| Structural highlights
Function
ZUP1_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 PubMed
Deubiquitinating 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 Also
References
- ↑ Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K. A family of unconventional deubiquitinases with modular chain specificity determinants. Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094 doi:http://dx.doi.org/10.1038/s41467-018-03148-5
- ↑ Hewings DS, Heideker J, Ma TP, AhYoung AP, El Oualid F, Amore A, Costakes GT, Kirchhofer D, Brasher B, Pillow T, Popovych N, Maurer T, Schwerdtfeger C, Forrest WF, Yu K, Flygare J, Bogyo M, Wertz IE. Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes. Nat Commun. 2018 Mar 21;9(1):1162. PMID:29563501 doi:10.1038/s41467-018-03511-6
- ↑ 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. 2018 Mar 21. pii: S1097-2765(18)30142-4. doi:, 10.1016/j.molcel.2018.02.023. PMID:29576527 doi:http://dx.doi.org/10.1016/j.molcel.2018.02.023
- ↑ Haahr P, Borgermann N, Guo X, Typas D, Achuthankutty D, Hoffmann S, Shearer R, Sixma TK, Mailand N. ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability. Mol Cell. 2018 Apr 5;70(1):165-174.e6. PMID:29576528 doi:10.1016/j.molcel.2018.02.024
- ↑ Hermanns T, Pichlo C, Woiwode I, Klopffleisch K, Witting KF, Ovaa H, Baumann U, Hofmann K. A family of unconventional deubiquitinases with modular chain specificity determinants. Nat Commun. 2018 Feb 23;9(1):799. doi: 10.1038/s41467-018-03148-5. PMID:29476094 doi:http://dx.doi.org/10.1038/s41467-018-03148-5
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