id: F6WDM0 gene_symbol: GEMIN5 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9796 label: Equus caballus description: GEMIN5 (gem-associated protein 5) is a large WD40-repeat RNA-binding protein and the snRNA-recognition subunit of the SMN complex. Its N-terminal tandem seven-bladed WD40 propellers bind the Sm site and the 7-methylguanosine cap of Sm-class small nuclear RNA precursors, so that the SMN complex selects these RNAs for assembly of the heptameric Sm core of spliceosomal snRNPs in the cytoplasm. A central TPR-like region mediates dimerization, and a C-terminal non-canonical RNA-binding region binds structured mRNAs. GEMIN5 also binds the SMN mRNA 3'-UTR to promote its translation and binds 60S ribosomal subunits, dampening global translation. It is mainly cytoplasmic, with a smaller pool in the nucleoplasm and in gems. Horse F6WDM0 is the full-length (1517 aa) product of the horse GEMIN5 gene, a one-to-one ortholog of human GEMIN5 in PANTHER subfamily PTHR46362:SF1 (89% identity). All residues known to contact snRNA or the cap are conserved. None of these functions has been tested in horse; they are inferred from the human (and mouse) protein and from the phylogenetic placement of the gene. existing_annotations: - term: id: GO:0000340 label: RNA 7-methylguanosine cap binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Binding of the m7G cap of pre-snRNAs by the WD40 module, inferred from the human ortholog; all cap-contact residues are conserved in horse. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 binds the m7G cap directly in pull-downs (PMID:19750007), and the cap analogue binds at a defined site in the crystal structure of the WD40 module (PMID:27881601). All five residues implicated by mutation or by the soaked structure (W286, F338, Y474, L580, N582) are identical in F6WDM0. PAINT did not place this term at node PTN005299808, which spans vertebrate and insect members; that omission is a node-level judgement and does not count against transfer between one-to-one mammalian orthologs, but it means this activity is not phylogenetically established beyond mammals. supported_by: - &id011 reference_id: PMID:19750007 supporting_text: Gemin5 binds directly to the m7G cap structure. - &id012 reference_id: PMID:27881600 supporting_text: the WD40 domain of Gemin5 recognizes the Sm site and m7G cap of pre-snRNAs via two distinct binding sites - &id013 reference_id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-bioinformatics/RESULTS.md supporting_text: '- Cap-binding residues identified by mutation (PMID:19750007): W286, F338 -- all identical.' - &id014 reference_id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-bioinformatics/RESULTS.md supporting_text: '- m7G cap contacts in the m7GTP-soaked structure (PMID:27881601): Y474, L580, N582 -- all identical.' - term: id: GO:0000387 label: spliceosomal snRNP assembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - PANTHER:PTN005299808 - UniProtKB:Q8TEQ6 review: summary: Core process. PAINT places spliceosomal snRNP assembly at PTN005299808, and F6WDM0 is a full-length member of the same subfamily. action: ACCEPT reason: 'The IBA is the phylogenetic judgement that snRNP assembly is ancestral to the GEMIN5 clade. F6WDM0 is in PTHR46362:SF1 and keeps the complete WD40 snRNA-recognition module with every mapped contact residue, so nothing argues for loss of function in horse. The experimental grounding is human: GEMIN5 binds snRNAs and depletion lowers Sm-core assembly (PMID:16857593); it delivers pre-snRNAs to the SMN complex (PMID:20513430). GEMIN5 does work in this process, recognising the snRNA substrate and handing it to the assembly machine.' supported_by: - &id004 reference_id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-uniprot.txt record_section: ["DR:PANTHER"] supporting_text: DR PANTHER; PTHR46362:SF1; GEM-ASSOCIATED PROTEIN 5; 1. - &id001 reference_id: PMID:16857593 supporting_text: Reduction of Gemin5 results in reduced capacity of the SMN complex to bind snRNAs and to assemble Sm cores. - &id002 reference_id: PMID:20513430 supporting_text: highlighting Gemin5's function in delivering pre-snRNAs as substrates for Sm core assembly and processing - &id007 reference_id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-bioinformatics/RESULTS.md supporting_text: '- snRNA Sm-site contacts mutated in PMID:27881601: N13, W14, Y15, R33, R335, M357, R359, F381, Y383, M403, W422, Y474 -- all identical.' - term: id: GO:0000387 label: spliceosomal snRNP assembly evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Same claim as the IBA row; agrees with the phylogenetic inference. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. The term matches the PAINT IBA from PTN005299808 and is the core process of GEMIN5. supported_by: - *id001 - *id002 - term: id: GO:0003723 label: RNA binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: True but uninformative; the specific RNA-binding activities are snRNA binding and mRNA 3'-UTR binding, both already carried. action: MODIFY reason: 'This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. GEMIN5 binds RNA, but the parent term hides what is known: Sm-site/cap recognition of snRNAs by the WD40 module and binding of the SMN mRNA 3''-UTR. Both descendants are annotated to this entry, so the general term should be replaced by them.' proposed_replacement_terms: - id: GO:0017069 label: snRNA binding - id: GO:0003730 label: mRNA 3'-UTR binding supported_by: - &id006 reference_id: PMID:16857593 supporting_text: Gemin5 binds directly and specifically to the unique features, including the Sm site, of snRNAs. - &id003 reference_id: PMID:25911097 supporting_text: Gemin5 directly binds to the mature SMN 3′-UTR immediately upstream of the poly(A) tail. - term: id: GO:0003730 label: mRNA 3'-UTR binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - MGI:MGI:2449311 - PANTHER:PTN005299808 - UniProtKB:Q8TEQ6 review: summary: PAINT places mRNA 3'-UTR binding at PTN005299808 (human and mouse donors); F6WDM0 is a full-length subfamily member. action: ACCEPT reason: Human GEMIN5 binds the SMN mRNA 3'-UTR directly and raises SMN translation (PMID:25911097). PAINT propagated the term from PTN005299808 with mouse and human donors. F6WDM0 retains all regions of the human protein, including the C-terminal RBS region, so the inheritance is uncontested. supported_by: - *id003 - *id004 - term: id: GO:0003730 label: mRNA 3'-UTR binding evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables supporting_entities: - ARBA:ARBA00028422 - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Same claim as the IBA row; agrees with it. action: ACCEPT reason: Combined electronic annotation (ARBA plus ortholog transfer) consistent with the PAINT IBA for the same term. supported_by: - *id003 - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - FB:FBgn0250850 - PANTHER:PTN005299808 - UniProtKB:Q8TEQ6 review: summary: Correct but general; the nuclear pool is nucleoplasmic and concentrated in gems, both carried by this entry. action: MODIFY reason: PAINT placed nucleus at PTN005299808. Human immunolocalisation shows the nuclear pool in the nucleoplasm and in gems with SMN (PMID:11714716). The specific descendants nucleoplasm and Gemini of Cajal bodies are both annotated to F6WDM0, as in the human review. The nuclear pool is minor relative to the cytoplasmic one. proposed_replacement_terms: - id: GO:0005654 label: nucleoplasm - id: GO:0097504 label: Gemini of Cajal bodies supported_by: - &id005 reference_id: PMID:11714716 supporting_text: Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems. propagation_review: root_cause: TERM_SCOPING_PROBLEM failure_modes: - GRANULARITY_MISMATCH source_entities: - source_id: PANTHER:PTN005299808 source_status: SUPPORTS_TRANSFER comment: Gemin5 family node; F6WDM0 is a full-length PTHR46362:SF1 member. The nuclear pool is supported by human and Drosophila donors, so the transfer is sound; only the granularity (nucleus vs nucleoplasm/gems) is refined. - source_id: FB:FBgn0250850 source_label: rig source_status: SUPPORTS_TRANSFER comment: Drosophila Gemin5 ortholog with experimental nuclear localization. - source_id: UniProtKB:Q8TEQ6 source_label: GEMIN5 source_status: SUPPORTS_TRANSFER comment: Human ortholog; immunolocalized to nucleoplasm and gems (PMID:11714716). residue_claims_not_applicable: Localization granularity question, not a residue-level argument. - term: id: GO:0005654 label: nucleoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 - UniProtKB-SubCell:SL-0190 review: summary: Minor nucleoplasmic pool, inferred from the human ortholog. action: KEEP_AS_NON_CORE reason: Human GEMIN5 has a nuclear pool besides the dominant cytoplasmic one (PMID:11714716). snRNP assembly by GEMIN5 occurs in the cytoplasm, so this location is peripheral. supported_by: - *id005 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 - UniProtKB-SubCell:SL-0086 review: summary: Correct but general; GEMIN5 acts in the cytosol, which this entry already carries. action: MODIFY reason: Human GEMIN5 is predominantly cytoplasmic and the SMN complex assembles Sm cores in the cytosol. Following the human review, the specific term cytosol is preferred. proposed_replacement_terms: - id: GO:0005829 label: cytosol supported_by: - *id005 - &id010 reference_id: PMID:18984161 supporting_text: The SMN complex subsequently binds to these Sm protein units, dissociates pICln, and catalyzes ring closure on snRNA. - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Main site of GEMIN5 activity, inferred from the human ortholog. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 delivers pre-snRNAs to the SMN complex for cytoplasmic Sm-core assembly, and binds ribosomes and mRNA there. supported_by: - *id005 - *id002 - term: id: GO:0006417 label: regulation of translation evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Correct but general; the human evidence supports both a positive (SMN mRNA) and a negative (global) effect on translation. action: MODIFY reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. In human cells GEMIN5 binding to the SMN 3'-UTR increases SMN translation (PMID:25911097), while GEMIN5 bound to the 60S subunit dampens global protein synthesis (PMID:27507887). Both descendants are listed, as in the human review. PAINT did not propagate any translation-regulation term, so this role rests only on mammalian orthology and is not core. proposed_replacement_terms: - id: GO:0045727 label: positive regulation of translation - id: GO:0017148 label: negative regulation of translation supported_by: - &id015 reference_id: PMID:25911097 supporting_text: Gemin5 binding to the SMN 3′-UTR activates expression of SMN protein by increasing translation of the SMN mRNA. - reference_id: PMID:27507887 supporting_text: Gemin5 siRNA depletion decreased the polysome/80S ratio, and enhanced global protein synthesis. - term: id: GO:0016604 label: nuclear body evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Correct but general; the nuclear bodies are gems, which this entry carries. action: MODIFY reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. The human nuclear-body signal is in gems with SMN (PMID:11714716); the specific term is Gemini of Cajal bodies. proposed_replacement_terms: - id: GO:0097504 label: Gemini of Cajal bodies supported_by: - *id005 - term: id: GO:0017069 label: snRNA binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Core activity. Sm-site recognition of snRNAs by the tandem WD40 propellers, inferred from the human ortholog with every contact residue conserved. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 binds snRNAs directly and specifically through the Sm site and adjacent features (PMID:16857593), using its 13-WD-repeat domain (PMID:19377484). All 12 residues mutated in the crystal-structure study (PMID:27881601) are identical in F6WDM0. PAINT did not place snRNA binding at PTN005299808 although it placed snRNP assembly there; the omission is noted as a question, and does not weaken transfer to a one-to-one mammalian ortholog with an intact binding surface. supported_by: - *id006 - &id008 reference_id: PMID:19377484 supporting_text: The entire WD repeat domain, comprising 13 WD motifs, is both necessary and sufficient for sequence-specific, high-affinity binding of Gemin5 to its RNA targets. - *id007 - term: id: GO:0030619 label: U1 snRNA binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: U1 snRNA (and pre-snRNA) binding by the WD40 module, inferred from the human ortholog. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 binds U1 through its Sm site and cap (PMID:19377484, PMID:27881600); the binding surface is conserved in horse. supported_by: - reference_id: PMID:27881600 supporting_text: the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs - *id008 - *id007 - term: id: GO:0030621 label: U4 snRNA binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: U4 snRNA binding, inferred from the human ortholog; the structural study used U4 snRNA. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. The human WD40 module binds full-length U4 and a U4 Sm-site fragment (PMID:27881601); every contact residue is conserved in F6WDM0. supported_by: - reference_id: PMID:27881601 supporting_text: As shown in Figure 2A, G5N binds well to the full-length U4 snRNA and a synthetic 30-nt U4 snRNA fragment containing the Sm site and an adjacent 3′ stem–loop - *id007 - term: id: GO:0030622 label: U4atac snRNA binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: U4atac (minor-spliceosome) snRNA binding, inferred from the human ortholog. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 binds Sm-class pre-snRNAs, including minor-spliceosome U4atac, and delivers them to the SMN complex (PMID:20513430). supported_by: - *id002 - *id006 - term: id: GO:0032797 label: SMN complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of supporting_entities: - FB:FBgn0250850 - PANTHER:PTN005299808 - UniProtKB:Q8TEQ6 review: summary: GEMIN5 is the snRNA-binding subunit of the SMN complex; PAINT places this at PTN005299808. action: ACCEPT reason: The IBA rests on human and Drosophila donors. Human GEMIN5 is a peripheral but essential component of the SMN complex (PMID:17178713). F6WDM0 is a full-length subfamily member. supported_by: - &id009 reference_id: PMID:17178713 supporting_text: Finally, we show that the peripheral component Gemin5 contributes an essential activity to the SMN complex - *id004 - term: id: GO:0032797 label: SMN complex evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Same claim as the IBA row. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Consistent with the PAINT IBA for the same term. supported_by: - *id009 - term: id: GO:0034718 label: SMN-Gemin2 complex evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Association with the SMN-Gemin2 subcomplex, inferred from the human ortholog; peripheral to the full SMN complex function. action: KEEP_AS_NON_CORE reason: 'This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. The human review keeps this as non-core: GEMIN5 is a peripheral subunit, and the functional unit is the full SMN complex, which is accepted separately.' supported_by: - *id009 - term: id: GO:0034719 label: SMN-Sm protein complex evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: GEMIN5 is part of the SMN-Sm protein assembly complex that loads Sm proteins onto snRNA, inferred from the human ortholog. action: ACCEPT reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Human GEMIN5 binds several Sm proteins (PMID:11714716), and the SMN complex binds Sm units and closes the ring on snRNA (PMID:18984161). supported_by: - reference_id: PMID:11714716 supporting_text: Gemin5 interacts with several of the snRNP core proteins including SmB, SmD1, SmD2, SmD3, and SmE, suggesting that it participates in the activities of the SMN complex in snRNP assembly. - *id010 - term: id: GO:0043022 label: ribosome binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8TEQ6 - ensembl:ENSP00000285873 review: summary: Ribosome (60S) binding, inferred from one human study; plausible but secondary to snRNA recognition. action: KEEP_AS_NON_CORE reason: This is an Ensembl Compara transfer from the one-to-one human ortholog Q8TEQ6 (same PANTHER subfamily PTHR46362:SF1, 88.8% identity over the full length). No horse protein has been tested experimentally. Purified human GEMIN5 binds 60S and 80S particles through its N-terminal region (PMID:27507887). The evidence comes from a single laboratory and PAINT did not propagate this term, so it is kept as a mammalian-orthology inference outside the core function. supported_by: - reference_id: PMID:27507887 supporting_text: His-Gemin5 binds to ribosome particles via its N-terminal domain. - term: id: GO:0097504 label: Gemini of Cajal bodies evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0127 review: summary: Minor pool in gems with SMN, inferred from the human ortholog. action: KEEP_AS_NON_CORE reason: The UniProt subcellular location (from an ARBA rule) agrees with human immunolocalisation of GEMIN5 in gems (PMID:11714716). The location is real but peripheral to cytoplasmic snRNP assembly. supported_by: - *id005 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:16857593 title: The Gemin5 protein of the SMN complex identifies snRNAs. full_text_unavailable: true findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (abstract cached). Establishes GEMIN5 as the snRNA-binding subunit of the SMN complex and its requirement for Sm-core assembly. Source of the transferred snRNA-binding and snRNP-assembly claims. - id: PMID:19377484 title: Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains. full_text_unavailable: true findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (abstract cached). Maps snRNA binding to the 13-WD-repeat domain. - id: PMID:19750007 title: Identification of gemin5 as a novel 7-methylguanosine cap-binding protein. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (full text cached). Direct m7G cap binding; W286 and F338 mutants reduce cap binding. Both residues are conserved in F6WDM0. - id: PMID:20513430 title: Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (full text cached). GEMIN5 delivers pre-snRNAs, including minor-spliceosome snRNAs, to the SMN complex. - id: PMID:27881600 title: Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly. full_text_unavailable: true findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 WD40 structure (abstract cached). Two distinct binding sites for the Sm site and the m7G cap. - id: PMID:27881601 title: Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 WD40 crystal structure (full text cached). Source of the RNA- and cap-contact residues checked for conservation in GEMIN5__F6WDM0-bioinformatics/RESULTS.md. - id: PMID:25911097 title: Gemin5 Binds to the Survival Motor Neuron mRNA to Regulate SMN Expression. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (full text cached). Direct binding to the SMN 3'-UTR and positive regulation of SMN translation. - id: PMID:27507887 title: The RNA-binding protein Gemin5 binds directly to the ribosome and regulates global translation. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Human GEMIN5 in HEK293 cells and purified protein (full text cached). Ribosome binding and negative effect on global translation; single-lab evidence. - id: PMID:11714716 title: Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. full_text_unavailable: true findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human GEMIN5 (abstract cached). Identification as an SMN-complex component that binds Sm proteins; cytoplasmic, nucleoplasmic and gem localization. - id: PMID:17178713 title: A comprehensive interaction map of the human survival of motor neuron (SMN) complex. full_text_unavailable: true findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Human SMN complex interaction map (abstract cached). GEMIN5 is a peripheral component contributing an essential activity. - id: PMID:18984161 title: An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. full_text_unavailable: true findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: SMN complex assembly mechanism (abstract cached); context for the SMN-Sm protein complex and cytosolic Sm-ring closure. - id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-bioinformatics/RESULTS.md title: Horse GEMIN5 (F6WDM0) versus human GEMIN5 (Q8TEQ6) findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Reproducible alignment of F6WDM0 to human Q8TEQ6 (script compare_to_human.py, raw output results.txt) and conservation check of experimentally mapped contact residues. - id: file:HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-uniprot.txt title: UniProtKB entry F6WDM0 (F6WDM0_HORSE) findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Unreviewed TrEMBL record. Used only for PANTHER/InterPro classification; its ARBA-derived names, keywords and locations are not used as evidence. core_functions: - description: Recognizes the Sm site of Sm-class pre-snRNAs through its tandem WD40 propellers and delivers them to the SMN complex for cytoplasmic Sm-core assembly of spliceosomal snRNPs. Inferred from the human ortholog (same PANTHER subfamily, PAINT node PTN005299808 for the process) with all RNA-contact residues conserved; not tested in horse. molecular_function: id: GO:0017069 label: snRNA binding directly_involved_in: - id: GO:0000387 label: spliceosomal snRNP assembly locations: - id: GO:0005829 label: cytosol in_complex: id: GO:0032797 label: SMN complex supported_by: - *id006 - *id001 - *id002 - *id007 - description: Binds the 7-methylguanosine cap of pre-snRNAs at a second site on the WD40 module, contributing to snRNA selection. Inferred from the human ortholog; cap-contact residues conserved. molecular_function: id: GO:0000340 label: RNA 7-methylguanosine cap binding directly_involved_in: - id: GO:0000387 label: spliceosomal snRNP assembly locations: - id: GO:0005829 label: cytosol supported_by: - *id011 - *id012 - *id013 - *id014 - description: Binds the SMN mRNA 3'-UTR and promotes SMN translation. The binding activity is placed at PAINT node PTN005299808; the translational effect is inferred from human data only. molecular_function: id: GO:0003730 label: mRNA 3'-UTR binding directly_involved_in: - id: GO:0045727 label: positive regulation of translation locations: - id: GO:0005829 label: cytosol supported_by: - *id003 - *id015 suggested_questions: - question: PAINT node PTN005299808 propagates spliceosomal snRNP assembly, SMN complex, nucleus and mRNA 3'-UTR binding, but not snRNA binding or RNA 7-methylguanosine cap binding, although human GEMIN5 has IDA support for both and they are the activities through which it acts in snRNP assembly. Is the omission deliberate (for example because the Drosophila member Rigor mortis lacks the snRNA-binding evidence), and should snRNA binding be placed at a mammalian or vertebrate node? - question: Does the 9-residue insertion in the second WD40 propeller of horse GEMIN5 (after human position 618) reflect a genuine horse-specific exon feature, and does it affect the fold or RNA binding? suggested_experiments: - description: Electrophoretic mobility shift or filter-binding assays with recombinant horse GEMIN5 WD40 module and U4 snRNA Sm-site and m7G-cap probes, with W14A/Y15A and Y474 mutants as controls, to confirm in this species the snRNA- and cap-binding activities inferred from human.