ArticleMolecular & cellular proteomics : MCP2018
Mining the Human Tissue Proteome for Protein Citrullination.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 121 citations in OpenAlex.
- Decoding isozyme-specific substrate recognition in protein arginine deiminases by in vitro lysate-based citrullination mapping.Nature communications · 2026Article
- Differential histone tail citrullination by PAD Enzymes observed via NMR spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- Development of motif-specific monoclonal antibodies for global protein citrullination detection with minimal cross-reactivity to homocitrullination.Cell reports methods · 2026Article
- Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response.iScience · 2026Article
- Inhibition of PADI2-mediated vimentin citrullination alleviates silica-induced pulmonary fibrosis in mice.Particle and fibre toxicology · 2026Article
- An ELIXIR scoping review on domain-specific evaluation metrics for synthetic data in life sciences.NAR genomics and bioinformatics · 2026Article
- High-throughput chemical proteomics workflow for profiling protein citrullination dynamics.Nature communications · 2026Article
- Immune functions of the esophagus.The Journal of allergy and clinical immunology · 2026Review
- Optimized Directed Evolution of E. coli leucyl-tRNA Synthetase adds many Noncanonical Amino Acids into the Eukaryotic Genetic Code Including Ornithine and NAngewandte Chemie (International ed. in English) · 2025Article
- Deep Learning Enhances Precision of Citrullination Identification in Human and Plant Tissue Proteomes.Molecular & cellular proteomics : MCP · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Proteomic insights into the extracellular matrix: a focus on proteoforms and their implications in health and disease.Expert review of proteomics · 2024Review
- A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates.Nature structural & molecular biology · 2024Article
- The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CURTAIN-A unique web-based tool for exploration and sharing of MS-based proteomics data.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mass Spectrometry-Based Precise Identification of Citrullinated Histones via Limited Digestion and Biotin Derivative Tag Enrichment.Analytical chemistry · 2024Article
- Protein Citrullination in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases.Journal of experimental neurology · 2024Article
- Citrullination profile analysis reveals peptidylarginine deaminase 3 as an HSV-1 target to dampen the activity of candidate antiviral restriction factors.PLoS pathogens · 2023Article
- Citrullination of matrisomal proteins in health and diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrullination is a posttranslational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations, and while the modification has been linked to several diseases, including rheumatoid arthritis (RA) and cancer, its physiological or pathophysiological roles remain largely unclear. In part, this is owing to limitations in available methodology to robustly enrich, detect, and localize the modification. As a result, only a few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass-spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ∼70 million tandem mass spectra yielded ∼13,000 candidate spectra, which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetized ∼2,200 citrullinated and 1,300 deamidated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new, and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in the brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundant proteins, arguing that the development of specific enrichment methods would be required in order to study the full extent of cellular protein citrullination.
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