The Single ENTH‐Domain Protein of Trypanosomes; Endocytic Functions and Evolutionary Relationship with Epsin
Bibliographic record
Abstract
Epsin N-terminal homology (ENTH) domains occur in proteins of either the epsin or epsin-related (epsinR) form. They principally function in clathrin-mediated trafficking and membrane deformation. Both epsin and epsinR possess clathrin-binding motifs, but only epsin incorporates a ubiquitin-interaction motif (UIM). To better understand the origins of ENTH-domain proteins and their functions, we performed detailed comparative genomics and phylogenetics on the epsin family. The epsin ENTH-UIM configuration is an architecture restricted to yeast and animals. Further, we undertook functional analysis in Trypanosoma brucei (T. brucei), a divergent organism possessing a single ENTH-domain protein (TbEpsinR). TbEpsinR has a cellular location similar to both epsin and epsinR at plasma membrane clathrin budding sites and endosomal compartments, and associates with clathrin, as demonstrated by coimmunoprecipitation. Knockdown of TbEpsinR leads to a significant decrease in the intracellular pools of multiple surface antigens, without affecting bulk membrane internalization. Therefore, despite lacking the UIM, TbEpsinR maintains a similar role to metazoan epsin in endocytosis and participates as a clathrin-associated adaptor. We suggest that recruitment of a UIM to the ENTH-domain proteins was not essential for participation in endocytosis of ubiquitylated molecules, and is presumably a specific innovation restricted to higher 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 | 0.000 | 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".