Dataset Information

Methylation in the human proteome: A meta-analysis of publicly available data sets

ABSTRACT: Lysine and arginine methylation are fundamental post-translational modifications (PTMs) that can regulate biological processes such as chromatin dynamics, transcriptional activity, and cellular signaling, with misregulation implicated in cancer and neurodevelopmental disorders. While advances in mass spectrometry (MS)-based proteomics have enabled proteome-wide mapping of methylation sites, the confident detection and localization of these modifications remains challenging. In this study, we have reanalyzed publicly available human methylation-enriched datasets using a standardized computational pipeline, to generate a high-confidence atlas of human methylation. Our workflow integrates database searching via the Trans-Proteomic Pipeline with a decoy-based statistical method for the independent estimation of false localization rates. This process yielded a high-confidence Human Methylation Atlas of 1,858 sites (87 methyl-lysine, 1,771 methyl-arginine) across 1,068 proteins, classified into Gold, Silver, and Bronze confidence tiers.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Shengbo Wang

LAB HEAD: Juan Antonio Vizcaino

PROVIDER: PXD076372 | Pride | 2026-06-09

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2024-04-04-decoys-contam-uniprotkb_proteome_UP000005640.fasta	Fasta
	PXD003700.GndCl.KR.mzML.zip	Mzml
	PXD003700.GndCl.KR_Site_PSM_centric.tsv	Tabular
	PXD003700.GndCl.KR_Site_Peptidoform_centric.tsv	Tabular
	PXD003700.GndCl.KR_interact-ipro.ptm.pep.mzid.zip	Mzid

Items per page:

1 - 5 of 38

Similar Datasets

Project description:Protein methylation has been implicated in many important biological contexts including signaling, metabolism, and transcriptional control. Despite the importance of this post- translational modification, the global analysis of protein methylation by mass spectrometry-based proteomics has not been extensively studied due to the lack of robust, well-characterized techniques for methyl-peptidemethyl peptide enrichment. Here, to better investigate protein methylation, we optimized and compared two methods for methyl-peptidemethyl peptide enrichment: immunoaffinity purification (IAP) and high pH strong cation exchange (SCX). Comparison of these methods revealed that they are largely orthogonal for monomethyl arginine (MMA), suggesting that the usage of both techniques is required to provide a global view of protein methylation. Using both IAP and SCX, we investigated changes in protein methylation downstream of protein arginine methyltransferase 1 (PRMT1). Together, these techniques allowed us to quantify over ~1,000 arginine methylation sites on 407 proteins. Of these methylation sites, PRMT1 knockdown resulted in significant changes to 110 arginine methylation sites on 59 proteins. In contrast, zero lysine methylation sites were significantly changed upon PRMT1 knockdown. In PRMT1 knockdown cells, 24 MMA sites exhibited both significant downregulation (ie, putative PRMT1-mediated MMA targets) and 63 significant upregulation (ie, putative PRMT1-mediated ADMA targets). PRMT1 knockdown induced significant changes in asymmetric dimethyl arginine (ADMA), consistent with being PRMT1 targets. Additionally, We also observed that PRMT1 knockdown induced significant increases in symmetric dimethyl arginine (SDMA) methylation, suggesting that loss of PRMT1 activity allows scavenging of PRMT1 substrates by Type II PRMTs. Analysis of the subcellular localization and protein function of the significantly changing methyl-proteins revealed that the majority of PRMT1 substrates are localized to the nucleus and involved in RNA and DNA binding. Taken together, our results suggest that deep protein methylation profiling by mass spectrometry requires orthogonal enrichment techniques, identify novel PRMT1 methylation targets, and highlight in order to understand the dynamic interplay between methyltransferases in mammalian cells.

Dataset Information

Methylation in the human proteome: A meta-analysis of publicly available data sets

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets