{"gene":"SUN3","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2010,"finding":"During mouse spermiogenesis, SUN3 forms a novel LINC complex with Nesprin1, distinct from a second LINC complex containing Sun1eta and Nesprin3; these two complexes polarize to opposite spermatid poles, likely linking the differentiating nucleus to surrounding cytoskeletal structures to enable directed shaping and elongation.","method":"Co-transfection/immunoprecipitation, expression analysis, immunofluorescence localization","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with localization data in a single lab, two complementary methods","pmids":["20711465"],"is_preprint":false},{"year":2015,"finding":"Sun4 localizes to the posterior nuclear envelope in spermatids and likely interacts with Sun3/Nesprin1 LINC components; Sun4 deficiency causes mislocalization of other LINC components including Sun3-associated proteins and disrupts manchette formation, leading to a globozoospermia-like phenotype.","method":"Immunofluorescence localization, Sun4 knockout mouse analysis, co-localization studies","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mouse with defined cellular phenotype and LINC component mislocalization, single lab","pmids":["26621829"],"is_preprint":false},{"year":2020,"finding":"SUN3 is essential for sperm head shaping during spermiogenesis: CRISPR/Cas9 Sun3 knockout male mice are infertile with globozoospermia-like phenotype, absent manchette microtubules, failed nuclear elongation, and acrosome defects. SUN3 physically interacts with SUN4 in mouse testes, and SUN4 protein levels are drastically reduced in Sun3-null mice.","method":"CRISPR/Cas9 knockout, co-immunoprecipitation (SUN3-SUN4 interaction), immunofluorescence, electron microscopy","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO with detailed phenotypic characterization plus Co-IP interaction data, multiple orthogonal methods in a single rigorous study","pmids":["32156700"],"is_preprint":false},{"year":2018,"finding":"The luminal domain of SUN3 forms oligomers and has defined mobility within the nuclear envelope of living cells, as characterized by fluorescence fluctuation spectroscopy (tsMSQ).","method":"Time-shifted mean-segmented Q (tsMSQ) fluorescence fluctuation spectroscopy in live cells","journal":"Methods (San Diego, Calif.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct biophysical measurement in live cells, single lab, single method","pmids":["30268407"],"is_preprint":false},{"year":2023,"finding":"SUN4 forms heteromeric assemblies with SUN3 in vivo and regulates SUN3 expression; SUN4 is an inner nuclear membrane protein with its C-terminal SUN domain in the perinuclear space and N-terminus in the nucleoplasm interacting with lamin B3.","method":"Co-immunoprecipitation, immunofluorescence, topology/domain analysis in spermatid nuclear envelope","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and topology experiments with multiple markers, single lab","pmids":["36825599"],"is_preprint":false}],"current_model":"SUN3 is a testis-specific inner nuclear membrane SUN-domain protein that forms a spermiogenesis-specific LINC complex with Nesprin1, physically interacts with SUN4 (and regulates its stability), and is essential for transducing cytoskeletal forces via the manchette to the nuclear envelope for sperm head elongation and shaping, as demonstrated by infertility and globozoospermia in Sun3 knockout mice."},"narrative":{"mechanistic_narrative":"SUN3 is a testis-specific SUN-domain protein of the inner nuclear membrane that assembles a spermiogenesis-specific LINC complex to couple the differentiating spermatid nucleus to surrounding cytoskeletal structures, enabling directed sperm head elongation and shaping [PMID:20711465, PMID:32156700]. During spermiogenesis SUN3 pairs with Nesprin1 to form a LINC complex that polarizes to one spermatid pole, distinct from a second Sun1eta–Nesprin3 complex at the opposite pole [PMID:20711465]. SUN3 physically interacts with SUN4 in testes, forming heteromeric assemblies within the nuclear envelope, and the two proteins are mutually interdependent: SUN4 levels are drastically reduced in Sun3-null mice, while SUN4 in turn regulates SUN3 expression and localization [PMID:32156700, PMID:36825599]. The luminal SUN3 domain self-associates into oligomers with defined mobility in the nuclear envelope [PMID:30268407]. CRISPR/Cas9 Sun3 knockout males are infertile and display a globozoospermia-like phenotype with absent manchette microtubules, failed nuclear elongation, and acrosome defects, establishing SUN3 as essential for transmitting manchette-derived cytoskeletal forces across the nuclear envelope during sperm head morphogenesis [PMID:32156700].","teleology":[{"year":2010,"claim":"Identified SUN3 as a component of a spermiogenesis-specific LINC complex, defining how the differentiating spermatid nucleus might physically engage the cytoskeleton for shaping.","evidence":"Co-IP and immunofluorescence localization in mouse spermatids showing SUN3–Nesprin1 association polarized opposite a Sun1eta–Nesprin3 complex","pmids":["20711465"],"confidence":"Medium","gaps":["Functional consequence of the SUN3–Nesprin1 complex not tested by loss-of-function","Cytoskeletal element bridged by the complex not directly identified"]},{"year":2015,"claim":"Placed SUN3 within a broader spermatid LINC network by showing SUN4 loss mislocalizes SUN3-associated components and disrupts manchette formation, hinting at interdependence among posterior nuclear envelope SUN proteins.","evidence":"Sun4 knockout mouse analysis with immunofluorescence and co-localization studies","pmids":["26621829"],"confidence":"Medium","gaps":["Direct SUN3–SUN4 physical interaction not yet demonstrated here","SUN3 own loss-of-function phenotype not addressed"]},{"year":2018,"claim":"Characterized the biophysical behavior of the SUN3 luminal domain, establishing that it oligomerizes within the nuclear envelope of living cells.","evidence":"Time-shifted mean-segmented Q (tsMSQ) fluorescence fluctuation spectroscopy in live cells","pmids":["30268407"],"confidence":"Medium","gaps":["Oligomeric stoichiometry in native spermatids not resolved","Relationship of oligomerization to LINC assembly untested"]},{"year":2020,"claim":"Established SUN3 as essential and non-redundant for sperm head shaping and defined its physical and regulatory dependence on SUN4.","evidence":"CRISPR/Cas9 Sun3 knockout mice with EM and immunofluorescence phenotyping plus SUN3–SUN4 Co-IP","pmids":["32156700"],"confidence":"High","gaps":["Mechanism by which SUN3 loss abolishes manchette microtubules not resolved","Direct force-transmission measurement not performed"]},{"year":2023,"claim":"Defined SUN4 topology and its reciprocal regulation of SUN3, completing the picture of a SUN3–SUN4 heteromeric assembly anchored to the nuclear lamina.","evidence":"Co-IP, immunofluorescence, and topology analysis showing SUN4 C-terminal SUN domain in perinuclear space and N-terminus contacting lamin B3","pmids":["36825599"],"confidence":"Medium","gaps":["SUN3 own membrane topology and lamin contacts not directly mapped here","Stoichiometry of SUN3–SUN4 heteromers unknown"]},{"year":null,"claim":"How the SUN3–SUN4 LINC complex mechanically couples manchette microtubule forces to nuclear envelope deformation, and what drives complex assembly, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct measurement of force transmission through the complex","Structural model of the SUN3–SUN4 assembly absent","Upstream signals timing complex assembly during spermiogenesis unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,1,2,3,4]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2]}],"complexes":["LINC complex (SUN3–Nesprin1)"],"partners":["SUN4","SYNE1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TAQ9","full_name":"SUN domain-containing protein 3","aliases":["Sad1/unc-84 domain-containing protein 1"],"length_aa":357,"mass_kda":40.5,"function":"As a probable component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nuclear remodeling during sperm head formation in spermatogenesis. A probable SUN3:SYNE1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette","subcellular_location":"Membrane; Nucleus envelope; Nucleus inner membrane","url":"https://www.uniprot.org/uniprotkb/Q8TAQ9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SUN3","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1207,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SUN3","total_profiled":1310},"omim":[{"mim_id":"618984","title":"SAD1 AND UNC84 DOMAIN-CONTAINING PROTEIN 3; SUN3","url":"https://www.omim.org/entry/618984"},{"mim_id":"610861","title":"SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 3; SYNE3","url":"https://www.omim.org/entry/610861"},{"mim_id":"608441","title":"SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 1; SYNE1","url":"https://www.omim.org/entry/608441"},{"mim_id":"607723","title":"SAD1 AND UNC84 DOMAIN-CONTAINING PROTEIN 1; SUN1","url":"https://www.omim.org/entry/607723"},{"mim_id":"603038","title":"SPERM-ASSOCIATED ANTIGEN 4; SPAG4","url":"https://www.omim.org/entry/603038"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"testis","ntpm":38.8}],"url":"https://www.proteinatlas.org/search/SUN3"},"hgnc":{"alias_symbol":["MGC33329"],"prev_symbol":["SUNC1"]},"alphafold":{"accession":"Q8TAQ9","domains":[{"cath_id":"2.60.120.260","chopping":"191-354","consensus_level":"high","plddt":92.701,"start":191,"end":354},{"cath_id":"1.20.5","chopping":"57-109","consensus_level":"medium","plddt":69.3411,"start":57,"end":109}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TAQ9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TAQ9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TAQ9-F1-predicted_aligned_error_v6.png","plddt_mean":76.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SUN3","jax_strain_url":"https://www.jax.org/strain/search?query=SUN3"},"sequence":{"accession":"Q8TAQ9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TAQ9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TAQ9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TAQ9"}},"corpus_meta":[{"pmid":"20711465","id":"PMC_20711465","title":"Mammalian sperm head formation involves different polarization of two novel LINC complexes.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20711465","citation_count":122,"is_preprint":false},{"pmid":"19193627","id":"PMC_19193627","title":"A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.","date":"2009","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19193627","citation_count":91,"is_preprint":false},{"pmid":"26621829","id":"PMC_26621829","title":"The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility.","date":"2015","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/26621829","citation_count":60,"is_preprint":false},{"pmid":"32156700","id":"PMC_32156700","title":"The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32156700","citation_count":53,"is_preprint":false},{"pmid":"21711156","id":"PMC_21711156","title":"SPAG4L, a novel nuclear envelope protein involved in the meiotic stage of spermatogenesis.","date":"2011","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21711156","citation_count":35,"is_preprint":false},{"pmid":"24010407","id":"PMC_24010407","title":"A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthritis and spondyloarthropathy.","date":"2013","source":"Clinical proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/24010407","citation_count":20,"is_preprint":false},{"pmid":"36825599","id":"PMC_36825599","title":"SUN4 is a spermatid type II inner nuclear membrane protein that forms heteromeric assemblies with SUN3 and interacts with lamin B3.","date":"2023","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/36825599","citation_count":9,"is_preprint":false},{"pmid":"30268407","id":"PMC_30268407","title":"Protein oligomerization and mobility within the nuclear envelope evaluated by the time-shifted mean-segmented Q factor.","date":"2018","source":"Methods (San Diego, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/30268407","citation_count":9,"is_preprint":false},{"pmid":"33763102","id":"PMC_33763102","title":"Evolution and Functional Divergence of SUN Genes in Plants.","date":"2021","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/33763102","citation_count":7,"is_preprint":false},{"pmid":"30359793","id":"PMC_30359793","title":"Molecular evolution of SUN-domain containing proteins in diverse plant species and their expression profiling in response to developmental and perturbation stimuli.","date":"2018","source":"Phytochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30359793","citation_count":6,"is_preprint":false},{"pmid":"31531877","id":"PMC_31531877","title":"CBP-triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer.","date":"2019","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/31531877","citation_count":3,"is_preprint":false},{"pmid":"39434140","id":"PMC_39434140","title":"Screening differentially expressed proteins to distinguish thymoma (B1 and B3) from thymic cysts based on tandem mass tag (TMT) technology.","date":"2024","source":"Journal of cardiothoracic surgery","url":"https://pubmed.ncbi.nlm.nih.gov/39434140","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7716,"output_tokens":1163,"usd":0.020296,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7781,"output_tokens":2192,"usd":0.046852,"stage2_stop_reason":"end_turn"},"total_usd":0.067148,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"During mouse spermiogenesis, SUN3 forms a novel LINC complex with Nesprin1, distinct from a second LINC complex containing Sun1eta and Nesprin3; these two complexes polarize to opposite spermatid poles, likely linking the differentiating nucleus to surrounding cytoskeletal structures to enable directed shaping and elongation.\",\n      \"method\": \"Co-transfection/immunoprecipitation, expression analysis, immunofluorescence localization\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with localization data in a single lab, two complementary methods\",\n      \"pmids\": [\"20711465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Sun4 localizes to the posterior nuclear envelope in spermatids and likely interacts with Sun3/Nesprin1 LINC components; Sun4 deficiency causes mislocalization of other LINC components including Sun3-associated proteins and disrupts manchette formation, leading to a globozoospermia-like phenotype.\",\n      \"method\": \"Immunofluorescence localization, Sun4 knockout mouse analysis, co-localization studies\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse with defined cellular phenotype and LINC component mislocalization, single lab\",\n      \"pmids\": [\"26621829\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SUN3 is essential for sperm head shaping during spermiogenesis: CRISPR/Cas9 Sun3 knockout male mice are infertile with globozoospermia-like phenotype, absent manchette microtubules, failed nuclear elongation, and acrosome defects. SUN3 physically interacts with SUN4 in mouse testes, and SUN4 protein levels are drastically reduced in Sun3-null mice.\",\n      \"method\": \"CRISPR/Cas9 knockout, co-immunoprecipitation (SUN3-SUN4 interaction), immunofluorescence, electron microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO with detailed phenotypic characterization plus Co-IP interaction data, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"32156700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The luminal domain of SUN3 forms oligomers and has defined mobility within the nuclear envelope of living cells, as characterized by fluorescence fluctuation spectroscopy (tsMSQ).\",\n      \"method\": \"Time-shifted mean-segmented Q (tsMSQ) fluorescence fluctuation spectroscopy in live cells\",\n      \"journal\": \"Methods (San Diego, Calif.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct biophysical measurement in live cells, single lab, single method\",\n      \"pmids\": [\"30268407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SUN4 forms heteromeric assemblies with SUN3 in vivo and regulates SUN3 expression; SUN4 is an inner nuclear membrane protein with its C-terminal SUN domain in the perinuclear space and N-terminus in the nucleoplasm interacting with lamin B3.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, topology/domain analysis in spermatid nuclear envelope\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and topology experiments with multiple markers, single lab\",\n      \"pmids\": [\"36825599\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SUN3 is a testis-specific inner nuclear membrane SUN-domain protein that forms a spermiogenesis-specific LINC complex with Nesprin1, physically interacts with SUN4 (and regulates its stability), and is essential for transducing cytoskeletal forces via the manchette to the nuclear envelope for sperm head elongation and shaping, as demonstrated by infertility and globozoospermia in Sun3 knockout mice.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SUN3 is a testis-specific SUN-domain protein of the inner nuclear membrane that assembles a spermiogenesis-specific LINC complex to couple the differentiating spermatid nucleus to surrounding cytoskeletal structures, enabling directed sperm head elongation and shaping [#0, #2]. During spermiogenesis SUN3 pairs with Nesprin1 to form a LINC complex that polarizes to one spermatid pole, distinct from a second Sun1eta–Nesprin3 complex at the opposite pole [#0]. SUN3 physically interacts with SUN4 in testes, forming heteromeric assemblies within the nuclear envelope, and the two proteins are mutually interdependent: SUN4 levels are drastically reduced in Sun3-null mice, while SUN4 in turn regulates SUN3 expression and localization [#2, #4]. The luminal SUN3 domain self-associates into oligomers with defined mobility in the nuclear envelope [#3]. CRISPR/Cas9 Sun3 knockout males are infertile and display a globozoospermia-like phenotype with absent manchette microtubules, failed nuclear elongation, and acrosome defects, establishing SUN3 as essential for transmitting manchette-derived cytoskeletal forces across the nuclear envelope during sperm head morphogenesis [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified SUN3 as a component of a spermiogenesis-specific LINC complex, defining how the differentiating spermatid nucleus might physically engage the cytoskeleton for shaping.\",\n      \"evidence\": \"Co-IP and immunofluorescence localization in mouse spermatids showing SUN3–Nesprin1 association polarized opposite a Sun1eta–Nesprin3 complex\",\n      \"pmids\": [\"20711465\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional consequence of the SUN3–Nesprin1 complex not tested by loss-of-function\", \"Cytoskeletal element bridged by the complex not directly identified\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed SUN3 within a broader spermatid LINC network by showing SUN4 loss mislocalizes SUN3-associated components and disrupts manchette formation, hinting at interdependence among posterior nuclear envelope SUN proteins.\",\n      \"evidence\": \"Sun4 knockout mouse analysis with immunofluorescence and co-localization studies\",\n      \"pmids\": [\"26621829\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct SUN3–SUN4 physical interaction not yet demonstrated here\", \"SUN3 own loss-of-function phenotype not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Characterized the biophysical behavior of the SUN3 luminal domain, establishing that it oligomerizes within the nuclear envelope of living cells.\",\n      \"evidence\": \"Time-shifted mean-segmented Q (tsMSQ) fluorescence fluctuation spectroscopy in live cells\",\n      \"pmids\": [\"30268407\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Oligomeric stoichiometry in native spermatids not resolved\", \"Relationship of oligomerization to LINC assembly untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established SUN3 as essential and non-redundant for sperm head shaping and defined its physical and regulatory dependence on SUN4.\",\n      \"evidence\": \"CRISPR/Cas9 Sun3 knockout mice with EM and immunofluorescence phenotyping plus SUN3–SUN4 Co-IP\",\n      \"pmids\": [\"32156700\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism by which SUN3 loss abolishes manchette microtubules not resolved\", \"Direct force-transmission measurement not performed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined SUN4 topology and its reciprocal regulation of SUN3, completing the picture of a SUN3–SUN4 heteromeric assembly anchored to the nuclear lamina.\",\n      \"evidence\": \"Co-IP, immunofluorescence, and topology analysis showing SUN4 C-terminal SUN domain in perinuclear space and N-terminus contacting lamin B3\",\n      \"pmids\": [\"36825599\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"SUN3 own membrane topology and lamin contacts not directly mapped here\", \"Stoichiometry of SUN3–SUN4 heteromers unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the SUN3–SUN4 LINC complex mechanically couples manchette microtubule forces to nuclear envelope deformation, and what drives complex assembly, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct measurement of force transmission through the complex\", \"Structural model of the SUN3–SUN4 assembly absent\", \"Upstream signals timing complex assembly during spermiogenesis unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 2, 3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"LINC complex (SUN3–Nesprin1)\"],\n    \"partners\": [\"SUN4\", \"SYNE1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}