Proteomics

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Site-specific Profiling of Lysine Itaconylation via a Thiol-based Probe


ABSTRACT: Lysine itaconylation is a novel post-translational modification (PTM) that was recently discovered in macrophage proteomes mediated by the immunoregulatory metabolite, itaconate. However, there is currently an absence of comprehensive and high-accuracy analytical methods for the global identification of itaconylation sites in proteomes, which limits its biological function study. Here, we developed a thiol-based bioorthogonal probe, BMAyne probe, to site-specifically profile itaconylation in macrophage proteomes by an Activity-based Protein Profiling (ABPP) strategy. Notably, 31 endogenous itaconylation sites on 29 proteins were identified in lipopolysaccharide (LPS)-stimulated macrophages using a thiol-based probe, BMAyne probe, which complemented the results obtained by previous promiscuous antibody enrichment. Our effort provides a unique chemical tool to enrich endogenous lysine itaconylation and establishes a rich database for guiding subsequent functional studies of this unique lysine itaconylation PTM.

ORGANISM(S): Mus Musculus Bos Taurus

SUBMITTER: Chu Wang  

PROVIDER: PXD077428 | iProX | Tue Apr 21 00:00:00 BST 2026

REPOSITORIES: iProX

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Site-specific profiling of lysine itaconylation via a thiol-based probe.

Fu Xia-Ping XP   Tang Ziming Z   Wang Chu C  

Bioorganic & medicinal chemistry letters 20260711


Lysine itaconylation is a novel post-translational modification (PTM) that was recently discovered in macrophage proteomes mediated by the immunoregulatory metabolite, itaconate. However, comprehensive and high-accuracy analytical methods are currently lacking for the global identification of itaconylation sites in proteomes, which limits the study of their biological functions. Here, we developed a thiol-based bioorthogonal probe, BMAyne, to site-specifically profile itaconylation in macrophage  ...[more]

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