{"gene":"NAB1","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1995,"finding":"NAB1 was identified as a nuclear protein that interacts with the inhibitory domain of NGFI-A (Egr-1) and represses NGFI-A- and Krox20-mediated transcription, but does not repress Egr3 or NGFI-G, establishing differential regulation of the Egr family.","method":"Yeast two-hybrid screen, transcriptional repression assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — yeast two-hybrid identification replicated in functional transcription assays; foundational paper replicated by multiple subsequent labs","pmids":["7624335"],"is_preprint":false},{"year":1998,"finding":"NAB1 repression does not work by blocking DNA binding or nuclear localization of NGFI-A; instead NAB1 is an active transcriptional repressor whose repression activity is localized to the conserved NCD2 (Nab conserved domain 2) in its C-terminal half. NAB1 tethered directly to DNA represses constitutively active promoters independently of promoter identity, enhancer presence, or distance from the binding site. A bipartite-like nuclear localization sequence was also identified in NAB1.","method":"Replacement mutagenesis of NCD2, DNA-tethered repression assays, nuclear localization mapping","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal methods including mutagenesis and tethered repression assays in a single rigorous study","pmids":["9418898"],"is_preprint":false},{"year":2000,"finding":"The inhibitory domain of Egr-1 (located between the activation domain and zinc finger DNA-binding region) acts as a docking site for NAB1 via protein-protein interaction, bringing NAB1 into proximity of the transcription unit. A GAL4-NAB1 fusion protein repressed transcription from both proximal and distal positions, confirming that NAB1 carries intrinsic transcriptional repressor activity independent of position.","method":"Overexpression studies, GAL4-fusion transcriptional repression assays, transient transfection","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — GAL4-fusion assays with position-independent repression, single lab, two orthogonal functional approaches","pmids":["11018254"],"is_preprint":false},{"year":2001,"finding":"Aspirin-triggered lipoxin A4 analog (ATLa) rapidly up-regulates NAB1 gene expression in human neutrophils via a G protein-coupled receptor pathway, as demonstrated by blockade with pertussis toxin. ATLa also stimulated NAB1 expression in murine lung vascular smooth muscle in vivo.","method":"Differential display RT-PCR, pertussis toxin blockade experiment, in vivo gene expression analysis","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pertussis toxin blockade provides pathway placement, single lab with two complementary experimental contexts (in vitro and in vivo)","pmids":["11687510"],"is_preprint":false},{"year":2011,"finding":"Valproic acid (VA) upregulates NAB1 expression and recruits NAB1 to the mPGES-1 promoter in human chondrocytes, and NAB1 silencing by siRNA blocks VA-mediated suppression of IL-1β-induced mPGES-1 expression, placing NAB1 downstream of VA and upstream of mPGES-1 in this pathway.","method":"Chromatin immunoprecipitation (ChIP), siRNA knockdown, transient transfection/promoter activity assays, Western blotting","journal":"The Journal of rheumatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and siRNA knockdown with defined promoter readout, single lab, multiple orthogonal methods","pmids":["21239760"],"is_preprint":false},{"year":2002,"finding":"Screening of 87 patients with peripheral neuropathies failed to identify any disease-causing mutations in the EGR2-interacting domains or complete coding regions of NAB1, indicating NAB1 mutations are most likely not involved in the pathogenesis of inherited peripheral neuropathies.","method":"Mutation screening of genomic DNA from 87 neuropathy patients","journal":"Neurogenetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic mutation screen across a defined patient cohort; negative result replicated across full coding region","pmids":["12030330"],"is_preprint":false}],"current_model":"NAB1 (NGFI-A-binding protein 1) is a nuclear transcriptional corepressor that interacts via protein-protein contact with the inhibitory domain of Egr family transcription factors (NGFI-A/Egr-1, Krox20/Egr2, NGFI-C) but not all family members (not Egr3), and exerts active, position-independent transcriptional repression through its conserved C-terminal NCD2 domain; its expression is inducible by anti-inflammatory lipid mediators (lipoxins) via a G protein-coupled receptor/pertussis toxin-sensitive pathway, and it is recruited to target gene promoters (e.g., mPGES-1) where it suppresses Egr-1-driven transcription, as demonstrated by ChIP and siRNA experiments."},"narrative":{"mechanistic_narrative":"NAB1 is a nuclear transcriptional corepressor that selectively restrains the Egr family of immediate-early transcription factors [PMID:7624335]. It functions not by blocking DNA binding or nuclear import of its targets but as an active repressor: it docks onto the inhibitory domain of Egr factors such as NGFI-A/Egr-1 and Krox20/Egr2 — while sparing other family members like Egr3 — thereby positioning its intrinsic repressor activity at the transcription unit [PMID:7624335, PMID:11018254]. This repressor activity resides in the conserved C-terminal NCD2 domain and is position-independent: when tethered directly to DNA, NAB1 silences constitutively active promoters regardless of promoter identity, enhancer presence, or distance from its binding site [PMID:9418898, PMID:11018254]. NAB1 expression is itself inducible by anti-inflammatory signals — aspirin-triggered lipoxin A4 analog upregulates it through a pertussis-toxin-sensitive G protein-coupled receptor pathway [PMID:11687510] — and in chondrocytes valproic acid recruits NAB1 to the mPGES-1 promoter to suppress IL-1β-induced mPGES-1 transcription [PMID:21239760], linking its corepressor function to control of inflammatory gene expression. Screening of peripheral neuropathy patients found no disease-causing NAB1 mutations, indicating it is not a common cause of inherited peripheral neuropathy [PMID:12030330].","teleology":[{"year":1995,"claim":"Established that a dedicated nuclear partner exists to selectively regulate the Egr transcription factor family, answering how Egr-driven transcription is dampened.","evidence":"Yeast two-hybrid screen against the NGFI-A inhibitory domain plus transcriptional repression assays in cells","pmids":["7624335"],"confidence":"High","gaps":["Did not define the molecular mechanism of repression","Did not map the repressor domain of NAB1","Basis for selectivity (Egr-1/Krox20 vs Egr3/NGFI-G) not resolved"]},{"year":1998,"claim":"Resolved that NAB1 acts as an active repressor rather than a passive blocker, and localized this activity to a discrete domain.","evidence":"Replacement mutagenesis of NCD2 and DNA-tethered (heterologous) repression assays, plus nuclear localization sequence mapping","pmids":["9418898"],"confidence":"High","gaps":["Corepressor machinery recruited by NCD2 not identified","No structural model of the NCD2 repression domain"]},{"year":2000,"claim":"Confirmed the docking logic — the Egr-1 inhibitory domain serves as the recruitment site bringing NAB1's position-independent repressor activity to the promoter.","evidence":"GAL4-NAB1 fusion repression assays from proximal and distal positions and overexpression studies in transient transfection","pmids":["11018254"],"confidence":"Medium","gaps":["Single-lab functional assays without structural confirmation of the interaction interface","Endogenous target genes not surveyed"]},{"year":2001,"claim":"Placed NAB1 downstream of an anti-inflammatory lipid-mediator signaling pathway, connecting its expression to GPCR-driven control.","evidence":"Differential display RT-PCR with pertussis toxin blockade in human neutrophils and in vivo expression in murine lung vascular smooth muscle","pmids":["11687510"],"confidence":"Medium","gaps":["Specific GPCR mediating induction not identified","Functional consequence of induced NAB1 on inflammatory transcription not assessed in this work"]},{"year":2011,"claim":"Demonstrated an endogenous promoter target and a causal role for NAB1 in suppressing inflammatory gene expression.","evidence":"ChIP showing NAB1 recruitment to the mPGES-1 promoter and siRNA knockdown abolishing valproic-acid-mediated suppression in human chondrocytes","pmids":["21239760"],"confidence":"Medium","gaps":["Whether recruitment requires an Egr factor at the mPGES-1 promoter not directly tested","Single cell type and single lab","Corepressor complex composition at this promoter unknown"]},{"year":2002,"claim":"Tested and excluded NAB1 as a frequent genetic cause of inherited peripheral neuropathy.","evidence":"Mutation screening of EGR2-interacting domains and full coding region in 87 neuropathy patients","pmids":["12030330"],"confidence":"Medium","gaps":["Negative result does not exclude rare or regulatory variants","Does not address NAB1 function in nervous system development"]},{"year":null,"claim":"The corepressor effector machinery NAB1 recruits through NCD2 and the structural basis of its Egr-domain docking remain unidentified in this corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No interactome of the NCD2 repression module","No structure of the NAB1–Egr inhibitory domain complex","Genome-wide endogenous target gene set undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,4]}],"complexes":[],"partners":["EGR1","EGR2"],"other_free_text":[]}},"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":98,"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":75,"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":51,"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":13,"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":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":"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":"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":5,"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":8204,"output_tokens":1566,"usd":0.024051,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8318,"output_tokens":2237,"usd":0.048758,"stage2_stop_reason":"end_turn"},"total_usd":0.072809,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1995,\n      \"finding\": \"NAB1 was identified as a nuclear protein that interacts with the inhibitory domain of NGFI-A (Egr-1) and represses NGFI-A- and Krox20-mediated transcription, but does not repress Egr3 or NGFI-G, establishing differential regulation of the Egr family.\",\n      \"method\": \"Yeast two-hybrid 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 / Strong — yeast two-hybrid identification replicated in functional transcription assays; foundational paper replicated by multiple subsequent labs\",\n      \"pmids\": [\"7624335\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"NAB1 repression does not work by blocking DNA binding or nuclear localization of NGFI-A; instead NAB1 is an active transcriptional repressor whose repression activity is localized to the conserved NCD2 (Nab conserved domain 2) in its C-terminal half. NAB1 tethered directly to DNA represses constitutively active promoters independently of promoter identity, enhancer presence, or distance from the binding site. A bipartite-like nuclear localization sequence was also identified in NAB1.\",\n      \"method\": \"Replacement mutagenesis of NCD2, DNA-tethered repression assays, nuclear localization mapping\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal methods including mutagenesis and tethered repression assays in a single rigorous study\",\n      \"pmids\": [\"9418898\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The inhibitory domain of Egr-1 (located between the activation domain and zinc finger DNA-binding region) acts as a docking site for NAB1 via protein-protein interaction, bringing NAB1 into proximity of the transcription unit. A GAL4-NAB1 fusion protein repressed transcription from both proximal and distal positions, confirming that NAB1 carries intrinsic transcriptional repressor activity independent of position.\",\n      \"method\": \"Overexpression studies, GAL4-fusion transcriptional repression assays, transient transfection\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — GAL4-fusion assays with position-independent repression, single lab, two orthogonal functional approaches\",\n      \"pmids\": [\"11018254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Aspirin-triggered lipoxin A4 analog (ATLa) rapidly up-regulates NAB1 gene expression in human neutrophils via a G protein-coupled receptor pathway, as demonstrated by blockade with pertussis toxin. ATLa also stimulated NAB1 expression in murine lung vascular smooth muscle in vivo.\",\n      \"method\": \"Differential display RT-PCR, pertussis toxin blockade experiment, in vivo gene expression analysis\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pertussis toxin blockade provides pathway placement, single lab with two complementary experimental contexts (in vitro and in vivo)\",\n      \"pmids\": [\"11687510\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Valproic acid (VA) upregulates NAB1 expression and recruits NAB1 to the mPGES-1 promoter in human chondrocytes, and NAB1 silencing by siRNA blocks VA-mediated suppression of IL-1β-induced mPGES-1 expression, placing NAB1 downstream of VA and upstream of mPGES-1 in this pathway.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), siRNA knockdown, transient transfection/promoter activity assays, Western blotting\",\n      \"journal\": \"The Journal of rheumatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and siRNA knockdown with defined promoter readout, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"21239760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Screening of 87 patients with peripheral neuropathies failed to identify any disease-causing mutations in the EGR2-interacting domains or complete coding regions of NAB1, indicating NAB1 mutations are most likely not involved in the pathogenesis of inherited peripheral neuropathies.\",\n      \"method\": \"Mutation screening of genomic DNA from 87 neuropathy patients\",\n      \"journal\": \"Neurogenetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic mutation screen across a defined patient cohort; negative result replicated across full coding region\",\n      \"pmids\": [\"12030330\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NAB1 (NGFI-A-binding protein 1) is a nuclear transcriptional corepressor that interacts via protein-protein contact with the inhibitory domain of Egr family transcription factors (NGFI-A/Egr-1, Krox20/Egr2, NGFI-C) but not all family members (not Egr3), and exerts active, position-independent transcriptional repression through its conserved C-terminal NCD2 domain; its expression is inducible by anti-inflammatory lipid mediators (lipoxins) via a G protein-coupled receptor/pertussis toxin-sensitive pathway, and it is recruited to target gene promoters (e.g., mPGES-1) where it suppresses Egr-1-driven transcription, as demonstrated by ChIP and siRNA experiments.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NAB1 is a nuclear transcriptional corepressor that selectively restrains the Egr family of immediate-early transcription factors [#0]. It functions not by blocking DNA binding or nuclear import of its targets but as an active repressor: it docks onto the inhibitory domain of Egr factors such as NGFI-A/Egr-1 and Krox20/Egr2 — while sparing other family members like Egr3 — thereby positioning its intrinsic repressor activity at the transcription unit [#0, #2]. This repressor activity resides in the conserved C-terminal NCD2 domain and is position-independent: when tethered directly to DNA, NAB1 silences constitutively active promoters regardless of promoter identity, enhancer presence, or distance from its binding site [#1, #2]. NAB1 expression is itself inducible by anti-inflammatory signals — aspirin-triggered lipoxin A4 analog upregulates it through a pertussis-toxin-sensitive G protein-coupled receptor pathway [#3] — and in chondrocytes valproic acid recruits NAB1 to the mPGES-1 promoter to suppress IL-1\\u03b2-induced mPGES-1 transcription [#4], linking its corepressor function to control of inflammatory gene expression. Screening of peripheral neuropathy patients found no disease-causing NAB1 mutations, indicating it is not a common cause of inherited peripheral neuropathy [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Established that a dedicated nuclear partner exists to selectively regulate the Egr transcription factor family, answering how Egr-driven transcription is dampened.\",\n      \"evidence\": \"Yeast two-hybrid screen against the NGFI-A inhibitory domain plus transcriptional repression assays in cells\",\n      \"pmids\": [\"7624335\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Did not define the molecular mechanism of repression\",\n        \"Did not map the repressor domain of NAB1\",\n        \"Basis for selectivity (Egr-1/Krox20 vs Egr3/NGFI-G) not resolved\"\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Resolved that NAB1 acts as an active repressor rather than a passive blocker, and localized this activity to a discrete domain.\",\n      \"evidence\": \"Replacement mutagenesis of NCD2 and DNA-tethered (heterologous) repression assays, plus nuclear localization sequence mapping\",\n      \"pmids\": [\"9418898\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Corepressor machinery recruited by NCD2 not identified\",\n        \"No structural model of the NCD2 repression domain\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Confirmed the docking logic — the Egr-1 inhibitory domain serves as the recruitment site bringing NAB1's position-independent repressor activity to the promoter.\",\n      \"evidence\": \"GAL4-NAB1 fusion repression assays from proximal and distal positions and overexpression studies in transient transfection\",\n      \"pmids\": [\"11018254\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab functional assays without structural confirmation of the interaction interface\",\n        \"Endogenous target genes not surveyed\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Placed NAB1 downstream of an anti-inflammatory lipid-mediator signaling pathway, connecting its expression to GPCR-driven control.\",\n      \"evidence\": \"Differential display RT-PCR with pertussis toxin blockade in human neutrophils and in vivo expression in murine lung vascular smooth muscle\",\n      \"pmids\": [\"11687510\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific GPCR mediating induction not identified\",\n        \"Functional consequence of induced NAB1 on inflammatory transcription not assessed in this work\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated an endogenous promoter target and a causal role for NAB1 in suppressing inflammatory gene expression.\",\n      \"evidence\": \"ChIP showing NAB1 recruitment to the mPGES-1 promoter and siRNA knockdown abolishing valproic-acid-mediated suppression in human chondrocytes\",\n      \"pmids\": [\"21239760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether recruitment requires an Egr factor at the mPGES-1 promoter not directly tested\",\n        \"Single cell type and single lab\",\n        \"Corepressor complex composition at this promoter unknown\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Tested and excluded NAB1 as a frequent genetic cause of inherited peripheral neuropathy.\",\n      \"evidence\": \"Mutation screening of EGR2-interacting domains and full coding region in 87 neuropathy patients\",\n      \"pmids\": [\"12030330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative result does not exclude rare or regulatory variants\",\n        \"Does not address NAB1 function in nervous system development\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The corepressor effector machinery NAB1 recruits through NCD2 and the structural basis of its Egr-domain docking remain unidentified in this corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No interactome of the NCD2 repression module\",\n        \"No structure of the NAB1\\u2013Egr inhibitory domain complex\",\n        \"Genome-wide endogenous target gene set undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EGR1\", \"EGR2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}