A proximity map of RAB GTPases delineates roles for RAB14 in EARP complex and UHRF1BP1 endosomal recruitments
Bibliographic record
Abstract
RAB GTPases, the most abundant small GTPase family, regulate membrane trafficking, including cargo sorting, vesicle budding, transport, docking, and fusion. Guanine exchange factors and GTPase-activating proteins control their activity. Activated RABs recruit effectors to mediate trafficking, but identifying RAB-associated proteins is challenging due to the transient nature of their interactions. Recent proximity labeling techniques enable covalent tagging of nearby proteins, allowing for comprehensive mapping of RAB GTPases neighboring proteins. Here we report APEX2 proximity labeling of 23 human RABs and their neighboring proteomes. Bioinformatic analyses revealed proximal proteins for a broad range of RABs. Notably, we identified a novel interaction between RAB25 and DENND6A, with RAB25 overexpression promoting DENND6A recruitment to recycling endosomes. We also uncovered functional links between RAB14 and the EARP complex, as well as SHIP164 and its ortholog UHRF1BP1. Our dataset offers a valuable resource for exploring new functional connections between RAB GTPases and their associated proteins. Proximity labeling proteomics of RAB GTPases identifies an array of neighboring RAB proteins. Functional validation studies reveal links between RAB25 and DENND6A, or between RAB14 and either the EARP complex or the lipid transport protein UHRF1BP1.
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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) | 0.003 | 0.001 |
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".