Welcome to ZnCPT – The zinc binding cysteine proteome database!
Zinc is an essential micronutrient that regulates a wide range of physiological processes, principally through Zn2+ binding to protein cysteine residues. Despite being critical for modulation of protein function, for the vast majority of the human proteome the cysteine sites subject to Zn2+ binding remain undefined. Here we develop ZnCPT, a comprehensive and quantitative mapping of the zinc binding cysteine proteome. We define thousands of zinc binding protein cysteines, uncovering protein families across major domains of biology that are subject to either constitutive or inducible modification by zinc. ZnCPT enables systematic discovery of zinc binding structural, enzymatic, and allosteric functional domains. We provide ZnCPT as a resource for understanding mechanisms of zinc regulation of protein function. ZnCPT determines the zinc binding status across HCT116 cells, as well as primary human hepatocytes and prostate epithelial cells.
Please Cite: Burger et al. A comprehensive landscape of the zinc-regulated human proteome. bioRxiv 2024.01.04.574225; doi: https://doi.org/10.1101/2024.01.04.574225
Background
Zinc is an essential micronutrient that regulates a wide range of physiological processes, principally through Zn2+ binding to protein cysteine residues. Despite being critical for modulation of protein function, for the vast majority of the human proteome the cysteine sites subject to Zn2+ binding remain undefined. Here we develop ZnCPT, a comprehensive and quantitative mapping of the zinc binding cysteine proteome. We define thousands of zinc binding protein cysteines, uncovering protein families across major domains of biology that are subject to either constitutive or inducible modification by zinc. ZnCPT enables systematic discovery of zinc binding structural, enzymatic, and allosteric functional domains. We provide ZnCPT as a resource for understanding mechanisms of zinc regulation of protein function. ZnCPT determines the zinc binding status across HCT116 cells, as well as primary human hepatocytes and prostate epithelial cells.
Guide to exploring ZnCPT
- Select the cell type in which you would like to explore zinc binding to your favorite protein
- Add the UniProt Name, Gene Name or UniProt ID of your favorite protein into the search query box and select the appropriate category under search for
- If your protein is not found, likely it was not mapped in the selected dataset. Please ensure you have entered the correct name or ID
- The average ratio of labelled cysteines compared to the untreated control (level of accessibility) is provided. Statistical significance between control and treatment is shown.
- Under the structure tab quantified cysteines can be explored on a primary sequence and structural level.
- Cysteine data for individual proteins can be downloaded from the search window.
- The entire dataset can be downloaded from the “Download” window.
Note the cysteine site numbers indicate the cysteine(s) that were labelled for a given peptide.
The ZnCPT web application was developed by Shelley Wei (Chouchani Lab, DFCI) and Nils Burger (Chouchani Lab, DFCI/HMS).
Please Cite: Burger et al. A comprehensive landscape of the zinc-regulated human proteome. bioRxiv 2024.01.04.574225; doi: https://doi.org/10.1101/2024.01.04.574225
Enter your search query:
The ZnCPT dataset was done in HCT116 cells, primary human prostate epithelial cells, and primary human hepatocytes. Use the toggle function to choose the cell line you want to search in.
TPEN Treatment
ZnCl2 Treatment
2D Sequence Structure
Protein Sequence
3D Alphafold Structure
Search query does not exist in dataset. Please recheck your search and enter a valid query.
Bulk Download Data Files
Download flat files (comma-separated) containing all data displayed in the ZnCPT website.
Download cysteine accessibility data:
Download All HCT Cysteine Data (csv) Download All Prostate Cysteine Data (csv) Download All Hepatocytes Cysteine Data (csv) Download Protein Sequences (csv)
Individual datasets:
Download HCT Zinc Data (csv) Download HCT TPEN Data (csv) Download HCT EDTA 1mM Data (csv) Download HCT EDTA 5mM Data (csv)Download Prostate Zinc Data (csv) Download Prostate TPEN Data (csv)
Download Hepatocytes Zinc Data (csv) Download Hepatocytes TPEN Data (csv)
Acknowledgements
The ZnCPT website uses the following tools/frameworks/libraries:
• Shiny: https://shiny.posit.co
• AlphaFold: https://alphafold.ebi.ac.uk
Copyright and License Information
The ZnCPT website was developed and is licensed under the Creative Commons Attribution-ShareAlike 4.0 International License.
Images presented and generated on the ZnCPT website are licensed under the Creative Commons Attribution-ShareAlike 4.0 International License.