Identification of a novel motif important for the activity of ring-type E3 ligases using MARCH1 as a model (100.52)
Bibliographic record
Abstract
Abstract The MARCH family of proteins are RING-CH type E3 ubiquitin ligases responsible for the ubiquitination and endocytosis of cell surface proteins related to immune response. We are particularty interested in MARCH1 and 8, two members of the family that are known to downregulate the cell surface expression of MHC II, CD86 , TfR and CD95. Canonical sorting motifs in the cytoplasmic portions of murine MARCH1 and human MARCH8 were identified and reported by others to be necessary for the function. We hypothesized that such motifs in human MARCH1 are important for it’s function. Methods: We used co-immunoprecipitations and FRET to monitor interaction of MARCH1 with various proteins. Protein expression, function and localization were determined by flow cytometry, confocal microscopy and western blotting. Results: Our results showed the presence of functional sorting motifs in both N- and C-terminal cytoplasmic portions of human MARCH1. However, these signals are not essential for the activity of MARCH1. We used a series of mutants to identify functional regions on MARCH1. Our results point to a novel motif. Interestingly, that motif is found in many other proteins and appears to be important for the function of other RING-type E3 ligases. Conclusions: Our results confirmed the presence of sorting motifs in MARCH1 and highlight important species-specific functional domains. The newly identified domain of MARCH1 will shed light on the structure of RING-type E3 ubiquitin ligases.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".