id: A0A9L0R5P7 gene_symbol: GEMIN5 product_type: PROTEIN status: IN_PROGRESS 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 7-methylguanosine cap of small nuclear RNAs, so that the SMN complex can select snRNAs for Sm-core (snRNP) assembly in the cytoplasm. A central TPR-like dimerization region and a C-terminal non-canonical RNA-binding region support interactions with structured mRNAs and ribosomes. Through these GEMIN5 binds the SMN mRNA 3'-UTR and regulates translation. The protein is mainly cytoplasmic, with a smaller nuclear pool in gems. This horse entry (1433 aa) is an alternative-transcript product of the GEMIN5 gene. It keeps the complete WD40 module, with all of its mapped RNA-contact residues, and the C-terminal regions. It lacks a 76-residue disordered linker (human 723-798) that lies just after the WD40 fold and carries phosphorylation and SUMOylation sites. existing_annotations: - term: id: GO:0003730 label: mRNA 3'-UTR binding evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables supporting_entities: - ARBA:ARBA00028422 review: action: ACCEPT summary: GEMIN5 binds the SMN mRNA 3'-UTR. The activity is inherited within PANTHER subfamily PTHR46362:SF1, and this isoform keeps the RNA-binding regions. reason: Human GEMIN5, in the same PANTHER subfamily (PTHR46362:SF1, sequence identity 89%), binds the SMN 3'-UTR directly (PMID:25911097). PAINT curators placed mRNA 3'-UTR binding at node PTN005299808, with mouse and human donors, and propagated it as an IBA to the full-length horse product F6WDM0 of this same gene. The earlier review marked this row UNDECIDED because the isoform has an internal deletion. Re-analysis shows that the missing block (human 723-798) lies C-terminal to the folded tandem WD40 domain (residues 3-722 in the crystal structure). It falls in a region annotated as disordered. All mapped RNA-contact residues and the TPR-like and RBS regions are retained. Nothing therefore argues against inheritance. The ARBA term agrees with the phylogenetic inference. supported_by: - reference_id: PMID:25911097 supporting_text: Gemin5 directly binds to the mature SMN 3′-UTR immediately upstream of the poly(A) tail. - reference_id: file:HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md supporting_text: It therefore sits C-terminal to the structured RNA-recognition module, not inside it. - reference_id: file:HORSE/GEMIN5/GEMIN5-uniprot.txt record_section: ["DR:PANTHER"] supporting_text: DR PANTHER; PTHR46362:SF1; GEM-ASSOCIATED PROTEIN 5; 1. - term: id: GO:0005654 label: nucleoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0190 review: action: KEEP_AS_NON_CORE summary: GEMIN5 has a minor nuclear pool that colocalizes with SMN in gems. reason: Immunolocalization of the human ortholog shows a nuclear pool in addition to the predominant cytoplasmic one. PAINT also placed nucleus (is_active_in) at PTN005299808. The isoform-specific deletion does not remove any region known to determine localization. snRNP assembly by the SMN complex takes place mainly in the cytoplasm, so the nuclear pool is peripheral to the core function. supported_by: - reference_id: PMID:11714716 supporting_text: "Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and\ \ \nin the nucleus, where it colocalizes with SMN in gems." - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0086 review: action: ACCEPT summary: GEMIN5 is predominantly cytoplasmic, where the SMN complex assembles snRNPs. reason: The human ortholog (same PANTHER subfamily) is found in the cytoplasm. The SMN complex assembles Sm cores on snRNAs in the cytoplasm. The cytoplasm is where the core activity of GEMIN5 takes place. supported_by: - reference_id: PMID:11714716 supporting_text: "Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and\ \ \nin the nucleus, where it colocalizes with SMN in gems." - reference_id: PMID:11714716 supporting_text: "The SMN complex plays an important role in \nthe cytoplasmic assembly of small\ \ nuclear ribonucleoproteins (snRNPs)" - 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: action: KEEP_AS_NON_CORE summary: Nuclear GEMIN5 colocalizes with SMN in gems. reason: Gems are the specific nuclear body where human GEMIN5 colocalizes with SMN. The term is as precise as the evidence allows. It describes a minor pool rather than the site of the core cytoplasmic assembly function. supported_by: - reference_id: PMID:11714716 supporting_text: "Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and\ \ \nin the nucleus, where it colocalizes with SMN in gems." references: - 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:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: PMID:25911097 title: Gemin5 Binds to the Survival Motor Neuron mRNA to Regulate SMN Expression. full_text_unavailable: false findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human study; direct binding of Gemin5 to the SMN 3'-UTR and regulation of SMN translation. - id: file:HORSE/GEMIN5/GEMIN5-bioinformatics/RESULTS.md title: HORSE/GEMIN5/GEMIN5-bioinformatics/RESULTS.md findings: [] reference_review: relevance: MEDIUM correctness: DISPUTED review_notes: >- Earlier human-horse comparison. Its identity figures and the deleted segment (human 723-798) were reproduced in the 2026-10-20 re-review. However, its description of the deletion as spanning the end of the WD40 RNA-recognition module uses the 1-739 construct boundary. In the solved structure the folded WD40 region is residues 3-722 (PMID:27881601), so the deletion lies outside the fold. This file is no longer cited as support and is superseded by rereview/RESULTS-rereview.md. - id: file:HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md title: HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Re-review analysis. It aligns all four horse GEMIN5 gene-model products to human Q8TEQ6 and maps the RNA-contact residues from PMID:27881601. Scripts and raw outputs are in the same folder. - id: file:HORSE/GEMIN5/GEMIN5-uniprot.txt title: HORSE/GEMIN5/GEMIN5-uniprot.txt findings: [] - 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 study (abstract cached). Identifies Gemin5 as an SMN-binding component of the SMN complex and reports its cytoplasmic and nuclear (gem) localization. - id: PMID:16857593 title: The Gemin5 protein of the SMN complex identifies snRNAs. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Human study (abstract cached). Shows that Gemin5 is the snRNA-binding protein of the SMN complex and is required for Sm-core assembly. - 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 crystal structure (full text cached). Gives the folded WD40 boundary (residues 3-722) and the mutated RNA-contact residues used in the residue-conservation check. core_functions: - description: Recognizes the Sm site and cap of snRNAs through its tandem WD40 propellers. It selects and delivers snRNAs to the SMN complex for spliceosomal Sm-core (snRNP) assembly in the cytoplasm. molecular_function: id: GO:0017069 label: snRNA binding directly_involved_in: - id: GO:0000387 label: spliceosomal snRNP assembly locations: - id: GO:0005737 label: cytoplasm in_complex: id: GO:0032797 label: SMN complex supported_by: - reference_id: PMID:16857593 supporting_text: Gemin5 binds directly and specifically to the unique features, including the Sm site, of snRNAs. - reference_id: PMID:27881601 supporting_text: The 2.0 Å structure shows that the G5N region encompassing residues 3–722 is folded into two seven-bladed WD40 repeat domains. - reference_id: file:HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md supporting_text: All 12 human residues mutated in PMID:27881601 (N13, W14, Y15, R33, R335, M357, R359, F381, Y383, M403, W422, Y474) are identical at the aligned positions in both A0A9L0R5P7 and F6WDM0. - description: Binds the SMN mRNA 3'-UTR and regulates translation of this mRNA. molecular_function: id: GO:0003730 label: mRNA 3'-UTR binding directly_involved_in: - id: GO:0006417 label: regulation of translation supported_by: - reference_id: PMID:25911097 supporting_text: Gemin5 directly binds to the mature SMN 3′-UTR immediately upstream of the poly(A) tail. suggested_questions: - question: PAINT node PTN005299808 propagates spliceosomal snRNP assembly, SMN complex, nucleus and mRNA 3'-UTR binding, but not snRNA binding or 7-methylguanosine cap binding, although the human ortholog has IDA support for both. Is leaving them out a deliberate judgement, for example that they belong to a narrower clade, or is it a gap? - question: Is the horse transcript ENSECAT00000103662 (A0A9L0R5P7), which skips the linker equivalent to human 723-798, expressed as protein? Does losing this phosphorylation/SUMOylation-rich linker change GEMIN5 regulation? suggested_experiments: - description: RT-PCR or long-read RNA-seq across the exon junction encoding the human 723-798 equivalent in horse tissues, to establish whether the shorter isoform is expressed and how abundant it is relative to the full-length F6WDM0 transcript.