PXD018215-1

PXD018215 is an original dataset announced via ProteomeXchange.

Title	Human DDI2 is a ubiquitin-directed endo-protease
Description	The Ddi1/DDI2 proteins are classified as ubiquitin shuttling factors and are implicated in a wide range of cellular functions. In addition to ubiquitin-binding and ubiquitin-like domains, these proteins contain a conserved region with similarity to retroviral proteases, but whether and how they function as proteases has remained unknown. Here we show that human 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. Thus far, no evidence for DDI2 acting as a de-ubiquitylating enzyme has been uncovered, suggesting that it might cleave 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 capable of cleaving NRF1 in vitro, but only when NRF1 protein is poly-ubiquitylated. Together, these data suggest that DDI2 represents the first example of a ubiquitin-directed endo-protease.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_00:42:42.480.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Faull
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-26 04:38:42	ID requested
⏵ 1	2021-09-09 00:42:43	announced
2	2024-10-22 05:28:11	announced	2024-10-22: Updated project metadata.

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: Human, SILAC, DDI2, ubiquitin

Bram Snijders
contact affiliation	Proteomics Science and Technology Platform The Francis Crick Institute United Kingdom
contact email	bram.snijders@crick.ac.uk
lab head
Peter Faull
contact affiliation	The Francis Crick Institute
contact email	peter.faull@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018215
     1. Label: PRIDE project
     2. Name: Human DDI2 is a ubiquitin-directed endo-protease