Citrullination Analysis Service

Citrullination transforms arginine residues and rewires immune signaling, inflammation, and disease pathways. At Creative Proteomics, we deliver high-resolution LC–MS/MS citrullination analysis combined with specific probe enrichment to accurately identify and quantify modified arginine sites—helping researchers reveal functional mechanisms in immunity, cancer, and neurodegeneration.

Comprehensive detection: Identify and quantify citrullinated proteins and site-specific arginine modifications.
Advanced technology: LC–MS/MS + citrulline-specific probe enrichment for precision and depth.
Functional insights: Integrated bioinformatics for motif, pathway, and network interpretation.
Research impact: Clarify PAD enzyme regulation in autoimmune, inflammatory, and oncogenic processes.

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What Is Citrullination?

Citrullination is a post-translational modification (PTM) of arginine, catalysed by a group of enzymes known as peptidyl arginine deaminases (PADIs). PAD enzymes require Ca²⁺ to catalyze citrullination, converting arginine (Arg) into citrulline with the release of ammonia. This reaction represents a calcium-dependent hydrolytic process in which the highly basic, positively charged arginine side chain is transformed into a neutral urea group. Despite the conversion only resulting in a small mass shift, the modification may impart a large functional impact on the protein, as citrullination of arginine causes a loss of positive charge and change electron acceptor properties. This change in physiochemical properties may alter protein structure, protein–protein interactions, and protein localization within the cell. However, the implications of citrullination at the cellular level remain not fully understood. Citrullination is known to play important physiological roles in maintaining stem cell potency, during the innate immune response, and in maintaining the skin barrier. Furthermore, dysregulation of citrullination is known to be a driving factor in rheumatoid arthritis (RA), psoriasis, and cancer.

Citrullination Service at Creative Proteomics

To elucidate the functional implications of citrullination, it is crucial to be able to detect citrullination events in an unbiased manner. Furthermore, it is important to identify not only the citrullinated target proteins, but also the specific arginine residues that are targeted for citrullination.

Creative Proteomics has established a highly sensitive LC-MS/MS pipeline that can analyze citrullination in both eukaryotic and prokaryotic organisms. Furthermore, we have optimized our protocol, to facilitate more rapid and sensitive site mapping service for citrullination. We rely on C18 column and Thermo Fisher Easy-nLC 1000 and Thermo Fisher LTQ Obitrap ETD to provide citrullination analysis service packages. We will take care of all aspects of the project, including protein extraction, probe labeling and enrichment, proteolysis, mass spectrometry analysis, raw mass spectrometry data analysis, and bioinformatics analysis.

Citrullination Research Platforms

Easy-nLC 1000 nanoliter liquid chromatography system

Easy-nLC 1000 (Figure from Thermo Scientific)

Thermo Fisher LTQ Orbitrap ETD mass spectrometer, combined with linear ion trap and Orbitrap technology, supports ETD fragmentation mode

Thermo Fisher LTQ Obitrap ETD (Figure from Thermo Scientific)

Workflow of Citrullination Analysis

Advantages Our Citrullination Service

Professional detection and analysis capability: Experienced research team, strict and matured techniques.
Breadth: we could skillfully deal with protein samples derived from a wide range of sources, encompassing cell, animal and plant tissues, etc.
High specificity and accuracy: Skillful quantification proteomics techniques, and PTMs enrichment methods.
High stability and reproducible: Obtain consistent and reproducible inter- and intra- assay results for data analysis.
Advanced Analytical Platforms: Use of high-sensitivity mass spectrometry and state-of-the-art tools, ensuring precise, repeatable results.
End-to-End Support: Offer full-spectrum services from design to data interpretation, with continuous technical support throughout the research process.

Applications of Citrullination

Biomarkers and Drug development^[1]

Citrullinated proteins can be used as potential biomarkers for disease diagnosis and prognosis evaluation.

Small molecule inhibitors that target PADI enzymes, such as Cl-amidine, are being developed for the treatment of rheumatoid arthritis, cancer, and neurodegenerative diseases.

Autoimmune disease research

Citrullinated proteins play a key role in rheumatoid arthritis (RA) and are prime targets for anti-citrullinated protein antibodies (ACPA), which can be used for early diagnosis and disease surveillance^[2].

Tumor

Citrullination can regulate the expression of oncogenes and tumor suppressor genes by altering chromatin structure, and it may be a potential target for tumor therapy^[3].

Neurodegenerative disease

In Alzheimer's disease (AD) and Parkinson's disease (PD), citrullinated modification is closely associated with neuroinflammation, protein aggregation, and may affect the function of tau and α-synuclein.

Citrullinated modification may become a novel biomarker for neurodegenerative diseases for early detection and intervention.

Cardiometabolic health

There is evidence that L-citrulline has atheroes-endothelial protective effects and is beneficial for muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/elderly populations^[4].

Citrullination Service Sample Requirements

Sample	Sample Quantity
Tissue	animal tissue	200-500mg
Tissue	fresh plant	200-500mg
Cell	suspension cell	> 3x10⁷
Cell	adherent cell	> 3x10⁷
Protein	Total protein > 5mg and concentration >1 μg/μL

Demo Result of Citrullination Service

Bar plo

MS/MS spectrum

PCA plot show the clustering and differences of citrullination levels in the different groups.

PCA analysis

Heatmap

The plot is used to show the enrichment of citrullination modification proteins in different pathways.

KEGG analysis

GO analysis

The protein-protein interaction network demonstrated the interactions between all citrullination modification proteins.

PPI

FAQs of Citrullination Service

Which sample types are accepted by the service?

We accept a variety of sample types including cells, tissues, plant tissue and more. If you have other special sample types, please consult in advance.

Whether the sample needs pretreatment?

We recommend that customers provide fresh or frozen samples, which should avoid repeated freezing and thawing, and we will be responsible for subsequent protein extraction and pretreatment. If you have already extracted the protein, please communicate with us in advance about the sample handling method.

Learn about other Q&A.

Case Study

Article

Publications

Here are some publications in Proteomics research from our clients:

In Vitro Identification of Phosphorylation Sites on TcPolβ by Protein Kinases TcCK1, TcCK2, TcAUK1, and TcPKC1 and Effect of Phorbol Ester on Activation by TcPKC of TcPolβ in Trypanosoma cruzi Epimastigotes. 2024. https://doi.org/10.3390/microorganisms12050907
Parkinson’s disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes. 2019. https://doi.org/10.1016/j.yjmcc.2007.03.738
Mechanistic and biomarker studies to demonstrate immune tolerance in multiple sclerosis. 2022. https://doi.org/10.3389/fimmu.2021.787498
Parkinson’s disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes. 2019. https://doi.org/10.1186/s40478-019-0716-4
Microglia-mediated synaptic pruning in the nucleus accumbens during adolescence: A preliminary study of the proteomic consequences and putative female-specific pruning target. 2023. https://doi.org/10.1101/2023.05.03.539317

More Publications

References

Zhu, D., Zhang, Y., & Wang, S. (2021). Histone citrullination: a new target for tumors. Molecular cancer, 20(1), 90. https://doi.org/10.1186/s12943-021-01373-z
Ciesielski, O., Biesiekierska, M., Panthu, B., Soszyński, M., Pirola, L., & Balcerczyk, A. (2022). Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives. Cellular and molecular life sciences: CMLS, 79(2), 94. https://doi.org/10.1007/s00018-022-04126-3
Allerton, T. D., Proctor, D. N., Stephens, J. M., Dugas, T. R., Spielmann, G., & Irving, B. A. (2018). l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients, 10(7), 921. https://doi.org/10.3390/nu10070921

Proteomics Sample Submission Guidelines

Ensure your samples are prepared and submitted correctly by downloading our comprehensive Proteomics Sample Submission Guidelines. This document provides detailed instructions and essential information to facilitate a smooth submission process. Click the link below to access the PDF and ensure your submission meets all necessary criteria.

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* For Research Use Only. Not for use in diagnostic procedures.

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From Our Clients

"I recently used their proteomics service for a project analyzing protein interactions in yeast models. The team was very responsive and helped clarify the methodology they employed, which made me feel confident in the results. The data quality was solid, with clear identification of several key proteins involved in our study. Their thorough analysis enabled me to pinpoint specific interactions that I hadn't considered before, which significantly improved the direction of my research. I appreciate their professionalism and support throughout the process."

Sarah Thompson, University of California, Berkeley

"Our lab collaborated with them on a project studying cancer biomarkers. The proteomics analysis provided was detailed and focused, specifically highlighting the differential expression of proteins between healthy and tumor samples. Their clear explanations of the data helped my team understand the biological implications. I also appreciated their willingness to revise the reports based on our feedback, ensuring that we had everything we needed for our publication. This collaborative spirit was invaluable."

Emily Rodriguez, Stanford University

"Our lab worked with them on a project studying the effects of diet on gut microbiota using proteomics. They used a label-free quantification method to analyze proteins in fecal samples before and after dietary intervention. The results showed significant changes in protein expression linked to microbial activity. This was pivotal for our hypothesis about diet-microbiota interactions. The clarity of their data presentation made it easy for our team to integrate these findings into our ongoing research."

Dr. Lisa Wong, University of Toronto

"My experience with Creative Proteomics during the mass spectrometry analysis was excellent. We sent in human saliva and mouse brain tissue samples, which they expertly analyzed using both LC-MS and GC-MS techniques. The results were invaluable, revealing key metabolites in the saliva and identifying biomarkers linked to brain function in the brain tissue."

Dr. Emily Carter, Senior Research Scientist

"The overall service from Creative Proteomics was outstanding. They made the entire process seamless and efficient, allowing us to focus on our research. We worked with leaf and root samples from various Arabidopsis genotypes for targeted metabolomics analysis. Their thorough profiling of primary and secondary metabolites gave us important insights into how the plants respond metabolically to environmental stress."

Dr. Laura Henderson, Plant Physiologist

"We had a pleasant collaboration with Creative Proteomics on mass spectrometry analysis of lipids. They conducted a detailed analysis of lipid species, providing us with important insights into lipid metabolism and its relationship with metabolic syndrome disease states."

Dr. Sarah Mitchell, Research Scientist

Online Inquiry

Please submit a detailed description of your project. We will provide you with a customized project plan to meet your research requests. You can also send emails directly to for inquiries.