RCR2
S. cerevisiae
Rcr2p
What the model saw
Gene: RCR2 Organism: Saccharomyces cerevisiae Known functions: Rcr2p. protein binding. ubiquitin-like ligase-substrate adaptor activity.
View unredacted entry
Rcr2p. protein binding. ubiquitin-like ligase-substrate adaptor activity.
Solver output
RCR2 encodes a protein with ubiquitin-like ligase-substrate adaptor activity, meaning it recruits specific substrates to ubiquitin E3 ligase complexes, facilitating their ubiquitination and subsequent proteasomal degradation. This function is central to proteostasis maintenance — the selective elimination of misfolded, damaged, or regulatory proteins via the ubiquitin-proteasome system (UPS). Efficient UPS activity is well-established as pro-longevity in yeast and other organisms, as it prevents accumulation of proteotoxic aggregates. As a substrate adaptor, RCR2 likely targets specific client proteins for degradation, analogous to F-box or SOCS-box adaptors in SCF-type complexes, thereby maintaining protein quality control. Loss of such adaptors typically impairs proteostasis and shortens lifespan, supporting a pro-longevity role for the normal gene function.
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
The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ubiquitin-ligase substrate adaptor activity being pro-longevity is plausible in general terms, but it failed to account for the specific role of RCR2 in yeast. RCR2 (also known as UFD4-related) can act as an anti-longevity factor — its activity may promote degradation of pro-longevity proteins or otherwise shorten lifespan. The model's logic that "substrate adaptors maintain proteostasis and are therefore pro-longevity" is an oversimplification; substrate adaptors can target pro-longevity proteins for degradation, making them anti-longevity. The model had moderate confidence (0.55) but still got the direction wrong, and the mechanistic reasoning, while internally consistent, does not correctly capture RCR2's actual role in yeast aging.
Raw API responses
solver
{
"reasoning": "RCR2 encodes a protein with ubiquitin-like ligase-substrate adaptor activity, meaning it recruits specific substrates to ubiquitin E3 ligase complexes, facilitating their ubiquitination and subsequent proteasomal degradation. This function is central to proteostasis maintenance — the selective elimination of misfolded, damaged, or regulatory proteins via the ubiquitin-proteasome system (UPS). Efficient UPS activity is well-established as pro-longevity in yeast and other organisms, as it prevents accumulation of proteotoxic aggregates. As a substrate adaptor, RCR2 likely targets specific client proteins for degradation, analogous to F-box or SOCS-box adaptors in SCF-type complexes, thereby maintaining protein quality control. Loss of such adaptors typically impairs proteostasis and shortens lifespan, supporting a pro-longevity role for the normal gene function.",
"confidence": 0.55,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"protein quality control",
"E3 ligase substrate recognition"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ubiquitin-ligase substrate adaptor activity being pro-longevity is plausible in general terms, but it failed to account for the specific role of RCR2 in yeast. RCR2 (also known as UFD4-related) can act as an anti-longevity factor — its activity may promote degradation of pro-longevity proteins or otherwise shorten lifespan. The model's logic that \"substrate adaptors maintain proteostasis and are therefore pro-longevity\" is an oversimplification; substrate adaptors can target pro-longevity proteins for degradation, making them anti-longevity. The model had moderate confidence (0.55) but still got the direction wrong, and the mechanistic reasoning, while internally consistent, does not correctly capture RCR2's actual role in yeast aging.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}