{"gene":"COIL","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":1991,"finding":"p80-coilin was identified as an 80-kDa nuclear protein specifically enriched in the coiled body (Cajal body). Human autoantibodies recognized this protein by immunoblotting, affinity-purified anti-p80 antibody reproduced fluorescent staining of nuclear coiled bodies by immunofluorescence, and colloidal gold immunoelectron microscopy confirmed localization to the coiled body ultrastructure. A cDNA was cloned encoding a 405-amino-acid open reading frame from the COOH-terminal region.","method":"Immunoblotting, affinity purification of autoantibody, immunofluorescence, colloidal gold immunoelectron microscopy, cDNA expression cloning from lambda gt-11 library","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (immunoblot, immunofluorescence, immunoelectron microscopy, expression cloning) in founding paper; widely replicated subsequently","pmids":["2033369"],"is_preprint":false},{"year":1994,"finding":"The amino-terminal region (first 102 amino acids) of human p80-coilin is necessary and sufficient for targeting to the sphere organelle (homologue of coiled bodies) in the Xenopus germinal vesicle. A construct lacking the first 92 amino acids was imported into the nucleus but failed to localize to the sphere organelle, establishing a specific N-terminal targeting domain distinct from the nuclear localization signal.","method":"Microinjection of myc-tagged p80-coilin mRNA into Xenopus oocytes, immunofluorescence with anti-myc antibody on spread germinal vesicle contents, deletion construct analysis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic deletion series with direct localization readout in live-cell microinjection system; multiple constructs tested with clear domain boundaries defined","pmids":["7532471"],"is_preprint":false},{"year":1994,"finding":"The human p80-coilin gene (COIL) contains 7 exons spanning approximately 25 kb and is located on chromosome 17q22-23. The full-length protein consists of 576 amino acids with a predicted molecular mass of 62,608 Da, and a 2.7-kb mRNA is expressed. The protein contains two conserved N- and C-terminal domains. A putative pseudogene was also detected.","method":"5'-RACE for full-length cDNA, genomic library screening, Northern blot analysis, FISH for chromosomal localization","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple methods (RACE, genomic cloning, Northern blot, FISH) in single lab; structural/genomic characterization of the gene locus","pmids":["7971277"],"is_preprint":false},{"year":1995,"finding":"Mutational analysis of p80 coilin identified functionally distinct domains: (1) a nuclear localization signal insufficient alone for coiled body targeting; (2) a carboxy-terminal domain whose deletion generates pseudo-coiled bodies that cannot recruit splicing snRNPs and causes loss of endogenous coiled bodies; (3) separate domains whose mutation produces fibrillar structures surrounding nucleoli, causes loss of endogenous coiled bodies, disrupts nucleolar architecture with segregation of nucleolar antigens, and abolishes RNA polymerase I activity. p80 coilin was shown to be ubiquitously expressed in human tissues.","method":"Transient transfection of deletion/truncation mutants in HeLa cells, immunofluorescence, co-localization with snRNP markers, RNA polymerase I activity assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic domain-deletion mutagenesis with multiple orthogonal functional readouts (snRNP recruitment, nucleolar architecture, Pol I activity) establishing distinct functional domains","pmids":["7490287"],"is_preprint":false},{"year":1995,"finding":"p80-coilin is an integral constituent of interchromatin granule-associated zones (IGAZs) in addition to coiled bodies. Both low-salt and high-salt (nuclear matrix) extractions preserved p80-coilin in these structures, indicating p80-coilin is a matrix-associated component of IGAZs.","method":"Immunoelectron microscopy with anti-p80-coilin antibody after low-salt loosening and high-salt/DNase I nuclear matrix extraction, in situ hybridization with snRNA probes","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, immunoelectron microscopy with biochemical fractionation; extends known localization to a new nuclear compartment","pmids":["7622600"],"is_preprint":false},{"year":2000,"finding":"The murine p80 coilin gene (Coil) maps to the distal portion of chromosome band 11D and is composed of 7 exons spanning nearly 30 kb, producing an approximately 2.6-kb transcript expressed in all tissues with highest levels in brain and testis. The predicted amino acid sequence reveals two conserved N- and C-terminal domains orthologous to human p80-coilin and Xenopus SPH-1.","method":"Genomic library cloning, Northern blot analysis, chromosomal mapping, sequence analysis","journal":"Journal of structural biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple methods (cloning, Northern blot, chromosomal mapping) confirming gene structure and expression; provides genetic model foundation but primarily structural/genomic characterization","pmids":["10806077"],"is_preprint":false},{"year":2003,"finding":"p80 coilin physically interacts with ataxin-1 (the SCA1 gene product). Yeast two-hybrid and co-immunoprecipitation demonstrated the interaction, and deletion mapping showed that the C-terminal regions of both ataxin-1 and p80 coilin are required for the interaction. In co-transfected HeLa cells, p80 coilin co-localizes with ataxin-1 aggregates in the nucleoplasm.","method":"Yeast two-hybrid screen, co-immunoprecipitation, deletion mutant mapping, immunofluorescence co-localization in HeLa cells and SCA1 transgenic mouse Purkinje cells","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus yeast two-hybrid plus domain mapping in single lab; interaction confirmed by two orthogonal methods","pmids":["12757932"],"is_preprint":false},{"year":2006,"finding":"CGI-55 co-localizes with p80-coilin-positive nuclear coiled bodies. Yeast two-hybrid screening identified CGI-55 interactions with nuclear body-associated proteins, and GFP-fusion protein imaging in HeLa cells showed CGI-55 localization to p80-coilin-positive nuclear foci.","method":"Yeast two-hybrid screen, GFP/RFP fusion protein co-localization imaging in HeLa cells","journal":"Cell biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, co-localization only without direct binding assay between CGI-55 and p80-coilin; p80-coilin used as a marker rather than as the studied protein","pmids":["16679534"],"is_preprint":false}],"current_model":"p80-coilin (COIL) is the defining marker protein of Cajal bodies (coiled bodies), nuclear organelles involved in snRNP biogenesis and subnuclear organization; its N-terminal domain (first ~102 amino acids) is necessary and sufficient for Cajal body targeting, its C-terminal domain is required for recruiting splicing snRNPs to Cajal bodies, and additional internal domains functionally interact with nucleolar architecture and RNA polymerase I activity; p80-coilin also physically interacts with ataxin-1 via their respective C-terminal regions, and the protein is ubiquitously expressed with the COIL gene located on chromosome 17q22-23."},"narrative":{"mechanistic_narrative":"p80-coilin (COIL) is the defining marker protein of the Cajal body (coiled body), a nuclear organelle, and is an integral structural component required for the organization of this compartment and its recruitment of splicing snRNPs [PMID:2033369, PMID:7490287]. Coilin localization is governed by separable domains: its amino-terminal region (first ~102 amino acids) is necessary and sufficient for targeting to the coiled-body organelle, acting independently of the nuclear localization signal, while the carboxy-terminal domain is required to recruit splicing snRNPs—deletion of the C-terminus produces pseudo-coiled bodies and eliminates endogenous coiled bodies [PMID:7532471, PMID:7490287]. Internal domains of coilin functionally couple it to nucleolar architecture, since their mutation generates perinucleolar fibrillar structures, segregates nucleolar antigens, and abolishes RNA polymerase I activity [PMID:7490287]. Beyond coiled bodies, coilin is a nuclear-matrix-associated constituent of interchromatin granule-associated zones [PMID:7622600], and it physically interacts with ataxin-1 (the SCA1 gene product) through the C-terminal regions of both proteins, co-localizing with ataxin-1 aggregates in the nucleoplasm [PMID:12757932]. The ubiquitously expressed protein is encoded by a 7-exon gene on chromosome 17q22-23 [PMID:7971277, PMID:7490287].","teleology":[{"year":1991,"claim":"Established the existence of a dedicated coiled-body marker protein, defining the molecular identity of this previously ultrastructurally-described nuclear organelle.","evidence":"Autoantibody-based immunoblot, immunofluorescence, immunoelectron microscopy, and cDNA expression cloning identifying an 80-kDa coiled-body protein","pmids":["2033369"],"confidence":"High","gaps":["Function within the coiled body not yet defined","Full-length sequence and domain organization not yet resolved"]},{"year":1994,"claim":"Mapped a discrete N-terminal targeting determinant, showing coiled-body localization is encoded separately from nuclear import.","evidence":"Microinjection of myc-tagged coilin mRNA and deletion constructs into Xenopus oocytes with germinal-vesicle immunofluorescence","pmids":["7532471"],"confidence":"High","gaps":["Molecular partner that reads the N-terminal targeting signal unknown","Mechanism of organelle assembly versus targeting not distinguished"]},{"year":1994,"claim":"Defined the gene locus and full-length protein architecture, providing the structural framework of two conserved N- and C-terminal domains.","evidence":"5'-RACE, genomic library screening, Northern blot, and FISH mapping to chromosome 17q22-23","pmids":["7971277"],"confidence":"Medium","gaps":["Functional roles of the conserved domains not assigned here","Discrepancy between predicted mass and apparent 80-kDa size unexplained"]},{"year":1995,"claim":"Assigned distinct functions to coilin domains, separating snRNP recruitment from nucleolar/Pol I coupling and revealing coilin as an organizer of multiple nuclear compartments.","evidence":"Systematic deletion/truncation mutagenesis in HeLa cells with snRNP co-localization, nucleolar antigen imaging, and RNA polymerase I activity assays","pmids":["7490287"],"confidence":"High","gaps":["Direct biochemical mechanism linking coilin to Pol I activity not established","Identity of snRNP-recruiting binding partners not defined"]},{"year":1995,"claim":"Extended coilin localization to interchromatin granule-associated zones as a nuclear-matrix-associated component, broadening its structural role beyond coiled bodies.","evidence":"Immunoelectron microscopy after low-salt and high-salt/DNase nuclear matrix extraction with snRNA in situ hybridization","pmids":["7622600"],"confidence":"Medium","gaps":["Functional consequence of IGAZ localization unknown","Single-lab observation by IEM only"]},{"year":2003,"claim":"Identified a direct protein partner, ataxin-1, linking coilin to a neurodegenerative disease protein and to nucleoplasmic aggregate biology.","evidence":"Yeast two-hybrid, reciprocal co-immunoprecipitation, deletion mapping, and co-localization in HeLa cells and SCA1 transgenic mouse Purkinje cells","pmids":["12757932"],"confidence":"Medium","gaps":["Functional consequence of coilin-ataxin-1 binding for either coiled bodies or SCA1 pathology not established","Single-lab interaction"]},{"year":2006,"claim":"Used coilin as a coiled-body marker to place CGI-55 in this compartment, indicating the coiled body recruits additional nuclear-body-associated proteins.","evidence":"Yeast two-hybrid screen and GFP/RFP-fusion co-localization imaging in HeLa cells","pmids":["16679534"],"confidence":"Low","gaps":["Co-localization only; no direct binding assay between CGI-55 and coilin","Coilin studied as a marker, not as the functional subject"]},{"year":null,"claim":"The biochemical mechanism by which coilin assembles and maintains Cajal bodies, recruits snRNPs, and couples to RNA polymerase I activity remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the coilin-driven assembly","Direct molecular partners for snRNP recruitment and Pol I coupling unidentified","Physiological role of ataxin-1 interaction unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[4,6]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,3]}],"complexes":["Cajal body (coiled body)","interchromatin granule-associated zones"],"partners":["ATXN1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P38432","full_name":"Coilin","aliases":["p80-coilin"],"length_aa":576,"mass_kda":62.6,"function":"Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs","subcellular_location":"Nucleus; Nucleus, Cajal body","url":"https://www.uniprot.org/uniprotkb/P38432/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/COIL","classification":"Not Classified","n_dependent_lines":289,"n_total_lines":1208,"dependency_fraction":0.2392384105960265},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000121058","cell_line_id":"CID000868","localizations":[{"compartment":"nuclear_punctae","grade":3},{"compartment":"nucleoplasm","grade":2}],"interactors":[{"gene":"G3BP2","stoichiometry":0.2},{"gene":"PSME3","stoichiometry":0.2},{"gene":"SF3A1","stoichiometry":0.2},{"gene":"SNRPB","stoichiometry":0.2},{"gene":"SNRPB2","stoichiometry":0.2},{"gene":"VAPB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000868","total_profiled":1310},"omim":[{"mim_id":"621572","title":"TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 6; TMCO6","url":"https://www.omim.org/entry/621572"},{"mim_id":"621571","title":"TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 5A; TMCO5A","url":"https://www.omim.org/entry/621571"},{"mim_id":"621569","title":"TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 2; TMCO2","url":"https://www.omim.org/entry/621569"},{"mim_id":"621568","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 87; CCDC87","url":"https://www.omim.org/entry/621568"},{"mim_id":"621555","title":"TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 4; TMCO4","url":"https://www.omim.org/entry/621555"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear bodies","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Nucleoli fibrillar center","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":92.1}],"url":"https://www.proteinatlas.org/search/COIL"},"hgnc":{"alias_symbol":["CLN80","p80-coilin"],"prev_symbol":[]},"alphafold":{"accession":"P38432","domains":[{"cath_id":"3.10.20.90","chopping":"7-86","consensus_level":"high","plddt":92.2885,"start":7,"end":86},{"cath_id":"-","chopping":"464-563","consensus_level":"high","plddt":85.8535,"start":464,"end":563}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P38432","model_url":"https://alphafold.ebi.ac.uk/files/AF-P38432-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P38432-F1-predicted_aligned_error_v6.png","plddt_mean":58.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=COIL","jax_strain_url":"https://www.jax.org/strain/search?query=COIL"},"sequence":{"accession":"P38432","fasta_url":"https://rest.uniprot.org/uniprotkb/P38432.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P38432/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P38432"}},"corpus_meta":[{"pmid":"15837514","id":"PMC_15837514","title":"The design of coiled-coil structures and assemblies.","date":"2005","source":"Advances in protein chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15837514","citation_count":469,"is_preprint":false},{"pmid":"1464329","id":"PMC_1464329","title":"A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes.","date":"1992","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/1464329","citation_count":341,"is_preprint":false},{"pmid":"2033369","id":"PMC_2033369","title":"Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin.","date":"1991","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/2033369","citation_count":329,"is_preprint":false},{"pmid":"9989405","id":"PMC_9989405","title":"Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains.","date":"1999","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/9989405","citation_count":327,"is_preprint":false},{"pmid":"11292353","id":"PMC_11292353","title":"Socket: a program for identifying and analysing coiled-coil motifs within protein structures.","date":"2001","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11292353","citation_count":305,"is_preprint":false},{"pmid":"9080177","id":"PMC_9080177","title":"The concept of a random coil. 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acta","url":"https://pubmed.ncbi.nlm.nih.gov/12757932","citation_count":20,"is_preprint":false},{"pmid":"35725768","id":"PMC_35725768","title":"Cytoskeletal regulation of a transcription factor by DNA mimicry via coiled-coil interactions.","date":"2022","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/35725768","citation_count":20,"is_preprint":false},{"pmid":"32487230","id":"PMC_32487230","title":"Coiled-coil inspired functional inclusion bodies.","date":"2020","source":"Microbial cell factories","url":"https://pubmed.ncbi.nlm.nih.gov/32487230","citation_count":19,"is_preprint":false},{"pmid":"33574262","id":"PMC_33574262","title":"Designed folding pathway of modular coiled-coil-based proteins.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33574262","citation_count":19,"is_preprint":false},{"pmid":"24875765","id":"PMC_24875765","title":"Gene delivery from supercharged coiled-coil protein and cationic lipid hybrid complex.","date":"2014","source":"Biomaterials","url":"https://pubmed.ncbi.nlm.nih.gov/24875765","citation_count":19,"is_preprint":false},{"pmid":"30411434","id":"PMC_30411434","title":"Coiled-Coil Peptide Beacon: A Tunable Conformational Switch for Protein Detection.","date":"2018","source":"Angewandte Chemie (International ed. in English)","url":"https://pubmed.ncbi.nlm.nih.gov/30411434","citation_count":19,"is_preprint":false},{"pmid":"29844016","id":"PMC_29844016","title":"The trimeric coiled-coil HSBP1 protein promotes WASH complex assembly at centrosomes.","date":"2018","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/29844016","citation_count":19,"is_preprint":false},{"pmid":"31360792","id":"PMC_31360792","title":"Neuromodulation with electromagnetic stimulation for seizure suppression: From electrode to magnetic coil.","date":"2019","source":"IBRO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31360792","citation_count":19,"is_preprint":false},{"pmid":"31660743","id":"PMC_31660743","title":"Multiple Synthetic Routes to the Mini-Protein Omomyc and Coiled-Coil Domain Truncations.","date":"2019","source":"The Journal of organic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31660743","citation_count":18,"is_preprint":false},{"pmid":"29601728","id":"PMC_29601728","title":"Engineered Coiled-Coil Protein for Delivery of Inverse Agonist for Osteoarthritis.","date":"2018","source":"Biomacromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/29601728","citation_count":18,"is_preprint":false},{"pmid":"16844448","id":"PMC_16844448","title":"Ureteral stents: coil strength and durometer.","date":"2006","source":"Urology","url":"https://pubmed.ncbi.nlm.nih.gov/16844448","citation_count":17,"is_preprint":false},{"pmid":"31253765","id":"PMC_31253765","title":"Artificial coiled coil biomineralisation protein for the synthesis of magnetic nanoparticles.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31253765","citation_count":17,"is_preprint":false},{"pmid":"36172799","id":"PMC_36172799","title":"Recent advances in coiled-coil peptide materials and their biomedical applications.","date":"2022","source":"Chemical communications (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/36172799","citation_count":17,"is_preprint":false},{"pmid":"9858154","id":"PMC_9858154","title":"SF-assemblin, striated fibers, and segmented coiled coil proteins.","date":"1998","source":"Cell motility and the cytoskeleton","url":"https://pubmed.ncbi.nlm.nih.gov/9858154","citation_count":17,"is_preprint":false},{"pmid":"31016294","id":"PMC_31016294","title":"Structural determinants of coiled coil mechanics.","date":"2019","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/31016294","citation_count":16,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":41481,"output_tokens":2572,"usd":0.081512,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9409,"output_tokens":2507,"usd":0.05486,"stage2_stop_reason":"end_turn"},"total_usd":0.136372,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the COIL gene (p80-coilin, CLN80) - the nuclear coiled body marker protein. Most papers in this corpus are about \"coiled-coil\" protein motifs in general, which is a completely different topic (structural motif vs. the specific protein p80-coilin/COIL).\n\nPapers specifically about p80-coilin/COIL gene:\n- PMID:2033369 - original cloning of p80-coilin\n- PMID:7490287 - mutational analysis of p80 coilin\n- PMID:7532471 - p80-coilin targeting in Xenopus\n- PMID:7971277 - gene structure of p80-coilin\n- PMID:7622600 - p80-coilin in interchromatin granule-associated zones\n- PMID:10806077 - murine Coil gene structure\n- PMID:12757932 - p80 coilin interaction with ataxin-1\n- PMID:16679534 - CGI-55 co-localizes to p80-coilin positive coiled bodies\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1991,\n      \"finding\": \"p80-coilin was identified as an 80-kDa nuclear protein specifically enriched in the coiled body (Cajal body). Human autoantibodies recognized this protein by immunoblotting, affinity-purified anti-p80 antibody reproduced fluorescent staining of nuclear coiled bodies by immunofluorescence, and colloidal gold immunoelectron microscopy confirmed localization to the coiled body ultrastructure. A cDNA was cloned encoding a 405-amino-acid open reading frame from the COOH-terminal region.\",\n      \"method\": \"Immunoblotting, affinity purification of autoantibody, immunofluorescence, colloidal gold immunoelectron microscopy, cDNA expression cloning from lambda gt-11 library\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (immunoblot, immunofluorescence, immunoelectron microscopy, expression cloning) in founding paper; widely replicated subsequently\",\n      \"pmids\": [\"2033369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The amino-terminal region (first 102 amino acids) of human p80-coilin is necessary and sufficient for targeting to the sphere organelle (homologue of coiled bodies) in the Xenopus germinal vesicle. A construct lacking the first 92 amino acids was imported into the nucleus but failed to localize to the sphere organelle, establishing a specific N-terminal targeting domain distinct from the nuclear localization signal.\",\n      \"method\": \"Microinjection of myc-tagged p80-coilin mRNA into Xenopus oocytes, immunofluorescence with anti-myc antibody on spread germinal vesicle contents, deletion construct analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic deletion series with direct localization readout in live-cell microinjection system; multiple constructs tested with clear domain boundaries defined\",\n      \"pmids\": [\"7532471\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The human p80-coilin gene (COIL) contains 7 exons spanning approximately 25 kb and is located on chromosome 17q22-23. The full-length protein consists of 576 amino acids with a predicted molecular mass of 62,608 Da, and a 2.7-kb mRNA is expressed. The protein contains two conserved N- and C-terminal domains. A putative pseudogene was also detected.\",\n      \"method\": \"5'-RACE for full-length cDNA, genomic library screening, Northern blot analysis, FISH for chromosomal localization\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple methods (RACE, genomic cloning, Northern blot, FISH) in single lab; structural/genomic characterization of the gene locus\",\n      \"pmids\": [\"7971277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Mutational analysis of p80 coilin identified functionally distinct domains: (1) a nuclear localization signal insufficient alone for coiled body targeting; (2) a carboxy-terminal domain whose deletion generates pseudo-coiled bodies that cannot recruit splicing snRNPs and causes loss of endogenous coiled bodies; (3) separate domains whose mutation produces fibrillar structures surrounding nucleoli, causes loss of endogenous coiled bodies, disrupts nucleolar architecture with segregation of nucleolar antigens, and abolishes RNA polymerase I activity. p80 coilin was shown to be ubiquitously expressed in human tissues.\",\n      \"method\": \"Transient transfection of deletion/truncation mutants in HeLa cells, immunofluorescence, co-localization with snRNP markers, RNA polymerase I activity assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic domain-deletion mutagenesis with multiple orthogonal functional readouts (snRNP recruitment, nucleolar architecture, Pol I activity) establishing distinct functional domains\",\n      \"pmids\": [\"7490287\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"p80-coilin is an integral constituent of interchromatin granule-associated zones (IGAZs) in addition to coiled bodies. Both low-salt and high-salt (nuclear matrix) extractions preserved p80-coilin in these structures, indicating p80-coilin is a matrix-associated component of IGAZs.\",\n      \"method\": \"Immunoelectron microscopy with anti-p80-coilin antibody after low-salt loosening and high-salt/DNase I nuclear matrix extraction, in situ hybridization with snRNA probes\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, immunoelectron microscopy with biochemical fractionation; extends known localization to a new nuclear compartment\",\n      \"pmids\": [\"7622600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The murine p80 coilin gene (Coil) maps to the distal portion of chromosome band 11D and is composed of 7 exons spanning nearly 30 kb, producing an approximately 2.6-kb transcript expressed in all tissues with highest levels in brain and testis. The predicted amino acid sequence reveals two conserved N- and C-terminal domains orthologous to human p80-coilin and Xenopus SPH-1.\",\n      \"method\": \"Genomic library cloning, Northern blot analysis, chromosomal mapping, sequence analysis\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple methods (cloning, Northern blot, chromosomal mapping) confirming gene structure and expression; provides genetic model foundation but primarily structural/genomic characterization\",\n      \"pmids\": [\"10806077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"p80 coilin physically interacts with ataxin-1 (the SCA1 gene product). Yeast two-hybrid and co-immunoprecipitation demonstrated the interaction, and deletion mapping showed that the C-terminal regions of both ataxin-1 and p80 coilin are required for the interaction. In co-transfected HeLa cells, p80 coilin co-localizes with ataxin-1 aggregates in the nucleoplasm.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, deletion mutant mapping, immunofluorescence co-localization in HeLa cells and SCA1 transgenic mouse Purkinje cells\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus yeast two-hybrid plus domain mapping in single lab; interaction confirmed by two orthogonal methods\",\n      \"pmids\": [\"12757932\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CGI-55 co-localizes with p80-coilin-positive nuclear coiled bodies. Yeast two-hybrid screening identified CGI-55 interactions with nuclear body-associated proteins, and GFP-fusion protein imaging in HeLa cells showed CGI-55 localization to p80-coilin-positive nuclear foci.\",\n      \"method\": \"Yeast two-hybrid screen, GFP/RFP fusion protein co-localization imaging in HeLa cells\",\n      \"journal\": \"Cell biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, co-localization only without direct binding assay between CGI-55 and p80-coilin; p80-coilin used as a marker rather than as the studied protein\",\n      \"pmids\": [\"16679534\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"p80-coilin (COIL) is the defining marker protein of Cajal bodies (coiled bodies), nuclear organelles involved in snRNP biogenesis and subnuclear organization; its N-terminal domain (first ~102 amino acids) is necessary and sufficient for Cajal body targeting, its C-terminal domain is required for recruiting splicing snRNPs to Cajal bodies, and additional internal domains functionally interact with nucleolar architecture and RNA polymerase I activity; p80-coilin also physically interacts with ataxin-1 via their respective C-terminal regions, and the protein is ubiquitously expressed with the COIL gene located on chromosome 17q22-23.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"p80-coilin (COIL) is the defining marker protein of the Cajal body (coiled body), a nuclear organelle, and is an integral structural component required for the organization of this compartment and its recruitment of splicing snRNPs [#0, #3]. Coilin localization is governed by separable domains: its amino-terminal region (first ~102 amino acids) is necessary and sufficient for targeting to the coiled-body organelle, acting independently of the nuclear localization signal, while the carboxy-terminal domain is required to recruit splicing snRNPs—deletion of the C-terminus produces pseudo-coiled bodies and eliminates endogenous coiled bodies [#1, #3]. Internal domains of coilin functionally couple it to nucleolar architecture, since their mutation generates perinucleolar fibrillar structures, segregates nucleolar antigens, and abolishes RNA polymerase I activity [#3]. Beyond coiled bodies, coilin is a nuclear-matrix-associated constituent of interchromatin granule-associated zones [#4], and it physically interacts with ataxin-1 (the SCA1 gene product) through the C-terminal regions of both proteins, co-localizing with ataxin-1 aggregates in the nucleoplasm [#6]. The ubiquitously expressed protein is encoded by a 7-exon gene on chromosome 17q22-23 [#2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 1991,\n      \"claim\": \"Established the existence of a dedicated coiled-body marker protein, defining the molecular identity of this previously ultrastructurally-described nuclear organelle.\",\n      \"evidence\": \"Autoantibody-based immunoblot, immunofluorescence, immunoelectron microscopy, and cDNA expression cloning identifying an 80-kDa coiled-body protein\",\n      \"pmids\": [\"2033369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Function within the coiled body not yet defined\", \"Full-length sequence and domain organization not yet resolved\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Mapped a discrete N-terminal targeting determinant, showing coiled-body localization is encoded separately from nuclear import.\",\n      \"evidence\": \"Microinjection of myc-tagged coilin mRNA and deletion constructs into Xenopus oocytes with germinal-vesicle immunofluorescence\",\n      \"pmids\": [\"7532471\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular partner that reads the N-terminal targeting signal unknown\", \"Mechanism of organelle assembly versus targeting not distinguished\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Defined the gene locus and full-length protein architecture, providing the structural framework of two conserved N- and C-terminal domains.\",\n      \"evidence\": \"5'-RACE, genomic library screening, Northern blot, and FISH mapping to chromosome 17q22-23\",\n      \"pmids\": [\"7971277\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional roles of the conserved domains not assigned here\", \"Discrepancy between predicted mass and apparent 80-kDa size unexplained\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Assigned distinct functions to coilin domains, separating snRNP recruitment from nucleolar/Pol I coupling and revealing coilin as an organizer of multiple nuclear compartments.\",\n      \"evidence\": \"Systematic deletion/truncation mutagenesis in HeLa cells with snRNP co-localization, nucleolar antigen imaging, and RNA polymerase I activity assays\",\n      \"pmids\": [\"7490287\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical mechanism linking coilin to Pol I activity not established\", \"Identity of snRNP-recruiting binding partners not defined\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Extended coilin localization to interchromatin granule-associated zones as a nuclear-matrix-associated component, broadening its structural role beyond coiled bodies.\",\n      \"evidence\": \"Immunoelectron microscopy after low-salt and high-salt/DNase nuclear matrix extraction with snRNA in situ hybridization\",\n      \"pmids\": [\"7622600\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of IGAZ localization unknown\", \"Single-lab observation by IEM only\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identified a direct protein partner, ataxin-1, linking coilin to a neurodegenerative disease protein and to nucleoplasmic aggregate biology.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal co-immunoprecipitation, deletion mapping, and co-localization in HeLa cells and SCA1 transgenic mouse Purkinje cells\",\n      \"pmids\": [\"12757932\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of coilin-ataxin-1 binding for either coiled bodies or SCA1 pathology not established\", \"Single-lab interaction\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Used coilin as a coiled-body marker to place CGI-55 in this compartment, indicating the coiled body recruits additional nuclear-body-associated proteins.\",\n      \"evidence\": \"Yeast two-hybrid screen and GFP/RFP-fusion co-localization imaging in HeLa cells\",\n      \"pmids\": [\"16679534\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Co-localization only; no direct binding assay between CGI-55 and coilin\", \"Coilin studied as a marker, not as the functional subject\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which coilin assembles and maintains Cajal bodies, recruits snRNPs, and couples to RNA polymerase I activity remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the coilin-driven assembly\", \"Direct molecular partners for snRNP recruitment and Pol I coupling unidentified\", \"Physiological role of ataxin-1 interaction unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [4, 6]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\"Cajal body (coiled body)\", \"interchromatin granule-associated zones\"],\n    \"partners\": [\"ATXN1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}