Identification of a putative human mitochondrial thymidine monophosphate kinase associated with monocytic/macrophage terminal differentiation
Bibliographic record
Abstract
Mitochondrial DNA synthesis requires the supply of thymidine triphosphate (dTTP) independent of nuclear DNA replication. In resting and differentiating cells that withdraw from the cell cycle, mitochondrial thymidine kinase 2 (TK2) mediates thymidine monophosphate (dTMP) formation for the dTTP biosynthesis in mitochondria. However, a thymidine monophosphate kinase (TMPK) that phosphorylates dTMP to form thymidine diphosphate (dTDP) in mitochondria remains undefined. Here, we identified an expressed sequence tag cDNA, which encodes a TMPK with a mitochondrial import sequence at its N-terminus designated as TMPK2. HeLa cells expressing TMPK2 fused to green fluorescent protein (GFP) displayed green fluorescence in mitochondria. Over-expression of TMPK2 increased the steady-state level of cellular dTTP and promoted the conversion of radioactive labeled-thymidine and -dTMP to dTDP and dTTP in mitochondria. TMPK2 RNA was detected in several tissues and erythroblastoma cell lines. We also generated TMPK2 antibody and used it for immunofluorescence staining to demonstrate endogenous expression of TMPK2 in mitochondria of erythroblastoma cells. Finally, we showed that TMPK2 protein expression was upregulated in monocyte/macrophage differentiating cells, suggesting the coordinated regulation of TMPK2 expression with the terminal differentiation program.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".