PXD043565 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | VCF1 is a p97 cofactor promoting recruitment of p97-UFD1-NPL4 to ubiquitylated substrates |
Description | The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to ubiquitylated client proteins via multiple cofactors, most of which interact with the p97 N-domain. Here, we discovered that FAM104A, a protein of unknown function that we named VCF1, acts as a novel p97 cofactor in human cells. Detailed structure-function studies revealed that VCF1 directly binds p97 via a conserved novel alpha-helical motif that recognizes the p97 N-domain with unusually high affinity exceeding that of other cofactors. We show that VCF1 engages in joint p97 complex formation with the heterodimeric primary p97 cofactor UFD1-NPL4 and promotes p97-UFD1-NPL4-dependent proteasomal degradation of ubiquitylated substrates in cells. Mechanistically, VCF1 stimulates the affinity of the p97-UFD1-NPL4 complex for ubiquitin conjugates indirectly via its binding to p97 but does not itself interact with ubiquitin. Collectively, our findings establish VCF1 as an unconventional p97 cofactor that promotes p97-dependent protein turnover by facilitating p97-UFD1-NPL4 recruitment to ubiquitylated targets. |
HostingRepository | PRIDE |
AnnounceDate | 2024-03-14 |
AnnouncementXML | Submission_2024-03-14_04:14:06.244.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andreas Mund |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Bruker Daltonics timsTOF series |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-05 12:05:58 | ID requested | |
⏵ 1 | 2024-03-14 04:14:06 | announced | |
Publication List
Keyword List
Contact List
Andreas Mund |
contact affiliation | Universisity of Copehangen, Novo Nordisk Foundation Center for Protein Research |
contact email | andreas.mund@cpr.ku.dk |
lab head | |
Andreas Mund |
contact affiliation | University of Copenhagen |
contact email | andreas.mund@cpr.ku.dk |
dataset submitter | |
Full Dataset Link List
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/2024/03/PXD043565 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043565
- Label: PRIDE project
- Name: VCF1 is a p97 cofactor promoting recruitment of p97-UFD1-NPL4 to ubiquitylated substrates