{"gene":"JTB","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":1999,"finding":"JTB (Jumping Translocation Breakpoint) was identified as a novel gene at chromosome 1q21 encoding a transmembrane protein. In a jumping translocation, JTB fused with telomeric repeats of acceptor telomeres, resulting in a truncated hJTB product devoid of the transmembrane domain.","method":"Molecular cloning, chromosomal breakpoint mapping, sequence analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cloning and characterization of the breakpoint junction with sequence analysis in a single lab; transmembrane domain prediction confirmed by conservation across species","pmids":["10321732"],"is_preprint":false},{"year":2007,"finding":"JTB protein is processed at its N-terminus and localizes predominantly to mitochondria (not to the plasma membrane as originally predicted). When overexpressed, JTB induces clustering of mitochondria around the nuclear periphery, swelling of mitochondria, and significant reduction of mitochondrial membrane potential (assessed by JC-1 probe). These mitochondrial changes are dependent on N-terminal processing, as a cleavage-resistant mutant fails to produce these effects. JTB expression retards cell growth and confers resistance to TGF-β1-induced apoptosis.","method":"Subcellular fractionation, fluorescence microscopy (JC-1 membrane potential probe), overexpression of wild-type vs. cleavage-resistant mutant, cell growth assays, apoptosis assays","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (fractionation, live-cell imaging, mutagenesis of cleavage site, functional readouts) in a single lab","pmids":["17369841"],"is_preprint":false}],"current_model":"JTB encodes a transmembrane protein that, after N-terminal processing, localizes predominantly to mitochondria, where it disrupts mitochondrial membrane potential and morphology (causing clustering and swelling), retards cell growth, and confers resistance to TGF-β1-induced apoptosis; chromosomal jumping translocations at 1q21 truncate JTB and eliminate its transmembrane domain."},"narrative":{"mechanistic_narrative":"JTB (Jumping Translocation Breakpoint) encodes a transmembrane protein originally identified at chromosome 1q21, where jumping translocations fuse the gene to telomeric repeats and yield a truncated product lacking the transmembrane domain [PMID:10321732]. The mature protein undergoes N-terminal processing and localizes predominantly to mitochondria rather than the plasma membrane originally predicted [PMID:17369841]. Upon overexpression, JTB drives mitochondrial clustering around the nuclear periphery, mitochondrial swelling, and a marked reduction in mitochondrial membrane potential, all dependent on N-terminal cleavage since a cleavage-resistant mutant abolishes these effects [PMID:17369841]. Functionally, JTB retards cell growth and confers resistance to TGF-β1-induced apoptosis [PMID:17369841]. Beyond these findings, no further mechanistic detail — molecular partners, the protease responsible for processing, or the basis of apoptosis resistance — has been characterized in the available corpus.","teleology":[{"year":1999,"claim":"Established JTB as a gene whose disruption is structurally linked to cancer-associated chromosomal rearrangements, defining the truncation event at 1q21.","evidence":"Molecular cloning and chromosomal breakpoint mapping of a jumping translocation junction with sequence analysis","pmids":["10321732"],"confidence":"Medium","gaps":["Functional consequence of the truncation not tested","Subcellular localization and biochemical activity of the protein unresolved at this stage","Single-lab breakpoint characterization"]},{"year":2007,"claim":"Revised the predicted plasma-membrane localization to a mitochondrial one and tied JTB's processing to functional control of mitochondrial integrity, growth, and apoptosis resistance.","evidence":"Subcellular fractionation, JC-1 membrane-potential imaging, wild-type versus cleavage-resistant mutant overexpression, and growth/apoptosis assays in a single lab","pmids":["17369841"],"confidence":"Medium","gaps":["Protease responsible for N-terminal processing not identified","Molecular partners or mechanism connecting JTB to membrane potential loss unknown","Mechanism of TGF-β1-induced apoptosis resistance not defined","Effects shown under overexpression; endogenous role not established"]},{"year":null,"claim":"How JTB processing mechanistically perturbs mitochondrial physiology and links to apoptosis resistance and growth control remains unresolved.","evidence":"No further mechanistic studies present in the timeline","pmids":[],"confidence":"Medium","gaps":["No identified direct binding partners or substrates","No structural model","No loss-of-function (endogenous) phenotype characterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[1]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O76095","full_name":"Protein JTB","aliases":["Jumping translocation breakpoint protein","Prostate androgen-regulated protein","PAR protein"],"length_aa":146,"mass_kda":16.4,"function":"Required for normal cytokinesis during mitosis. Plays a role in the regulation of cell proliferation. May be a component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Increases AURKB activity. Inhibits apoptosis induced by TGFB1 (By similarity). Overexpression induces swelling of mitochondria and reduces mitochondrial membrane potential (By similarity)","subcellular_location":"Membrane; Mitochondrion; Cytoplasm; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/O76095/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/JTB","classification":"Not Classified","n_dependent_lines":153,"n_total_lines":1208,"dependency_fraction":0.12665562913907286},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"GPR107","stoichiometry":0.2},{"gene":"TMED10","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/JTB","total_profiled":1310},"omim":[{"mim_id":"620867","title":"ARMADILLO-LIKE HELICAL DOMAIN-CONTAINING PROTEIN 3; ARMH3","url":"https://www.omim.org/entry/620867"},{"mim_id":"620652","title":"SH3 DOMAIN-BINDING PROTEIN 5-LIKE; SH3BP5L","url":"https://www.omim.org/entry/620652"},{"mim_id":"607138","title":"cAMP RESPONSE ELEMENT-BINDING PROTEIN 3-LIKE 4; CREB3L4","url":"https://www.omim.org/entry/607138"},{"mim_id":"605612","title":"SH3 DOMAIN-BINDING PROTEIN 5; SH3BP5","url":"https://www.omim.org/entry/605612"},{"mim_id":"604671","title":"JUMPING TRANSLOCATION BREAKPOINT; JTB","url":"https://www.omim.org/entry/604671"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"},{"location":"Mitochondria","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/JTB"},"hgnc":{"alias_symbol":["hJT","PAR"],"prev_symbol":[]},"alphafold":{"accession":"O76095","domains":[{"cath_id":"3.30.720.220","chopping":"47-97","consensus_level":"high","plddt":87.2822,"start":47,"end":97},{"cath_id":"1.20.5","chopping":"99-146","consensus_level":"medium","plddt":90.3198,"start":99,"end":146}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O76095","model_url":"https://alphafold.ebi.ac.uk/files/AF-O76095-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O76095-F1-predicted_aligned_error_v6.png","plddt_mean":78.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=JTB","jax_strain_url":"https://www.jax.org/strain/search?query=JTB"},"sequence":{"accession":"O76095","fasta_url":"https://rest.uniprot.org/uniprotkb/O76095.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O76095/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O76095"}},"corpus_meta":[{"pmid":"22391446","id":"PMC_22391446","title":"On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1.","date":"2012","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/22391446","citation_count":621,"is_preprint":false},{"pmid":"17981131","id":"PMC_17981131","title":"The PAR proteins: fundamental players in animal cell polarization.","date":"2007","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/17981131","citation_count":605,"is_preprint":false},{"pmid":"16525119","id":"PMC_16525119","title":"The PAR-aPKC system: lessons in polarity.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16525119","citation_count":575,"is_preprint":false},{"pmid":"9020112","id":"PMC_9020112","title":"Interactions of mast cell tryptase with thrombin receptors and PAR-2.","date":"1997","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9020112","citation_count":511,"is_preprint":false},{"pmid":"12629552","id":"PMC_12629552","title":"The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl.","date":"2003","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12629552","citation_count":453,"is_preprint":false},{"pmid":"14675534","id":"PMC_14675534","title":"Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells.","date":"2003","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/14675534","citation_count":345,"is_preprint":false},{"pmid":"15723051","id":"PMC_15723051","title":"PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1.","date":"2005","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15723051","citation_count":313,"is_preprint":false},{"pmid":"9834192","id":"PMC_9834192","title":"PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos.","date":"1999","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/9834192","citation_count":252,"is_preprint":false},{"pmid":"20833361","id":"PMC_20833361","title":"Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation.","date":"2010","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/20833361","citation_count":214,"is_preprint":false},{"pmid":"11433294","id":"PMC_11433294","title":"PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.","date":"2001","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11433294","citation_count":205,"is_preprint":false},{"pmid":"22213601","id":"PMC_22213601","title":"Identification of RNA-protein interaction networks using PAR-CLIP.","date":"2011","source":"Wiley interdisciplinary reviews. 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proteinase-activated receptor 1-4 (PAR 1-4) in human cancer.","date":"2010","source":"Journal of molecular histology","url":"https://pubmed.ncbi.nlm.nih.gov/20563836","citation_count":46,"is_preprint":false},{"pmid":"25128809","id":"PMC_25128809","title":"PAR polarity: from complexity to design principles.","date":"2014","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25128809","citation_count":44,"is_preprint":false},{"pmid":"10321732","id":"PMC_10321732","title":"JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation.","date":"1999","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/10321732","citation_count":43,"is_preprint":false},{"pmid":"28236972","id":"PMC_28236972","title":"Regulation of Cell Polarity by PAR-1/MARK Kinase.","date":"2016","source":"Current topics in developmental 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[et al.]","url":"https://pubmed.ncbi.nlm.nih.gov/19184346","citation_count":40,"is_preprint":false},{"pmid":"35110404","id":"PMC_35110404","title":"Mice expressing fluorescent PAR2 reveal that endocytosis mediates colonic inflammation and pain.","date":"2022","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/35110404","citation_count":39,"is_preprint":false},{"pmid":"21091637","id":"PMC_21091637","title":"NAD+ depletion or PAR polymer formation: which plays the role of executioner in ischaemic cell death?","date":"2011","source":"Acta physiologica (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21091637","citation_count":38,"is_preprint":false},{"pmid":"16143343","id":"PMC_16143343","title":"Thrombin and PAR-1-AP increase proinflammatory cytokine expression in C6 cells.","date":"2005","source":"The Journal of surgical research","url":"https://pubmed.ncbi.nlm.nih.gov/16143343","citation_count":38,"is_preprint":false},{"pmid":"16425301","id":"PMC_16425301","title":"Expression of protease activated receptor-2 (PAR-2) in gastric cancer.","date":"2006","source":"Journal of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/16425301","citation_count":37,"is_preprint":false},{"pmid":"22885304","id":"PMC_22885304","title":"Quantitative mass spectrometry and PAR-CLIP to identify RNA-protein interactions.","date":"2012","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/22885304","citation_count":36,"is_preprint":false},{"pmid":"31434613","id":"PMC_31434613","title":"PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib.","date":"2019","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/31434613","citation_count":34,"is_preprint":false},{"pmid":"20530726","id":"PMC_20530726","title":"Protease-activated receptor-2 (PAR(2)) in human periodontitis.","date":"2010","source":"Journal of dental research","url":"https://pubmed.ncbi.nlm.nih.gov/20530726","citation_count":33,"is_preprint":false},{"pmid":"25977476","id":"PMC_25977476","title":"Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin-Gαi3 signaling.","date":"2015","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/25977476","citation_count":33,"is_preprint":false},{"pmid":"28554895","id":"PMC_28554895","title":"PAR-1 promotes microtubule breakdown during dendrite pruning in Drosophila.","date":"2017","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/28554895","citation_count":33,"is_preprint":false},{"pmid":"17369841","id":"PMC_17369841","title":"Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-beta1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17369841","citation_count":31,"is_preprint":false},{"pmid":"16382046","id":"PMC_16382046","title":"Regulation of cancer cell survival by Par-4.","date":"2005","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/16382046","citation_count":31,"is_preprint":false},{"pmid":"18836307","id":"PMC_18836307","title":"Apoptosis and tumor resistance conferred by Par-4.","date":"2008","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/18836307","citation_count":30,"is_preprint":false},{"pmid":"26416962","id":"PMC_26416962","title":"PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division.","date":"2015","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/26416962","citation_count":30,"is_preprint":false},{"pmid":"25262242","id":"PMC_25262242","title":"Canonical and noncanonical roles of Par-1/MARK kinases in cell migration.","date":"2014","source":"International review of cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/25262242","citation_count":29,"is_preprint":false},{"pmid":"33078834","id":"PMC_33078834","title":"The PAR-1 antagonist vorapaxar ameliorates kidney injury and tubulointerstitial fibrosis.","date":"2020","source":"Clinical science (London, England : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/33078834","citation_count":29,"is_preprint":false},{"pmid":"26455305","id":"PMC_26455305","title":"A Par-1-Par-3-Centrosome Cell Polarity Pathway and Its Tuning for Isotropic Cell Adhesion.","date":"2015","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/26455305","citation_count":29,"is_preprint":false},{"pmid":"31124192","id":"PMC_31124192","title":"HIV-1 Tat promotes astrocytic release of CCL2 through MMP/PAR-1 signaling.","date":"2019","source":"Glia","url":"https://pubmed.ncbi.nlm.nih.gov/31124192","citation_count":29,"is_preprint":false},{"pmid":"35417695","id":"PMC_35417695","title":"A particle size threshold governs diffusion and segregation of PAR-3 during cell polarization.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/35417695","citation_count":28,"is_preprint":false},{"pmid":"21613819","id":"PMC_21613819","title":"Systemic Par-4 inhibits non-autochthonous tumor growth.","date":"2011","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/21613819","citation_count":28,"is_preprint":false},{"pmid":"18676842","id":"PMC_18676842","title":"Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity.","date":"2008","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/18676842","citation_count":28,"is_preprint":false},{"pmid":"17761536","id":"PMC_17761536","title":"PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17761536","citation_count":28,"is_preprint":false},{"pmid":"34030964","id":"PMC_34030964","title":"Studying PAR-Dependent Chromatin Remodeling to Tackle PARPi Resistance.","date":"2021","source":"Trends in molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34030964","citation_count":27,"is_preprint":false},{"pmid":"25689283","id":"PMC_25689283","title":"Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis.","date":"2015","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25689283","citation_count":27,"is_preprint":false},{"pmid":"12506061","id":"PMC_12506061","title":"Human corneal epithelial cells express functional PAR-1 and PAR-2.","date":"2003","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/12506061","citation_count":27,"is_preprint":false},{"pmid":"32084408","id":"PMC_32084408","title":"A Conserved PDZ-Binding Motif in aPKC Interacts with Par-3 and Mediates Cortical Polarity.","date":"2020","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/32084408","citation_count":27,"is_preprint":false},{"pmid":"10664248","id":"PMC_10664248","title":"The two-receptor system PAR-1/PAR-4 mediates alpha-thrombin-induced [Ca(2+)](i) mobilization in human astrocytoma cells.","date":"2000","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/10664248","citation_count":26,"is_preprint":false},{"pmid":"33565714","id":"PMC_33565714","title":"Par-3 family proteins in cell polarity & adhesion.","date":"2021","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/33565714","citation_count":25,"is_preprint":false},{"pmid":"17936340","id":"PMC_17936340","title":"Protease-activated receptor-2 (PAR-2) in cervical cancer proliferation.","date":"2007","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/17936340","citation_count":25,"is_preprint":false},{"pmid":"11743661","id":"PMC_11743661","title":"PAR-1- and PAR-3-type thrombin receptor expression in primary cultures of human renal cell carcinoma cells.","date":"2002","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/11743661","citation_count":25,"is_preprint":false},{"pmid":"26020638","id":"PMC_26020638","title":"Macrophage Migration Inhibitory Factor Mediates PAR-Induced Bladder Pain.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26020638","citation_count":25,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":41971,"output_tokens":865,"usd":0.069444,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7006,"output_tokens":1189,"usd":0.032377,"stage2_stop_reason":"end_turn"},"total_usd":0.101821,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical JTB gene (Jumping Translocation Breakpoint, also known as hJT or PAR in the HGNC alias sense). \n\nThe vast majority of papers in this corpus are about completely different genes/proteins that happen to share aliases:\n- \"PAR\" proteins (PAR-1, PAR-2, PAR-3, PAR-4, PAR-6) in cell polarity (C. elegans/Drosophila/mammalian)\n- \"PAR\" = Protease-Activated Receptors (PAR-1 through PAR-4)\n- \"PAR\" = Poly(ADP-ribose)\n- \"PAR-4\" = Prostate Apoptosis Response-4 (a different protein from JTB)\n- Pseudoautosomal regions (PAR)\n- PAR-CLIP methodology\n\nOnly **paper [66]** and **paper [80]** are about the canonical JTB gene.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"JTB (Jumping Translocation Breakpoint) was identified as a novel gene at chromosome 1q21 encoding a transmembrane protein. In a jumping translocation, JTB fused with telomeric repeats of acceptor telomeres, resulting in a truncated hJTB product devoid of the transmembrane domain.\",\n      \"method\": \"Molecular cloning, chromosomal breakpoint mapping, sequence analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cloning and characterization of the breakpoint junction with sequence analysis in a single lab; transmembrane domain prediction confirmed by conservation across species\",\n      \"pmids\": [\"10321732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"JTB protein is processed at its N-terminus and localizes predominantly to mitochondria (not to the plasma membrane as originally predicted). When overexpressed, JTB induces clustering of mitochondria around the nuclear periphery, swelling of mitochondria, and significant reduction of mitochondrial membrane potential (assessed by JC-1 probe). These mitochondrial changes are dependent on N-terminal processing, as a cleavage-resistant mutant fails to produce these effects. JTB expression retards cell growth and confers resistance to TGF-β1-induced apoptosis.\",\n      \"method\": \"Subcellular fractionation, fluorescence microscopy (JC-1 membrane potential probe), overexpression of wild-type vs. cleavage-resistant mutant, cell growth assays, apoptosis assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (fractionation, live-cell imaging, mutagenesis of cleavage site, functional readouts) in a single lab\",\n      \"pmids\": [\"17369841\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"JTB encodes a transmembrane protein that, after N-terminal processing, localizes predominantly to mitochondria, where it disrupts mitochondrial membrane potential and morphology (causing clustering and swelling), retards cell growth, and confers resistance to TGF-β1-induced apoptosis; chromosomal jumping translocations at 1q21 truncate JTB and eliminate its transmembrane domain.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"JTB (Jumping Translocation Breakpoint) encodes a transmembrane protein originally identified at chromosome 1q21, where jumping translocations fuse the gene to telomeric repeats and yield a truncated product lacking the transmembrane domain [#0]. The mature protein undergoes N-terminal processing and localizes predominantly to mitochondria rather than the plasma membrane originally predicted [#1]. Upon overexpression, JTB drives mitochondrial clustering around the nuclear periphery, mitochondrial swelling, and a marked reduction in mitochondrial membrane potential, all dependent on N-terminal cleavage since a cleavage-resistant mutant abolishes these effects [#1]. Functionally, JTB retards cell growth and confers resistance to TGF-\\u03b21-induced apoptosis [#1]. Beyond these findings, no further mechanistic detail \\u2014 molecular partners, the protease responsible for processing, or the basis of apoptosis resistance \\u2014 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established JTB as a gene whose disruption is structurally linked to cancer-associated chromosomal rearrangements, defining the truncation event at 1q21.\",\n      \"evidence\": \"Molecular cloning and chromosomal breakpoint mapping of a jumping translocation junction with sequence analysis\",\n      \"pmids\": [\"10321732\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the truncation not tested\",\n        \"Subcellular localization and biochemical activity of the protein unresolved at this stage\",\n        \"Single-lab breakpoint characterization\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Revised the predicted plasma-membrane localization to a mitochondrial one and tied JTB's processing to functional control of mitochondrial integrity, growth, and apoptosis resistance.\",\n      \"evidence\": \"Subcellular fractionation, JC-1 membrane-potential imaging, wild-type versus cleavage-resistant mutant overexpression, and growth/apoptosis assays in a single lab\",\n      \"pmids\": [\"17369841\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Protease responsible for N-terminal processing not identified\",\n        \"Molecular partners or mechanism connecting JTB to membrane potential loss unknown\",\n        \"Mechanism of TGF-\\u03b21-induced apoptosis resistance not defined\",\n        \"Effects shown under overexpression; endogenous role not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How JTB processing mechanistically perturbs mitochondrial physiology and links to apoptosis resistance and growth control remains unresolved.\",\n      \"evidence\": \"No further mechanistic studies present in the timeline\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No identified direct binding partners or substrates\",\n        \"No structural model\",\n        \"No loss-of-function (endogenous) phenotype characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}