{"gene":"GEMIN6","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2001,"finding":"Gemin6 was identified as a novel component of the SMN complex by mass spectrometry of native purified complexes. Co-immunoprecipitation and in vitro binding experiments demonstrated that Gemin6 is a component of the SMN complex, localizes to gems in both cytoplasm and nucleus, and interacts with several Sm proteins of spliceosomal snRNPs.","method":"Affinity chromatography purification, mass spectrometry, co-immunoprecipitation, immunolocalization, in vitro binding experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP, in vitro binding, and immunolocalization with multiple orthogonal methods; foundational identification paper","pmids":["11748230"],"is_preprint":false},{"year":2002,"finding":"Gemin6 is part of the SMN complex that associates with snRNPs throughout their cytoplasmic assembly pathway, from newly exported snRNAs through Sm core assembly and m3G capping to formation of the preimport complex with snurportin1.","method":"Immunoprecipitation, sedimentation analysis, characterization of distinct cytoplasmic SMN complex intermediates","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple biochemical methods in a single lab identifying pathway intermediates containing Gemin6","pmids":["12192051"],"is_preprint":false},{"year":2002,"finding":"Gemin7 was identified as a novel SMN complex component that interacts directly with both SMN and Gemin6, and mediates the association of Gemin6 with the SMN complex. Gemin6 cannot associate with SMN in the absence of Gemin7.","method":"Native purified SMN complexes, mass spectrometry, co-immunoprecipitation, in vitro binding experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding shown by in vitro assays plus co-IP, functional dependency established; replicated in subsequent studies","pmids":["12065586"],"is_preprint":false},{"year":2005,"finding":"Crystal structure of the Gemin6-Gemin7 heterodimer revealed that both proteins adopt canonical Sm folds despite no sequence similarity to Sm proteins, and they form a heterodimer via an interface similar to that mediating Sm protein interactions. The Gemin6/Gemin7 complex binds to Sm proteins.","method":"X-ray crystallography, in vitro binding experiments","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional validation by binding experiments; definitive structural determination","pmids":["15939020"],"is_preprint":false},{"year":2005,"finding":"RNAi knockdown of Gemin6 strongly decreases the snRNP assembly activity of the SMN complex and leads to disappearance of Gems, demonstrating that Gemin6 is critical for the function of the SMN complex.","method":"RNA interference (RNAi), snRNP assembly assay, immunofluorescence for Gems","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Moderate — RNAi knockdown with defined functional readout (snRNP assembly assay) and cellular phenotype (Gem loss)","pmids":["15843395"],"is_preprint":false},{"year":2005,"finding":"Unrip interacts directly with Gemin6 and Gemin7, and unrip-containing SMN complexes are necessary and sufficient to mediate the assembly of spliceosomal snRNPs.","method":"Co-immunoprecipitation, in vitro binding assays, snRNP assembly reconstitution","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding demonstrated by in vitro assay; functional sufficiency shown by reconstitution","pmids":["15848170"],"is_preprint":false},{"year":2005,"finding":"Gemin6 co-localizes with SMN and profilin II in the cytoplasm and neurite-like extensions (including growth cones) of differentiating PC12 cells, indicating it is a component of SMN complexes transported in neurites.","method":"Immunofluorescence microscopy, cell fractionation of neurite extensions","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization by immunofluorescence in multiple cell contexts, replicated across two labs","pmids":["15975577"],"is_preprint":false},{"year":2006,"finding":"Gemin8 interacts directly with the Gemin6-Gemin7 heterodimer and, together with Unrip, these proteins form a heteromeric subunit of the SMN complex. Gemin8-containing SMN complexes are competent to carry out snRNP assembly.","method":"Mass spectrometry of purified SMN complexes, co-immunoprecipitation, in vitro binding assays, snRNP assembly assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP and direct binding experiments with functional snRNP assembly assay; replicated in subsequent paper (17023415)","pmids":["16434402"],"is_preprint":false},{"year":2006,"finding":"Gemin8 knockdown causes loss of Gemin6, Gemin7, and Unrip interaction with SMN, demonstrating that Gemin8 mediates the association of the Gemin6/Gemin7/Unrip subunit with SMN. Without Gemin8, SMN complex loses Sm protein association but retains snRNA association, impairing snRNP assembly.","method":"RNAi knockdown, co-immunoprecipitation, monoclonal antibodies, snRNP assembly assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — RNAi loss-of-function with mechanistic dissection of complex architecture using multiple orthogonal methods","pmids":["17023415"],"is_preprint":false},{"year":2007,"finding":"Sedimentation and immunoprecipitation experiments identified a stable SMN-independent subunit comprising Gemin6, Gemin7, and Unrip that persists when SMN is reduced. This subunit is distinct from the Gemin3-Gemin4-Gemin5 subunit and from the SMN-Gemin2 module.","method":"Sedimentation analysis, immunoprecipitation from cell extracts","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical fractionation with two methods revealing modular complex architecture","pmids":["17640873"],"is_preprint":false},{"year":2009,"finding":"The Gemin6-Gemin7 heterodimer acts as a surrogate for the SmD3-SmB particle during snRNP assembly. During the assembly reaction, the Gemin6-Gemin7 heterodimer in the subcore is exchanged by the SmD3-SmB particle to form snRNP, a process requiring Unrip for removal of Gemin6-Gemin7 from the SMN complex.","method":"Mammalian two-hybrid, in vitro stability assay, siRNA knockdown, in vitro snRNP assembly assay with knockdown lysates","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro assembly assay with knockdown conditions and multiple binding assays, single lab","pmids":["19321448"],"is_preprint":false},{"year":2010,"finding":"Live cell imaging of GFP-Gemin6 in neuronal cells showed that Gemin6-containing SMN complexes localize to two distinct subsets of neurite bodies: stationary bodies and smaller dynamic (motile) bodies, demonstrating that Gemin6 participates in neurite granule transport.","method":"Live cell fluorescence imaging of GFP-tagged Gemin6 in neuronal cells","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct live imaging with functional context, replicated finding from two related papers","pmids":["20188701"],"is_preprint":false},{"year":2010,"finding":"Gemin6 was detected in stationary neurite granules in SH-SY5Y human neuronal cells but not in all SMN-containing neurite granule subtypes, suggesting metamorphic composition of SMN complexes in axonal transport.","method":"Immunofluorescence microscopy with antibodies against Gemin6 in differentiated SH-SY5Y cells","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single immunofluorescence study without functional manipulation","pmids":["20515655"],"is_preprint":false},{"year":2017,"finding":"In Drosophila, the Gemin6/7/Unrip module can be recruited to the SMN complex via the SMN-associated Gemin8 orthologue, mirroring the human SMN complex architecture and supporting conservation of this interaction module in metazoans.","method":"In vivo interaction methods (Drosophila genetic/co-immunoprecipitation approach)","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo interaction methods in Drosophila model establishing conserved complex architecture","pmids":["28949413"],"is_preprint":false},{"year":2023,"finding":"In fission yeast (S. pombe), a minimal SMN complex consisting of SMN/Gemin2/Gemin6-8 is necessary and sufficient for Sm core assembly when reconstituted with recombinant proteins. The S. pombe Gemin6-8 module functions sequentially after ICln in the assembly pathway.","method":"Reconstitution with recombinant proteins, in vitro snRNP assembly assay, genetic approaches in S. pombe","journal":"iScience","confidence":"High","confidence_rationale":"Tier 1 / Moderate — biochemical reconstitution with recombinant proteins plus genetic validation, single lab but rigorous in vitro reconstitution","pmids":["37664592"],"is_preprint":false},{"year":2025,"finding":"LGI3 interacts with GEMIN6 and inhibits its proteasomal degradation by decreasing its ubiquitination. GEMIN6 upregulation in turn promotes mRNA maturation of Aurora B kinase (AURKB), contributing to TFE3-rearranged renal cell carcinoma progression.","method":"Co-immunoprecipitation (LGI3-GEMIN6 interaction), ubiquitination assay, AURKB mRNA maturation assay, knockdown/overexpression functional studies","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP for interaction, ubiquitination assay for PTM regulation, mRNA assay for downstream function; single lab","pmids":["40849584"],"is_preprint":false},{"year":2026,"finding":"The SMN/Gemin6-8 subcomplex alone is sufficient to displace the assembly chaperone ICln from the ICln/5Sm complex during snRNP assembly in fission yeast, identifying the Gemin6-8-containing module as the ICln-release machinery. The Gemin2-binding domain of SMN is dispensable when this subcomplex is functional.","method":"Engineered Brr1 (eBrr1) system in S. pombe, biochemical reconstitution, genetic rescue experiments","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution with engineered proteins plus genetic validation in fission yeast; mechanistic dissection of stepwise ICln release","pmids":["42261780"],"is_preprint":false}],"current_model":"GEMIN6 is a core component of the SMN complex that adopts a canonical Sm fold and forms a stable heterodimer with GEMIN7; this Gemin6-Gemin7 heterodimer, together with Gemin8 and Unrip, constitutes a stable SMN-independent subunit that is recruited to SMN via Gemin8, interacts with Sm proteins to act as a surrogate SmD3-SmB particle during snRNP assembly, and—as part of the Gemin6-8 module—is sufficient to displace the ICln assembly chaperone from Sm proteins, thereby driving spliceosomal snRNP biogenesis; additionally, GEMIN6 stability is regulated by LGI3-mediated protection from ubiquitination, and GEMIN6 promotes AURKB mRNA maturation in a cancer context."},"narrative":{"mechanistic_narrative":"GEMIN6 is a core component of the SMN complex that drives the cytoplasmic assembly of spliceosomal snRNPs [PMID:11748230, PMID:15843395]. Despite lacking sequence similarity to Sm proteins, GEMIN6 adopts a canonical Sm fold and forms a stable heterodimer with GEMIN7 through an Sm-like interface, and this heterodimer binds Sm proteins directly [PMID:15939020]. GEMIN7 mediates GEMIN6's association with SMN, as GEMIN6 cannot join the complex in GEMIN7's absence [PMID:12065586]; together with Unrip, GEMIN6 and GEMIN7 constitute a stable, SMN-independent subunit that is recruited to SMN via GEMIN8 [PMID:16434402, PMID:17023415, PMID:17640873]. Functionally, the GEMIN6-GEMIN7 heterodimer acts as a surrogate SmD3-SmB particle within the assembling snRNP subcore, and is later exchanged for the authentic SmD3-SmB pair in an Unrip-dependent step [PMID:19321448]. Reconstitution in fission yeast established that the SMN/GEMIN6-8 module is necessary and sufficient for Sm core assembly and functions sequentially after the ICln chaperone, acting as the machinery that displaces ICln from the ICln/5Sm intermediate [PMID:37664592, PMID:42261780]. RNAi loss of GEMIN6 abolishes SMN-complex snRNP assembly activity and Gems [PMID:15843395], and the module's architecture is conserved across metazoans [PMID:28949413]. GEMIN6 protein stability is controlled by LGI3, which limits its ubiquitination and proteasomal degradation, and elevated GEMIN6 promotes AURKB mRNA maturation in TFE3-rearranged renal cell carcinoma [PMID:40849584].","teleology":[{"year":2001,"claim":"Established GEMIN6 as a bona fide constituent of the SMN complex, placing it within the machinery for spliceosomal snRNP biogenesis.","evidence":"Mass spectrometry of native SMN complexes with co-IP, in vitro binding, and immunolocalization to gems","pmids":["11748230"],"confidence":"High","gaps":["Did not define how GEMIN6 is recruited to SMN","No structural basis for Sm-protein contacts"]},{"year":2002,"claim":"Showed GEMIN6 accompanies snRNPs through the cytoplasmic assembly pathway, placing it across multiple maturation intermediates.","evidence":"Immunoprecipitation and sedimentation analysis of cytoplasmic SMN complex intermediates","pmids":["12192051"],"confidence":"Medium","gaps":["Did not resolve GEMIN6's catalytic role at each step","Intermediate composition inferred biochemically"]},{"year":2002,"claim":"Resolved the recruitment logic by identifying GEMIN7 as the direct bridge that tethers GEMIN6 to SMN.","evidence":"Native complex purification, co-IP, and in vitro binding showing GEMIN6 requires GEMIN7 to associate with SMN","pmids":["12065586"],"confidence":"High","gaps":["Did not yet explain how the GEMIN6-GEMIN7 unit links to the rest of the complex"]},{"year":2005,"claim":"Provided the structural explanation: GEMIN6 and GEMIN7 are cryptic Sm-fold proteins that dimerize via an Sm-like interface and bind Sm proteins.","evidence":"X-ray crystallography of the GEMIN6-GEMIN7 heterodimer plus in vitro Sm-protein binding","pmids":["15939020"],"confidence":"High","gaps":["Structure did not capture the heterodimer engaged with Sm proteins or SMN","Functional consequence of Sm mimicry not yet tested"]},{"year":2005,"claim":"Demonstrated GEMIN6 is functionally required, not merely associated, for SMN-complex snRNP assembly.","evidence":"RNAi knockdown with snRNP assembly assay and loss of Gems by immunofluorescence","pmids":["15843395"],"confidence":"High","gaps":["Did not pinpoint which assembly step GEMIN6 enables"]},{"year":2005,"claim":"Identified Unrip as a direct GEMIN6/GEMIN7 partner and showed Unrip-containing complexes suffice for snRNP assembly.","evidence":"Co-IP, in vitro binding, and snRNP assembly reconstitution","pmids":["15848170"],"confidence":"Medium","gaps":["Unrip's mechanistic contribution to the GEMIN6 module unresolved at this stage"]},{"year":2006,"claim":"Defined the modular architecture by showing GEMIN8 binds the GEMIN6-GEMIN7 heterodimer and links the GEMIN6/7/Unrip subunit to SMN.","evidence":"Mass spectrometry, reciprocal co-IP, in vitro binding, RNAi, and snRNP assembly assays across two studies","pmids":["16434402","17023415"],"confidence":"High","gaps":["GEMIN8-dependent loss removed Sm association but not snRNA association; the molecular coupling was not fully resolved"]},{"year":2007,"claim":"Established that GEMIN6/GEMIN7/Unrip form a discrete, SMN-independent subunit distinct from other SMN-complex modules.","evidence":"Sedimentation and immunoprecipitation from cell extracts under reduced SMN","pmids":["17640873"],"confidence":"Medium","gaps":["Did not establish the in vivo assembly order of the module relative to other subunits"]},{"year":2009,"claim":"Assigned a mechanistic role: the GEMIN6-GEMIN7 heterodimer is a surrogate SmD3-SmB particle that is exchanged for authentic Sm proteins during assembly.","evidence":"Mammalian two-hybrid, in vitro stability and assembly assays with siRNA knockdown lysates","pmids":["19321448"],"confidence":"Medium","gaps":["Surrogate-exchange model rests on a single lab's in vitro system","Kinetics and trigger of the exchange not defined"]},{"year":2010,"claim":"Extended GEMIN6 function to neuronal transport, showing GEMIN6-containing complexes occupy stationary and motile neurite granules.","evidence":"Live-cell imaging of GFP-GEMIN6 and immunofluorescence in neuronal cell lines","pmids":["20188701","20515655"],"confidence":"Medium","gaps":["Cargo and physiological role of neuritic GEMIN6 granules unestablished","Granule composition heterogeneity not mechanistically explained"]},{"year":2017,"claim":"Demonstrated evolutionary conservation by recapitulating GEMIN8-mediated recruitment of the GEMIN6/7/Unrip module in Drosophila.","evidence":"In vivo interaction methods in Drosophila","pmids":["28949413"],"confidence":"Medium","gaps":["Did not test functional sufficiency for assembly in the fly"]},{"year":2023,"claim":"Defined the minimal sufficient machinery: reconstituted SMN/Gemin2/Gemin6-8 carries out Sm core assembly, acting sequentially after ICln.","evidence":"Recombinant-protein reconstitution, in vitro snRNP assembly, and genetics in S. pombe","pmids":["37664592"],"confidence":"High","gaps":["Did not yet identify the specific step the module catalyzes within the pathway"]},{"year":2025,"claim":"Revealed post-translational control of GEMIN6 and a cancer-context output, linking GEMIN6 stability to AURKB mRNA maturation.","evidence":"Co-IP, ubiquitination assays, AURKB mRNA maturation assay, and knockdown/overexpression in TFE3-rearranged RCC","pmids":["40849584"],"confidence":"Medium","gaps":["Mechanism by which GEMIN6 affects AURKB mRNA maturation unresolved","Single-lab; relationship to canonical snRNP role unclear"]},{"year":2026,"claim":"Pinpointed the catalytic step: the SMN/Gemin6-8 subcomplex alone displaces ICln from the ICln/5Sm complex, identifying it as the ICln-release machinery.","evidence":"Engineered eBrr1 system, biochemical reconstitution, and genetic rescue in S. pombe","pmids":["42261780"],"confidence":"High","gaps":["Structural basis of ICln displacement not resolved","Whether human module operates identically not directly shown"]},{"year":null,"claim":"How GEMIN6's canonical snRNP-assembly role mechanistically connects to its neuronal granule transport and its AURKB-promoting cancer function remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of the human module engaging Sm proteins or ICln","Molecular mechanism of GEMIN6 in AURKB mRNA maturation undefined","Physiological cargo of neuritic GEMIN6 complexes unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,10]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,10,16]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[6,11]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,4,14,16]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[4,7]}],"complexes":["SMN complex","Gemin6-Gemin7 heterodimer","Gemin6/Gemin7/Unrip subunit","SMN/Gemin6-8 module"],"partners":["GEMIN7","GEMIN8","SMN1","STRAP","SNRPD3","SNRPB","LGI3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WXD5","full_name":"Gem-associated protein 6","aliases":["SIP2"],"length_aa":167,"mass_kda":18.8,"function":"The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP","subcellular_location":"Nucleus, nucleoplasm; Nucleus, gem; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q8WXD5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/GEMIN6","classification":"Common Essential","n_dependent_lines":1108,"n_total_lines":1208,"dependency_fraction":0.9172185430463576},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SMN1","stoichiometry":10.0},{"gene":"SNRPC","stoichiometry":4.0},{"gene":"SNRPF","stoichiometry":4.0},{"gene":"SNRPA","stoichiometry":0.2},{"gene":"SNRPB","stoichiometry":0.2},{"gene":"SNRPD2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GEMIN6","total_profiled":1310},"omim":[{"mim_id":"607419","title":"GEM NUCLEAR ORGANELLE-ASSOCIATED PROTEIN 7; GEMIN7","url":"https://www.omim.org/entry/607419"},{"mim_id":"607006","title":"GEM NUCLEAR ORGANELLE-ASSOCIATED PROTEIN 6; GEMIN6","url":"https://www.omim.org/entry/607006"},{"mim_id":"606229","title":"ARGONAUTE RISC COMPONENT 2; AGO2","url":"https://www.omim.org/entry/606229"},{"mim_id":"605986","title":"SERINE/THREONINE KINASE RECEPTOR-ASSOCIATED PROTEIN; STRAP","url":"https://www.omim.org/entry/605986"},{"mim_id":"602595","title":"GEM NUCLEAR ORGANELLE-ASSOCIATED PROTEIN 2; GEMIN2","url":"https://www.omim.org/entry/602595"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear bodies","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GEMIN6"},"hgnc":{"alias_symbol":["FLJ23459"],"prev_symbol":[]},"alphafold":{"accession":"Q8WXD5","domains":[{"cath_id":"2.30.30.100","chopping":"2-83","consensus_level":"high","plddt":93.477,"start":2,"end":83},{"cath_id":"3.30.250","chopping":"95-164","consensus_level":"high","plddt":83.1796,"start":95,"end":164}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXD5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXD5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXD5-F1-predicted_aligned_error_v6.png","plddt_mean":86.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GEMIN6","jax_strain_url":"https://www.jax.org/strain/search?query=GEMIN6"},"sequence":{"accession":"Q8WXD5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WXD5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WXD5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXD5"}},"corpus_meta":[{"pmid":"11914277","id":"PMC_11914277","title":"miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.","date":"2002","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/11914277","citation_count":827,"is_preprint":false},{"pmid":"11748230","id":"PMC_11748230","title":"Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11748230","citation_count":114,"is_preprint":false},{"pmid":"15975577","id":"PMC_15975577","title":"A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells.","date":"2005","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/15975577","citation_count":111,"is_preprint":false},{"pmid":"12192051","id":"PMC_12192051","title":"The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12192051","citation_count":108,"is_preprint":false},{"pmid":"12065586","id":"PMC_12065586","title":"Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12065586","citation_count":92,"is_preprint":false},{"pmid":"16434402","id":"PMC_16434402","title":"Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16434402","citation_count":87,"is_preprint":false},{"pmid":"15843395","id":"PMC_15843395","title":"Gemins modulate the expression and activity of the SMN complex.","date":"2005","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15843395","citation_count":83,"is_preprint":false},{"pmid":"15848170","id":"PMC_15848170","title":"Unrip is a component of SMN complexes active in snRNP assembly.","date":"2005","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15848170","citation_count":66,"is_preprint":false},{"pmid":"17640873","id":"PMC_17640873","title":"SMN-independent subunits of the SMN complex. Identification of a small nuclear ribonucleoprotein assembly intermediate.","date":"2007","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17640873","citation_count":55,"is_preprint":false},{"pmid":"17023415","id":"PMC_17023415","title":"Gemin8 is required for the architecture and function of the survival motor neuron complex.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17023415","citation_count":49,"is_preprint":false},{"pmid":"15939020","id":"PMC_15939020","title":"The Gemin6-Gemin7 heterodimer from the survival of motor neurons complex has an Sm protein-like structure.","date":"2005","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/15939020","citation_count":43,"is_preprint":false},{"pmid":"20515655","id":"PMC_20515655","title":"Analysis of SMN-neurite granules: Core Cajal body components are absent from SMN-cytoplasmic complexes.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20515655","citation_count":24,"is_preprint":false},{"pmid":"19321448","id":"PMC_19321448","title":"Role of survival motor neuron complex components in small nuclear ribonucleoprotein assembly.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19321448","citation_count":21,"is_preprint":false},{"pmid":"20188701","id":"PMC_20188701","title":"SMN and the Gemin proteins form sub-complexes that localise to both stationary and dynamic neurite granules.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20188701","citation_count":20,"is_preprint":false},{"pmid":"28949413","id":"PMC_28949413","title":"Novel interactors of the Drosophila Survival Motor Neuron (SMN) Complex suggest its full conservation.","date":"2017","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/28949413","citation_count":17,"is_preprint":false},{"pmid":"37664592","id":"PMC_37664592","title":"Mechanism of assembly of snRNP cores assisted by ICln and the SMN complex in fission yeast.","date":"2023","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/37664592","citation_count":7,"is_preprint":false},{"pmid":"40849584","id":"PMC_40849584","title":"LGI3 promotes the progression of TFE3-rearranged renal cell carcinoma through GEMIN6/AURKB axis.","date":"2025","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/40849584","citation_count":0,"is_preprint":false},{"pmid":"30786668","id":"PMC_30786668","title":"Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?","date":"2018","source":"Folia neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/30786668","citation_count":0,"is_preprint":false},{"pmid":"42261780","id":"PMC_42261780","title":"A stand-alone ICln release module revealed by deconstructing the SMN complex with engineered Brr1.","date":"2026","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/42261780","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10470,"output_tokens":3735,"usd":0.043717,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11433,"output_tokens":4069,"usd":0.079445,"stage2_stop_reason":"end_turn"},"total_usd":0.123162,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Gemin6 was identified as a novel component of the SMN complex by mass spectrometry of native purified complexes. Co-immunoprecipitation and in vitro binding experiments demonstrated that Gemin6 is a component of the SMN complex, localizes to gems in both cytoplasm and nucleus, and interacts with several Sm proteins of spliceosomal snRNPs.\",\n      \"method\": \"Affinity chromatography purification, mass spectrometry, co-immunoprecipitation, immunolocalization, in vitro binding experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP, in vitro binding, and immunolocalization with multiple orthogonal methods; foundational identification paper\",\n      \"pmids\": [\"11748230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Gemin6 is part of the SMN complex that associates with snRNPs throughout their cytoplasmic assembly pathway, from newly exported snRNAs through Sm core assembly and m3G capping to formation of the preimport complex with snurportin1.\",\n      \"method\": \"Immunoprecipitation, sedimentation analysis, characterization of distinct cytoplasmic SMN complex intermediates\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple biochemical methods in a single lab identifying pathway intermediates containing Gemin6\",\n      \"pmids\": [\"12192051\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Gemin7 was identified as a novel SMN complex component that interacts directly with both SMN and Gemin6, and mediates the association of Gemin6 with the SMN complex. Gemin6 cannot associate with SMN in the absence of Gemin7.\",\n      \"method\": \"Native purified SMN complexes, mass spectrometry, co-immunoprecipitation, in vitro binding experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding shown by in vitro assays plus co-IP, functional dependency established; replicated in subsequent studies\",\n      \"pmids\": [\"12065586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Crystal structure of the Gemin6-Gemin7 heterodimer revealed that both proteins adopt canonical Sm folds despite no sequence similarity to Sm proteins, and they form a heterodimer via an interface similar to that mediating Sm protein interactions. The Gemin6/Gemin7 complex binds to Sm proteins.\",\n      \"method\": \"X-ray crystallography, in vitro binding experiments\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional validation by binding experiments; definitive structural determination\",\n      \"pmids\": [\"15939020\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"RNAi knockdown of Gemin6 strongly decreases the snRNP assembly activity of the SMN complex and leads to disappearance of Gems, demonstrating that Gemin6 is critical for the function of the SMN complex.\",\n      \"method\": \"RNA interference (RNAi), snRNP assembly assay, immunofluorescence for Gems\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi knockdown with defined functional readout (snRNP assembly assay) and cellular phenotype (Gem loss)\",\n      \"pmids\": [\"15843395\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Unrip interacts directly with Gemin6 and Gemin7, and unrip-containing SMN complexes are necessary and sufficient to mediate the assembly of spliceosomal snRNPs.\",\n      \"method\": \"Co-immunoprecipitation, in vitro binding assays, snRNP assembly reconstitution\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding demonstrated by in vitro assay; functional sufficiency shown by reconstitution\",\n      \"pmids\": [\"15848170\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Gemin6 co-localizes with SMN and profilin II in the cytoplasm and neurite-like extensions (including growth cones) of differentiating PC12 cells, indicating it is a component of SMN complexes transported in neurites.\",\n      \"method\": \"Immunofluorescence microscopy, cell fractionation of neurite extensions\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization by immunofluorescence in multiple cell contexts, replicated across two labs\",\n      \"pmids\": [\"15975577\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Gemin8 interacts directly with the Gemin6-Gemin7 heterodimer and, together with Unrip, these proteins form a heteromeric subunit of the SMN complex. Gemin8-containing SMN complexes are competent to carry out snRNP assembly.\",\n      \"method\": \"Mass spectrometry of purified SMN complexes, co-immunoprecipitation, in vitro binding assays, snRNP assembly assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP and direct binding experiments with functional snRNP assembly assay; replicated in subsequent paper (17023415)\",\n      \"pmids\": [\"16434402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Gemin8 knockdown causes loss of Gemin6, Gemin7, and Unrip interaction with SMN, demonstrating that Gemin8 mediates the association of the Gemin6/Gemin7/Unrip subunit with SMN. Without Gemin8, SMN complex loses Sm protein association but retains snRNA association, impairing snRNP assembly.\",\n      \"method\": \"RNAi knockdown, co-immunoprecipitation, monoclonal antibodies, snRNP assembly assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RNAi loss-of-function with mechanistic dissection of complex architecture using multiple orthogonal methods\",\n      \"pmids\": [\"17023415\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Sedimentation and immunoprecipitation experiments identified a stable SMN-independent subunit comprising Gemin6, Gemin7, and Unrip that persists when SMN is reduced. This subunit is distinct from the Gemin3-Gemin4-Gemin5 subunit and from the SMN-Gemin2 module.\",\n      \"method\": \"Sedimentation analysis, immunoprecipitation from cell extracts\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical fractionation with two methods revealing modular complex architecture\",\n      \"pmids\": [\"17640873\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The Gemin6-Gemin7 heterodimer acts as a surrogate for the SmD3-SmB particle during snRNP assembly. During the assembly reaction, the Gemin6-Gemin7 heterodimer in the subcore is exchanged by the SmD3-SmB particle to form snRNP, a process requiring Unrip for removal of Gemin6-Gemin7 from the SMN complex.\",\n      \"method\": \"Mammalian two-hybrid, in vitro stability assay, siRNA knockdown, in vitro snRNP assembly assay with knockdown lysates\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro assembly assay with knockdown conditions and multiple binding assays, single lab\",\n      \"pmids\": [\"19321448\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Live cell imaging of GFP-Gemin6 in neuronal cells showed that Gemin6-containing SMN complexes localize to two distinct subsets of neurite bodies: stationary bodies and smaller dynamic (motile) bodies, demonstrating that Gemin6 participates in neurite granule transport.\",\n      \"method\": \"Live cell fluorescence imaging of GFP-tagged Gemin6 in neuronal cells\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct live imaging with functional context, replicated finding from two related papers\",\n      \"pmids\": [\"20188701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Gemin6 was detected in stationary neurite granules in SH-SY5Y human neuronal cells but not in all SMN-containing neurite granule subtypes, suggesting metamorphic composition of SMN complexes in axonal transport.\",\n      \"method\": \"Immunofluorescence microscopy with antibodies against Gemin6 in differentiated SH-SY5Y cells\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single immunofluorescence study without functional manipulation\",\n      \"pmids\": [\"20515655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In Drosophila, the Gemin6/7/Unrip module can be recruited to the SMN complex via the SMN-associated Gemin8 orthologue, mirroring the human SMN complex architecture and supporting conservation of this interaction module in metazoans.\",\n      \"method\": \"In vivo interaction methods (Drosophila genetic/co-immunoprecipitation approach)\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo interaction methods in Drosophila model establishing conserved complex architecture\",\n      \"pmids\": [\"28949413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In fission yeast (S. pombe), a minimal SMN complex consisting of SMN/Gemin2/Gemin6-8 is necessary and sufficient for Sm core assembly when reconstituted with recombinant proteins. The S. pombe Gemin6-8 module functions sequentially after ICln in the assembly pathway.\",\n      \"method\": \"Reconstitution with recombinant proteins, in vitro snRNP assembly assay, genetic approaches in S. pombe\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — biochemical reconstitution with recombinant proteins plus genetic validation, single lab but rigorous in vitro reconstitution\",\n      \"pmids\": [\"37664592\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"LGI3 interacts with GEMIN6 and inhibits its proteasomal degradation by decreasing its ubiquitination. GEMIN6 upregulation in turn promotes mRNA maturation of Aurora B kinase (AURKB), contributing to TFE3-rearranged renal cell carcinoma progression.\",\n      \"method\": \"Co-immunoprecipitation (LGI3-GEMIN6 interaction), ubiquitination assay, AURKB mRNA maturation assay, knockdown/overexpression functional studies\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP for interaction, ubiquitination assay for PTM regulation, mRNA assay for downstream function; single lab\",\n      \"pmids\": [\"40849584\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The SMN/Gemin6-8 subcomplex alone is sufficient to displace the assembly chaperone ICln from the ICln/5Sm complex during snRNP assembly in fission yeast, identifying the Gemin6-8-containing module as the ICln-release machinery. The Gemin2-binding domain of SMN is dispensable when this subcomplex is functional.\",\n      \"method\": \"Engineered Brr1 (eBrr1) system in S. pombe, biochemical reconstitution, genetic rescue experiments\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution with engineered proteins plus genetic validation in fission yeast; mechanistic dissection of stepwise ICln release\",\n      \"pmids\": [\"42261780\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GEMIN6 is a core component of the SMN complex that adopts a canonical Sm fold and forms a stable heterodimer with GEMIN7; this Gemin6-Gemin7 heterodimer, together with Gemin8 and Unrip, constitutes a stable SMN-independent subunit that is recruited to SMN via Gemin8, interacts with Sm proteins to act as a surrogate SmD3-SmB particle during snRNP assembly, and—as part of the Gemin6-8 module—is sufficient to displace the ICln assembly chaperone from Sm proteins, thereby driving spliceosomal snRNP biogenesis; additionally, GEMIN6 stability is regulated by LGI3-mediated protection from ubiquitination, and GEMIN6 promotes AURKB mRNA maturation in a cancer context.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GEMIN6 is a core component of the SMN complex that drives the cytoplasmic assembly of spliceosomal snRNPs [#0, #4]. Despite lacking sequence similarity to Sm proteins, GEMIN6 adopts a canonical Sm fold and forms a stable heterodimer with GEMIN7 through an Sm-like interface, and this heterodimer binds Sm proteins directly [#3]. GEMIN7 mediates GEMIN6's association with SMN, as GEMIN6 cannot join the complex in GEMIN7's absence [#2]; together with Unrip, GEMIN6 and GEMIN7 constitute a stable, SMN-independent subunit that is recruited to SMN via GEMIN8 [#7, #8, #9]. Functionally, the GEMIN6-GEMIN7 heterodimer acts as a surrogate SmD3-SmB particle within the assembling snRNP subcore, and is later exchanged for the authentic SmD3-SmB pair in an Unrip-dependent step [#10]. Reconstitution in fission yeast established that the SMN/GEMIN6-8 module is necessary and sufficient for Sm core assembly and functions sequentially after the ICln chaperone, acting as the machinery that displaces ICln from the ICln/5Sm intermediate [#14, #16]. RNAi loss of GEMIN6 abolishes SMN-complex snRNP assembly activity and Gems [#4], and the module's architecture is conserved across metazoans [#13]. GEMIN6 protein stability is controlled by LGI3, which limits its ubiquitination and proteasomal degradation, and elevated GEMIN6 promotes AURKB mRNA maturation in TFE3-rearranged renal cell carcinoma [#15].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established GEMIN6 as a bona fide constituent of the SMN complex, placing it within the machinery for spliceosomal snRNP biogenesis.\",\n      \"evidence\": \"Mass spectrometry of native SMN complexes with co-IP, in vitro binding, and immunolocalization to gems\",\n      \"pmids\": [\"11748230\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how GEMIN6 is recruited to SMN\", \"No structural basis for Sm-protein contacts\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Showed GEMIN6 accompanies snRNPs through the cytoplasmic assembly pathway, placing it across multiple maturation intermediates.\",\n      \"evidence\": \"Immunoprecipitation and sedimentation analysis of cytoplasmic SMN complex intermediates\",\n      \"pmids\": [\"12192051\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve GEMIN6's catalytic role at each step\", \"Intermediate composition inferred biochemically\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Resolved the recruitment logic by identifying GEMIN7 as the direct bridge that tethers GEMIN6 to SMN.\",\n      \"evidence\": \"Native complex purification, co-IP, and in vitro binding showing GEMIN6 requires GEMIN7 to associate with SMN\",\n      \"pmids\": [\"12065586\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not yet explain how the GEMIN6-GEMIN7 unit links to the rest of the complex\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Provided the structural explanation: GEMIN6 and GEMIN7 are cryptic Sm-fold proteins that dimerize via an Sm-like interface and bind Sm proteins.\",\n      \"evidence\": \"X-ray crystallography of the GEMIN6-GEMIN7 heterodimer plus in vitro Sm-protein binding\",\n      \"pmids\": [\"15939020\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure did not capture the heterodimer engaged with Sm proteins or SMN\", \"Functional consequence of Sm mimicry not yet tested\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrated GEMIN6 is functionally required, not merely associated, for SMN-complex snRNP assembly.\",\n      \"evidence\": \"RNAi knockdown with snRNP assembly assay and loss of Gems by immunofluorescence\",\n      \"pmids\": [\"15843395\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not pinpoint which assembly step GEMIN6 enables\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified Unrip as a direct GEMIN6/GEMIN7 partner and showed Unrip-containing complexes suffice for snRNP assembly.\",\n      \"evidence\": \"Co-IP, in vitro binding, and snRNP assembly reconstitution\",\n      \"pmids\": [\"15848170\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Unrip's mechanistic contribution to the GEMIN6 module unresolved at this stage\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined the modular architecture by showing GEMIN8 binds the GEMIN6-GEMIN7 heterodimer and links the GEMIN6/7/Unrip subunit to SMN.\",\n      \"evidence\": \"Mass spectrometry, reciprocal co-IP, in vitro binding, RNAi, and snRNP assembly assays across two studies\",\n      \"pmids\": [\"16434402\", \"17023415\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"GEMIN8-dependent loss removed Sm association but not snRNA association; the molecular coupling was not fully resolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that GEMIN6/GEMIN7/Unrip form a discrete, SMN-independent subunit distinct from other SMN-complex modules.\",\n      \"evidence\": \"Sedimentation and immunoprecipitation from cell extracts under reduced SMN\",\n      \"pmids\": [\"17640873\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not establish the in vivo assembly order of the module relative to other subunits\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Assigned a mechanistic role: the GEMIN6-GEMIN7 heterodimer is a surrogate SmD3-SmB particle that is exchanged for authentic Sm proteins during assembly.\",\n      \"evidence\": \"Mammalian two-hybrid, in vitro stability and assembly assays with siRNA knockdown lysates\",\n      \"pmids\": [\"19321448\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Surrogate-exchange model rests on a single lab's in vitro system\", \"Kinetics and trigger of the exchange not defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Extended GEMIN6 function to neuronal transport, showing GEMIN6-containing complexes occupy stationary and motile neurite granules.\",\n      \"evidence\": \"Live-cell imaging of GFP-GEMIN6 and immunofluorescence in neuronal cell lines\",\n      \"pmids\": [\"20188701\", \"20515655\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo and physiological role of neuritic GEMIN6 granules unestablished\", \"Granule composition heterogeneity not mechanistically explained\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated evolutionary conservation by recapitulating GEMIN8-mediated recruitment of the GEMIN6/7/Unrip module in Drosophila.\",\n      \"evidence\": \"In vivo interaction methods in Drosophila\",\n      \"pmids\": [\"28949413\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not test functional sufficiency for assembly in the fly\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the minimal sufficient machinery: reconstituted SMN/Gemin2/Gemin6-8 carries out Sm core assembly, acting sequentially after ICln.\",\n      \"evidence\": \"Recombinant-protein reconstitution, in vitro snRNP assembly, and genetics in S. pombe\",\n      \"pmids\": [\"37664592\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not yet identify the specific step the module catalyzes within the pathway\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed post-translational control of GEMIN6 and a cancer-context output, linking GEMIN6 stability to AURKB mRNA maturation.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, AURKB mRNA maturation assay, and knockdown/overexpression in TFE3-rearranged RCC\",\n      \"pmids\": [\"40849584\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which GEMIN6 affects AURKB mRNA maturation unresolved\", \"Single-lab; relationship to canonical snRNP role unclear\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Pinpointed the catalytic step: the SMN/Gemin6-8 subcomplex alone displaces ICln from the ICln/5Sm complex, identifying it as the ICln-release machinery.\",\n      \"evidence\": \"Engineered eBrr1 system, biochemical reconstitution, and genetic rescue in S. pombe\",\n      \"pmids\": [\"42261780\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of ICln displacement not resolved\", \"Whether human module operates identically not directly shown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GEMIN6's canonical snRNP-assembly role mechanistically connects to its neuronal granule transport and its AURKB-promoting cancer function remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of the human module engaging Sm proteins or ICln\", \"Molecular mechanism of GEMIN6 in AURKB mRNA maturation undefined\", \"Physiological cargo of neuritic GEMIN6 complexes unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 10]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 10, 16]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [6, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 4, 14, 16]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"complexes\": [\n      \"SMN complex\",\n      \"Gemin6-Gemin7 heterodimer\",\n      \"Gemin6/Gemin7/Unrip subunit\",\n      \"SMN/Gemin6-8 module\"\n    ],\n    \"partners\": [\n      \"GEMIN7\",\n      \"GEMIN8\",\n      \"SMN1\",\n      \"STRAP\",\n      \"SNRPD3\",\n      \"SNRPB\",\n      \"LGI3\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":7,"faith_pct":85.71428571428571}}