Ten years in the life of an enzyme: the story of the human MMP-13 (collagenase-3)
Bibliographic record
Abstract
In 1994, a new human matrix metalloproteinase (MMP) was identified and cloned. This enzyme displayed the structural characteristics of a collagenase and was named collagenase-3, or MMP-13 according to MMP nomenclature. This review describes the research advances in the understanding of the function/production of the human MMP-13 at the tissular, cellular, biochemical, and molecular levels. In contrast to many human MMPs, the MMP-13 distribution pattern is restrictive in normal tissues and selective in pathological conditions. This enzyme plays a premier role in tissue remodeling as well as in some pathological processes such as cancer and arthritis. MMP-13 demonstrates versatility in its substrate utilization. In addition to being highly active on type II collagen, MMP-13 cleaves other substrates, mostly macromolecules of the extracellular matrix, but also molecules such as connective tissue (CTGF) and fibrinogen. MMP-13 is controlled at multiple levels: i.e., the expression/synthesis, activation, and inhibition of the active enzyme. Unlike other MMPs, the human MMP-13 gene is transcribed into several transcripts which could yield proteins with activities and functions different from those of the original MMP-13. Activation of MMP-13 involves a proteolytic cascade including MMP-14 (MT1-MMP) and MMP-2. Transcription is regulated by numer-ous agents, mostly by growth factors, proinflammatory cytokines and mechanical stimuli. Cloning of the MMP-13 promoter revealed the presence of a number of binding sites implicated in transcriptional regulation: TATA box, AP-1, PEA-3, OSE-2, and the newly identified negative regulator, AGRE. MMP-13 constitutes a more complex system than was originally thought. Although our knowledge of MMP-13 biochemistry and regulation has greatly increased over the years, there is still much to discover.
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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 | 0.001 | 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".