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Effects of post-translational modifications on protein function

2024· article· W7125614161 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueInternational Journal of Advanced Biochemistry Research · 2024
Typearticle
Language
FieldMedicine
TopicPeptidase Inhibition and Analysis
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsAcetylationCrosstalkPhosphorylationUbiquitinProteomicsGlycosylationPosttranslational modificationSubcellular localizationEnzyme

Abstract

fetched live from OpenAlex

Over 200 distinct types of post-translational modifications have been identified in eukaryotic proteomes, yet the functional consequences of most remain poorly characterized. This research investigated the effects of major post-translational modifications on protein function using an integrated computational and experimental approach. A dataset comprising 847 well-characterized proteins from human cell lines was analyzed for modification patterns and functional outcomes between January 2021 and November 2022 at the Westbrook Institute of Biomedical Research. Mass spectrometry-based proteomics identified modification sites, while functional assays assessed enzymatic activity, protein stability, subcellular localization, and protein-protein interactions. Phosphorylation represented the most prevalent modification at 38.7% of detected sites, followed by ubiquitination at 22.4% and acetylation at 15.3%. Functional impact analysis revealed that phosphorylation predominantly affected enzymatic activity with 82.1% of phosphorylated enzymes showing altered catalytic parameters. Ubiquitination primarily targeted proteins for degradation, reducing stability in 76.8% of modified substrates. Acetylation demonstrated the strongest influence on DNA-binding proteins, with 78.4% of acetylated transcription factors exhibiting modified binding affinity. Glycosylation showed particular importance for protein stability at 81.2% and subcellular localization at 62.4%. Heatmap analysis of modification-function relationships revealed context-dependent effects whereby identical modifications produced opposing outcomes depending on target protein identity and cellular environment. The research identified 127 proteins subject to crosstalk between multiple modification types, suggesting coordinated regulatory networks. These findings establish quantitative relationships between specific modifications and functional outcomes, providing a framework for predicting how alterations in modification machinery contribute to disease pathogenesis and identifying potential therapeutic intervention points.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.028
Threshold uncertainty score0.890

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.025
GPT teacher head0.390
Teacher spread0.364 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it