year":2025,"finding":"A novel protein NAB1-356, encoded by circNAB1, interacts with EGR1 (as full-length NAB1 does) and also regulates Runx1 and Gadd45b transcription, reducing atrial fibrosis and inflammation; circNAB1 overexpression reduced AF susceptibility in transgenic mice.","method":"CircRNA sequencing, transgenic mouse model, protein-protein interaction assay, functional overexpression/silencing assays","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 — multiple functional assays and in vivo model, but single lab and novel protein","pmids":["40145839"],"is_preprint":false}],"current_model":"NAB1 is a nuclear transcriptional corepressor that is recruited to Egr-family transcription factors (primarily NGFI-A/Egr-1 and Krox20) via protein-protein interaction with their inhibitory domain, and represses transcription through an active mechanism localized to its conserved NCD2 domain, operating independently of blocking DNA binding; its expression is regulated by lipid mediators and histone deacetylase inhibitors, and it functions at specific gene promoters (e.g., mPGES-1) to modulate inflammation-related transcription."},"narrative":{"teleology":[{"year":1995,"claim":"Identification of NAB1 as an Egr-family corepressor resolved how NGFI-A and Krox20 transcriptional activity is negatively modulated through their inhibitory domains, while establishing selectivity within the Egr family (no interaction with Egr3).","evidence":"Yeast two-hybrid screen and transcriptional repression assays","pmids":["7624335"],"confidence":"High","gaps":["Mechanism of repression (passive vs. active) was not determined","No mapping of the repression domain within NAB1","In vivo relevance not tested"]},{"year":1998,"claim":"Dissection of NAB1 domain architecture established that repression is an active, NCD2-dependent mechanism independent of blocking DNA binding or nuclear entry, resolving the question of how NAB1 silences transcription after being recruited to Egr targets.","evidence":"Systematic deletion and replacement mutagenesis with tethered repression assays and nuclear localization analysis","pmids":["9418898"],"confidence":"High","gaps":["Identity of downstream effectors recruited by NCD2 (e.g., histone deacetylases, chromatin remodelers) was not determined","Structural basis of NCD2-mediated repression unknown"]},{"year":2000,"claim":"Demonstration that GAL4-NAB1 represses transcription from both proximal and distal promoter positions confirmed that NAB1 harbors intrinsic repressor activity independent of its Egr-docking mechanism, strengthening the model that Egr-1's inhibitory domain serves solely as a recruitment platform.","evidence":"GAL4-tethered repression and co-expression assays in human cell lines","pmids":["11018254"],"confidence":"High","gaps":["Native chromatin context not examined","Genome-wide target repertoire unknown"]},{"year":2001,"claim":"Discovery that aspirin-triggered lipoxin A4 rapidly induces NAB1 expression through a pertussis toxin-sensitive GPCR pathway placed NAB1 within anti-inflammatory lipid mediator signaling, revealing an upstream regulatory input.","evidence":"Differential display RT-PCR with pertussis toxin blockade in human neutrophils and in vivo murine lung model","pmids":["11687510"],"confidence":"Medium","gaps":["Specific GPCR identity not established","Downstream Egr-dependent gene targets in neutrophils not characterized","Single-lab finding without independent replication"]},{"year":2011,"claim":"Showing that valproic acid induces NAB1 recruitment to the mPGES-1 promoter and that siRNA knockdown of NAB1 abolishes suppression of mPGES-1 provided the first direct chromatin-level evidence of NAB1 functioning at a specific endogenous inflammatory gene locus.","evidence":"Chromatin immunoprecipitation, siRNA knockdown, and promoter-reporter assays in IL-1β-stimulated chondrocytes","pmids":["21239760"],"confidence":"Medium","gaps":["Whether NAB1 directly or indirectly modulates histone modifications at the mPGES-1 locus was not tested","Generalizability to other Egr-1 target promoters not demonstrated","Single-lab finding"]},{"year":2025,"claim":"Identification of a circNAB1-encoded protein (NAB1-356) that interacts with EGR1 and regulates Runx1/Gadd45b transcription to reduce atrial fibrosis extended the NAB1 functional paradigm to circular RNA-derived products with in vivo cardioprotective roles.","evidence":"CircRNA sequencing, transgenic mouse overexpression model, protein-protein interaction and functional assays","pmids":["40145839"],"confidence":"Medium","gaps":["Relationship between NAB1-356 and full-length NAB1 repressor activity is unclear","Whether NAB1-356 uses the NCD2 mechanism is not established","Single-lab finding with a novel protein requiring independent confirmation"]},{"year":null,"claim":"The cofactors and chromatin-modifying complexes recruited by the NCD2 repression domain remain unidentified, and no genome-wide map of NAB1 occupancy at endogenous loci exists.","evidence":"","pmids":[],"confidence":"High","gaps":["No proteomic identification of NCD2-interacting effectors","No ChIP-seq or CUT&RUN genome-wide occupancy data","No structural model of NAB1 or NAB1-Egr complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,2,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3]}],"complexes":[],"partners":["EGR1","EGR2"],"other_free_text":[]},"mechanistic_narrative":"NAB1 is a nuclear transcriptional corepressor that physically interacts with the inhibitory domain of Egr-family transcription factors (specifically NGFI-A/Egr-1 and Krox20, but not Egr3) to repress their transcriptional activity [PMID:7624335]. Repression is mediated by an active mechanism localized to the conserved NCD2 domain in the C-terminus and does not operate by blocking DNA binding or nuclear localization; NAB1 possesses intrinsic, position-independent repressor activity when tethered to a promoter [PMID:9418898, PMID:11018254]. NAB1 expression is induced by lipid mediators such as aspirin-triggered lipoxin A4 via G protein-coupled receptor signaling and by histone deacetylase inhibitors such as valproic acid, and NAB1 is recruited to specific target promoters (e.g., mPGES-1) to suppress Egr-1-dependent inflammatory gene expression [PMID:11687510, PMID:21239760]."},"prefetch_data":{"uniprot":{"accession":"Q13506","full_name":"NGFI-A-binding protein 1","aliases":["EGR-1-binding protein 1","Transcriptional regulatory protein p54"],"length_aa":487,"mass_kda":54.4,"function":"Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q13506/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NAB1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NAB1","total_profiled":1310},"omim":[{"mim_id":"602381","title":"NGFIA-BINDING PROTEIN 2; NAB2","url":"https://www.omim.org/entry/602381"},{"mim_id":"600800","title":"NGFIA-BINDING PROTEIN; NAB1","url":"https://www.omim.org/entry/600800"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NAB1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q13506","domains":[{"cath_id":"1.10.150","chopping":"8-81","consensus_level":"high","plddt":93.1492,"start":8,"end":81},{"cath_id":"1.20.120.2010","chopping":"192-318","consensus_level":"high","plddt":89.6042,"start":192,"end":318}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13506","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13506-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13506-F1-predicted_aligned_error_v6.png","plddt_mean":64.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NAB1","jax_strain_url":"https://www.jax.org/strain/search?query=NAB1"},"sequence":{"accession":"Q13506","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13506.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13506/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13506"}},"corpus_meta":[{"pmid":"7624335","id":"PMC_7624335","title":"Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription.","date":"1995","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7624335","citation_count":240,"is_preprint":false},{"pmid":"11018254","id":"PMC_11018254","title":"The human transcriptional repressor protein NAB1: expression and biological activity.","date":"2000","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/11018254","citation_count":99,"is_preprint":false},{"pmid":"16284312","id":"PMC_16284312","title":"NAB1 is an RNA binding protein involved in the light-regulated differential expression of the light-harvesting antenna of Chlamydomonas reinhardtii.","date":"2005","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/16284312","citation_count":98,"is_preprint":false},{"pmid":"9418898","id":"PMC_9418898","title":"Nab1, a corepressor of NGFI-A (Egr-1), contains an active transcriptional repression domain.","date":"1998","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9418898","citation_count":97,"is_preprint":false},{"pmid":"22231427","id":"PMC_22231427","title":"NAB-1 instructs synapse assembly by linking adhesion molecules and F-actin to active zone proteins.","date":"2012","source":"Nature neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22231427","citation_count":71,"is_preprint":false},{"pmid":"11687510","id":"PMC_11687510","title":"Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.","date":"2001","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/11687510","citation_count":50,"is_preprint":false},{"pmid":"21239760","id":"PMC_21239760","title":"Valproic acid suppresses interleukin-1ß-induced microsomal prostaglandin E2 synthase-1 expression in chondrocytes through upregulation of NAB1.","date":"2011","source":"The Journal of rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/21239760","citation_count":12,"is_preprint":false},{"pmid":"12030330","id":"PMC_12030330","title":"Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies.","date":"2002","source":"Neurogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/12030330","citation_count":8,"is_preprint":false},{"pmid":"34113174","id":"PMC_34113174","title":"Ubenimex Suppresses the Ability of Migration and Invasion in Gastric Cancer Cells by Alleviating the Activity of the CD13/NAB1/MAPK Pathway.","date":"2021","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/34113174","citation_count":8,"is_preprint":false},{"pmid":"40145839","id":"PMC_40145839","title":"A Novel Protein NAB1-356 Encoded by circRNA circNAB1 Mitigates Atrial Fibrillation by Reducing Inflammation and Fibrosis.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40145839","citation_count":7,"is_preprint":false},{"pmid":"38814199","id":"PMC_38814199","title":"N6-Methyladenosine modified circ-NAB1 modulates cell cycle and epithelial-mesenchymal transition via CDKN3 in endometrial cancer.","date":"2024","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/38814199","citation_count":4,"is_preprint":false},{"pmid":"25919092","id":"PMC_25919092","title":"Solution structure of the RNA-binding cold-shock domain of the Chlamydomonas reinhardtii NAB1 protein and insights into RNA recognition.","date":"2015","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/25919092","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7485,"output_tokens":1447,"usd":0.02208},"stage2":{"model":"claude-opus-4-6","input_tokens":4685,"output_tokens":3625,"usd":0.171075},"total_usd":0.193155,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1995,\n      \"finding\": \"NAB1 was identified as a transcriptional corepressor that physically interacts with the inhibitory domain of NGFI-A (Egr-1) and Krox20, repressing their transcriptional activity, but does not affect Egr3 or NGFI-G, thus providing differential regulation within the Egr family.\",\n      \"method\": \"Yeast two-hybrid interaction screen, transcriptional repression assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — original discovery paper with direct protein-protein interaction assay and functional transcriptional repression assay, highly cited and replicated\",\n      \"pmids\": [\"7624335\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"NAB1 represses transcription through an active repression mechanism localized to the conserved NCD2 domain in its C-terminus; it does not block DNA binding or nuclear localization of NGFI-A, and its repression is not activator-specific. A bipartite-like nuclear localization sequence was identified. Replacement mutagenesis of residues conserved with corepressors Dr1 and E1b 55-kDa protein within NCD2 interfered with NAB1 repression.\",\n      \"method\": \"Domain deletion/replacement mutagenesis, tethered repression assays, nuclear localization analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple mutagenesis experiments with functional readouts, mechanistic dissection with controls, highly cited\",\n      \"pmids\": [\"9418898\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The inhibitory domain of Egr-1 serves as a docking site for NAB1 via protein-protein interaction, bringing NAB1 into proximity of the transcription unit to repress transcription; a GAL4-NAB1 fusion protein represses transcription from both proximal and distal positions, demonstrating intrinsic repressor activity independent of position.\",\n      \"method\": \"Fusion protein transcriptional repression assays, co-expression overexpression studies, GAL4-tethered repression\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal functional assays in human cell lines, consistent with prior foundational work\",\n      \"pmids\": [\"11018254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Aspirin-triggered lipoxin A4 analog (ATLa) rapidly upregulates NAB1 gene expression in human neutrophils via a G protein-coupled receptor pathway, as demonstrated by pertussis toxin blockade of ATLa-induced NAB1 upregulation.\",\n      \"method\": \"Differential display RT-PCR, pertussis toxin inhibition assay, in vivo murine lung model\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional pathway placement via pharmacological inhibitor, but single lab study\",\n      \"pmids\": [\"11687510\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Valproic acid suppresses IL-1β-induced mPGES-1 expression in chondrocytes by inducing NAB1 expression and its recruitment to the mPGES-1 promoter; NAB1 silencing with siRNA blocked this suppressive effect, placing NAB1 as a mediator of Egr-1 inhibition at the mPGES-1 promoter.\",\n      \"method\": \"Chromatin immunoprecipitation, siRNA knockdown, Western blotting, promoter-reporter assays\",\n      \"journal\": \"The Journal of rheumatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP and siRNA knockdown with defined promoter-level readout, single lab\",\n      \"pmids\": [\"21239760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A novel protein NAB1-356, encoded by circNAB1, interacts with EGR1 (as full-length NAB1 does) and also regulates Runx1 and Gadd45b transcription, reducing atrial fibrosis and inflammation; circNAB1 overexpression reduced AF susceptibility in transgenic mice.\",\n      \"method\": \"CircRNA sequencing, transgenic mouse model, protein-protein interaction assay, functional overexpression/silencing assays\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple functional assays and in vivo model, but single lab and novel protein\",\n      \"pmids\": [\"40145839\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NAB1 is a nuclear transcriptional corepressor that is recruited to Egr-family transcription factors (primarily NGFI-A/Egr-1 and Krox20) via protein-protein interaction with their inhibitory domain, and represses transcription through an active mechanism localized to its conserved NCD2 domain, operating independently of blocking DNA binding; its expression is regulated by lipid mediators and histone deacetylase inhibitors, and it functions at specific gene promoters (e.g., mPGES-1) to modulate inflammation-related transcription.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NAB1 is a nuclear transcriptional corepressor that physically interacts with the inhibitory domain of Egr-family transcription factors (specifically NGFI-A/Egr-1 and Krox20, but not Egr3) to repress their transcriptional activity [PMID:7624335]. Repression is mediated by an active mechanism localized to the conserved NCD2 domain in the C-terminus and does not operate by blocking DNA binding or nuclear localization; NAB1 possesses intrinsic, position-independent repressor activity when tethered to a promoter [PMID:9418898, PMID:11018254]. NAB1 expression is induced by lipid mediators such as aspirin-triggered lipoxin A4 via G protein-coupled receptor signaling and by histone deacetylase inhibitors such as valproic acid, and NAB1 is recruited to specific target promoters (e.g., mPGES-1) to suppress Egr-1-dependent inflammatory gene expression [PMID:11687510, PMID:21239760].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Identification of NAB1 as an Egr-family corepressor resolved how NGFI-A and Krox20 transcriptional activity is negatively modulated through their inhibitory domains, while establishing selectivity within the Egr family (no interaction with Egr3).\",\n      \"evidence\": \"Yeast two-hybrid screen and transcriptional repression assays\",\n      \"pmids\": [\"7624335\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism of repression (passive vs. active) was not determined\",\n        \"No mapping of the repression domain within NAB1\",\n        \"In vivo relevance not tested\"\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Dissection of NAB1 domain architecture established that repression is an active, NCD2-dependent mechanism independent of blocking DNA binding or nuclear entry, resolving the question of how NAB1 silences transcription after being recruited to Egr targets.\",\n      \"evidence\": \"Systematic deletion and replacement mutagenesis with tethered repression assays and nuclear localization analysis\",\n      \"pmids\": [\"9418898\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of downstream effectors recruited by NCD2 (e.g., histone deacetylases, chromatin remodelers) was not determined\",\n        \"Structural basis of NCD2-mediated repression unknown\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstration that GAL4-NAB1 represses transcription from both proximal and distal promoter positions confirmed that NAB1 harbors intrinsic repressor activity independent of its Egr-docking mechanism, strengthening the model that Egr-1's inhibitory domain serves solely as a recruitment platform.\",\n      \"evidence\": \"GAL4-tethered repression and co-expression assays in human cell lines\",\n      \"pmids\": [\"11018254\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Native chromatin context not examined\",\n        \"Genome-wide target repertoire unknown\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Discovery that aspirin-triggered lipoxin A4 rapidly induces NAB1 expression through a pertussis toxin-sensitive GPCR pathway placed NAB1 within anti-inflammatory lipid mediator signaling, revealing an upstream regulatory input.\",\n      \"evidence\": \"Differential display RT-PCR with pertussis toxin blockade in human neutrophils and in vivo murine lung model\",\n      \"pmids\": [\"11687510\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific GPCR identity not established\",\n        \"Downstream Egr-dependent gene targets in neutrophils not characterized\",\n        \"Single-lab finding without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showing that valproic acid induces NAB1 recruitment to the mPGES-1 promoter and that siRNA knockdown of NAB1 abolishes suppression of mPGES-1 provided the first direct chromatin-level evidence of NAB1 functioning at a specific endogenous inflammatory gene locus.\",\n      \"evidence\": \"Chromatin immunoprecipitation, siRNA knockdown, and promoter-reporter assays in IL-1β-stimulated chondrocytes\",\n      \"pmids\": [\"21239760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NAB1 directly or indirectly modulates histone modifications at the mPGES-1 locus was not tested\",\n        \"Generalizability to other Egr-1 target promoters not demonstrated\",\n        \"Single-lab finding\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of a circNAB1-encoded protein (NAB1-356) that interacts with EGR1 and regulates Runx1/Gadd45b transcription to reduce atrial fibrosis extended the NAB1 functional paradigm to circular RNA-derived products with in vivo cardioprotective roles.\",\n      \"evidence\": \"CircRNA sequencing, transgenic mouse overexpression model, protein-protein interaction and functional assays\",\n      \"pmids\": [\"40145839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relationship between NAB1-356 and full-length NAB1 repressor activity is unclear\",\n        \"Whether NAB1-356 uses the NCD2 mechanism is not established\",\n        \"Single-lab finding with a novel protein requiring independent confirmation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cofactors and chromatin-modifying complexes recruited by the NCD2 repression domain remain unidentified, and no genome-wide map of NAB1 occupancy at endogenous loci exists.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No proteomic identification of NCD2-interacting effectors\",\n        \"No ChIP-seq or CUT&RUN genome-wide occupancy data\",\n        \"No structural model of NAB1 or NAB1-Egr complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0074160\", \"supporting_discovery_ids\": [0, 1, 2, 4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"EGR1\",\n      \"EGR2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway term_id. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"NAB1 is a nuclear transcriptional corepressor that physically interacts with the inhibitory domain of Egr-family transcription factors (specifically NGFI-A/Egr-1 and Krox20, but not Egr3) to repress their transcriptional activity [PMID:7624335]. Repression is mediated by an active mechanism localized to the conserved NCD2 domain in the C-terminus and does not operate by blocking DNA binding or nuclear localization; NAB1 possesses intrinsic, position-independent repressor activity when tethered to a promoter [PMID:9418898, PMID:11018254]. NAB1 expression is induced by lipid mediators such as aspirin-triggered lipoxin A4 via G protein-coupled receptor signaling and by histone deacetylase inhibitors such as valproic acid, and NAB1 is recruited to specific target promoters (e.g., mPGES-1) to suppress Egr-1-dependent inflammatory gene expression [PMID:11687510, PMID:21239760].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Identification of NAB1 as an Egr-family corepressor resolved how NGFI-A and Krox20 transcriptional activity is negatively modulated through their inhibitory domains, while establishing selectivity within the Egr family (no interaction with Egr3).\",\n      \"evidence\": \"Yeast two-hybrid screen and transcriptional repression assays\",\n      \"pmids\": [\"7624335\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism of repression (passive vs. active) was not determined\",\n        \"No mapping of the repression domain within NAB1\",\n        \"In vivo relevance not tested\"\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Dissection of NAB1 domain architecture established that repression is an active, NCD2-dependent mechanism independent of blocking DNA binding or nuclear entry, resolving the question of how NAB1 silences transcription after being recruited to Egr targets.\",\n      \"evidence\": \"Systematic deletion and replacement mutagenesis with tethered repression assays and nuclear localization analysis\",\n      \"pmids\": [\"9418898\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of downstream effectors recruited by NCD2 (e.g., histone deacetylases, chromatin remodelers) was not determined\",\n        \"Structural basis of NCD2-mediated repression unknown\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstration that GAL4-NAB1 represses transcription from both proximal and distal promoter positions confirmed that NAB1 harbors intrinsic repressor activity independent of its Egr-docking mechanism, strengthening the model that Egr-1's inhibitory domain serves solely as a recruitment platform.\",\n      \"evidence\": \"GAL4-tethered repression and co-expression assays in human cell lines\",\n      \"pmids\": [\"11018254\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Native chromatin context not examined\",\n        \"Genome-wide target repertoire unknown\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Discovery that aspirin-triggered lipoxin A4 rapidly induces NAB1 expression through a pertussis toxin-sensitive GPCR pathway placed NAB1 within anti-inflammatory lipid mediator signaling, revealing an upstream regulatory input.\",\n      \"evidence\": \"Differential display RT-PCR with pertussis toxin blockade in human neutrophils and in vivo murine lung model\",\n      \"pmids\": [\"11687510\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific GPCR identity not established\",\n        \"Downstream Egr-dependent gene targets in neutrophils not characterized\",\n        \"Single-lab finding without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showing that valproic acid induces NAB1 recruitment to the mPGES-1 promoter and that siRNA knockdown of NAB1 abolishes suppression of mPGES-1 provided the first direct chromatin-level evidence of NAB1 functioning at a specific endogenous inflammatory gene locus.\",\n      \"evidence\": \"Chromatin immunoprecipitation, siRNA knockdown, and promoter-reporter assays in IL-1β-stimulated chondrocytes\",\n      \"pmids\": [\"21239760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NAB1 directly or indirectly modulates histone modifications at the mPGES-1 locus was not tested\",\n        \"Generalizability to other Egr-1 target promoters not demonstrated\",\n        \"Single-lab finding\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of a circNAB1-encoded protein (NAB1-356) that interacts with EGR1 and regulates Runx1/Gadd45b transcription to reduce atrial fibrosis extended the NAB1 functional paradigm to circular RNA-derived products with in vivo cardioprotective roles.\",\n      \"evidence\": \"CircRNA sequencing, transgenic mouse overexpression model, protein-protein interaction and functional assays\",\n      \"pmids\": [\"40145839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relationship between NAB1-356 and full-length NAB1 repressor activity is unclear\",\n        \"Whether NAB1-356 uses the NCD2 mechanism is not established\",\n        \"Single-lab finding with a novel protein requiring independent confirmation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cofactors and chromatin-modifying complexes recruited by the NCD2 repression domain remain unidentified, and no genome-wide map of NAB1 occupancy at endogenous loci exists.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No proteomic identification of NCD2-interacting effectors\",\n        \"No ChIP-seq or CUT&RUN genome-wide occupancy data\",\n        \"No structural model of NAB1 or NAB1-Egr complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 2, 4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"EGR1\",\n      \"EGR2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}