PXD047866-2

PXD047866 is an original dataset announced via ProteomeXchange.

Title	Substrate identification and specificity profiling of deubiquitylases against endogenously-generated ubiquitin-protein conjugates
Description	Deubiquitylating enzymes (DUBs) remove ubiquitin from proteins thereby regulating their stability or activity. Our understanding of DUB-substrate specificity is limited because DUBs are typically not compared to each other against many physiological substrates. By broadly inhibiting DUBs in Xenopus egg extract, we generated hundreds of ubiquitylated proteins and compared the ability of 30 DUBs to deubiquitylate them using quantitative proteomics. We identified five high impact DUBs (USP7, USP9X, USP36, USP15 and USP24) that each reduced ubiquitylation of over ten percent of the isolated proteins. Candidate substrates of high impact DUBs showed substantial overlap and were enriched for disordered regions, suggesting this feature may promote substrate recognition. Other DUBs showed lower impact and non-overlapping specificity, targeting distinct non-disordered proteins including complexes such as the ribosome or the proteasome. Altogether our study identifies candidate DUB substrates and defines patterns of functional redundancy and specificity, revealing substrate characteristics that may influence DUB-substrate recognition.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:31.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-16 06:01:35	ID requested
1	2024-04-26 11:26:01	announced
⏵ 2	2024-10-22 06:37:31	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DUB substrates, Xenopus,Deubiquitylating enzymes, ubiquitin, TMT-proteomics

Randall W. King
contact affiliation	Department of Cell Biology Blavatnik Institute at Harvard Medical School Boston, MA 02115, USA
contact email	randy_king@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047866
     1. Label: PRIDE project
     2. Name: Substrate identification and specificity profiling of deubiquitylases against endogenously-generated ubiquitin-protein conjugates