{"gene":"JTB","run_date":"2026-04-28T18:06:54","timeline":{"discoveries":[{"year":1999,"finding":"JTB (Jumping Translocation Breakpoint) was identified as a novel gene at chromosomal locus 1q21 that encodes a transmembrane protein highly conserved across eukaryotic species. In a case of jumping translocation (JT), JTB fuses with telomeric repeats of acceptor telomeres, producing a truncated product devoid of the transmembrane domain. The gene resides in the Epidermal Differentiation Complex (EDC) gene-rich region at 1q21.","method":"Molecular cloning, positional mapping, sequence analysis of jumping translocation breakpoints","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 — original gene identification with direct sequencing, cloning, and structural characterization; foundational paper","pmids":["10321732"],"is_preprint":false},{"year":2000,"finding":"The PAR gene (identical to JTB) encodes a 146-amino acid protein with sequence motifs for myristoylation and phosphorylation by protein kinase C, suggesting membrane association and post-translational regulation. PAR/JTB was found to be overexpressed in prostate carcinoma cell lines and downregulated by androgens in androgen-sensitive (LNCaP) but not androgen-resistant prostate cancer cells.","method":"Representational difference analysis, cDNA sequencing, Northern blot, RT-PCR, sequence motif analysis","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 3 — sequence-based motif identification with expression characterization; single lab, limited mechanistic validation","pmids":["10762645"],"is_preprint":false},{"year":2009,"finding":"JTB protein interacts directly with hepatitis B surface antigen (HBsAg), specifically via the S region of HBsAg. Overexpression of JTB conferred resistance to ultraviolet radiation-induced apoptosis in 293FT cells, but co-overexpression of HBsAg compromised this protective effect, suggesting HBsAg sequesters JTB's anti-apoptotic function.","method":"Mammalian two-hybrid assay, co-immunoprecipitation, GST pull-down, laser scanning confocal microscopy, UV-induced apoptosis assay","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2-3 — multiple orthogonal binding assays (two-hybrid, co-IP, GST pull-down) plus functional apoptosis readout; single lab","pmids":["19487072"],"is_preprint":false},{"year":2011,"finding":"The NMR solution structure of the N-terminal ectodomain of human JTB was determined, revealing a fold architecture that is a new variant of a three-β-strand antiparallel β-meander. The JTB ectodomain has a distant structural relationship to the midkine/pleiotrophin fold, particularly in distinctive disulfide bridge patterns, suggesting potential involvement in protein–protein or extracellular matrix interactions. Translocations at the JTB locus produce a truncated gene potentially encoding a soluble secreted ectodomain.","method":"NMR spectroscopy, structural determination, sequence/structural comparison","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — experimental NMR structure determination with structural validation; single lab but rigorous method","pmids":["22079049"],"is_preprint":false},{"year":2011,"finding":"PAR/JTB protein is a short-lived protein that peaks in expression during the G2/M phase of the cell cycle and exhibits dynamic subcellular localization during mitosis: it localizes to centrosomes during prophase and metaphase, moves to the spindle midzone in anaphase, and concentrates at the midbody during telophase and cytokinesis. PAR/JTB forms complexes with Aurora A, survivin, Aurora B, and INCENP (chromosomal passenger proteins), colocalizes with Aurora A at centrosomes and with survivin at the midbody, and increases Aurora B kinase activity on histone H3. Depletion of PAR in DU145 cells caused defects in centrosome segregation, failed cytokinesis, chromosome misalignment, polyploidy, and increased apoptosis.","method":"Immunofluorescence microscopy, co-immunoprecipitation, in vitro kinase assay (Aurora B on histone H3), siRNA knockdown, flow cytometry","journal":"International journal of oncology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods: co-IP demonstrating complex formation, kinase activity assay, live/fixed-cell imaging of dynamic localization, and KD phenotype with specific mitotic readouts; single lab but comprehensive","pmids":["21225229"],"is_preprint":false},{"year":2012,"finding":"Knockdown of PAR/JTB expression by siRNA in human prostate cancer PC3 cells increased G2/M phase arrest and enhanced apoptosis. Mechanistically, PAR depletion decreased Bcl-2 expression, increased Bax expression, and elevated the Bax/Bcl-2 ratio, indicating JTB promotes cell survival at least partly through modulation of the Bcl-2/Bax apoptotic balance.","method":"siRNA knockdown, MTT proliferation assay, flow cytometry (cell cycle/apoptosis), Western blot (Bcl-2, Bax)","journal":"Zhonghua nan ke xue = National journal of andrology","confidence":"Medium","confidence_rationale":"Tier 3 — clean KD with defined phenotypic readouts (apoptosis, G2/M arrest) and molecular mechanism (Bcl-2/Bax); single lab, single method set","pmids":["23297497"],"is_preprint":false},{"year":2021,"finding":"Affinity-purification mass spectrometry (BioPlex 3.0) identified JTB as part of the human protein interactome in 293T cells, revealing physical interaction partners in the context of proteome-scale interaction mapping. JTB interactions were detected among the 118,162 interactions mapped across 14,586 proteins.","method":"Affinity-purification mass spectrometry (AP-MS), proteome-scale interaction network","journal":"Cell","confidence":"Low","confidence_rationale":"Tier 3 — large-scale AP-MS; JTB-specific interactions not individually validated in this study","pmids":["33961781"],"is_preprint":false},{"year":2022,"finding":"OpenCell endogenous tagging and confocal live-cell imaging localized JTB protein to a specific subcellular compartment in human cells, contributing to the cartography of human cellular organization. The localization data for JTB were derived from genome-engineered cells expressing endogenously tagged JTB.","method":"Genome engineering (endogenous tagging), confocal live-cell imaging, mass spectrometry","journal":"Science","confidence":"Low","confidence_rationale":"Tier 3 — endogenous tagging with live imaging provides localization data, but JTB-specific functional consequence not individually characterized in this large-scale study","pmids":["35271311"],"is_preprint":false}],"current_model":"JTB (Jumping Translocation Breakpoint) encodes a conserved transmembrane protein whose N-terminal ectodomain adopts a midkine-like three-β-strand antiparallel β-meander fold stabilized by disulfide bridges; the full-length protein contains myristoylation and PKC phosphorylation motifs, peaks in G2/M, dynamically localizes from centrosomes to the spindle midzone and midbody during mitosis, forms complexes with chromosomal passenger proteins Aurora A, Aurora B, survivin, and INCENP, stimulates Aurora B kinase activity on histone H3, and promotes cell survival by maintaining Bcl-2/Bax balance — functions disrupted by interaction with HBsAg or by chromosomal translocations that truncate the transmembrane domain."},"narrative":{"teleology":[{"year":1999,"claim":"Identification of JTB as a novel transmembrane gene at 1q21 established the locus disrupted in jumping translocations and showed that breakpoints truncate the transmembrane domain, potentially generating an aberrant soluble product.","evidence":"Molecular cloning and positional mapping of jumping translocation breakpoints in a leukemia patient","pmids":["10321732"],"confidence":"High","gaps":["No functional consequence of the truncation was demonstrated","Normal cellular role of the full-length protein was unknown","Expression pattern across normal tissues not characterized"]},{"year":2000,"claim":"Recognition that JTB (as PAR) is overexpressed in prostate cancer and carries myristoylation and PKC phosphorylation motifs suggested membrane-associated signaling roles and potential oncogenic relevance.","evidence":"Representational difference analysis, Northern blot, and RT-PCR in androgen-sensitive and -resistant prostate cancer lines","pmids":["10762645"],"confidence":"Medium","gaps":["Predicted post-translational modifications not experimentally verified","Mechanism linking androgen regulation to JTB expression unknown","Functional significance of overexpression in cancer not tested"]},{"year":2009,"claim":"Demonstration that JTB directly binds HBsAg and that this interaction abolishes JTB's anti-apoptotic activity revealed a host–virus interface and established JTB as a pro-survival factor.","evidence":"Mammalian two-hybrid, co-IP, GST pull-down, and UV-apoptosis assay in 293FT cells","pmids":["19487072"],"confidence":"Medium","gaps":["Downstream signaling pathway mediating anti-apoptotic effect was not identified","Relevance to HBV pathogenesis in hepatocytes not examined","Endogenous interaction stoichiometry not determined"]},{"year":2011,"claim":"Solving the NMR structure of the JTB ectodomain revealed a midkine-like β-meander fold, providing the first structural framework and suggesting potential extracellular interaction capabilities for the truncated soluble form.","evidence":"NMR solution structure determination and structural homology analysis","pmids":["22079049"],"confidence":"High","gaps":["No extracellular binding partner or ligand identified for the ectodomain","Functional consequence of the midkine-like fold not tested","Structure of the full-length transmembrane protein not determined"]},{"year":2011,"claim":"Discovery that JTB is a cell-cycle-regulated protein that peaks at G2/M, dynamically localizes to mitotic structures, complexes with chromosomal passenger proteins, and stimulates Aurora B kinase activity established its core mechanistic role in mitotic fidelity.","evidence":"Co-IP, in vitro Aurora B kinase assay on histone H3, immunofluorescence, siRNA knockdown with flow cytometry in DU145 cells","pmids":["21225229"],"confidence":"High","gaps":["Direct versus scaffolding mechanism of Aurora B stimulation not distinguished","Whether JTB is a formal CPC subunit or an accessory factor is unclear","Structural basis for interaction with Aurora kinases not resolved"]},{"year":2012,"claim":"Linking JTB depletion to increased Bax/Bcl-2 ratio and enhanced apoptosis in prostate cancer cells defined the molecular axis through which JTB promotes survival, connecting its mitotic and anti-apoptotic functions.","evidence":"siRNA knockdown, Western blot for Bcl-2 and Bax, flow cytometry for apoptosis and cell cycle in PC3 cells","pmids":["23297497"],"confidence":"Medium","gaps":["Whether JTB directly regulates Bcl-2 transcription or protein stability is unknown","Relationship between G2/M arrest and Bcl-2/Bax modulation not mechanistically dissected","Findings from a single prostate cancer cell line"]},{"year":null,"claim":"Key unresolved questions include how JTB structurally engages the CPC and Aurora kinases, whether the truncated soluble ectodomain has signaling activity, and what upstream signals regulate JTB turnover at G2/M.","evidence":"","pmids":[],"confidence":"High","gaps":["No reconstituted in vitro system for JTB-Aurora B activation","Physiological role of the ectodomain fold remains untested","In vivo knockout or transgenic models have not been reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[4]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[4]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[4,5]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[2,5]}],"complexes":[],"partners":["AURKA","AURKB","BIRC5","INCENP","HBSAG"],"other_free_text":[]},"mechanistic_narrative":"JTB (Jumping Translocation Breakpoint) is a conserved, short-lived transmembrane protein that functions in mitotic progression and cell survival. During mitosis, JTB dynamically relocalizes from centrosomes to the spindle midzone and midbody, forms complexes with chromosomal passenger proteins Aurora A, Aurora B, survivin, and INCENP, and stimulates Aurora B kinase activity on histone H3; its depletion causes centrosome segregation defects, chromosome misalignment, failed cytokinesis, and polyploidy [PMID:21225229]. JTB promotes cell survival by maintaining a low Bax/Bcl-2 ratio and confers resistance to UV-induced apoptosis, a protective function that is antagonized by direct interaction with hepatitis B surface antigen (HBsAg) [PMID:19487072, PMID:23297497]. The N-terminal ectodomain adopts a midkine-like three-β-strand antiparallel β-meander fold stabilized by disulfide bridges, and chromosomal translocations at the 1q21 locus can delete the transmembrane domain, potentially generating a soluble secreted form [PMID:10321732, PMID:22079049]."},"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 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National journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/23297497","citation_count":1,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"41249152","id":"PMC_41249152","title":"Knockdown of SUCLG2 inhibits glioblastoma proliferation and promotes apoptosis through LMNA acetylation and the mediation of H4K16la lactylation.","date":"2025","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/41249152","citation_count":1,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":42415,"output_tokens":430,"usd":0.066848},"stage2":{"model":"claude-opus-4-6","input_tokens":3443,"output_tokens":539,"usd":0.046035},"total_usd":0.329126,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":53127,"output_tokens":2929,"usd":0.101658},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5738,"output_tokens":1908,"usd":0.114585}},"stage1_raw":"Looking at the corpus, I need to identify papers about the human gene JTB (Jumping Translocation Breakpoint). Only one paper (PMID:10321732) directly describes JTB as a gene/protein. The vast majority of papers are about completely different proteins that share \"PAR\" nomenclature (PAR polarity proteins, PAR receptors, PARP, Par-4 apoptosis protein, PAR bZip transcription factors, etc.) — these are symbol collisions or unrelated genes.\n\nLet me extract the mechanistic finding from the one relevant paper:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"JTB (Jumping Translocation Breakpoint) encodes a transmembrane protein located at chromosomal region 1q21. In a case of jumping translocation, the JTB gene fuses with telomeric repeats of acceptor telomeres, resulting in a truncated JTB product that lacks the transmembrane domain.\",\n      \"method\": \"Molecular cloning, chromosomal mapping, and sequence analysis of the breakpoint in a jumping translocation case\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single study identifying gene structure and translocation consequence; no functional reconstitution or binding partner validation\",\n      \"pmids\": [\"10321732\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"JTB encodes a conserved eukaryotic transmembrane protein located at 1q21 that is disrupted by jumping translocations, producing a truncated product lacking its transmembrane domain; no further mechanistic characterization of its biochemical function, binding partners, or pathway position is available in the retrieved literature.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper and extract discoveries only from KEEP papers.\n\n**Classification:**\n\nFrom the main corpus (100 papers): The vast majority describe PAR proteins (PAR-1/2/3/4/6 polarity proteins, protease-activated receptors PAR-1/2/3/4, PAR bZip transcription factors, PARP/poly-ADP-ribose, pseudoautosomal region, etc.) — all EXCLUDE due to alias collision with non-JTB genes.\n\nFrom gene2pubmed-curated papers:\n- PMID:10321732 — JTB gene identification paper — KEEP\n- PMID:22079049 — NMR structure of JTB ectodomain — KEEP\n- PMID:21225229 — PAR/JTB protein cell cycle function — KEEP\n- PMID:19487072 — JTB interaction with HBsAg — KEEP\n- PMID:10762645 — PAR gene isolation (JTB/PAR, same gene) — KEEP\n- PMID:23297497 — PAR siRNA in PC3 cells — KEEP\n- PMID:12586295 — JTB overexpression in HCC — borderline (expression data primarily, but mentions jumping translocation context) — EXCLUDE (pure expression correlation)\n- PMID:27751357 — JT in MDS, JTB locus — clinical/cytogenetic, no mechanism — EXCLUDE\n- PMID:33961781 — BioPlex interactome (identifies JTB interactions) — KEEP\n- PMID:35271311 — OpenCell (JTB localization) — KEEP\n- PMID:21900206 — signal transduction PPI network — EXCLUDE (general network, JTB not specifically characterized)\n- PMID:21988832 — liver PPI network — EXCLUDE (general)\n- PMID:31536960 — mitochondrial interactome — KEEP if JTB specifically mentioned; general study — EXCLUDE\n- PMID:28986522 — APE1 interactome — EXCLUDE (about APE1)\n- Other cDNA/genomic papers (PMID:12477932, 15489334, 8619474, 9110174, 11042152, 21873635) — EXCLUDE (no mechanistic findings about JTB)\n- PMID:21832049 — TPPP/p25 — EXCLUDE\n- PMID:18029348 — subcellular atlas — borderline, general study — EXCLUDE (no JTB-specific mechanistic finding)\n- PMID:26472760 — gene essentiality screen — EXCLUDE (no JTB-specific mechanism)\n- PMID:32694731 — FASN GI screen — EXCLUDE\n- PMID:35559673 — CRISPR screens — EXCLUDE\n- PMID:41249152 — SUCLG2/GBM — EXCLUDE\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"JTB (Jumping Translocation Breakpoint) was identified as a novel gene at chromosomal locus 1q21 that encodes a transmembrane protein highly conserved across eukaryotic species. In a case of jumping translocation (JT), JTB fuses with telomeric repeats of acceptor telomeres, producing a truncated product devoid of the transmembrane domain. The gene resides in the Epidermal Differentiation Complex (EDC) gene-rich region at 1q21.\",\n      \"method\": \"Molecular cloning, positional mapping, sequence analysis of jumping translocation breakpoints\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — original gene identification with direct sequencing, cloning, and structural characterization; foundational paper\",\n      \"pmids\": [\"10321732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The PAR gene (identical to JTB) encodes a 146-amino acid protein with sequence motifs for myristoylation and phosphorylation by protein kinase C, suggesting membrane association and post-translational regulation. PAR/JTB was found to be overexpressed in prostate carcinoma cell lines and downregulated by androgens in androgen-sensitive (LNCaP) but not androgen-resistant prostate cancer cells.\",\n      \"method\": \"Representational difference analysis, cDNA sequencing, Northern blot, RT-PCR, sequence motif analysis\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — sequence-based motif identification with expression characterization; single lab, limited mechanistic validation\",\n      \"pmids\": [\"10762645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"JTB protein interacts directly with hepatitis B surface antigen (HBsAg), specifically via the S region of HBsAg. Overexpression of JTB conferred resistance to ultraviolet radiation-induced apoptosis in 293FT cells, but co-overexpression of HBsAg compromised this protective effect, suggesting HBsAg sequesters JTB's anti-apoptotic function.\",\n      \"method\": \"Mammalian two-hybrid assay, co-immunoprecipitation, GST pull-down, laser scanning confocal microscopy, UV-induced apoptosis assay\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — multiple orthogonal binding assays (two-hybrid, co-IP, GST pull-down) plus functional apoptosis readout; single lab\",\n      \"pmids\": [\"19487072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The NMR solution structure of the N-terminal ectodomain of human JTB was determined, revealing a fold architecture that is a new variant of a three-β-strand antiparallel β-meander. The JTB ectodomain has a distant structural relationship to the midkine/pleiotrophin fold, particularly in distinctive disulfide bridge patterns, suggesting potential involvement in protein–protein or extracellular matrix interactions. Translocations at the JTB locus produce a truncated gene potentially encoding a soluble secreted ectodomain.\",\n      \"method\": \"NMR spectroscopy, structural determination, sequence/structural comparison\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — experimental NMR structure determination with structural validation; single lab but rigorous method\",\n      \"pmids\": [\"22079049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PAR/JTB protein is a short-lived protein that peaks in expression during the G2/M phase of the cell cycle and exhibits dynamic subcellular localization during mitosis: it localizes to centrosomes during prophase and metaphase, moves to the spindle midzone in anaphase, and concentrates at the midbody during telophase and cytokinesis. PAR/JTB forms complexes with Aurora A, survivin, Aurora B, and INCENP (chromosomal passenger proteins), colocalizes with Aurora A at centrosomes and with survivin at the midbody, and increases Aurora B kinase activity on histone H3. Depletion of PAR in DU145 cells caused defects in centrosome segregation, failed cytokinesis, chromosome misalignment, polyploidy, and increased apoptosis.\",\n      \"method\": \"Immunofluorescence microscopy, co-immunoprecipitation, in vitro kinase assay (Aurora B on histone H3), siRNA knockdown, flow cytometry\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods: co-IP demonstrating complex formation, kinase activity assay, live/fixed-cell imaging of dynamic localization, and KD phenotype with specific mitotic readouts; single lab but comprehensive\",\n      \"pmids\": [\"21225229\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Knockdown of PAR/JTB expression by siRNA in human prostate cancer PC3 cells increased G2/M phase arrest and enhanced apoptosis. Mechanistically, PAR depletion decreased Bcl-2 expression, increased Bax expression, and elevated the Bax/Bcl-2 ratio, indicating JTB promotes cell survival at least partly through modulation of the Bcl-2/Bax apoptotic balance.\",\n      \"method\": \"siRNA knockdown, MTT proliferation assay, flow cytometry (cell cycle/apoptosis), Western blot (Bcl-2, Bax)\",\n      \"journal\": \"Zhonghua nan ke xue = National journal of andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — clean KD with defined phenotypic readouts (apoptosis, G2/M arrest) and molecular mechanism (Bcl-2/Bax); single lab, single method set\",\n      \"pmids\": [\"23297497\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Affinity-purification mass spectrometry (BioPlex 3.0) identified JTB as part of the human protein interactome in 293T cells, revealing physical interaction partners in the context of proteome-scale interaction mapping. JTB interactions were detected among the 118,162 interactions mapped across 14,586 proteins.\",\n      \"method\": \"Affinity-purification mass spectrometry (AP-MS), proteome-scale interaction network\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — large-scale AP-MS; JTB-specific interactions not individually validated in this study\",\n      \"pmids\": [\"33961781\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"OpenCell endogenous tagging and confocal live-cell imaging localized JTB protein to a specific subcellular compartment in human cells, contributing to the cartography of human cellular organization. The localization data for JTB were derived from genome-engineered cells expressing endogenously tagged JTB.\",\n      \"method\": \"Genome engineering (endogenous tagging), confocal live-cell imaging, mass spectrometry\",\n      \"journal\": \"Science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — endogenous tagging with live imaging provides localization data, but JTB-specific functional consequence not individually characterized in this large-scale study\",\n      \"pmids\": [\"35271311\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"JTB (Jumping Translocation Breakpoint) encodes a conserved transmembrane protein whose N-terminal ectodomain adopts a midkine-like three-β-strand antiparallel β-meander fold stabilized by disulfide bridges; the full-length protein contains myristoylation and PKC phosphorylation motifs, peaks in G2/M, dynamically localizes from centrosomes to the spindle midzone and midbody during mitosis, forms complexes with chromosomal passenger proteins Aurora A, Aurora B, survivin, and INCENP, stimulates Aurora B kinase activity on histone H3, and promotes cell survival by maintaining Bcl-2/Bax balance — functions disrupted by interaction with HBsAg or by chromosomal translocations that truncate the transmembrane domain.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"JTB (Jumping Translocation Breakpoint) encodes a transmembrane protein mapping to chromosomal region 1q21 that was identified at the breakpoint of a jumping translocation, where fusion with telomeric repeats generates a truncated product lacking its transmembrane domain [PMID:10321732]. Beyond its gene structure and involvement in this chromosomal rearrangement, the biochemical function, binding partners, and pathway context of JTB remain uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Cloning of the jumping translocation breakpoint revealed that JTB encodes a transmembrane protein at 1q21 and that the translocation truncates the transmembrane domain, establishing the gene's identity and structural consequence of the rearrangement.\",\n      \"evidence\": \"Molecular cloning, chromosomal mapping, and sequence analysis of the breakpoint in a jumping translocation case\",\n      \"pmids\": [\"10321732\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay was performed to determine the consequence of transmembrane domain loss\",\n        \"No binding partners or downstream signaling pathways identified\",\n        \"Single patient case; relevance of JTB truncation to oncogenesis not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity, subcellular trafficking, interacting partners, and physiological role of full-length JTB protein remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic or signaling activity assigned\",\n        \"No loss-of-function or gain-of-function phenotype characterized in model systems\",\n        \"No structural model available\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005886\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"JTB (Jumping Translocation Breakpoint) is a conserved, short-lived transmembrane protein that functions in mitotic progression and cell survival. During mitosis, JTB dynamically relocalizes from centrosomes to the spindle midzone and midbody, forms complexes with chromosomal passenger proteins Aurora A, Aurora B, survivin, and INCENP, and stimulates Aurora B kinase activity on histone H3; its depletion causes centrosome segregation defects, chromosome misalignment, failed cytokinesis, and polyploidy [PMID:21225229]. JTB promotes cell survival by maintaining a low Bax/Bcl-2 ratio and confers resistance to UV-induced apoptosis, a protective function that is antagonized by direct interaction with hepatitis B surface antigen (HBsAg) [PMID:19487072, PMID:23297497]. The N-terminal ectodomain adopts a midkine-like three-β-strand antiparallel β-meander fold stabilized by disulfide bridges, and chromosomal translocations at the 1q21 locus can delete the transmembrane domain, potentially generating a soluble secreted form [PMID:10321732, PMID:22079049].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Identification of JTB as a novel transmembrane gene at 1q21 established the locus disrupted in jumping translocations and showed that breakpoints truncate the transmembrane domain, potentially generating an aberrant soluble product.\",\n      \"evidence\": \"Molecular cloning and positional mapping of jumping translocation breakpoints in a leukemia patient\",\n      \"pmids\": [\"10321732\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No functional consequence of the truncation was demonstrated\",\n        \"Normal cellular role of the full-length protein was unknown\",\n        \"Expression pattern across normal tissues not characterized\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Recognition that JTB (as PAR) is overexpressed in prostate cancer and carries myristoylation and PKC phosphorylation motifs suggested membrane-associated signaling roles and potential oncogenic relevance.\",\n      \"evidence\": \"Representational difference analysis, Northern blot, and RT-PCR in androgen-sensitive and -resistant prostate cancer lines\",\n      \"pmids\": [\"10762645\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Predicted post-translational modifications not experimentally verified\",\n        \"Mechanism linking androgen regulation to JTB expression unknown\",\n        \"Functional significance of overexpression in cancer not tested\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Demonstration that JTB directly binds HBsAg and that this interaction abolishes JTB's anti-apoptotic activity revealed a host–virus interface and established JTB as a pro-survival factor.\",\n      \"evidence\": \"Mammalian two-hybrid, co-IP, GST pull-down, and UV-apoptosis assay in 293FT cells\",\n      \"pmids\": [\"19487072\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Downstream signaling pathway mediating anti-apoptotic effect was not identified\",\n        \"Relevance to HBV pathogenesis in hepatocytes not examined\",\n        \"Endogenous interaction stoichiometry not determined\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Solving the NMR structure of the JTB ectodomain revealed a midkine-like β-meander fold, providing the first structural framework and suggesting potential extracellular interaction capabilities for the truncated soluble form.\",\n      \"evidence\": \"NMR solution structure determination and structural homology analysis\",\n      \"pmids\": [\"22079049\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No extracellular binding partner or ligand identified for the ectodomain\",\n        \"Functional consequence of the midkine-like fold not tested\",\n        \"Structure of the full-length transmembrane protein not determined\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Discovery that JTB is a cell-cycle-regulated protein that peaks at G2/M, dynamically localizes to mitotic structures, complexes with chromosomal passenger proteins, and stimulates Aurora B kinase activity established its core mechanistic role in mitotic fidelity.\",\n      \"evidence\": \"Co-IP, in vitro Aurora B kinase assay on histone H3, immunofluorescence, siRNA knockdown with flow cytometry in DU145 cells\",\n      \"pmids\": [\"21225229\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct versus scaffolding mechanism of Aurora B stimulation not distinguished\",\n        \"Whether JTB is a formal CPC subunit or an accessory factor is unclear\",\n        \"Structural basis for interaction with Aurora kinases not resolved\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linking JTB depletion to increased Bax/Bcl-2 ratio and enhanced apoptosis in prostate cancer cells defined the molecular axis through which JTB promotes survival, connecting its mitotic and anti-apoptotic functions.\",\n      \"evidence\": \"siRNA knockdown, Western blot for Bcl-2 and Bax, flow cytometry for apoptosis and cell cycle in PC3 cells\",\n      \"pmids\": [\"23297497\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether JTB directly regulates Bcl-2 transcription or protein stability is unknown\",\n        \"Relationship between G2/M arrest and Bcl-2/Bax modulation not mechanistically dissected\",\n        \"Findings from a single prostate cancer cell line\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include how JTB structurally engages the CPC and Aurora kinases, whether the truncated soluble ectodomain has signaling activity, and what upstream signals regulate JTB turnover at G2/M.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No reconstituted in vitro system for JTB-Aurora B activation\",\n        \"Physiological role of the ectodomain fold remains untested\",\n        \"In vivo knockout or transgenic models have not been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [2, 5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"AURKA\",\n      \"AURKB\",\n      \"BIRC5\",\n      \"INCENP\",\n      \"HBsAg\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}