The N‐Terminal Atypical Region Regulates Non‐Mitochondrial Localization of Novel Hexokinase Isoform
Bibliographic record
Abstract
Post‐translational modifications (PTM) constitute the core dynamic signalling pathways in diverse physiological states. The PTMs render unique functionalization to proteins mediated by specific interactions and are often involved in modular interactions. Hexokinase, the first enzyme in the glucose utilization pathway, is an integral player in modulation of signalling pathways in diverse states. An integral feature of hexokinase functional regulation is binding to VDAC located in the outer‐mitochondrial membrane. The mitochondrial attachment of hexokinase is mediated by 15‐20 amino acid long hydrophobic domain located at N‐terminus of the enzyme.We observe that, in a novel isoform lacking this hydrophobic domain, the membranous interaction is modulated by virtue of PTMs. We cloned the full‐length isoform of hexokinase under CMV promoter in fusion with red fluorescent protein (RFP). Comparisons in parallel were carried out with constructs encoding the normal hexokinase variant fused to green fluorescent protein. The constructs were analyzed for localization by confocal analysis after transfection into HEK293 cells. The localization of these two isoforms showed a clearly distinct behavior. Moreover, the localization of the novel isoform was perturbed when the putative residues involved in the PTMs were mutated to alanine. The PTMs in the atypical region seems to provide an unique functional module. It is imperative to understand the mechanisms of such re‐functionalization in regulation of protein functions. Further insights into the role of myristoylation on the process of ATP generation, if any, and on regulation of glycolytic pathway should improve our understanding of previously un‐described functions.
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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".