PXD070424

PXD070424 is an original dataset announced via ProteomeXchange.

Title	ZNRF3 and RNF43 are active monomeric E3 ligases that self-associate
Description	Crosslinking mass spectrometry was used to identify the site of dimerization in the RING domain of ZNRF3. The two proteins, ZNRF3 and RNF43 have a key role in regulating the number of Frizzled (FZD) receptor on cells and their inactivation causes cancer. This is because they are RING E3 ligases that promote the ubiquitylation and internalisation of FZD, thereby turning off WNT signalling. Here we identify the key determinants of ubiquitin transfer by ZNRF3 and RNF43 and report the structure of the RING domain from ZNRF3. Our data indicate that the RING domain is monomeric, and that RING dimerization is not required for its ubiquitin ligase activity. However, the ectodomain of ZNRF3 forms dimers and our data supports a model where the cytoplasmic domains self-associate in cells even though RING dimerization is not required for activity.
HostingRepository	PRIDE
AnnounceDate	2026-07-30
AnnouncementXML	Submission_2026-07-30_13:14:10.968.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Torsten Kleffmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-06 16:23:00	ID requested
⏵ 1	2026-07-30 13:14:11	announced

10.1126/scisignal.aeb3656;

Padala P, Rossig C, Crowther JM, Dobson RCJ, Patel M, Kumar A, Kleffmann T, Middleton AJ, Day CL, ZNRF3 and RNF43 are active monomeric E3 ubiquitin ligases that self-associate. Sci Signal, 19(944):eaeb3656(2026) [pubmed]

submitter keyword: ZNRF3 E3 ligase,cross-linking, RING dimerization

Professor Catherine Day
contact affiliation	Department of Biochemistry, University of Otago, New Zealand
contact email	catherine.day@otago.ac.nz
lab head
Torsten Kleffmann
contact affiliation	Department of Biochemistry, University of Otago
contact email	torsten.kleffmann@otago.ac.nz
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/2026/07/PXD070424

PRIDE project URI

• PRIDE
  1. PXD070424
     1. Label: PRIDE project
     2. Name: ZNRF3 and RNF43 are active monomeric E3 ligases that self-associate