{"gene":"REXO1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2003,"finding":"REXO1 (EloA-BP1) was identified as a novel exonuclease domain-containing protein that physically binds the NH2-terminal ~120 amino acid region of Elongin A (and also the NH2-terminus of transcription factor SII) via in vitro binding assay and yeast two-hybrid screening. Double immunofluorescence labeling in COS7 cells showed REXO1 and Elongin A colocalize in the cell nucleus.","method":"Yeast two-hybrid screening, in vitro binding assay, double immunofluorescence labeling","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid plus in vitro binding assay and colocalization, single lab, two orthogonal methods","pmids":["12943681"],"is_preprint":false},{"year":2003,"finding":"Purified REXO1 (EloA-BP1) had no detectable effect on the rate of transcription elongation in vitro, despite binding Elongin A.","method":"In vitro transcription elongation assay with purified protein","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro assay with purified protein, single lab; negative result explicitly reported","pmids":["12943681"],"is_preprint":false},{"year":2025,"finding":"REXO1 belongs to a Rex3-related clade of DEDDh exoribonucleases that, in contrast to Rex1-related proteins, lacks an alkaline phosphatase (AlkP) domain but contains a KIX domain and a cysteine- and histidine-rich (CHORD) domain adjacent to a C-terminal DEDD catalytic domain. Structural analysis and sequence comparisons placed REXO1 in the same clade as yeast Rex3, which requires its N-terminal KIX domain region for RNase MRP processing in vivo.","method":"Protein structure modeling, sequence analysis, yeast deletion mutants with RNA processing readout (in vivo functional analysis of yeast Rex3 as ortholog)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — structural modeling combined with functional mutagenesis in yeast Rex3 ortholog; domain assignment for REXO1 based on structural homology, single lab","pmids":["40455837"],"is_preprint":false}],"current_model":"REXO1 is a nuclear DEDDh exoribonuclease homolog that physically binds the N-terminal region of transcription elongation factor Elongin A (and SII) but does not affect elongation rate in vitro; it belongs to the Rex3 structural clade, characterized by KIX and CHORD domains flanking its C-terminal catalytic DEDD domain, with the KIX domain implicated in RNA processing (based on yeast Rex3 ortholog studies), but its specific RNA substrates in human cells remain uncharacterized."},"narrative":{"mechanistic_narrative":"REXO1 (EloA-BP1) is a nuclear DEDDh-family exoribonuclease homolog that physically associates with the transcription elongation machinery. It was identified through its direct binding to the N-terminal ~120-amino-acid region of Elongin A and to the N-terminus of transcription factor SII, and it colocalizes with Elongin A in the nucleus [PMID:12943681]. Despite this interaction, purified REXO1 has no detectable effect on the rate of transcription elongation in vitro [PMID:12943681]. Structurally, REXO1 belongs to a Rex3-related clade of DEDDh exoribonucleases distinguished by a KIX domain and a cysteine- and histidine-rich (CHORD) domain flanking a C-terminal DEDD catalytic domain; its closest functional reference is yeast Rex3, whose KIX domain region is required for RNase MRP processing in vivo [PMID:40455837]. The specific RNA substrates of human REXO1 have not been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing that an uncharacterized exonuclease-domain protein could be linked to transcription elongation, REXO1 was found to bind the N-terminus of Elongin A and SII and to share nuclear localization with Elongin A.","evidence":"Yeast two-hybrid screening, in vitro binding assay, and double immunofluorescence in COS7 cells","pmids":["12943681"],"confidence":"Medium","gaps":["Interaction shown by Y2H and in vitro binding without reciprocal endogenous co-IP validation","Functional consequence of the Elongin A/SII interaction not established","RNA substrate or enzymatic activity not tested"]},{"year":2003,"claim":"To test whether REXO1 modulates the elongation complex it binds, its effect on transcription was assayed directly, showing it does not alter elongation rate in vitro and decoupling the binding interaction from any elongation-rate function.","evidence":"In vitro transcription elongation assay with purified REXO1","pmids":["12943681"],"confidence":"Medium","gaps":["Negative result does not exclude effects on elongation processivity, pausing, or termination","Does not address a role in vivo or under stress conditions","Catalytic exonuclease activity of REXO1 itself not assayed"]},{"year":2025,"claim":"Placing REXO1 in a structural and evolutionary framework, modeling assigned it to a Rex3-related DEDDh clade defined by KIX and CHORD domains adjacent to a DEDD catalytic domain, linking it via the yeast Rex3 ortholog to RNase MRP-type RNA processing.","evidence":"Protein structure modeling, sequence comparison, and in vivo RNA-processing analysis of yeast Rex3 deletion mutants","pmids":["40455837"],"confidence":"Medium","gaps":["Domain assignment for human REXO1 rests on structural homology, not direct biochemistry","RNase MRP processing role demonstrated only for yeast Rex3, not human REXO1","No human RNA substrate identified"]},{"year":null,"claim":"The endogenous RNA substrates and catalytic role of human REXO1, and how its Elongin A/SII binding integrates with its predicted exoribonuclease activity, remain undefined.","evidence":"No direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No human RNA substrate identified","Exoribonuclease activity of human REXO1 not directly demonstrated","Functional link between transcription-factor binding and RNA processing unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["ELOA","TCEB3","TCEA1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N1G1","full_name":"RNA exonuclease 1 homolog","aliases":["Elongin-A-binding protein 1","EloA-BP1","Transcription elongation factor B polypeptide 3-binding protein 1"],"length_aa":1221,"mass_kda":131.5,"function":"Seems to have no detectable effect on transcription elongation in vitro","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8N1G1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/REXO1","classification":"Not Classified","n_dependent_lines":20,"n_total_lines":1208,"dependency_fraction":0.016556291390728478},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SSRP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/REXO1","total_profiled":1310},"omim":[{"mim_id":"609614","title":"RNA EXONUCLEASE 1 HOMOLOG; REXO1","url":"https://www.omim.org/entry/609614"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/REXO1"},"hgnc":{"alias_symbol":["EloA-BP1","KIAA1138"],"prev_symbol":["TCEB3BP1"]},"alphafold":{"accession":"Q8N1G1","domains":[{"cath_id":"3.30.420.10","chopping":"922-960_1046-1221","consensus_level":"high","plddt":89.7818,"start":922,"end":1221},{"cath_id":"1.10.12","chopping":"811-874","consensus_level":"medium","plddt":90.4328,"start":811,"end":874},{"cath_id":"4.10.1130","chopping":"964-1038","consensus_level":"medium","plddt":85.4767,"start":964,"end":1038}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N1G1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N1G1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N1G1-F1-predicted_aligned_error_v6.png","plddt_mean":57.97},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=REXO1","jax_strain_url":"https://www.jax.org/strain/search?query=REXO1"},"sequence":{"accession":"Q8N1G1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N1G1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N1G1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N1G1"}},"corpus_meta":[{"pmid":"33407514","id":"PMC_33407514","title":"Circ-CCDC66 upregulates REXO1 expression to aggravate cervical cancer progression via restraining miR-452-5p.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/33407514","citation_count":15,"is_preprint":false},{"pmid":"12943681","id":"PMC_12943681","title":"Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain.","date":"2003","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/12943681","citation_count":10,"is_preprint":false},{"pmid":"37309009","id":"PMC_37309009","title":"Buffy coat signatures of breast cancer risk in a prospective cohort study.","date":"2023","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/37309009","citation_count":8,"is_preprint":false},{"pmid":"26001598","id":"PMC_26001598","title":"Effect of primary culture medium type for culture of canine fibroblasts on production of cloned dogs.","date":"2015","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/26001598","citation_count":5,"is_preprint":false},{"pmid":"39504821","id":"PMC_39504821","title":"Characterization of the regulatory network and pathways in duodenum affecting chicken abdominal fat deposition.","date":"2024","source":"Poultry science","url":"https://pubmed.ncbi.nlm.nih.gov/39504821","citation_count":4,"is_preprint":false},{"pmid":"40455837","id":"PMC_40455837","title":"Conserved domains and structural motifs that differentiate closely related Rex1 and Rex3 DEDDh exoribonucleases are required for their function in yeast.","date":"2025","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/40455837","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5541,"output_tokens":859,"usd":0.014754,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7286,"output_tokens":1547,"usd":0.037553,"stage2_stop_reason":"end_turn"},"total_usd":0.052307,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"REXO1 (EloA-BP1) was identified as a novel exonuclease domain-containing protein that physically binds the NH2-terminal ~120 amino acid region of Elongin A (and also the NH2-terminus of transcription factor SII) via in vitro binding assay and yeast two-hybrid screening. Double immunofluorescence labeling in COS7 cells showed REXO1 and Elongin A colocalize in the cell nucleus.\",\n      \"method\": \"Yeast two-hybrid screening, in vitro binding assay, double immunofluorescence labeling\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid plus in vitro binding assay and colocalization, single lab, two orthogonal methods\",\n      \"pmids\": [\"12943681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Purified REXO1 (EloA-BP1) had no detectable effect on the rate of transcription elongation in vitro, despite binding Elongin A.\",\n      \"method\": \"In vitro transcription elongation assay with purified protein\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro assay with purified protein, single lab; negative result explicitly reported\",\n      \"pmids\": [\"12943681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"REXO1 belongs to a Rex3-related clade of DEDDh exoribonucleases that, in contrast to Rex1-related proteins, lacks an alkaline phosphatase (AlkP) domain but contains a KIX domain and a cysteine- and histidine-rich (CHORD) domain adjacent to a C-terminal DEDD catalytic domain. Structural analysis and sequence comparisons placed REXO1 in the same clade as yeast Rex3, which requires its N-terminal KIX domain region for RNase MRP processing in vivo.\",\n      \"method\": \"Protein structure modeling, sequence analysis, yeast deletion mutants with RNA processing readout (in vivo functional analysis of yeast Rex3 as ortholog)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structural modeling combined with functional mutagenesis in yeast Rex3 ortholog; domain assignment for REXO1 based on structural homology, single lab\",\n      \"pmids\": [\"40455837\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"REXO1 is a nuclear DEDDh exoribonuclease homolog that physically binds the N-terminal region of transcription elongation factor Elongin A (and SII) but does not affect elongation rate in vitro; it belongs to the Rex3 structural clade, characterized by KIX and CHORD domains flanking its C-terminal catalytic DEDD domain, with the KIX domain implicated in RNA processing (based on yeast Rex3 ortholog studies), but its specific RNA substrates in human cells remain uncharacterized.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"REXO1 (EloA-BP1) is a nuclear DEDDh-family exoribonuclease homolog that physically associates with the transcription elongation machinery. It was identified through its direct binding to the N-terminal ~120-amino-acid region of Elongin A and to the N-terminus of transcription factor SII, and it colocalizes with Elongin A in the nucleus [#0]. Despite this interaction, purified REXO1 has no detectable effect on the rate of transcription elongation in vitro [#1]. Structurally, REXO1 belongs to a Rex3-related clade of DEDDh exoribonucleases distinguished by a KIX domain and a cysteine- and histidine-rich (CHORD) domain flanking a C-terminal DEDD catalytic domain; its closest functional reference is yeast Rex3, whose KIX domain region is required for RNase MRP processing in vivo [#2]. The specific RNA substrates of human REXO1 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that an uncharacterized exonuclease-domain protein could be linked to transcription elongation, REXO1 was found to bind the N-terminus of Elongin A and SII and to share nuclear localization with Elongin A.\",\n      \"evidence\": \"Yeast two-hybrid screening, in vitro binding assay, and double immunofluorescence in COS7 cells\",\n      \"pmids\": [\"12943681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction shown by Y2H and in vitro binding without reciprocal endogenous co-IP validation\",\n        \"Functional consequence of the Elongin A/SII interaction not established\",\n        \"RNA substrate or enzymatic activity not tested\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"To test whether REXO1 modulates the elongation complex it binds, its effect on transcription was assayed directly, showing it does not alter elongation rate in vitro and decoupling the binding interaction from any elongation-rate function.\",\n      \"evidence\": \"In vitro transcription elongation assay with purified REXO1\",\n      \"pmids\": [\"12943681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative result does not exclude effects on elongation processivity, pausing, or termination\",\n        \"Does not address a role in vivo or under stress conditions\",\n        \"Catalytic exonuclease activity of REXO1 itself not assayed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placing REXO1 in a structural and evolutionary framework, modeling assigned it to a Rex3-related DEDDh clade defined by KIX and CHORD domains adjacent to a DEDD catalytic domain, linking it via the yeast Rex3 ortholog to RNase MRP-type RNA processing.\",\n      \"evidence\": \"Protein structure modeling, sequence comparison, and in vivo RNA-processing analysis of yeast Rex3 deletion mutants\",\n      \"pmids\": [\"40455837\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Domain assignment for human REXO1 rests on structural homology, not direct biochemistry\",\n        \"RNase MRP processing role demonstrated only for yeast Rex3, not human REXO1\",\n        \"No human RNA substrate identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous RNA substrates and catalytic role of human REXO1, and how its Elongin A/SII binding integrates with its predicted exoribonuclease activity, remain undefined.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human RNA substrate identified\",\n        \"Exoribonuclease activity of human REXO1 not directly demonstrated\",\n        \"Functional link between transcription-factor binding and RNA processing unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"ELOA\", \"TCEB3\", \"TCEA1\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}