PXD076406

PXD076406 is an original dataset announced via ProteomeXchange.

Title	Lysine iminylation derived from ω-3 polyunsaturated fatty acids
Description	Protein post-translational modifications (PTMs) play a central role for regulating protein function and cellular processes, with many PTMs arising from reactions with electrophilic metabolites. Here we extend the known landscape of PTMs with the discovery of ‘lysine C3-iminylation’, the conjugation of protein lysine residues with propionaldehyde. To stabilize iminylation for mass spectrometric analyses and distinguish it from other isomeric PTMs, we developed a fixation and stable-isotope labeling approach based on parallel reduction of proteome with sodium borohydride and borodeuteride. Analyses of protein hydrolysates confirmed the presence of C3-iminylation in C. elegans and mouse. Additionally, proteomics results demonstrated specificity of this PTM in vitro and in vivo and revealed C3-iminylation in proteins related to critical metabolic pathways. Importantly, collective evidence from isotope tracing as well as genetic, dietary, and pharmacological manipulation experiments uncovered that C3-iminylation originates from cytochrome P450 (CYP)-mediated oxidation of omega-3 fatty acids. Correspondingly, C3-iminylation levels were elevated in C. elegans daf-2(e1370) mutants, an aging model, in which CYP activity is generally increased. These findings not only expand our understanding of the biochemical diversity of PTMs but also underscore the complex interplay between lipid metabolism and protein modifications, enabling further exploration of their biological and clinical implications.
HostingRepository	PRIDE
AnnounceDate	2026-08-19
AnnouncementXML	Submission_2026-08-19_08:33:41.784.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu-Heng Hsieh
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; scientific name: Caenorhabditis elegans; NCBI TaxID: NEWT:6239;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-31 07:11:40	ID requested
⏵ 1	2026-08-19 08:33:42	announced

10.1073/PNAS.2525618123;

submitter keyword: proteomics, C. elegans, cytochrome P450 , omega-3 polyunsaturated fatty acid,post-translational modification

Frank Schroeder
contact affiliation	Cornell University, Boyce Thompson Institiute
contact email	schroeder@cornell.edu
lab head
Yu-Heng Hsieh
contact affiliation	Cornell University
contact email	yh998@cornell.edu
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/2026/08/PXD076406

PRIDE project URI

• PRIDE
  1. PXD076406
     1. Label: PRIDE project
     2. Name: Lysine iminylation derived from ω-3 polyunsaturated fatty acids