6ei1
From Proteopedia
Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA
Structural highlights
FunctionZUP1_HUMAN Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains (PubMed:29476094, PubMed:29563501, PubMed:29576528). 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 (PubMed:29576527, PubMed:29576528). Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress (PubMed:29563501).[1] [2] [3] [4] Publication Abstract from PubMedDeubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response. A family of unconventional deubiquitinases with modular chain specificity determinants.,Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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