PXD067475

PXD067475 is an original dataset announced via ProteomeXchange.

Title	Isoleucyl-tRNA synthetase interactome
Description	Aminoacyl-tRNA synthetases are key enzymes in protein synthesis, as they catalyze the attachment of amino acids to their designated, cognate tRNAs. As such, mutations in aminoacyl-tRNA synthetases are associated with severe diseases, such as neurodevelopmental disorders. Many of these mutations fall into the catalytic active site or tRNA binding domains, however, others can affect protein complex formation. Here, we investigate a disease-causing mutation in the UNE-L domain of Isoleucyl-tRNA synthetase (IARS1, IleRS), which interferes with multisynthetase complex formation. Interestingly, levels of the resulting protein are severely reduced in comparison to wildtype IleRS. While bulk protein synthesis and cell proliferation were not affected, the integrated stress response signaling pathway was altered. This change was exacerbated in low glucose medium, suggesting that mutant cells could respond differently to cellular stress. Our study hints at a new underlying disease mechanism, where catalytic activity might not be affected but instead complex formation and protein stability.
HostingRepository	PRIDE
AnnounceDate	2026-03-02
AnnouncementXML	Submission_2026-03-01_17:11:39.013.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haissi Cui
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	carbamoylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-18 09:18:17	ID requested
⏵ 1	2026-03-01 17:11:39	announced

10.1016/j.jbc.2026.111196;

Gao H, Tennakoon R, Ara, ú, jo FP, Miller JM, Nyandwi SP, Shi Q, Padilla-Mart, í, nez JP, Peng H, Cui H, A disease-causing isoleucyl-tRNA synthetase variant leads to altered protein complex formation and cellular stress response. J Biol Chem, 302(3):111196(2026) [pubmed]

submitter keyword: tRNA,interactome

Haissi Cui
contact affiliation	University of Toronto
contact email	haissi.cui@utoronto.ca
lab head
Haissi Cui
contact affiliation	University of Toronto
contact email	haissi.cui@utoronto.ca
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/2026/03/PXD067475

PRIDE project URI

• PRIDE
  1. PXD067475
     1. Label: PRIDE project
     2. Name: Isoleucyl-tRNA synthetase interactome