PXD061808-1

PXD061808 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting
Description	Sorting nexin 17 (SNX17) functions as cargo receptor on endosomal membranes that enables the recycling of numerous membrane cargo proteins by binding to the Retriever complex. Yet, little is known how SNX17 activity or its membrane recruitment is regulated. Here, we report that phosphorylation of SNX17 at serine 38 (Ser38) within the phox (PX) domain serves as a critical regulatory switch governing its endosomal localization and function. A mutant form mimicking the phosphorylated state disrupts SNX17’s ability to bind phosphatidylinositol-3-phosphate (PI3P), which in turn impairs its association with early endosomal membranes and inactivates SNX17-dependent cargo-recycling in cells. Furthermore, our results demonstrate that Ser38 is part of an autoinhibitory mechanism to regulate SNX17 cargo binding. Collectively, these findings provide new insights into the dynamic regulation of SNX17 activity and Retriever-mediated sorting processes. It also highlights SNX17 Ser38 phosphorylation as a critical regulatory mechanism that controls SNX17’s endosomal localization and cargo recycling function.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:32:59.999.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-13 16:06:08	ID requested
⏵ 1	2025-06-29 16:33:00	announced

10.1016/j.jbc.2025.110222;

Speidel JD, Yu K, B, ö, ttcher RT, Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting. J Biol Chem, 301(6):110222(2025) [pubmed]

submitter keyword: endosome, intracellular trafficking,sorting nexin, Retriever, phosphorylation, integrin, phox domain

Ralph Thomas Böttcher
contact affiliation	Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany Current address: Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany
contact email	ralph.boettcher@helmholtz-munich.de
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.de
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/2025/06/PXD061808

PRIDE project URI

• PRIDE
  1. PXD061808
     1. Label: PRIDE project
     2. Name: Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting