PXD067419

PXD067419 is an original dataset announced via ProteomeXchange.

Title	myc-SHP2 IP to identify SHP2 interactors through proteomics IP
Description	Missense mutations in PTPN11, which encodes the protein tyrosine phosphatase SHP2, are common in several developmental disorders and cancers. While many mutations disrupt auto-inhibition and hyperactivate SHP2, several do not enhance catalytic activity. Both activating and non-activating mutations could potentially drive pathogenic signaling by altering SHP2 interactions or localization. We employed proximity-labeling proteomics to map the interaction networks of wild-type SHP2, ten clinically-relevant mutants, and SHP2 bound to an inhibitor that stabilizes its auto-inhibited state. Our analyses revealed mutation- and inhibitor-dependent alterations in the SHP2 interactome, with several mutations also changing localization. Some mutants had increased mitochondrial localization and impacted mitochondrial function. This study provides a resource for exploring SHP2 signaling and offers new insights into the molecular basis of SHP2-driven diseases. Furthermore, this work highlights the capacity for proximity-labeling proteomics to detect missense-mutation-dependent changes in protein interactions and localization.
HostingRepository	PRIDE
AnnounceDate	2025-08-31
AnnouncementXML	Submission_2025-08-31_04:02:55.040.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anne van Vlimmeren
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-16 19:04:47	ID requested
⏵ 1	2025-08-31 04:03:00	announced

van Vlimmeren AE, Tang LC, Jiang Z, Iyer A, Voleti R, Krismer K, Gaublomme JT, Jovanovic M, Shah NH, Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants. bioRxiv, ():(2025) [pubmed]

10.1101/2025.02.26.640373;

submitter keyword: SHP2, PTP, IP, interactomics

Neel H. Shah
contact affiliation	Neel H. Shah, Department of Chemistry, Columbia University in the City of New York
contact email	nhs2115@columbia.edu
lab head
Anne van Vlimmeren
contact affiliation	Columbia University
contact email	aev2133@columbia.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/2025/08/PXD067419

PRIDE project URI

• PRIDE
  1. PXD067419
     1. Label: PRIDE project
     2. Name: myc-SHP2 IP to identify SHP2 interactors through proteomics IP