PXD043098-1

PXD043098 is an original dataset announced via ProteomeXchange.

Title	TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity 1/2
Description	The functions of many human proteins remain unknown, highlighting major gaps in our understanding of cellular biology. TTC33 is an evolutionarily conserved tetratricopeptide repeat (TPR) protein expressed across human tissues, whose molecular role is not defined. Here we identify the TTC33 partners using comparative label-free mass spectrometry. The TTC33-associated network (TAN) comprises WDR61, CCDC97, UNG1/2, PP2A-B55α, PHF5A, and components of the U2 spliceosomal complex. Using a combination of biochemical assays, structural modeling and molecular dynamics we show that TTC33 directly recruits WDR61 and PHF5A to assemble into a trimeric core complex (TANC), which then forms distinct interactions with either UNG1/2 or SF3B–CCDC97. Somatic TTC33 mutations at key TANC interface residues reduce complex stability and weaken the interaction network. We further show that WDR61 stabilizes TTC33 by protecting it from proteolytic degradation. Loss of network components induces genomic instability and activates DNA damage markers, including γH2AX and p53 phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2026-07-09
AnnouncementXML	Submission_2026-07-09_04:36:08.315.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominik Cysewski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-19 05:12:59	ID requested
⏵ 1	2026-07-09 04:36:08	announced

Dataset with its publication pending

submitter keyword: WDR61 (Ski8), UNG, TTC33, PP2A, SF3AB, SKI complex, PAF complex, neurotransmitter, CCDC97, PPP2R2A (B55A), CGA, hormone, PHF5A

Agnieszka Tudek
contact affiliation	Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, 02-106 Warsaw, Poland
contact email	atudek@ibb.waw.pl
lab head
Dominik Cysewski
contact affiliation	Medical University of Bialystok
contact email	dominikcysewski@gmail.com
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/PXD043098

PRIDE project URI

• PRIDE
  1. PXD043098
     1. Label: PRIDE project
     2. Name: TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity 1/2