Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases.
Bibliographic record
Abstract
Arf and Rab family small GTPases and their regulators, GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), play a central role in membrane trafficking. In this study, we focused on a recently reported GAP for Arf (and potentially Rab) proteins, the CSW complex, a part of a small family of longin domain-containing proteins that form complexes with GAP activity. This family also includes folliculin and GATOR1, which are GAPs for the Rag/Gtr GTPases. All three complexes are associated with lysosomes and play a role in nutrient signaling, the latter two being directly involved in the mTOR pathway. The role of CSW is not clear, but in addition to having GAP activity on Arf proteins in vitro, its mutation causes severe neurodegenerative diseases. Here we update the reported pan-eukaryotic presence of folliculin and GATOR1, and demonstrate that CSW is also found throughout eukaryotes, though with sporadic distribution. We identify highly conserved motifs in all CSW subunits, some shared with the catalytic subunits of folliculin and GATOR1, that provide new potential avenues for experimental exploration. Remarkably, one such conserved sequence, the "GP" motif, is also found in structurally related longin proteins present in the archaeal ancestor of eukaryotes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".