GEMIN5

UniProt ID: A0A9L0R5P7
Organism: Equus caballus
Review Status: IN PROGRESS
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Gene 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 Review

GO Term Evidence Action Reason
GO:0003730 mRNA 3'-UTR binding
IEA
GO_REF:0000117
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.
Supporting Evidence:
PMID:25911097
Gemin5 directly binds to the mature SMN 3β€²-UTR immediately upstream of the poly(A) tail.
file:HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md
It therefore sits C-terminal to the structured RNA-recognition module, not inside it.
file:HORSE/GEMIN5/GEMIN5-uniprot.txt
DR PANTHER; PTHR46362:SF1; GEM-ASSOCIATED PROTEIN 5; 1.
GO:0005654 nucleoplasm
IEA
GO_REF:0000044
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.
Supporting Evidence:
PMID:11714716
Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
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.
Supporting Evidence:
PMID:11714716
Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems.
PMID:11714716
The SMN complex plays an important role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs)
GO:0097504 Gemini of Cajal bodies
IEA
GO_REF:0000044
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.
Supporting Evidence:
PMID:11714716
Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems.

Core Functions

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:
snRNA binding
Directly Involved In:
Cellular Locations:
In Complex:
SMN complex
Supporting Evidence:
  • PMID:16857593
    Gemin5 binds directly and specifically to the unique features, including the Sm site, of snRNAs.
  • PMID:27881601
    The 2.0 Γ… structure shows that the G5N region encompassing residues 3–722 is folded into two seven-bladed WD40 repeat domains.
  • file:HORSE/GEMIN5/GEMIN5-bioinformatics/rereview/RESULTS-rereview.md
    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.

Binds the SMN mRNA 3'-UTR and regulates translation of this mRNA.

Molecular Function:
mRNA 3'-UTR binding
Directly Involved In:
Supporting Evidence:
  • PMID:25911097
    Gemin5 directly binds to the mature SMN 3β€²-UTR immediately upstream of the poly(A) tail.

References

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Suggested Questions for Experts

Q: 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?

Q: 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

Experiment: 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.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML Β· GEMIN5-protnlm-predictions-review.yaml Β· Review status: COMPLETE

A0A9L0R5P7 is an alternative-transcript product of horse GEMIN5 that keeps the complete tandem WD40 snRNA/cap-recognition module and the C-terminal RNA-binding regions, and lacks only a disordered linker equivalent to human 723-798, which contains the protein's lysine-rich basic cluster (horse F6WDM0 748-757). Three ProtNLM2 predictions (spliceosomal snRNP assembly, RNA 7-methylguanosine cap binding, regulation of translation) depend on regions this product retains, are supported by human ortholog experiments within the same PANTHER subfamily, and are already carried by this gene in GOA (CNN). Nucleus and mRNA 3'-UTR binding are true of the gene but depend on determinants that have not been mapped, so whether the deleted basic linker is needed for them on this product is unresolved (UNC). Protein ubiquitination has no supporting evidence for GEMIN5 or its relatives (UNC).

Source documents: projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv Β· projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz Β· projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/GEMIN5.json Β· genes/HORSE/GEMIN5/GEMIN5-ai-review.yaml Β· genes/HORSE/GEMIN5__F6WDM0/GEMIN5__F6WDM0-ai-review.yaml

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0000387 spliceosomal snRNP assembly GO_BP
CNN β€” Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Human GEMIN5 binds the Sm site of snRNAs through its tandem WD40 domain and is required for SMN-complex Sm-core assembly. A0A9L0R5P7 is in the same PANTHER subfamily (PTHR46362:SF1), shares 89% identity with human, and keeps the complete folded WD40 module (human 3-722) with all 12 mutationally validated RNA-contact residues; its missing block (human 723-798) is a disordered linker outside the fold. The transfer is therefore justified, as an inference from the human ortholog. The gene already carries this term in GOA on its full-length product F6WDM0 (IBA from PAINT and Ensembl Compara IEA), and the gene review lists it as a core process of this product, so the prediction is correct but not novel.
Supporting Evidence:
GO:0016567 protein ubiquitination GO_BP
UNC β€” Uncertain Review score: 1/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: The characterised activities of GEMIN5 are snRNA and cap recognition for snRNP assembly, SMN mRNA 3'-UTR binding and ribosome-associated translation control. Neither the human nor the horse gene review, the GOA files of either horse product, nor a PubMed search for GEMIN5 with ubiquitin, ubiquitination or E3 (three hits, none describing a GEMIN5 role in ubiquitination) supports participation in protein ubiquitination. GEMIN5 has no ubiquitin-ligase or ubiquitin-binding domain, but the absence of a catalytic domain would not by itself refute a noncatalytic role. No evidence supports or refutes the prediction.
Supporting Evidence:
  • PMID:27881600: "the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs"
  • PMID:25911097: "Gemin5 binding to the SMN 3β€²-UTR activates expression of SMN protein by increasing translation of the SMN mRNA."
  • file:HORSE/GEMIN5/GEMIN5-uniprot.txt: "DR PANTHER; PTHR46362:SF1; GEM-ASSOCIATED PROTEIN 5; 1."
GO:0005634 nucleus GO_CC
UNC β€” Uncertain Review score: 1/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Immunolocalization of human GEMIN5 shows a minor nuclear pool that colocalizes with SMN in gems, besides the predominant cytoplasmic pool, so nucleus is true of the gene (and less specific than the nucleoplasm and Gemini of Cajal bodies annotations the gene carries). For this product the call is unresolved. A0A9L0R5P7 lacks the block equivalent to human 723-798, which in the full-length horse product F6WDM0 includes the basic-residue cluster at 748-757 (PKPKKKKK), a lysine run of the kind that can act as a classical monopartite nuclear localization signal; the product keeps a shorter KKRK motif at its residue 765. No nuclear-import determinant of GEMIN5 has been mapped, and its nuclear pool could instead depend on co-import with the SMN complex, so it cannot be told whether this product keeps what nuclear localization requires.
Supporting Evidence:
GO:0000340 RNA 7-methylguanosine cap binding GO_MF
CNN β€” Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Human GEMIN5 binds the m7G cap directly in pull-down assays, and a soaked m7GTP structure places the cap in the central pore of the second WD40 propeller, stacked by Tyr474 and contacted by Leu580 and Asn582. A0A9L0R5P7 keeps the complete folded WD40 module; the deletion lies C-terminal to it. A direct ungapped comparison of the downloaded sequences in this assessment shows the cap-site residues W286, F338, Y474, L580 and N582 identical to human. The transfer from the same PANTHER subfamily is therefore justified. The gene already carries this term in GOA on its full-length product F6WDM0 (Ensembl Compara IEA, accepted by its review), so the prediction is correct but not novel.
Supporting Evidence:
GO:0003730 mRNA 3'-UTR binding GO_MF
UNC β€” Uncertain Review score: 1/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Human GEMIN5 binds the SMN mRNA 3'-UTR directly, and PAINT places this activity at node PTN005299808, so the term is true of the gene, which carries it in GOA on both horse products. For this product the call is unresolved. A0A9L0R5P7 keeps the WD40 module and the C-terminal TPR-like and RBS regions, but lacks the block equivalent to human 723-798, which includes the lysine-rich basic cluster (F6WDM0 748-757), a type of segment that commonly contributes to RNA contacts. The SMN 3'-UTR binding interface has not been mapped to any region, so it cannot be told whether this product keeps what the activity requires.
Supporting Evidence:
GO:0006417 regulation of translation GO_BP
CNN β€” Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: In human cells GEMIN5 binding to the SMN 3'-UTR increases SMN translation, and GEMIN5 bound to ribosomes through its N-terminal domain dampens global protein synthesis, so it regulates translation in both directions. The horse product keeps the relevant RNA-binding regions and is in the same PANTHER subfamily, which justifies transfer as an inference. The full-length product F6WDM0 already carries regulation of translation in GOA (Ensembl Compara IEA), and the gene review of this product uses the same term in its core functions, so the prediction is correct but not novel.
Supporting Evidence:

Deep Research

Cyberian

(GEMIN5-deep-research-cyberian.md)

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πŸ“š Additional Documentation

Notes

(GEMIN5-notes.md)

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Bioinformatics Results

(RESULTS.md)

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πŸ“„ View Raw YAML

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