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PXD019152

PXD019152 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDDI2 is a ubiquitin-directed endoprotease, responsible for cleavage of transcription factor NRF1
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:07:47.170.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichele Puglia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-12 22:38:02ID requested
12020-06-23 23:46:46announced
22024-10-22 05:07:48announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.molcel.2020.05.035;
Dirac-Svejstrup AB, Walker J, Faull P, Encheva V, Akimov V, Puglia M, Perkins D, K, ΓΌ, 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]
Keyword List
submitter keyword: UbiSite, PRM,DDI2, Ubiquitin, HpH, LC-MS/MS
Contact List
Blagoy Blagoev
contact affiliationUniversity of Southern Denmark (SDU), Department of Biochemistry and Molecular Biology (BMB)
contact emailbab@bmb.sdu.dk
lab head
Michele Puglia
contact affiliationUniversity of Southern Denmark
contact emailmichelep@bmb.sdu.dk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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