Affinage

GEMIN6

Gem-associated protein 6 · UniProt Q8WXD5

Length
167 aa
Mass
18.8 kDa
Annotated
2026-04-28
18 papers in source corpus 15 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GEMIN6 is an essential component of the SMN complex that functions as a chaperone for the ATP-dependent assembly of spliceosomal snRNPs. Despite lacking sequence similarity to Sm proteins, GEMIN6 adopts a canonical Sm fold and heterodimerizes with GEMIN7 via an Sm-like interface; this heterodimer acts as a structural surrogate for the SmD3–SmB particle, organizing Sm proteins onto snRNA during snRNP core assembly and being exchanged out in an Unrip-facilitated step (PMID:15939020, PMID:19321448). The GEMIN6–GEMIN7–Unrip module exists as a stable cytoplasmic sub-complex that is linked to SMN through GEMIN8, and RNAi depletion of GEMIN6 abolishes snRNP assembly activity and eliminates nuclear gems (PMID:15843395, PMID:16434402, PMID:17640873). In vitro reconstitution of a minimal SMN complex (SMN/Gemin2/Gemin6–8) from fission yeast demonstrated that GEMIN6 is necessary and sufficient for Sm core assembly, confirming its conserved and indispensable role in the snRNP biogenesis machinery (PMID:37664592).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Establishing GEMIN6 as a bona fide SMN complex subunit resolved its identity, localization, and direct Sm protein contacts, providing the first evidence that the complex contained additional assembly factors beyond the originally known Gemins.

    Evidence Mass spectrometry of affinity-purified SMN complexes, co-IP, in vitro binding, immunolocalization in HeLa cells

    PMID:11748230

    Open questions at the time
    • Direct binding partners within the SMN complex not mapped
    • Functional contribution of GEMIN6 to snRNP assembly not yet tested
  2. 2002 High

    Identifying GEMIN7 as the obligate direct partner of GEMIN6 and showing that GEMIN6 requires GEMIN7 for SMN complex association defined the heterodimeric architecture through which GEMIN6 is integrated into the complex.

    Evidence In vitro binding and co-IP mapping direct GEMIN6–GEMIN7 interaction

    PMID:12065586

    Open questions at the time
    • Structural basis of the heterodimer unknown
    • Why GEMIN6 cannot bind SMN directly was unexplained
  3. 2005 High

    The crystal structure of the GEMIN6–GEMIN7 heterodimer revealed unexpected Sm-fold architecture and an Sm-like dimerization interface, fundamentally reframing GEMIN6 as an Sm protein surrogate rather than a mere scaffolding component.

    Evidence X-ray crystallography at atomic resolution plus in vitro Sm protein binding assays

    PMID:15939020

    Open questions at the time
    • How the Sm-like fold functions during assembly was not directly demonstrated
    • No structure of the full SMN complex context
  4. 2005 High

    RNAi knockdown of GEMIN6 abolished snRNP assembly and eliminated nuclear gems, providing the first functional proof that GEMIN6 is required for SMN complex activity, not merely a structural passenger.

    Evidence siRNA knockdown in HeLa cells with snRNP assembly assay and immunofluorescence

    PMID:15843395

    Open questions at the time
    • Whether the defect is due to loss of GEMIN6 per se or destabilization of the entire sub-complex was not distinguished
  5. 2005 High

    Discovery that Unrip directly binds GEMIN6/GEMIN7 and that Unrip-containing complexes are assembly-competent placed GEMIN6 within a defined functional sub-module of the SMN machinery.

    Evidence Co-IP, in vitro binding, and snRNP assembly reconstitution

    PMID:15848170

    Open questions at the time
    • Role of Unrip in regulating GEMIN6 within the sub-complex was unclear
  6. 2006 High

    GEMIN8 was identified as the bridge linking the GEMIN6–GEMIN7–Unrip sub-complex to SMN, completing the hierarchical assembly map and explaining why GEMIN6 depends on intermediary factors for SMN association.

    Evidence Co-IP, RNAi of GEMIN8 with snRNP assembly readout and sub-complex disruption analysis

    PMID:16434402 PMID:17023415

    Open questions at the time
    • Stoichiometry and dynamics of the GEMIN8-mediated connection not resolved
  7. 2007 High

    Demonstration that a GEMIN6–GEMIN7–Unrip sub-complex persists independently of SMN established this module as a pre-assembled unit, suggesting a stepwise pathway of SMN complex formation.

    Evidence Sucrose gradient sedimentation and co-IP under SMN-depleted conditions

    PMID:17640873

    Open questions at the time
    • Whether this free sub-complex has independent activity was not tested
  8. 2009 Medium

    Functional studies showed GEMIN6–GEMIN7 acts as a placeholder for SmD3–SmB during assembly intermediate formation, with Unrip facilitating the exchange, providing the first mechanistic model for how the Sm-fold surrogate operates during snRNP biogenesis.

    Evidence Mammalian two-hybrid, in vitro stability and assembly assays, siRNA knockdown

    PMID:19321448

    Open questions at the time
    • Exchange mechanism from a single laboratory
    • Kinetics and regulation of the exchange step not characterized
    • No direct structural visualization of the intermediate
  9. 2023 High

    Reconstitution of a minimal SMN complex (SMN/Gemin2/Gemin6–8) sufficient for Sm core assembly in vitro from recombinant fission yeast proteins proved that GEMIN6 is part of the evolutionarily conserved core snRNP assembly machinery.

    Evidence Full in vitro reconstitution with purified recombinant proteins and snRNP assembly assay in S. pombe system

    PMID:37664592

    Open questions at the time
    • Whether mammalian GEMIN6 can be reconstituted with equal sufficiency not shown
    • Role of peripheral Gemins (3–5) relative to the minimal core not addressed
  10. 2025 Medium

    LGI3 was found to stabilize GEMIN6 by inhibiting its ubiquitin-mediated degradation, and elevated GEMIN6 promotes AURKB mRNA maturation to drive TFE3-rearranged renal cell carcinoma, linking GEMIN6 protein turnover to oncogenic RNA processing.

    Evidence Co-IP, ubiquitination assays, mRNA maturation analysis, pharmacological inhibition in organoid models

    PMID:40849584

    Open questions at the time
    • Whether GEMIN6-dependent AURKB mRNA maturation operates through canonical snRNP assembly or a distinct mechanism is unknown
    • Findings from a single study
    • In vivo validation in animal models not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the GEMIN6–GEMIN7 surrogate exchange with SmD3–SmB is structurally coordinated within the intact SMN complex, and whether GEMIN6 contributes to RNA processing beyond canonical snRNP assembly (e.g., in miRNP function or mRNA maturation), remain unresolved.
  • No high-resolution structure of GEMIN6 within the full mammalian SMN complex
  • Independent confirmation of GEMIN6 in miRNP complexes lacking
  • Mechanism linking GEMIN6 to specific mRNA maturation events not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0044183 protein folding chaperone 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
GEMIN7GEMIN8LGI3SMN1STRAP
Complex memberships
GEMIN6-GEMIN7-Unrip sub-complexSMN complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Gemin6 was identified as a novel component of the SMN complex by mass spectrometry from affinity-purified native SMN complexes. Co-immunoprecipitation and in vitro binding experiments demonstrated that Gemin6 is a bona fide component of the SMN complex, localizes to gems (nuclear Cajal body-related structures) in both cytoplasm and nucleus, and interacts with several Sm proteins of spliceosomal snRNPs. Mass spectrometry, affinity chromatography, co-immunoprecipitation, immunolocalization, in vitro binding experiments The Journal of biological chemistry High 11748230
2002 Gemin6 and Gemin4 are components of a separate complex (miRNP) that contains eIF2C2 (an Argonaute family protein) and numerous microRNAs, distinct from the canonical SMN complex, indicating Gemin6 participates in multiple RNP complexes. Co-immunoprecipitation, mass spectrometry, RNA cloning Genes & development Medium 11914277
2002 The SMN complex (containing Gemin6 among other Gemins) associates with snRNPs throughout their entire cytoplasmic biogenesis pathway, including newly exported snRNAs, assembled Sm cores, and pre-import complexes bound to snurportin1, suggesting multiple functions during snRNP biogenesis. Sedimentation, co-immunoprecipitation, immunolocalization Molecular and cellular biology Medium 12192051
2002 Gemin7 interacts directly with Gemin6 and mediates the association of Gemin6 with the SMN complex; Gemin6 alone does not directly associate with SMN but requires Gemin7 as a bridge. Co-immunoprecipitation, in vitro binding experiments, mass spectrometry The Journal of biological chemistry High 12065586
2005 Crystal structure of the Gemin6-Gemin7 heterodimer revealed that both proteins adopt canonical Sm protein folds despite having no significant sequence similarity to Sm proteins. Gemin6 and Gemin7 heterodimerize via an interface analogous to Sm protein interactions, and the Gemin6/Gemin7 complex binds to Sm proteins, suggesting it acts as an Sm-like module to organize Sm proteins for snRNP assembly. X-ray crystallography, in vitro binding experiments Structure (London, England : 1993) High 15939020
2005 RNA interference knockdown of Gemin6 strongly decreases snRNP assembly activity of the SMN complex and causes disappearance of nuclear Gems, demonstrating that Gemin6 is critical for the functional activity of the SMN complex. RNA interference (RNAi), snRNP assembly assay, immunofluorescence Human molecular genetics High 15843395
2005 Unrip (unr-interacting protein) directly interacts with Gemin6 and Gemin7, and unrip-containing SMN complexes are necessary and sufficient for snRNP assembly, placing Gemin6 in the snRNP-assembly-competent sub-complex. Co-immunoprecipitation, in vitro binding, snRNP assembly assay FEBS letters High 15848170
2005 Gemin6 co-localizes with SMN and profilin II in cytoplasmic neurite-like extensions and growth cones of differentiating PC12 cells, suggesting Gemin6-containing SMN complexes participate in axonal transport of mRNPs. Immunofluorescence co-localization, live cell imaging in differentiating PC12 cells Experimental cell research Medium 15975577
2006 Gemin8 binds directly to the Gemin6-Gemin7 heterodimer and mediates its interaction with SMN; Gemin6, Gemin7, and Unrip form a stable cytoplasmic sub-complex whose association with SMN requires Gemin8. Loss of Gemin8 prevents Gemin6/Gemin7/Unrip interaction with SMN and impairs Sm protein recruitment to the snRNP assembly pathway. Co-immunoprecipitation, RNA interference, snRNP assembly assay, monoclonal antibodies The Journal of biological chemistry High 16434402 17023415
2007 Sedimentation and immunoprecipitation experiments identified a stable Gemin6-Gemin7-Unrip sub-complex that exists independently of SMN and persists when SMN is reduced. This sub-complex represents a modular unit of the SMN complex involved in snRNP assembly. Sucrose gradient sedimentation, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 17640873
2009 The Gemin6-Gemin7 heterodimer functions as a surrogate for the SmD3-SmB particle in forming a snRNP assembly subcore intermediate; Unrip facilitates removal of the Gemin6-Gemin7 heterodimer from the SMN complex to allow exchange with SmD3-SmB during snRNP formation. Mammalian two-hybrid, in vitro stability assay, siRNA knockdown, in vitro snRNP assembly assay The Journal of biological chemistry Medium 19321448
2010 Live cell imaging of GFP-Gemin6 in neurites showed that Gemin6 localizes to two distinct subsets of bodies in neurites: stationary bodies and smaller dynamic (motile) bodies, consistent with a role in axonal transport of mRNPs. Live cell fluorescence imaging of GFP-tagged Gemin6 in neuronal cells Biochemical and biophysical research communications Medium 20188701
2023 In fission yeast (Schizosaccharomyces pombe), a minimal SMN complex containing SMN/Gemin2/Gemin6-8 is necessary and sufficient for Sm core snRNP assembly in vitro using reconstituted recombinant proteins, demonstrating that Gemin6 is an essential component of the conserved snRNP assembly chaperone machinery. Reconstitution with recombinant proteins, in vitro snRNP assembly assay, genetic approaches iScience High 37664592
2025 LGI3 interacts with GEMIN6 and inhibits its ubiquitination-mediated degradation, stabilizing GEMIN6 protein levels. Elevated GEMIN6 promotes mRNA maturation of Aurora B kinase (AURKB), thereby driving progression of TFE3-rearranged renal cell carcinoma. Drugs targeting GEMIN6 suppress TFE3-RCC cell and organoid growth. Co-immunoprecipitation, ubiquitination assay, mRNA maturation assay, pharmacological inhibition, organoid models Oncogene Medium 40849584

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes & development 826 11914277
2001 Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. The Journal of biological chemistry 113 11748230
2005 A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells. Experimental cell research 110 15975577
2002 The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway. Molecular and cellular biology 108 12192051
2002 Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex. The Journal of biological chemistry 92 12065586
2006 Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. The Journal of biological chemistry 87 16434402
2005 Gemins modulate the expression and activity of the SMN complex. Human molecular genetics 83 15843395
2005 Unrip is a component of SMN complexes active in snRNP assembly. FEBS letters 66 15848170
2007 SMN-independent subunits of the SMN complex. Identification of a small nuclear ribonucleoprotein assembly intermediate. The Journal of biological chemistry 55 17640873
2006 Gemin8 is required for the architecture and function of the survival motor neuron complex. The Journal of biological chemistry 49 17023415
2005 The Gemin6-Gemin7 heterodimer from the survival of motor neurons complex has an Sm protein-like structure. Structure (London, England : 1993) 43 15939020
2010 Analysis of SMN-neurite granules: Core Cajal body components are absent from SMN-cytoplasmic complexes. Biochemical and biophysical research communications 24 20515655
2009 Role of survival motor neuron complex components in small nuclear ribonucleoprotein assembly. The Journal of biological chemistry 21 19321448
2010 SMN and the Gemin proteins form sub-complexes that localise to both stationary and dynamic neurite granules. Biochemical and biophysical research communications 20 20188701
2017 Novel interactors of the Drosophila Survival Motor Neuron (SMN) Complex suggest its full conservation. FEBS letters 17 28949413
2023 Mechanism of assembly of snRNP cores assisted by ICln and the SMN complex in fission yeast. iScience 6 37664592
2025 LGI3 promotes the progression of TFE3-rearranged renal cell carcinoma through GEMIN6/AURKB axis. Oncogene 0 40849584
2018 Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration? Folia neuropathologica 0 30786668