Biochemical and Functional Analyses of PANX1 Variants
Bibliographic record
Abstract
Pannexin 1 (PANX1) is a glycoprotein capable of forming large-pore single-membrane channels permeable to signaling molecules such as ATP. In this study, we interrogated different domains by introducing naturally occurring variants reported in melanoma and assessed their impact on the channel function of PANX1 at the cell surface. From this, we discovered a novel tyrosine phosphorylation site at Tyr150, that when disrupted via a missense mutation resulted in hypo-glycosylation and a greater capacity to traffic to the cell-surface and enhanced dye uptake. We have also uncovered a highly conserved ancestral allele, Gln5His, that has a greater allele frequency than the derived allele Gln5 in global and cancer cohorts but was not associated with cancer aggressiveness. Furthermore, Gln5His also did not impact glycosylation, cell-surface localization and channel-function in cancer cells. Our findings demonstrate the utility of studying naturally occurring variants in understanding diverse mechanisms that regulate PANX1 channel function.
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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".