Affinage

GEMIN5

Gem-associated protein 5 · UniProt Q8TEQ6

Length
1508 aa
Mass
168.6 kDa
Annotated
2026-06-10
53 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GEMIN5 is a multidomain, predominantly cytoplasmic RNA-binding protein that operates at the interface of small nuclear ribonucleoprotein (snRNP) biogenesis and translational control (PMID:11714716, PMID:27507887). As the snRNA-recognition subunit of the SMN complex, its N-terminal tandem WD40 domain provides a contiguous, sequence-specific surface that simultaneously reads the Sm site and the m7G cap of pre-snRNAs through base-stacking and hydrogen-bonding by aromatic and arginine residues, thereby delivering pre-snRNA substrates to the SMN complex for Sm core assembly (PMID:16857593, PMID:19377484, PMID:27881600, PMID:27881601). Acting upstream in the cytoplasm, GEMIN5 captures and escorts pre-snRNAs—and disposes of truncated or unassembled U1 species—before dissociating prior to nuclear storage (PMID:20513430, PMID:17640370, PMID:27881600, PMID:29537490). Independently of snRNP assembly, GEMIN5 is an autonomous translation regulator: its N-terminal WD40 domain binds directly to ribosomes and to ribosomal proteins L3 and L4 to globally repress protein synthesis, an activity that additionally requires self-oligomerization through a central TPR-like dimerization module that forms a canoe-shaped dimer and a higher-order decameric assembly (PMID:27507887, PMID:31799608, PMID:36056043, PMID:38942768). Its intrinsically disordered C-terminal non-canonical RNA-binding sites (RBS1/RBS2) engage viral IRES elements, the SMN and GEMIN5 mRNAs, and selective mRNA classes bearing 5'TOP or histone stem-loop motifs to fine-tune their translation, including positive autoregulation of its own message (PMID:23221641, PMID:24598255, PMID:25911097, PMID:29771365, PMID:35987821). This dimerization module is the principal hub for SMN, Gemin2, and Gemin4 binding and for ribosome association, and its activity is tuned by phosphorylation of specific residues and by viral L-protease cleavage that generates stable fragments with altered regulatory output (PMID:22362733, PMID:31799608, PMID:36420152, PMID:37369805, PMID:38942768, PMID:40734649). Loss-of-function GEMIN5 mutations cause a neurodevelopmental disorder, disrupting protein dimerization, ribosome association, snRNP assembly, and partner interactions, with SMN acting as a genetic suppressor of GEMIN5-mediated neurodegeneration (PMID:33963192, PMID:35393353, PMID:37369805).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2001 High

    Established GEMIN5 as a bona fide SMN complex component, defining its first molecular context within the snRNP assembly machinery.

    Evidence Co-immunoprecipitation and immunolocalization showing direct SMN binding, Sm protein interactions, and colocalization in gems

    PMID:11714716

    Open questions at the time
    • RNA-binding role not yet defined
    • domain responsible for SMN binding unmapped
  2. 2006 High

    Identified GEMIN5 as the snRNA-recognition subunit of the SMN complex, answering how snRNA substrates are selected for Sm core assembly.

    Evidence Direct RNA-binding assays, shRNA knockdown, and Sm core assembly assays

    PMID:16857593

    Open questions at the time
    • RNA-binding domain not localized
    • structural basis of Sm site recognition unknown
  3. 2006 Medium

    First linked GEMIN5 to the translation apparatus by identifying a direct eIF4E interaction, hinting at a role beyond snRNP assembly.

    Evidence SILAC proteomics, Co-IP, and confocal immunofluorescence showing P-body colocalization

    PMID:16739988

    Open questions at the time
    • functional consequence of eIF4E binding unresolved
    • single lab
  4. 2007 Medium

    Resolved where GEMIN5 acts in the snRNP pathway, showing it functions in cytoplasmic snRNA capture and dissociates before nuclear storage.

    Evidence Subcellular fractionation, sucrose gradient sedimentation, and compartment-specific Co-IP

    PMID:17640370

    Open questions at the time
    • mechanism of dissociation from SMN complex unknown
    • single lab
  5. 2007 Medium

    Extended GEMIN5 function to stress signaling by defining it as a scaffold for the ASK1–SEK1–JNK1 module promoting apoptosis.

    Evidence Co-IP, RNAi knockdown, and kinase activation assays in HeLa cells

    PMID:17541429

    Open questions at the time
    • relationship to snRNP/translation roles unclear
    • not independently replicated
  6. 2008 High

    Defined an autonomous translation-regulatory role, showing GEMIN5 binds viral IRES elements and represses both cap-dependent and IRES-driven initiation.

    Evidence Riboproteomics, photocrosslinking IP, shRNA knockdown, and in vitro translation assays

    PMID:19066202

    Open questions at the time
    • domain mediating IRES binding not yet mapped
    • mechanism of repression undefined
  7. 2009 High

    Mapped the snRNA- and cap-recognition activity to the WD40 repeat domain, defining it as a novel RNA-binding module.

    Evidence Hydroxyl radical probing, MS, deletion/mutagenesis, cap-affinity chromatography, and UV crosslinking

    PMID:19377484 PMID:19750007

    Open questions at the time
    • atomic structure of WD40–RNA contacts not yet determined
  8. 2010 High

    Demonstrated GEMIN5 acts as a substrate-delivery factor, capturing pre-snRNA intermediates for Sm core assembly and processing.

    Evidence High-throughput SMN inhibitor screening with formaldehyde crosslinking riboproteomics and sequencing of crosslinked RNAs

    PMID:20513430

    Open questions at the time
    • handoff mechanism to downstream SMN complex unresolved
  9. 2012 High

    Localized IRES repression activity to the C-terminal region and showed GEMIN5 remodels IRES structure and outcompetes PTB.

    Evidence Reconstitution with purified proteins, truncation in vitro translation, and SHAPE probing

    PMID:23221641

    Open questions at the time
    • precise RNA-binding residues within C-terminus not yet defined
  10. 2012 Medium

    Identified GEMIN5 as a specific FMDV L-protease substrate, revealing a viral strategy to remodel its regulatory functions via cleavage.

    Evidence Cleavage assays in FMDV-infected cells with L protease expression and cleavage-site mutagenesis

    PMID:22362733

    Open questions at the time
    • functional consequences of p85/p57 fragments not yet characterized
    • single lab
  11. 2014 High

    Resolved the C-terminal RNA-binding architecture into two non-canonical sites, separating RNA affinity (RBS1) from translation repression (RBS2).

    Evidence In vitro binding with purified polypeptides, NMR of RBS1, and cell-based translation reporter assays

    PMID:24598255

    Open questions at the time
    • how RBS2 represses initiation mechanistically unclear
  12. 2015 High

    Revealed selective positive translation control, showing GEMIN5 activates SMN mRNA translation through its 3'-UTR in an SMN-responsive feedback loop.

    Evidence In vitro and in vivo RNA-binding assays and polysome profiling after knockdown

    PMID:25911097

    Open questions at the time
    • molecular basis of activation versus repression switch undefined
  13. 2016 High

    Provided atomic basis for snRNA recognition, showing tandem WD40 domains read the Sm site and m7G cap via distinct base-specific surfaces.

    Evidence Crystal structures of WD40–RNA complexes with ITC and mutagenesis (two concurrent studies)

    PMID:27881600 PMID:27881601

    Open questions at the time
    • structure of full-length GEMIN5 not determined
    • dynamics of cap/Sm co-recognition unresolved
  14. 2016 High

    Defined the molecular basis of global translation repression, showing the N-terminal domain binds ribosomes directly via L3/L4.

    Evidence Fractionation, His-tag ribosome pulldown, L3/L4 Co-IP, mutagenesis (F381A/Y474A), polysome profiling, and metabolic labeling

    PMID:27507887

    Open questions at the time
    • how ribosome binding mechanistically lowers initiation unclear
  15. 2018 Medium

    Established autoregulation, showing RBS1 binds GEMIN5's own mRNA stem-loop to upregulate its translation and counterbalance global repression.

    Evidence CLIP, RIP, translation reporters, and stem-loop mutagenesis

    PMID:29771365

    Open questions at the time
    • quantitative contribution of autoregulation to GEMIN5 homeostasis unclear
    • single lab
  16. 2018 Medium

    Implicated GEMIN5 in surveillance of defective snRNPs, showing its depletion clears unassembled U1 granules in SMN-deficient cells.

    Evidence IP, colocalization microscopy, and knockdown rescue in SMN-deficient cells

    PMID:29537490

    Open questions at the time
    • mechanism routing unassembled U1 to disposal unknown
    • single lab
  17. 2020 High

    Identified the central TPR-like dimerization module as a self-assembly and protein-interaction hub required for functional consequences of viral cleavage.

    Evidence Crystallography, in-cell Co-IP, dimerization-surface point mutagenesis, and translation assays

    PMID:31799608

    Open questions at the time
    • full higher-order assembly state not yet resolved at this stage
  18. 2020 Medium

    Defined RBS1 RNA-recognition determinants, mapping the PXSS motif as essential for stem-loop binding and translation stimulation.

    Evidence Coevolution analysis, footprinting, gel-shift, mutagenesis, and translation reporters

    PMID:32476560

    Open questions at the time
    • structural model of RBS1–RNA complex incomplete
    • single lab
  19. 2021 Medium

    Characterized RBS1 as an intrinsically disordered module that recognizes RNA via conserved arginine/aromatic π–π interactions and charge.

    Evidence Solution NMR, exhaustive mutagenesis, and RNA-binding assays

    PMID:34424823

    Open questions at the time
    • how disorder confers RNA selectivity unresolved
    • single lab
  20. 2021 High

    Linked GEMIN5 to human disease, showing loss-of-function mutations disrupt protein distribution, stability, and snRNP assembly with in vivo developmental and motor deficits.

    Evidence Patient iPSC-derived neurons, Western blotting, snRNP assembly assays, and Drosophila rigor mortis knockdown

    PMID:33963192

    Open questions at the time
    • causal pathway from snRNP defect to neuronal phenotype not fully resolved
  21. 2022 High

    Refined the higher-order architecture, showing the C-terminus forms a homodecamer (dimer of pentamers) critical for RNA binding and translation control.

    Evidence Cryo-EM/crystal structure determination with mutagenesis and functional RNA/translation assays

    PMID:36056043

    Open questions at the time
    • physiological stoichiometry of oligomer in cells unclear
  22. 2022 Medium

    Connected disease variants to mechanism, showing TPR-domain and RBS1 patient mutations disrupt dimerization, ribosome association, and stability.

    Evidence Dimerization, ribosome association, MS interactome, and protein stability assays on patient variants

    PMID:35393353

    Open questions at the time
    • genotype–phenotype correlation across variants incomplete
    • single lab
  23. 2022 Medium

    Identified the mRNA classes selectively activated by GEMIN5, showing it promotes polysome loading of 5'TOP ribosomal and histone stem-loop mRNAs.

    Evidence Polysome profiling with RNA-seq, RIP, motif mutagenesis, and translation reporters

    PMID:35987821

    Open questions at the time
    • how motif recognition selects for activation vs repression unclear
    • single lab
  24. 2022 Medium

    Revealed phosphoregulation, showing T897 in the dimerization domain tunes the GEMIN5 interactome and translation regulation.

    Evidence MS phosphosite mapping, T897A/T897E mutagenesis, translation and interactome assays, and structural analysis

    PMID:36420152

    Open questions at the time
    • upstream kinase not identified
    • single lab
  25. 2023 High

    Established a therapeutically relevant SMN–GEMIN5 axis, showing SMN binds the GEMIN5 C-terminus and suppresses GEMIN5-mediated neurodegeneration.

    Evidence Co-IP with SMN Tudor mutants, SMN gene therapy/ASO treatment, iPSC neurons, and Drosophila epistasis

    PMID:37369805

    Open questions at the time
    • mechanism by which SMN restores GEMIN5 levels incomplete
  26. 2024 Medium

    Unified oligomerization with function, showing both WD40 and TPR dimerization modules are required for ribosome binding and translation repression.

    Evidence Interactome comparison of oligomerization-proficient vs -deficient constructs, polysome profiling, ribosome association, and Co-IP

    PMID:38942768

    Open questions at the time
    • how the two domains cooperate on ribosomes structurally unknown
    • single lab
  27. 2024 Medium

    Identified an HSPA8–GEMIN5 complex coupling splicing and translation, linking GEMIN5 to ribosome biogenesis in cancer cells.

    Evidence Chemical proteomics, CETSA, SPR, proximity labeling, Co-IP, and whole-transcriptome sequencing with rMATS

    PMID:41545989

    Open questions at the time
    • generality beyond colorectal cancer context unknown
    • single lab
  28. 2024 Low

    Suggested a specific mRNA target relevant to neuronal function, showing GEMIN5 binds Kdm6b mRNA and supports neurite extension responses.

    Evidence RIP, RT-qPCR, immunodetection, and siRNA knockdown with neurite extension assay in NSC34 cells

    PMID:39337533

    Open questions at the time
    • limited mechanistic detail; binding-to-phenotype causality not established
    • single lab
  29. 2025 Medium

    Delimited GEMIN5 specificity in snRNP assembly, showing it does not recognize the U7 Sm site, where PTBP1/IGF2BP3 substitute.

    Evidence Affinity purification, protein identification, and binding specificity assays

    PMID:40592581

    Open questions at the time
    • structural basis for U7 Sm-site exclusion not defined
    • establishes a negative result
  30. 2025 Medium

    Extended phosphoregulation of translation, showing Ser/Thr 847 and 852-854 phosphorylation tunes ribosome binding and cap-dependent synthesis.

    Evidence Non-phosphorylatable and phosphomimetic mutagenesis, ribosome association, protein synthesis assays, and dsRNA stimulation

    PMID:40734649

    Open questions at the time
    • responsible kinase(s) and signaling input unidentified
    • single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GEMIN5 dynamically partitions between its snRNP-assembly and translation-regulatory functions, and how phosphorylation and oligomerization are coordinated to switch between global repression and selective mRNA activation, remains unresolved.
  • no integrated structure of full-length GEMIN5 on the ribosome
  • upstream kinases and signaling triggers undefined
  • molecular switch between repression and activation modes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 10 GO:0045182 translation regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005840 ribosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1643685 Disease 3
Partners
EIF4EGEMIN2GEMIN4HSPA8RPL3RPL4SMD1SMN1
Complex memberships
SMN complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Gemin5 is a novel WD repeat protein component of the SMN complex that binds SMN directly and interacts with snRNP core proteins SmB, SmD1, SmD2, SmD3, and SmE. It colocalizes with SMN in cytoplasmic and nuclear gems. Co-immunoprecipitation, immunolocalization, direct binding assays The Journal of biological chemistry High 11714716
2006 Gemin5 is the snRNA-binding protein of the SMN complex, binding directly and specifically to snRNA features including the Sm site. Reduction of Gemin5 decreases SMN complex binding to snRNAs and reduces Sm core assembly. Direct RNA-binding assays, shRNA knockdown, Sm core assembly assay Molecular cell High 16857593
2009 Gemin5's WD repeat domain (13 WD motifs) is both necessary and sufficient for sequence-specific, high-affinity binding to snRNAs. Specific amino acids in the WD repeat domain contact snRNAs, as demonstrated by mutagenesis. The WD repeat domain constitutes a previously undescribed RNA-binding domain. RNA-mediated hydroxyl radical probing, mass spectrometry, deletion analysis, site-directed mutagenesis, binding assays Nature structural & molecular biology High 19377484
2009 Gemin5 binds directly and specifically to the 7-methylguanosine (m7G) cap structure via its WD repeat domains. Two proximal aromatic residues within the WD repeat region are required for m7G cap association. Cap-affinity chromatography, UV crosslinking to radiolabeled cap, deletion analysis, site-directed mutagenesis PloS one High 19750007
2006 Gemin5 interacts directly with eIF4E through a YXXXXLPhi motif and co-localizes with eIF4E in cytoplasmic P-bodies. Quantitative proteomics (SILAC), co-immunoprecipitation, confocal immunofluorescence Journal of proteome research Medium 16739988
2008 Gemin5 binds to the FMDV and HCV IRES elements and functions as a down-regulator of both cap-dependent and IRES-driven translation initiation. Gemin5 forms an IRES-ribonucleoprotein complex and an IRES-independent complex containing eIF4E. Riboproteomic analysis, photocrosslinking immunoprecipitation, shRNA knockdown, in vitro translation assays, pull-down assays Nucleic acids research High 19066202
2010 Gemin5 delivers pre-snRNA precursors to the SMN complex as substrates for Sm core assembly and processing. A transient pre-snRNA–Gemin5 intermediate accumulates upon protein synthesis inhibition. The 3' sequences of pre-snRNAs function to enhance snRNP biogenesis. High-throughput screening of SMN complex inhibitors, formaldehyde crosslinking riboproteomic strategy, high-throughput sequencing of crosslinked RNAs Molecular cell High 20513430
2007 Gemin5 is predominantly cytoplasmic and is largely absent from SMN complexes in nuclear gems/Cajal bodies, suggesting Gemin5 functions in cytoplasmic snRNA capture but dissociates before nuclear storage. Subcellular fractionation, sucrose density gradient sedimentation, immunohistochemistry, co-immunoprecipitation from nuclear vs. cytoplasmic extracts BMC cell biology Medium 17640370
2007 Gemin5 functions as a scaffold protein for the ASK1–SEK1–JNK1 signaling module: Gemin5 physically interacts with ASK1, SEK1, and JNK1, promotes their interactions with each other, and potentiates H2O2-induced activation of this cascade. Depletion of Gemin5 by RNAi reduces ASK1 and JNK1 activation and H2O2/TNFα-induced apoptosis. Co-immunoprecipitation, RNAi knockdown, kinase activation assays in HeLa cells Cell death and differentiation Medium 17541429
2012 The C-terminal region of Gemin5 mediates interaction with viral IRES elements and is necessary and sufficient to repress IRES-dependent translation. Gemin5 binding induces a specific local conformational change in the IRES structure and out-competes PTB binding. RNA-binding assays with purified proteins, in vitro translation with truncation constructs, SHAPE reactivity analysis Nucleic acids research High 23221641
2012 Gemin5 is cleaved by FMDV L protease (but not other picornavirus proteases) at a novel RKAR motif, yielding stable products p85 and p57. The (R)(R/K)(L/A)(R) sequence defines a novel Lpro recognition motif. Proteolysis assays in FMDV-infected cells, L protease expression, mutational analysis of cleavage sites, in silico identification of target sequences Nucleic acids research Medium 22362733
2014 The C-terminal region of Gemin5 bears two non-canonical bipartite RNA-binding sites (RBS1: aa 1297–1412; RBS2: aa 1383–1508). RBS1 has greater RNA-binding affinity but does not repress IRES translation; the lower-affinity RBS2 (aa 1383–1508) is the minimal element sufficient to repress internal initiation of translation. RNA-binding assays with purified polypeptides, NMR structural analysis of RBS1, expression of truncation constructs in G5-depleted mammalian cells, translation reporter assays Nucleic acids research High 24598255
2015 Gemin5 binds directly and specifically to sequence and structural elements in the SMN mRNA 3'-UTR and functions as an activator of SMN translation: reduction of Gemin5 shifts SMN mRNA from heavy polysomes to lighter polysomes/monosomes. SMN levels regulate the mRNA-binding activity of Gemin5, providing a feedback mechanism. In vitro RNA-binding assays, in vivo immunoprecipitation, polysome profiling after Gemin5 knockdown The Journal of biological chemistry High 25911097
2016 Crystal structures of the Gemin5 WD40 domain in complex with the Sm site and m7G cap of pre-snRNA reveal that the WD40 domain recognizes the Sm site and m7G cap via two distinct binding sites through base-specific interactions. Gemin5 also escorts truncated U1 pre-snRNA forms for disposal. Crystal structure determination, isothermal titration calorimetry (ITC), mutagenesis assays Genes & development High 27881600
2016 Crystal structure of the double WD40 repeat domain of Gemin5 in complex with Sm site RNA reveals that the tandem WD40 domains form a contiguous RNA-binding surface. Base-stacking interactions by four aromatic residues and hydrogen bonding by arginine pairs are crucial for specific Sm sequence recognition. An adenine 5' to the Sm site is required for efficient binding. X-ray crystallography, biochemical binding assays, mutagenesis Genes & development High 27881601
2016 Gemin5 sediments with the ribosome fraction and its N-terminal domain binds directly to ribosome particles and ribosomal proteins L3 and L4. Mutations F381A and Y474A abolish ribosome binding. Gemin5 depletion increases global protein synthesis while overexpression decreases it; Gemin5 and its N-terminal domain are detected on polysome fractions. Subcellular fractionation, His-tag pulldown with ribosomes, Co-IP of L3/L4, site-directed mutagenesis, polysome profiling, metabolic labeling Nucleic acids research High 27507887
2018 The RBS1 domain of Gemin5 C-terminus recognizes the Gemin5 mRNA itself as its most abundant cellular target, interacting with a thermodynamically stable stem-loop to upregulate Gemin5 mRNA translation, counteracting the global translation repression by full-length Gemin5. CLIP methodology, RNA immunoprecipitation, translation reporter assays, stem-loop mutagenesis Nucleic acids research Medium 29771365
2018 Gemin5 is involved in unassembled U1 snRNP disposal in SMN-deficient conditions: non-Sm-associated U1 snRNA and U1A accumulate in cytoplasmic P body granules. Gemin5 knockdown eliminates these unassembled U1 snRNP granules and rescues U1 snRNA levels. Immunoprecipitation, co-localization microscopy, Gemin5 knockdown in SMN-deficient cells FEBS letters Medium 29537490
2020 Crystal structure of a tetratricopeptide repeat (TPR)-like domain in the central region of human Gemin5 reveals self-assembly into a canoe-shaped dimer. The dimerization module recruits endogenous Gemin5 and the viral cleavage fragment p85; disruption of the dimerization surface by point mutation prevents p85–Gemin5 interaction and abrogates p85-induced translation enhancement. X-ray crystallography, co-immunoprecipitation in living cells, point mutagenesis of dimerization surface, translation assays Nucleic acids research High 31799608
2020 The PXSS motif (P1297, S1299, S1300) within the RBS1 domain of Gemin5 is required for RNA binding through coevolved nucleotide interactions. Substitutions at these residues drastically reduce binding to the stem-loop SL1 of Gemin5 mRNA and abolish translation stimulation by RBS1 in cells. Computational coevolution analysis, RBS1 footprint assays, gel-shift assays, mutagenesis, cell-based translation reporter assays RNA biology Medium 32476560
2021 The RBS1 domain of Gemin5 is intrinsically disordered (predominantly unfolded even in presence of RNA) and requires evolutionarily conserved arginine and aromatic residues (R, S, W, H) for RNA recognition via π–π interactions. Net charge and aromatic amino acid density are key determinants of RBS1 RNA binding. Solution NMR, exhaustive mutational analysis, RNA-binding assays RNA biology Medium 34424823
2021 Loss-of-function GEMIN5 mutations perturb subcellular distribution, stability, and expression of Gemin5 and its interacting partners in patient iPSC-derived neurons, and disrupt snRNP complex assembly. Knockdown of rigor mortis (Drosophila GEMIN5 ortholog) causes developmental defects, motor dysfunction, and reduced lifespan. Patient iPSC-derived neurons, Western blotting, snRNP assembly assay, Drosophila knockdown with behavioral and survival readouts Nature communications High 33963192
2022 Cryo-EM/crystal structure of the Gemin5 C-terminal region reveals a homodecamer (dimer of pentamers) architecture. The intact pentamer/decamer is critical for RNA binding and mRNA translation regulation. Pentamerization enables coordinated RNA ligand binding. 3D structure determination, mutagenesis, RNA-binding assays, translation assays Nature communications High 36056043
2022 TPR-like domain variants found in patients with neurodevelopmental disorders disrupt Gemin5 protein dimerization and fail to associate with native ribosomes; the RBS1 variant confers protein instability. All mutants are defective in interaction with protein networks involved in translation and RNA pathways. Dimerization assays, ribosome association assays, interactome analysis by mass spectrometry, protein stability assays Life science alliance Medium 35393353
2022 Gemin5 selectively promotes polysome association of ribosomal protein mRNAs (via 5'TOP motif) and histone mRNAs (via 3' histone stem-loop). Disruption of the TOP motif impairs Gemin5-RNA interaction; Gemin5 stimulates translation of reporters bearing intact TOP or hSL motifs. Polysome profiling with RNA-seq, RNA-immunoprecipitation, TOP motif mutagenesis, translation reporter assays Cellular and molecular life sciences Medium 35987821
2022 Phosphorylation of T897 in the TPR-like dimerization domain of Gemin5 modulates its protein interaction network and translation regulation. T897A mutation strongly abrogates association with translation-related cellular proteins; phosphomimetic T897E partially rescues translation regulatory activity. Structural analysis indicates phosphorylation causes local rearrangements at loop 2-3 that propagate across the dimerization interface. Mass spectrometry identification of phosphoresidues, site-directed mutagenesis (T897A, T897E), translation assays, MS interactome analysis, computational structural analysis Computational and structural biotechnology journal Medium 36420152
2023 SMN physically binds to the C-terminus of Gemin5 via the SMN Tudor domain, and SMN upregulation (by gene therapy or antisense oligonucleotide nusinersen) increases endogenous GEMIN5 levels. SMN acts as a genetic suppressor of GEMIN5-mediated neurodegeneration in vivo and ameliorates snRNP biogenesis and alternative splicing defects caused by loss of GEMIN5. Co-immunoprecipitation, SMN Tudor domain mutants, SMN gene therapy/ASO treatment in mammalian cells and iPSC neurons, Drosophila genetic epistasis Acta neuropathologica High 37369805
2024 Gemin5 oligomerization (via its TPR dimerization module) is required for association with native ribosomes and negative regulation of global translation. The WD40 domain and the TPR dimerization module are both required for ribosome binding. SMN, Gemin2, and Gemin4 interactions are determined primarily by the dimerization module, independent of the WD40 domain. Interactome analysis of oligomerization-proficient vs. deficient constructs, polysome profiling, ribosome association assays, Co-IP Cell death discovery Medium 38942768
2025 Phosphorylation of residues Ser/Thr 847 and 852-854 in the Gemin5 dimerization domain regulates ribosome binding and cap-dependent protein synthesis. Non-phosphorylatable substitutions decrease ribosome binding and protein stability; phosphomimetic triple substitution (STS852-854DDD) significantly alters cap-dependent protein synthesis. Site-directed mutagenesis (non-phosphorylatable and phosphomimetic substitutions), ribosome association assays, protein synthesis assays, dsRNA mimic stimulation RNA biology Medium 40734649
2025 PTBP1 and IGF2BP3 bind U7 snRNA at its unique Sm site (not recognized by Gemin5) and may substitute for Gemin5 in assembly of the U7-specific Sm ring. Gemin5 does not bind the Sm site of U7 snRNA. Affinity purification from mammalian extracts, protein identification, binding specificity assays RNA (New York, N.Y.) Medium 40592581
2024 GEMIN5 is identified as a functional interactor of HSPA8 in colorectal cancer cells. The HSPA8-GEMIN5 complex mediates 'splicing-translation coupling'; disruption of this complex by deoxyshikonin causes aberrant splicing of ribosomal protein genes mediated by GEMIN5, impeding ribosome biogenesis. Chemical proteomics, CETSA, SPR, SPIDER proximity labeling, Co-IP, GST pulldown, confocal microscopy, whole-transcriptome sequencing, rMATS Journal of experimental & clinical cancer research Medium 41545989
2024 GEMIN5 binds to Kdm6b mRNA; Gemin5 depletion reduces Kdm6b mRNA and protein levels and impairs responses to flunarizine including neurite extension in motor neuron-like NSC34 cells. RNA-immunoprecipitation, RT-qPCR, immunodetection, siRNA knockdown with functional neurite extension assay International journal of molecular sciences Low 39337533

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. The Journal of biological chemistry 136 11714716
2006 The Gemin5 protein of the SMN complex identifies snRNAs. Molecular cell 133 16857593
2010 Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis. Molecular cell 117 20513430
2008 A novel role for Gemin5 in mRNA translation. Nucleic acids research 94 19066202
2009 Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains. Nature structural & molecular biology 86 19377484
2016 Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly. Genes & development 61 27881600
2012 Gemin5 promotes IRES interaction and translation control through its C-terminal region. Nucleic acids research 60 23221641
2016 The RNA-binding protein Gemin5 binds directly to the ribosome and regulates global translation. Nucleic acids research 56 27507887
2012 Gemin5 proteolysis reveals a novel motif to identify L protease targets. Nucleic acids research 52 22362733
2014 Identification of novel non-canonical RNA-binding sites in Gemin5 involved in internal initiation of translation. Nucleic acids research 47 24598255
2009 Identification of gemin5 as a novel 7-methylguanosine cap-binding protein. PloS one 45 19750007
2021 Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder. Nature communications 44 33963192
2016 Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5. Genes & development 44 27881601
2007 Absence of gemin5 from SMN complexes in nuclear Cajal bodies. BMC cell biology 41 17640370
2006 Quantitative proteomics identifies Gemin5, a scaffolding protein involved in ribonucleoprotein assembly, as a novel partner for eukaryotic initiation factor 4E. Journal of proteome research 41 16739988
2015 Gemin5 Binds to the Survival Motor Neuron mRNA to Regulate SMN Expression. The Journal of biological chemistry 37 25911097
2010 Drosophila SMN complex proteins Gemin2, Gemin3, and Gemin5 are components of U bodies. Experimental cell research 37 20452345
2008 Alterations in Gemin5 expression contribute to alternative mRNA splicing patterns and tumor cell motility. Cancer research 35 18245461
2020 Emerging Roles of Gemin5: From snRNPs Assembly to Translation Control. International journal of molecular sciences 33 32485878
2015 Gemin5: A Multitasking RNA-Binding Protein Involved in Translation Control. Biomolecules 31 25898402
2018 The landscape of the non-canonical RNA-binding site of Gemin5 unveils a feedback loop counteracting the negative effect on translation. Nucleic acids research 27 29771365
2020 Structural basis for the dimerization of Gemin5 and its role in protein recruitment and translation control. Nucleic acids research 24 31799608
2021 Pathogenic variants in the survival of motor neurons complex gene GEMIN5 cause cerebellar atrophy. Clinical genetics 21 34569062
2007 Positive regulation of ASK1-mediated c-Jun NH(2)-terminal kinase signaling pathway by the WD-repeat protein Gemin5. Cell death and differentiation 20 17541429
2019 Impact of RNA-Protein Interaction Modes on Translation Control: The Versatile Multidomain Protein Gemin5. BioEssays : news and reviews in molecular, cellular and developmental biology 19 30919488
2022 Autosomal Recessive Cerebellar Atrophy and Spastic Ataxia in Patients With Pathogenic Biallelic Variants in GEMIN5. Frontiers in cell and developmental biology 17 35295849
2022 Functional and structural deficiencies of Gemin5 variants associated with neurological disorders. Life science alliance 14 35393353
2020 RNA-protein coevolution study of Gemin5 uncovers the role of the PXSS motif of RBS1 domain for RNA binding. RNA biology 13 32476560
2022 Gemin5-dependent RNA association with polysomes enables selective translation of ribosomal and histone mRNAs. Cellular and molecular life sciences : CMLS 12 35987821
2022 Structural basis for Gemin5 decamer-mediated mRNA binding. Nature communications 11 36056043
2021 The RBS1 domain of Gemin5 is intrinsically unstructured and interacts with RNA through conserved Arg and aromatic residues. RNA biology 11 34424823
2016 The right pick: structural basis of snRNA selection by Gemin5. Genes & development 10 27881598
2024 Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment. European journal of human genetics : EJHG 9 38316953
2018 Gemin5 plays a role in unassembled-U1 snRNA disposal in SMN-deficient cells. FEBS letters 9 29537490
2023 SMN regulates GEMIN5 expression and acts as a modifier of GEMIN5-mediated neurodegeneration. Acta neuropathologica 8 37369805
2021 Mutation of Gemin5 Causes Defective Hematopoietic Stem/Progenitor Cells Proliferation in Zebrafish Embryonic Hematopoiesis. Frontiers in cell and developmental biology 8 33996826
2023 A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy. Genes 7 36980979
2024 Alternative splicing events driven by altered levels of GEMIN5 undergo translation. RNA biology 6 39194147
2022 Phosphorylation of T897 in the dimerization domain of Gemin5 modulates protein interactions and translation regulation. Computational and structural biotechnology journal 6 36420152
2024 Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies. Brain and behavior 5 38773790
2023 Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gene in two Chinese families. Journal of human genetics 5 37479787
2024 Oligomerization regulates the interaction of Gemin5 with members of the SMN complex and the translation machinery. Cell death discovery 4 38942768
2025 GEMIN5 and neurodevelopmental diseases: From functional insights to disease perception. Neural regeneration research 3 39819844
2025 Understanding GEMIN5 Interactions: From Structural and Functional Insights to Selective Translation. Wiley interdisciplinary reviews. RNA 3 40176294
2024 Function and dysfunction of GEMIN5: understanding a novel neurodevelopmental disorder. Neural regeneration research 3 38526274
2024 Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy. International journal of molecular sciences 2 39337533
2026 Disruption of HSPA8-GEMIN5 interaction suppresses colorectal cancer by impaired splicing-translation coupling-mediated proteostasis imbalance. Journal of experimental & clinical cancer research : CR 1 41545989
2019 Regulated expression of Gemin5, Xrn1, Cpeb and Stau1 in the uterus and ovaries after superovulation and the effect of exogenous estradiol and leptin in rodents. Molecular biology reports 1 30689188
2026 circPDE4B downregulation triggers GEMIN5‑dependent translational stress response and autophagy to reduce MAPT pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association 0 42080242
2025 Proteins that recognize unique features of U7 snRNA and may substitute for Gemin5 in the assembly of U7-specific Sm ring. RNA (New York, N.Y.) 0 40592581
2025 Impact of Gemin5 in protein synthesis: phosphoresidues of the dimerization domain regulate ribosome binding. RNA biology 0 40734649
2025 N7-Methylguanine Modification of SHMT2 Mediated by GEMIN5 Inhibits Cell Ferroptosis of Colorectal Cancer Cells. Journal of biochemical and molecular toxicology 0 41416630
2024 Corrigendum: Mutation of Gemin5 causes defective hematopoietic stem/progenitor cells proliferation in zebrafish embryonic hematopoiesis. Frontiers in cell and developmental biology 0 38655064

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