PXD008509

PXD008509 is an original dataset announced via ProteomeXchange.

Title	Discovery and characterization of ZUFSP, a novel DUB class important for genome stability
Description	Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two new ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.
HostingRepository	PRIDE
AnnounceDate	2018-10-22
AnnouncementXML	Submission_2018-10-22_09:31:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yogesh Kulathu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-12-20 01:26:29	ID requested
⏵ 1	2018-10-22 09:31:15	announced

Kwasna D, Abdul Rehman SA, Natarajan J, Matthews S, Madden R, De Cesare V, Weidlich S, Virdee S, Ahel I, Gibbs-Seymour I, Kulathu Y, Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability. Mol Cell, 70(1):150-164.e6(2018) [pubmed]

curator keyword: Biological

submitter keyword: Deubiquitinase, Ubiquitin binding domain, DNA damage

Yogesh Kulathu
contact affiliation	MRC Protein Phosphorylation & Ubiquitylation Unit School of Life Sciences Sir James Black Centre University of Dundee Dundee DD1 5EH, UK.
contact email	ykulathu@dundee.ac.uk
lab head
Yogesh Kulathu
contact affiliation	University of Dundee
contact email	ykulathu@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008509
     1. Label: PRIDE project
     2. Name: Discovery and characterization of ZUFSP, a novel DUB class important for genome stability