PXD019152

PXD019152 is an original dataset announced via ProteomeXchange.

Title	DDI2 is a ubiquitin-directed endoprotease, responsible for cleavage of transcription factor NRF1
Description	The Ddi1/DDI2 proteins are ubiquitin shuttling factors, implicated in a variety of cellular functions. In addition to ubiquitin-binding and ubiquitin-like domains, they contain a conserved region with similarity to retroviral proteases, but whether and how DDI2 functions as a protease has remained unknown. Here we show that DDI2 knock-out cells are sensitive to proteasome inhibition and accumulate high-molecular weight, ubiquitylated proteins that are poorly degraded by the proteasome. These proteins are targets for the protease activity of purified DDI2. No evidence for DDI2 acting as a de-ubiquitylating enzyme was uncovered, which could suggest that it cleaves the ubiquitylated protein itself. In support of this idea, cleavage of transcription factor NRF1 is known to require DDI2 activity in vivo. We show that DDI2 is indeed capable of cleaving NRF1 in vitro, but only when NRF1 protein is poly-ubiquitylated. Together, these data suggest that DDI2 is a ubiquitin-directed endo-protease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:07:47.170.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michele Puglia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-12 22:38:02	ID requested
1	2020-06-23 23:46:46	announced
⏵ 2	2024-10-22 05:07:48	announced	2024-10-22: Updated project metadata.

10.1016/j.molcel.2020.05.035;

Dirac-Svejstrup AB, Walker J, Faull P, Encheva V, Akimov V, Puglia M, Perkins D, K, ü, mper S, Hunjan SS, Blagoev B, Snijders AP, Powell DJ, Svejstrup JQ, DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1. Mol Cell, 79(2):332-341.e7(2020) [pubmed]

submitter keyword: UbiSite, PRM,DDI2, Ubiquitin, HpH, LC-MS/MS

Blagoy Blagoev
contact affiliation	University of Southern Denmark (SDU), Department of Biochemistry and Molecular Biology (BMB)
contact email	bab@bmb.sdu.dk
lab head
Michele Puglia
contact affiliation	University of Southern Denmark
contact email	michelep@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019152
     1. Label: PRIDE project
     2. Name: DDI2 is a ubiquitin-directed endoprotease, responsible for cleavage of transcription factor NRF1