PXD008970-3

PXD008970 is an original dataset announced via ProteomeXchange.

Title	Protein citrullination in human tissues
Description	Citrullination is a post-translational 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 and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only 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 synthetised ~2,200 citrullinated and 1,300 deamindated 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 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 abundance proteins arguing that the development of specific enrichment methods would be required in order to study the full extent of cellular protein citrullination.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:49:24.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chien-Yun Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	mono N-acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue; L-citrulline
Instrument	Thermo Scientific instrument model; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-16 03:41:04	ID requested
1	2018-04-04 03:28:52	announced
2	2018-04-10 01:10:32	announced	Updated publication reference for PubMed record(s): 29610271.
⏵ 3	2023-11-14 08:49:25	announced	2023-11-14: Updated project metadata.

Lee CY, Wang D, Wilhelm M, Zolg DP, Schmidt T, Schnatbaum K, Reimer U, Pont, é, n F, Uhl, é, n M, Hahne H, Kuster B, Mining the Human Tissue Proteome for Protein Citrullination. Mol Cell Proteomics, 17(7):1378-1391(2018) [pubmed]

ProteomeXchange project tag: ProteomeTools

curator keyword: Biological

submitter keyword: Citrullination, post-translational modification, peptidylarginine deiminase, human proteome, synthetic peptides

Bernhard Kuster
contact affiliation	Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany Bavarian Center for Biomolecular Mass Spectrometry, Freising, Germany
contact email	kuster@tum.de
lab head
Chien-Yun Lee
contact affiliation	Chair of Proteomics and Bioanalytics, Technical University of Munich, Germany
contact email	chienyun.lee@tum.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/04/PXD008970

PRIDE project URI

• PRIDE
  1. PXD008970
     1. Label: PRIDE project
     2. Name: Protein citrullination in human tissues