CTDSP2

UniProt ID: F7A4N8
Organism: Equus caballus
Review Status: DRAFT
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Gene Description

F7A4N8 is a 174-residue product predicted from one alternative transcript (ENSECAT00000020049) of the horse CTDSP2 gene (ENSECAG00000018788, chromosome 6), which encodes the small CTD phosphatase SCP2. Its first 84 residues are essentially identical to the N-terminal non-catalytic region of human CTDSP2, after which the transcript uses an extended exon whose extra sequence encodes 90 unrelated residues and a stop codon. The product therefore lacks the entire FCP1-homology (HAD-type) phosphatase domain, including the DxDx(T/V) motif that carries the nucleophilic and proton-donor aspartates. Other transcripts of the same gene (Ensembl canonical ENSECAT00000107019, UniProt A0A9L0T5X1, 312 aa; and ENSECAT00000138494, A0A9L0R207, 252 aa) do encode the complete catalytic domain, and the full-length product groups with CTDSP2 orthologs (PANTHER PTHR12210:SF187 members in human, mouse and cow) rather than with CTDSP1 or CTDSPL. In mammals the full-length enzyme is a nuclear Mg2+-dependent phosphatase that preferentially removes phosphate from Ser5 of the RNA polymerase II CTD and is recruited by REST to silence RE-1-containing neuronal genes in non-neuronal cells. Because the truncated F7A4N8 product lacks the catalytic domain and its transcript carries a premature stop codon upstream of four exon junctions, it has no demonstrable enzymatic function, and it may be a nonsense-mediated-decay transcript or annotation artefact rather than a stable protein.

References

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Suggested Questions for Experts

Q: Is ENSECAT00000020049, the transcript encoding F7A4N8, supported by horse RNA-seq or long-read data? Its 375-bp exon extends 273 nt upstream of the canonical 102-bp exon acceptor and introduces a premature stop codon upstream of four further exon junctions, the signature of a nonsense-mediated-decay or intron-retention isoform rather than a stable protein product.

Q: Which horse CTDSP2 model best represents the real full-length product? The Ensembl canonical model (A0A9L0T5X1, 312 aa) has an N-terminal extension that does not begin with methionine and omits the 13-residue SDLLQCLQYQFYQ exon present in human CTDSP2, whereas A0A9L0R207 (252 aa) keeps that exon but omits the 19-residue exon that forms part of the catalytic fold. Neither model reproduces the human 271-residue architecture exactly.

Q: If a short F7A4N8-like protein is made, does its retained N-terminal segment (which in the SCP proteins lies outside the catalytic domain) have any function, such as competing with full-length CTDSP2 for partners, or is it simply degraded?

Suggested Experiments

Experiment: Quantify junction-spanning reads for the extended exon versus the canonical 102-bp exon acceptor in public horse RNA-seq (e.g. FAANG tissues), and compare isoform abundance in horse cells with and without NMD inhibition (cycloheximide or UPF1 knockdown). Confirm full-length ORFs by long-read (Iso-Seq) sequencing.

Hypothesis: The F7A4N8-encoding transcript (ENSECAT00000020049) is a minor, NMD-targeted isoform, and the dominant horse CTDSP2 transcript encodes a full-length catalytic protein like human CTDSP2.

Type: transcript isoform quantification / NMD sensitivity

Experiment: Express the full-length horse CTDSP2 product and F7A4N8, and assay phosphate release from a Ser5-phosphorylated CTD heptapeptide substrate, with human CTDSP2 as a positive control and a catalytic-aspartate (D-to-A) mutant as a negative control.

Hypothesis: Phosphatase activity on RNA polymerase II CTD Ser5 is carried by the full-length horse CTDSP2 product and is absent from F7A4N8, which lacks the catalytic domain.

Type: in vitro phosphatase assay with Ser5-phosphorylated CTD substrate

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 · CTDSP2-protnlm-predictions-review.yaml · Review status: COMPLETE

Kinase activity is refuted for the selected 174-residue CTDSP2 product F7A4N8. The exact sequence contains no kinase machinery and lacks the FCP1-homology catalytic domain; the gene's full-length products and their human, mouse and cow orthologs are small CTD phosphatases (SCP2), not kinases. The horse gene has no GOA annotations, so the re-reviewed gene review and the human CTDSP2 review are the reference for this assessment.

Source documents: genes/HORSE/CTDSP2/CTDSP2-uniprot.txt · genes/HORSE/CTDSP2/CTDSP2-bioinformatics/RESULTS.md · genes/HORSE/CTDSP2/CTDSP2-bioinformatics/alignment.txt · genes/HORSE/CTDSP2/CTDSP2-bioinformatics/RESULTS-rereview.md · genes/HORSE/CTDSP2/CTDSP2-ai-review.yaml · genes/human/CTDSP2/CTDSP2-ai-review.yaml · genes/HORSE/CTDSP2/CTDSP2-hypotheses/horse40-kinase-activity/openscientist.md · genes/human/CTDSP2/CTDSP2-uniprot.txt

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

GO:0016301 kinase activity GO_MF
NPI — Nonparalog incorrect Review score: 0/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
DOMAIN ARCHITECTURE MISMATCH
Review rationale: Kinase activity is incorrect for F7A4N8 on two independent grounds. First, the exact 174-residue input shares only an 84-residue N-terminal prefix with human CTDSP2, lacks the FCP1-homology catalytic domain and its DxDx(T/V) motif, contains none of the eukaryotic protein-kinase catalytic motifs, and has no confidently folded catalytic domain in its AlphaFold model. Second, the CTDSP2 family itself is not a kinase family; the full-length horse products (A0A9L0T5X1, A0A9L0R207) retain the DLDET motif and group with CTDSP2 orthologs in PANTHER PTHR12210:SF187, whose characterised member, human SCP2, is a small CTD phosphatase that preferentially dephosphorylates Ser5 of the RNA polymerase II CTD. No literature reports kinase activity for any CTDSP2 ortholog (PubMed search of CTDSP2 with kinase, horse or equine). The prediction therefore has no support for this product or for the gene.
Supporting Evidence:

Deep Research

Cyberian

(CTDSP2-deep-research-cyberian.md)

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OpenScientist

(CTDSP2-hypotheses/horse40-kinase-activity/openscientist.md)

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📚 Additional Documentation

Notes

(CTDSP2-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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