Affinage

GEMIN6

Gem-associated protein 6 · UniProt Q8WXD5

Length
167 aa
Mass
18.8 kDa
Annotated
2026-06-10
19 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    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

    PMID:11748230

    Open questions at the time
    • Did not define how GEMIN6 is recruited to SMN
    • No structural basis for Sm-protein contacts
  2. 2002 Medium

    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

    PMID:12192051

    Open questions at the time
    • Did not resolve GEMIN6's catalytic role at each step
    • Intermediate composition inferred biochemically
  3. 2002 High

    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

    PMID:12065586

    Open questions at the time
    • Did not yet explain how the GEMIN6-GEMIN7 unit links to the rest of the complex
  4. 2005 High

    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

    PMID:15939020

    Open questions at the time
    • Structure did not capture the heterodimer engaged with Sm proteins or SMN
    • Functional consequence of Sm mimicry not yet tested
  5. 2005 High

    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

    PMID:15843395

    Open questions at the time
    • Did not pinpoint which assembly step GEMIN6 enables
  6. 2005 Medium

    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

    PMID:15848170

    Open questions at the time
    • Unrip's mechanistic contribution to the GEMIN6 module unresolved at this stage
  7. 2006 High

    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

    PMID:16434402 PMID:17023415

    Open questions at the time
    • GEMIN8-dependent loss removed Sm association but not snRNA association; the molecular coupling was not fully resolved
  8. 2007 Medium

    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

    PMID:17640873

    Open questions at the time
    • Did not establish the in vivo assembly order of the module relative to other subunits
  9. 2009 Medium

    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

    PMID:19321448

    Open questions at the time
    • Surrogate-exchange model rests on a single lab's in vitro system
    • Kinetics and trigger of the exchange not defined
  10. 2010 Medium

    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

    PMID:20188701 PMID:20515655

    Open questions at the time
    • Cargo and physiological role of neuritic GEMIN6 granules unestablished
    • Granule composition heterogeneity not mechanistically explained
  11. 2017 Medium

    Demonstrated evolutionary conservation by recapitulating GEMIN8-mediated recruitment of the GEMIN6/7/Unrip module in Drosophila.

    Evidence In vivo interaction methods in Drosophila

    PMID:28949413

    Open questions at the time
    • Did not test functional sufficiency for assembly in the fly
  12. 2023 High

    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

    PMID:37664592

    Open questions at the time
    • Did not yet identify the specific step the module catalyzes within the pathway
  13. 2025 Medium

    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

    PMID:40849584

    Open questions at the time
    • Mechanism by which GEMIN6 affects AURKB mRNA maturation unresolved
    • Single-lab; relationship to canonical snRNP role unclear
  14. 2026 High

    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

    PMID:42261780

    Open questions at the time
    • Structural basis of ICln displacement not resolved
    • Whether human module operates identically not directly shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GEMIN6's canonical snRNP-assembly role mechanistically connects to its neuronal granule transport and its AURKB-promoting cancer function remains unresolved.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
GEMIN7GEMIN8LGI3SMN1SNRPBSNRPD3STRAP
Complex memberships
Gemin6-Gemin7 heterodimerGemin6/Gemin7/Unrip subunitSMN complexSMN/Gemin6-8 module

Evidence

Reading pass · 17 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 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. Affinity chromatography purification, mass spectrometry, co-immunoprecipitation, immunolocalization, in vitro binding experiments The Journal of biological chemistry High 11748230
2002 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. Immunoprecipitation, sedimentation analysis, characterization of distinct cytoplasmic SMN complex intermediates Molecular and cellular biology Medium 12192051
2002 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. Native purified SMN complexes, mass spectrometry, co-immunoprecipitation, in vitro binding experiments The Journal of biological chemistry High 12065586
2005 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. X-ray crystallography, in vitro binding experiments Structure (London, England : 1993) High 15939020
2005 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. RNA interference (RNAi), snRNP assembly assay, immunofluorescence for Gems Human molecular genetics High 15843395
2005 Unrip interacts directly with Gemin6 and Gemin7, and unrip-containing SMN complexes are necessary and sufficient to mediate the assembly of spliceosomal snRNPs. Co-immunoprecipitation, in vitro binding assays, snRNP assembly reconstitution FEBS letters Medium 15848170
2005 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. Immunofluorescence microscopy, cell fractionation of neurite extensions Experimental cell research Medium 15975577
2006 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. Mass spectrometry of purified SMN complexes, co-immunoprecipitation, in vitro binding assays, snRNP assembly assay The Journal of biological chemistry High 16434402
2006 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. RNAi knockdown, co-immunoprecipitation, monoclonal antibodies, snRNP assembly assay The Journal of biological chemistry High 17023415
2007 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. Sedimentation analysis, immunoprecipitation from cell extracts The Journal of biological chemistry Medium 17640873
2009 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. Mammalian two-hybrid, in vitro stability assay, siRNA knockdown, in vitro snRNP assembly assay with knockdown lysates The Journal of biological chemistry Medium 19321448
2010 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. Live cell fluorescence imaging of GFP-tagged Gemin6 in neuronal cells Biochemical and biophysical research communications Medium 20188701
2010 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. Immunofluorescence microscopy with antibodies against Gemin6 in differentiated SH-SY5Y cells Biochemical and biophysical research communications Low 20515655
2017 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. In vivo interaction methods (Drosophila genetic/co-immunoprecipitation approach) FEBS letters Medium 28949413
2023 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. Reconstitution with recombinant proteins, in vitro snRNP assembly assay, genetic approaches in S. pombe iScience High 37664592
2025 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. Co-immunoprecipitation (LGI3-GEMIN6 interaction), ubiquitination assay, AURKB mRNA maturation assay, knockdown/overexpression functional studies Oncogene Medium 40849584
2026 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. Engineered Brr1 (eBrr1) system in S. pombe, biochemical reconstitution, genetic rescue experiments Nucleic acids research High 42261780

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes & development 827 11914277
2001 Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. The Journal of biological chemistry 114 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 111 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 7 37664592
2026 A stand-alone ICln release module revealed by deconstructing the SMN complex with engineered Brr1. Nucleic acids research 0 42261780
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

Missed literature

Know a paper Affinage missed for GEMIN6? Flag it for the maintainers and the community.

No submissions yet.