A0A9L0S961

UniProt ID: A0A9L0S961
Organism: Equus caballus
Review Status: COMPLETE
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Gene Description

PPP4R4 is a cytosolic regulatory subunit of protein phosphatase 4. It forms a stable complex with the PP4 catalytic subunit that is distinct from complexes containing PP4R1 or PP4R2–PP4R3. Its association changes PP4 activity and subcellular organization rather than providing intrinsic phosphatase catalysis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: cytoplasm: Affinity purification identifies PP4R4 as a stable cytosolic PP4c partner. The resulting complex has altered phosphatase activity and is distinct from PP4R1- and PP4R2/3-containing complexes.
Reason: Affinity purification identifies PP4R4 as a stable cytosolic PP4c partner. The resulting complex has altered phosphatase activity and is distinct from PP4R1- and PP4R2/3-containing complexes.
Supporting Evidence:
PMID:18715871
we identify a novel, stable cytosolic PP4c interacting partner, KIAA1622, which we have renamed PP4R4.
PMID:18715871
PP4c.PP4R4 complexes exhibit phosphatase activity toward a fluorogenic substrate and gammaH2AX, but this activity is lower than that associated with the PP4c.PP4R2.PP4R3 complex, which itself is less active than the free PP4c catalytic subunit.
file:HORSE/PPP4R4/PPP4R4-bioinformatics/RESULTS.md
The downloaded human Q6NUP7 sequence (873 residues) and selected horse A0A9L0S961 sequence (865 residues) share 95.0% identity among 865 paired residues. Paired coverage is 99.1% of human and 100.0% of horse.

Core Functions

PPP4R4 is a cytosolic regulatory subunit of protein phosphatase 4.

Cellular Locations:
Supporting Evidence:
  • PMID:18715871
    we identify a novel, stable cytosolic PP4c interacting partner, KIAA1622, which we have renamed PP4R4.
  • file:HORSE/PPP4R4/PPP4R4-bioinformatics/RESULTS.md
    The downloaded human Q6NUP7 sequence (873 residues) and selected horse A0A9L0S961 sequence (865 residues) share 95.0% identity among 865 paired residues. Paired coverage is 99.1% of human and 100.0% of horse.

References

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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 · PPP4R4-protnlm-predictions-review.yaml · Review status: COMPLETE

Phosphatase regulation and complex membership are supported by conserved PP4R4 biology; blastocyst hatching remains unverified.

Source documents: projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv · projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz · projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/PPP4R4.json

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

GO:0001835 blastocyst hatching GO_BP
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The primary human PP4R4 study establishes a cytosolic PP4 complex and altered phosphatase activity, not an embryonic hatching function. A nearly full-length horse homolog supports transfer of the molecular complex role but does not by itself establish this specific developmental process. Gene-specific embryo evidence or a traced functional mechanism is needed; absence of such evidence is not proof that the process is impossible.
Supporting Evidence:
GO:0019888 protein phosphatase regulator activity GO_MF
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human PP4R4 is an experimentally isolated stable cytosolic partner of PP4c and changes the activity of the complex. The selected horse protein is 95.0% identical across nearly the entire human sequence with no large domain deletion, supporting conserved complex membership and regulatory function. These claims are new relative to the frozen horse GOA; human evidence is not claimed to be absent from model training.
Supporting Evidence:
  • PMID:18715871: "we identify a novel, stable cytosolic PP4c interacting partner, KIAA1622, which we have renamed PP4R4."
  • PMID:18715871: "PP4c.PP4R4 complexes exhibit phosphatase activity toward a fluorogenic substrate and gammaH2AX, but this activity is lower than that associated with the PP4c.PP4R2.PP4R3 complex, which itself is less active than the free PP4c catalytic subunit."
  • file:HORSE/PPP4R4/PPP4R4-bioinformatics/RESULTS.md: "share 95.0% identity among 865 paired residues. Paired coverage is 99.1% of human and 100.0% of horse."
GO:0008287 protein serine/threonine phosphatase complex GO_CC
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human PP4R4 is an experimentally isolated stable cytosolic partner of PP4c and changes the activity of the complex. The selected horse protein is 95.0% identical across nearly the entire human sequence with no large domain deletion, supporting conserved complex membership and regulatory function. These claims are new relative to the frozen horse GOA; human evidence is not claimed to be absent from model training.
Supporting Evidence:
  • PMID:18715871: "we identify a novel, stable cytosolic PP4c interacting partner, KIAA1622, which we have renamed PP4R4."
  • PMID:18715871: "PP4c.PP4R4 complexes exhibit phosphatase activity toward a fluorogenic substrate and gammaH2AX, but this activity is lower than that associated with the PP4c.PP4R2.PP4R3 complex, which itself is less active than the free PP4c catalytic subunit."
  • file:HORSE/PPP4R4/PPP4R4-bioinformatics/RESULTS.md: "share 95.0% identity among 865 paired residues. Paired coverage is 99.1% of human and 100.0% of horse."

📚 Additional Documentation

Notes

(PPP4R4-notes.md)

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Bioinformatics Results

(RESULTS.md)

PPP4R4: human–horse sequence comparison

The downloaded human Q6NUP7 sequence (873 residues) and selected horse A0A9L0S961 sequence (865 residues) share 95.0% identity among 865 paired residues. Paired coverage is 99.1% of human and 100.0% of horse.

Full alignment, hashes, parameters and reproducible script: PPP4R4.json and compare.py.

Pairwise similarity supports homology but does not establish reciprocal orthology, intact gene models, conservation of targeting signals or every biological claim. Current UniProt sequences are compared; identity with the original ProtNLM input sequence is unverified.

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