Bibliographic record
Abstract
Analysis of the DNA sequence of the human genome suggests that the 23 chromosomes encode ˜20,000 protein-coding genes. A similar number is also found in rodents. As a consequence of alternative RNA splicing and RNA editing, these ˜20,000 genes give rise to ˜100,000 mRNA transcripts which are translated into proteins in the cytosol. These translated proteins then undergo various posttranslational modifications that further enhance their diversity, leading to >1 million protein and peptide isoforms. Posttranslational modifications can lead to both reversible (for example, phosphorylation, Cys-palmitoylation) and irreversible (for example, N-glycosylation, proteolytic cleavage, C-terminal amidation, N-terminal acetylation, sulfation, pyroglutamination, Glu-carboxylation) modifications of proteins. Some of the major irreversible posttranslational modifications are afforded by proteases, which either cleave peptide bonds within proteins and peptides, resulting in two or more products, or trim them from the N-terminus (aminopeptidases) or C-terminus (carboxypeptidases), leading to the generation or loss of functional activity. Proteases are either of a digestive nature, resulting in protein degradation via multiple cleavages of the protein/peptide substrate, or participate in the limited proteolysis of precursor proteins (proproteins) to generate diversity within the proteome by increasing the number of polypeptide products that result from a single proprotein. The cleavage process can take place either intracellularly, at the cell surface, or in the extracellular matrix. Within the cell, processing can occur in various subcellular locations and organelles, including the cytosol, nucleus, mitochondria, endoplasmic reticulum (ER), various lamellae of the Golgi apparatus, within secretory granules, endosomes, and lysosomes. In this review, we will concentrate only on the cleavage of proteins within the secretory pathway. This includes the processing of proteins that enter the ER (via a signal peptide or stop transfer hydrophobic sequences) and that either remain there or are transported to the Golgi apparatus and beyond, including the cell surface, dense-core secretory granules (SG), recycling endosomes, and lysosomes. Within the classic secretory pathway, at least two routes exist for cell surface secretion: a rapid (minutes) default constitutive secretion from small vesicles fusing with the plasma membrane and a slower (minutes to hours) regulated one allowing the stimulated secretion of dense-core secretory granule contents. Herein, we will concentrate on the role of specific proteolytic enzymes within both pathways.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.004 |
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".