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skr-5

C. elegans

Skp1-related protein

What the model saw

Gene: skr-5
Organism: Caenorhabditis elegans
Known functions: Skp1-related protein. cullin family protein binding.
View unredacted entry
Skp1-related protein. cullin family protein binding.

Solver output

Predicted influence
Unclear
Confidence
35%
Mechanism
Loss of proteostasis
Reasoning

SKR-5 is a Skp1-related protein in C. elegans that binds cullin family proteins, placing it as an adaptor subunit of SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complexes. SCF complexes mediate ubiquitin-dependent proteasomal degradation of specific substrates, which is central to proteostasis. However, the specific F-box protein partner(s) and substrates of SKR-5 are not defined by these annotations alone. C. elegans encodes ~21 skr paralogs with distinct substrate specificities; without knowing which substrates SKR-5 targets for degradation, it is impossible to determine whether its activity promotes or opposes longevity pathways (e.g., degrading pro-longevity vs. anti-longevity factors). The function is consistent with proteostasis regulation but the directionality remains ambiguous.

Key pathways
SCF E3 ubiquitin ligase complexubiquitin-proteasome systemcullin-RING ligase pathway
Longevity influence
Anti-longevity
Lifespan effect
Increase

GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.

Advisor judgment

Answer
Incorrect
Mechanism
Incorrect
Reasoning quality
3/5
Failure mode
Appropriately uncertain
Notes

The model predicted "unclear" while the ground truth is "anti_longevity." The model's reasoning is logically sound given the limited information provided - it correctly identifies SKR-5 as an SCF complex adaptor and notes the ambiguity in directionality without knowing specific substrates. However, the model failed to arrive at the correct answer. The mechanism class of "loss_of_proteostasis" is speculative and not confirmed. The model's uncertainty was appropriate given the sparse annotation, but it still got the answer wrong. This is a case of appropriate uncertainty rather than confident wrongness.

Raw API responses

solver

{
  "reasoning": "SKR-5 is a Skp1-related protein in C. elegans that binds cullin family proteins, placing it as an adaptor subunit of SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complexes. SCF complexes mediate ubiquitin-dependent proteasomal degradation of specific substrates, which is central to proteostasis. However, the specific F-box protein partner(s) and substrates of SKR-5 are not defined by these annotations alone. C. elegans encodes ~21 skr paralogs with distinct substrate specificities; without knowing which substrates SKR-5 targets for degradation, it is impossible to determine whether its activity promotes or opposes longevity pathways (e.g., degrading pro-longevity vs. anti-longevity factors). The function is consistent with proteostasis regulation but the directionality remains ambiguous.",
  "confidence": 0.35,
  "key_pathways": [
    "SCF E3 ubiquitin ligase complex",
    "ubiquitin-proteasome system",
    "cullin-RING ligase pathway"
  ],
  "mechanism_class": "loss_of_proteostasis",
  "longevity_influence": "unclear"
}

advisor

{
  "notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning is logically sound given the limited information provided - it correctly identifies SKR-5 as an SCF complex adaptor and notes the ambiguity in directionality without knowing specific substrates. However, the model failed to arrive at the correct answer. The mechanism class of \"loss_of_proteostasis\" is speculative and not confirmed. The model's uncertainty was appropriate given the sparse annotation, but it still got the answer wrong. This is a case of appropriate uncertainty rather than confident wrongness.",
  "failure_mode": "appropriately_uncertain",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}