{"gene":"SCMH1","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":1999,"finding":"SCMH1 protein contains two MBT (malignant brain tumor) domains and an SPM domain, characteristic of the Sex comb on midleg (Scm) family, and is expressed widely in adult human tissues; it maps to chromosome 1p34 and shares 41% identity with Drosophila Scm.","method":"cDNA cloning, sequence analysis, chromosomal mapping","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct molecular cloning and domain characterization, single lab but multiple methods (sequence analysis, mapping, expression profiling)","pmids":["10524249"],"is_preprint":false},{"year":2007,"finding":"SCMH1 (Scmh1) is a constituent of mammalian Polycomb Repressive Complex 1 (PRC1) and is required for survival of late pachytene spermatocytes; Scmh1 is excluded from the XY body at late pachytene together with other PRC1 components (Phc1, Phc2, Rnf110/Pcgf2, Bmi1, Cbx2), and loss of Scmh1 causes apoptotic elimination of spermatocytes accompanied by failure of chromatin modifications at the XY body.","method":"Knockout mouse model, immunostaining, genetic epistasis (Scmh1−/− × Phc2 double mutant rescue), chromatin modification analysis","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with defined cellular phenotype, genetic epistasis rescue by Phc2 mutation, multiple orthogonal methods (immunostaining, apoptosis assays, chromatin analysis)","pmids":["17215307"],"is_preprint":false},{"year":2007,"finding":"Genetic epistasis shows that Scmh1 exerts its molecular functions via its interaction with PRC1: restoration of Scmh1−/− spermatocyte defects by Phc2 mutation indicates Scmh1 functions through the PRC1 complex.","method":"Double mutant genetic epistasis (Scmh1−/− × Phc2 mutant)","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis in vivo with double-mutant rescue, well-controlled KO study","pmids":["17215307"],"is_preprint":false},{"year":2012,"finding":"Scmh1 possesses E3 ubiquitin ligase activity for both histone H2A and geminin as a substoichiometric component of PRC1; it provides PRC1 with a geminin-interaction domain and regulates geminin stability.","method":"In vitro ubiquitin ligase assays, Scmh1-deficient mouse model, domain-deletion constructs (geminin-binding domain deletion), western blotting","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay for E3 ligase activity plus domain mutagenesis (deletion of geminin-binding domain) in a single rigorous study with KO mouse validation","pmids":["23207902"],"is_preprint":false},{"year":2012,"finding":"Loss of Scmh1 causes derepression of Hoxb4 and Hoxa9 (direct PRC1 targets) in hematopoietic cells; Hoxb4 and Hoxa9 can each form a complex with Roc1-Ddb1-Cul4a to act as an E3 ubiquitin ligase for geminin, suggesting Scmh1 regulates geminin levels both directly and indirectly via transcriptional repression of these Hox genes.","method":"Scmh1-deficient mouse model, double knockdown of Hoxb4/Hoxa9, dominant-negative Hoxb4 transduction, co-immunoprecipitation of Roc1-Ddb1-Cul4a-Hox complexes, western blotting","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — KO mouse plus double knockdown epistasis plus Co-IP of E3 ligase complex, multiple orthogonal methods in one rigorous study","pmids":["23207902"],"is_preprint":false}],"current_model":"SCMH1 is a substoichiometric component of mammalian Polycomb Repressive Complex 1 (PRC1) that contributes E3 ubiquitin ligase activity toward histone H2A and geminin; it provides PRC1 with a geminin-interaction domain to regulate geminin stability, mediates transcriptional silencing of Hox genes (Hoxb4, Hoxa9) in hematopoietic cells, and is required for the exclusion of PRC1 from the XY body in pachytene spermatocytes and for spermatocyte survival, acting via its physical and functional interaction with the PRC1 complex."},"narrative":{"mechanistic_narrative":"SCMH1 is a substoichiometric component of mammalian Polycomb Repressive Complex 1 (PRC1) and a member of the Scm family, carrying two MBT domains and an SPM domain [PMID:10524249, PMID:17215307]. Within PRC1 it provides E3 ubiquitin ligase activity toward both histone H2A and geminin, and contributes a geminin-interaction domain through which it regulates geminin stability [PMID:23207902]. Through PRC1-mediated transcriptional silencing of Hox targets, loss of SCMH1 derepresses Hoxb4 and Hoxa9 in hematopoietic cells; because these Hox proteins themselves form Roc1-Ddb1-Cul4a E3 ligase complexes against geminin, SCMH1 governs geminin levels both directly and indirectly [PMID:23207902]. In the germ line, SCMH1 is required for survival of late pachytene spermatocytes and for the exclusion of PRC1 components from the XY body, and genetic epistasis demonstrates that these functions are executed through the PRC1 complex [PMID:17215307].","teleology":[{"year":1999,"claim":"Established SCMH1 as a human Scm-family protein, defining the domain architecture (two MBT domains, SPM domain) that predicts Polycomb-type function before any complex membership was known.","evidence":"cDNA cloning, sequence analysis, and chromosomal mapping of human SCMH1","pmids":["10524249"],"confidence":"Medium","gaps":["No demonstration of complex membership or molecular activity","Functional consequence of MBT/SPM domains not tested"]},{"year":2007,"claim":"Placed SCMH1 inside mammalian PRC1 and showed it is required for late pachytene spermatocyte survival, linking the protein to germ-cell biology and XY-body chromatin regulation.","evidence":"Knockout mouse, immunostaining of PRC1 components at the XY body, apoptosis and chromatin modification analysis","pmids":["17215307"],"confidence":"High","gaps":["Molecular activity of SCMH1 within PRC1 not yet defined","Mechanism of PRC1 exclusion from the XY body unresolved"]},{"year":2007,"claim":"Demonstrated by double-mutant rescue that SCMH1 acts through PRC1, ruling out a PRC1-independent route for its spermatocyte function.","evidence":"Scmh1-/- x Phc2 mutant genetic epistasis in mice","pmids":["17215307"],"confidence":"High","gaps":["Does not identify which biochemical activity of SCMH1 is required","Targets beyond the germ line not addressed"]},{"year":2012,"claim":"Defined SCMH1's molecular activity as an E3 ubiquitin ligase for histone H2A and geminin and identified its geminin-interaction domain, converting it from a structural PRC1 subunit into an enzymatic regulator of geminin stability.","evidence":"In vitro ubiquitin ligase assays, geminin-binding domain deletion constructs, Scmh1-deficient mouse, western blotting","pmids":["23207902"],"confidence":"High","gaps":["Stoichiometry and regulation of the ligase activity within intact PRC1 not resolved","Structural basis of geminin recognition not determined"]},{"year":2012,"claim":"Connected SCMH1's transcriptional silencing role to its geminin-regulating role by showing that derepressed Hoxb4/Hoxa9 form their own geminin-targeting E3 ligase, establishing dual direct and indirect control of geminin.","evidence":"Scmh1-deficient mouse, Hoxb4/Hoxa9 double knockdown, dominant-negative Hoxb4, Co-IP of Roc1-Ddb1-Cul4a-Hox complexes","pmids":["23207902"],"confidence":"High","gaps":["Relative contribution of direct vs indirect geminin regulation not quantified","Physiological consequence of geminin dysregulation in hematopoiesis not fully traced"]},{"year":null,"claim":"How SCMH1's MBT/SPM domains direct its substoichiometric incorporation into PRC1 and target it to specific loci remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of SCMH1 within PRC1","Genome-wide targeting determinants unknown","Function in tissues beyond germ line and hematopoietic cells uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[3]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[3]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[4]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[3]}],"complexes":["PRC1"],"partners":["GMNN","PHC2","HOXB4","HOXA9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96GD3","full_name":"Polycomb protein SCMH1","aliases":["Sex comb on midleg homolog 1"],"length_aa":660,"mass_kda":73.4,"function":"Associates with Polycomb group (PcG) multiprotein complexes; the complex class is required to maintain the transcriptionally repressive state of some genes","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q96GD3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SCMH1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SCMH1","total_profiled":1310},"omim":[{"mim_id":"616396","title":"SCM POLYCOMB GROUP PROTEIN HOMOLOG 1; SCMH1","url":"https://www.omim.org/entry/616396"},{"mim_id":"602978","title":"POLYHOMEOTIC HOMOLOG 1; PHC1","url":"https://www.omim.org/entry/602978"},{"mim_id":"602842","title":"GEMININ DNA REPLICATION INHIBITOR; GMNN","url":"https://www.omim.org/entry/602842"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear bodies","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SCMH1"},"hgnc":{"alias_symbol":["Scml3"],"prev_symbol":[]},"alphafold":{"accession":"Q96GD3","domains":[{"cath_id":"2.30.30.140","chopping":"29-49_159-227","consensus_level":"high","plddt":96.4826,"start":29,"end":227},{"cath_id":"2.30.30.140","chopping":"61-153","consensus_level":"high","plddt":95.5755,"start":61,"end":153},{"cath_id":"3.90.1150.190","chopping":"357-463","consensus_level":"high","plddt":91.628,"start":357,"end":463},{"cath_id":"1.10.150.50","chopping":"589-656","consensus_level":"high","plddt":91.0168,"start":589,"end":656}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GD3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GD3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GD3-F1-predicted_aligned_error_v6.png","plddt_mean":70.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SCMH1","jax_strain_url":"https://www.jax.org/strain/search?query=SCMH1"},"sequence":{"accession":"Q96GD3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96GD3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96GD3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GD3"}},"corpus_meta":[{"pmid":"32441115","id":"PMC_32441115","title":"Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models.","date":"2020","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/32441115","citation_count":307,"is_preprint":false},{"pmid":"17215307","id":"PMC_17215307","title":"Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes.","date":"2007","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/17215307","citation_count":52,"is_preprint":false},{"pmid":"40143778","id":"PMC_40143778","title":"Nose-to-Brain Delivery of Circular RNA SCMH1-Loaded Lipid Nanoparticles for Ischemic Stroke Therapy.","date":"2025","source":"Advanced materials (Deerfield Beach, Fla.)","url":"https://pubmed.ncbi.nlm.nih.gov/40143778","citation_count":39,"is_preprint":false},{"pmid":"34353342","id":"PMC_34353342","title":"Blocking circ-SCMH1 (hsa_circ_0011946) suppresses acquired DDP resistance of oral squamous cell carcinoma (OSCC) cells both in vitro and in vivo by sponging miR-338-3p and regulating LIN28B.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/34353342","citation_count":30,"is_preprint":false},{"pmid":"10524249","id":"PMC_10524249","title":"The human homolog of Sex comb on midleg (SCMH1) maps to chromosome 1p34.","date":"1999","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/10524249","citation_count":23,"is_preprint":false},{"pmid":"39659575","id":"PMC_39659575","title":"Circular RNA SCMH1 suppresses KMO expression to inhibit mitophagy and promote functional recovery following stroke.","date":"2024","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/39659575","citation_count":14,"is_preprint":false},{"pmid":"37544863","id":"PMC_37544863","title":"Exosomes from ADSCs ameliorate nerve damage in the hippocampus caused by post traumatic brain injury via the delivery of circ-Scmh1 promoting microglial M2 polarization.","date":"2023","source":"Injury","url":"https://pubmed.ncbi.nlm.nih.gov/37544863","citation_count":14,"is_preprint":false},{"pmid":"37664885","id":"PMC_37664885","title":"Transcriptome sequencing of circular RNA reveals the involvement of hsa-SCMH1_0001 in the pathogenesis of Parkinson's disease.","date":"2023","source":"CNS neuroscience & therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/37664885","citation_count":11,"is_preprint":false},{"pmid":"23207902","id":"PMC_23207902","title":"Scmh1 has E3 ubiquitin ligase activity for geminin and histone H2A and regulates geminin stability directly or indirectly via transcriptional repression of Hoxa9 and Hoxb4.","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/23207902","citation_count":9,"is_preprint":false},{"pmid":"36162459","id":"PMC_36162459","title":"CircRNA SCMH1 regulates the miR-200a-3p/ZEB1 signaling axis to promote diabetes-induced retinal epithelial-mesenchymal transition.","date":"2022","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/36162459","citation_count":5,"is_preprint":false},{"pmid":"41328340","id":"PMC_41328340","title":"PTBP1-mediated inhibition of circular RNA SCMH1 biogenesis impairs brain recovery after ischemic stroke.","date":"2026","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/41328340","citation_count":0,"is_preprint":false},{"pmid":"42093648","id":"PMC_42093648","title":"Circular RNA SCMH1 promotes persistent brain repair via N6-methyladenosine methylation post stroke.","date":"2026","source":"Brain : a journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/42093648","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8786,"output_tokens":1710,"usd":0.026004,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8080,"output_tokens":2078,"usd":0.046175,"stage2_stop_reason":"end_turn"},"total_usd":0.072179,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the papers, I need to classify each:\n\n- Papers [1], [3], [4], [6], [7], [8], [10], [11], [12]: These are about **circSCMH1** (circular RNA), a non-protein locus product derived from the SCMH1 locus. These are NOT the canonical SCMH1 protein and must be excluded per the rules.\n\n- Paper [5]: About SCMH1 protein - cloning, domain identification (MBT domains, SPM domain), chromosomal mapping. This establishes structural/domain features.\n\n- Paper [2]: About Scmh1 protein as a component of PRC1, its role in pachytene spermatocytes, exclusion from XY body, genetic epistasis with Phc2. This is the canonical protein.\n\n- Paper [9]: About Scmh1 protein - E3 ubiquitin ligase activity for geminin and histone H2A, regulation of Hox genes. This is the canonical protein.\n\nPapers [2], [5], and [9] are about the canonical SCMH1 protein. The rest are about circSCMH1 (circular RNA) and must be excluded.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"SCMH1 protein contains two MBT (malignant brain tumor) domains and an SPM domain, characteristic of the Sex comb on midleg (Scm) family, and is expressed widely in adult human tissues; it maps to chromosome 1p34 and shares 41% identity with Drosophila Scm.\",\n      \"method\": \"cDNA cloning, sequence analysis, chromosomal mapping\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct molecular cloning and domain characterization, single lab but multiple methods (sequence analysis, mapping, expression profiling)\",\n      \"pmids\": [\"10524249\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"SCMH1 (Scmh1) is a constituent of mammalian Polycomb Repressive Complex 1 (PRC1) and is required for survival of late pachytene spermatocytes; Scmh1 is excluded from the XY body at late pachytene together with other PRC1 components (Phc1, Phc2, Rnf110/Pcgf2, Bmi1, Cbx2), and loss of Scmh1 causes apoptotic elimination of spermatocytes accompanied by failure of chromatin modifications at the XY body.\",\n      \"method\": \"Knockout mouse model, immunostaining, genetic epistasis (Scmh1−/− × Phc2 double mutant rescue), chromatin modification analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with defined cellular phenotype, genetic epistasis rescue by Phc2 mutation, multiple orthogonal methods (immunostaining, apoptosis assays, chromatin analysis)\",\n      \"pmids\": [\"17215307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Genetic epistasis shows that Scmh1 exerts its molecular functions via its interaction with PRC1: restoration of Scmh1−/− spermatocyte defects by Phc2 mutation indicates Scmh1 functions through the PRC1 complex.\",\n      \"method\": \"Double mutant genetic epistasis (Scmh1−/− × Phc2 mutant)\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis in vivo with double-mutant rescue, well-controlled KO study\",\n      \"pmids\": [\"17215307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Scmh1 possesses E3 ubiquitin ligase activity for both histone H2A and geminin as a substoichiometric component of PRC1; it provides PRC1 with a geminin-interaction domain and regulates geminin stability.\",\n      \"method\": \"In vitro ubiquitin ligase assays, Scmh1-deficient mouse model, domain-deletion constructs (geminin-binding domain deletion), western blotting\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay for E3 ligase activity plus domain mutagenesis (deletion of geminin-binding domain) in a single rigorous study with KO mouse validation\",\n      \"pmids\": [\"23207902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Loss of Scmh1 causes derepression of Hoxb4 and Hoxa9 (direct PRC1 targets) in hematopoietic cells; Hoxb4 and Hoxa9 can each form a complex with Roc1-Ddb1-Cul4a to act as an E3 ubiquitin ligase for geminin, suggesting Scmh1 regulates geminin levels both directly and indirectly via transcriptional repression of these Hox genes.\",\n      \"method\": \"Scmh1-deficient mouse model, double knockdown of Hoxb4/Hoxa9, dominant-negative Hoxb4 transduction, co-immunoprecipitation of Roc1-Ddb1-Cul4a-Hox complexes, western blotting\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse plus double knockdown epistasis plus Co-IP of E3 ligase complex, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"23207902\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SCMH1 is a substoichiometric component of mammalian Polycomb Repressive Complex 1 (PRC1) that contributes E3 ubiquitin ligase activity toward histone H2A and geminin; it provides PRC1 with a geminin-interaction domain to regulate geminin stability, mediates transcriptional silencing of Hox genes (Hoxb4, Hoxa9) in hematopoietic cells, and is required for the exclusion of PRC1 from the XY body in pachytene spermatocytes and for spermatocyte survival, acting via its physical and functional interaction with the PRC1 complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCMH1 is a substoichiometric component of mammalian Polycomb Repressive Complex 1 (PRC1) and a member of the Scm family, carrying two MBT domains and an SPM domain [#0, #1]. Within PRC1 it provides E3 ubiquitin ligase activity toward both histone H2A and geminin, and contributes a geminin-interaction domain through which it regulates geminin stability [#3]. Through PRC1-mediated transcriptional silencing of Hox targets, loss of SCMH1 derepresses Hoxb4 and Hoxa9 in hematopoietic cells; because these Hox proteins themselves form Roc1-Ddb1-Cul4a E3 ligase complexes against geminin, SCMH1 governs geminin levels both directly and indirectly [#4]. In the germ line, SCMH1 is required for survival of late pachytene spermatocytes and for the exclusion of PRC1 components from the XY body, and genetic epistasis demonstrates that these functions are executed through the PRC1 complex [#1, #2].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established SCMH1 as a human Scm-family protein, defining the domain architecture (two MBT domains, SPM domain) that predicts Polycomb-type function before any complex membership was known.\",\n      \"evidence\": \"cDNA cloning, sequence analysis, and chromosomal mapping of human SCMH1\",\n      \"pmids\": [\"10524249\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstration of complex membership or molecular activity\", \"Functional consequence of MBT/SPM domains not tested\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Placed SCMH1 inside mammalian PRC1 and showed it is required for late pachytene spermatocyte survival, linking the protein to germ-cell biology and XY-body chromatin regulation.\",\n      \"evidence\": \"Knockout mouse, immunostaining of PRC1 components at the XY body, apoptosis and chromatin modification analysis\",\n      \"pmids\": [\"17215307\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular activity of SCMH1 within PRC1 not yet defined\", \"Mechanism of PRC1 exclusion from the XY body unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrated by double-mutant rescue that SCMH1 acts through PRC1, ruling out a PRC1-independent route for its spermatocyte function.\",\n      \"evidence\": \"Scmh1-/- x Phc2 mutant genetic epistasis in mice\",\n      \"pmids\": [\"17215307\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not identify which biochemical activity of SCMH1 is required\", \"Targets beyond the germ line not addressed\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined SCMH1's molecular activity as an E3 ubiquitin ligase for histone H2A and geminin and identified its geminin-interaction domain, converting it from a structural PRC1 subunit into an enzymatic regulator of geminin stability.\",\n      \"evidence\": \"In vitro ubiquitin ligase assays, geminin-binding domain deletion constructs, Scmh1-deficient mouse, western blotting\",\n      \"pmids\": [\"23207902\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and regulation of the ligase activity within intact PRC1 not resolved\", \"Structural basis of geminin recognition not determined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Connected SCMH1's transcriptional silencing role to its geminin-regulating role by showing that derepressed Hoxb4/Hoxa9 form their own geminin-targeting E3 ligase, establishing dual direct and indirect control of geminin.\",\n      \"evidence\": \"Scmh1-deficient mouse, Hoxb4/Hoxa9 double knockdown, dominant-negative Hoxb4, Co-IP of Roc1-Ddb1-Cul4a-Hox complexes\",\n      \"pmids\": [\"23207902\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contribution of direct vs indirect geminin regulation not quantified\", \"Physiological consequence of geminin dysregulation in hematopoiesis not fully traced\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SCMH1's MBT/SPM domains direct its substoichiometric incorporation into PRC1 and target it to specific loci remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of SCMH1 within PRC1\", \"Genome-wide targeting determinants unknown\", \"Function in tissues beyond germ line and hematopoietic cells uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"PRC1\"],\n    \"partners\": [\"GMNN\", \"PHC2\", \"HOXB4\", \"HOXA9\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}