ZUP1 zinc finger containing ubiquitin peptidase 1 [ Homo sapiens (human) ]
Gene ID: 221302, updated on 17-Jun-2019- Official Symbol
- ZUP1provided by HGNC
- Official Full Name
- zinc finger containing ubiquitin peptidase 1provided by HGNC
- Also known as
- DUB; ZUFSP; C6orf113
- Summary
- This gene encodes a protein containing zinc finger motifs and a cysteine peptidase domain. The encoded protein functions as a K63-specific de-ubiquitinating enzyme that specifically cleaves long K63-linked polyubiquitin chains in the middle of a chain (i.e. "endo cleavage) rather than by removing the terminal ubiquitin from a chain. This enzyme is thought to be involved in the regulation of DNA repair by cleaving K63-linked ubiquitin chains at repair foci. This protein is related to proteases for the ubiquitin-like modifiers Ufm1 (ubiquitin fold modifier 1) and Atg8/Gabarapl2, but does not have any activity on these modifiers. [provided by RefSeq, Mar 2018]
- Expression
- Ubiquitous expression in duodenum (RPKM 4.7), bone marrow (RPKM 4.6) and 25 other tissues See more
- Orthologs mouse all
- Preferred Names
- zinc finger-containing ubiquitin peptidase 1
- Names
- lys-63-specific deubiquitinase ZUFSP
- ubiquitin carboxyl-terminal hydrolase ZUFSP
- zinc finger with UFM1-specific peptidase domain protein
LOCUS NP_001348118 578 aa linear PRI 26-FEB-2019
DEFINITION zinc finger-containing ubiquitin peptidase 1 isoform 1 [Homo
sapiens].
ORIGIN 1 mlscnicget vtsepdmkah livhmeseii cpfcklsgvn ydemcfhiet ahfeqntler 61 nferintvqy gtsdnkkdnt lqcgmevnss ilsgcasnhp knsaqnltkd stlkhegfys 121 enltesrkfl ksrekqsslt eikgsvyett ysppecpfcg kieehsedme thvktkhanl 181 ldipledcdq plydcpmcgl ictnyhilqe hvdlhleens fqqgmdrvqc sgdlqlahql 241 qqeedrkrrs eesrqeieef qklqrqygld nsggykqqql rnmeievnrg rmppsefhrr 301 kadmmeslal gfddgktkts giiealhryy qnaatdvrrv wlssvvdhfh sslgdkgwgc 361 gyrnfqmlls sllqndaynd clkgmlipci pkiqsmieda wkegfdpqga sqlnnrlqgt 421 kawigacevy illtslrvkc hivdfhkstg plgthprlfe wilnyysseg egspkvvcts 481 kppiylqhqg hsrtvigiee kknrtlclli ldpgcpsrem qkllkqdiea sslkqlrksm 541 gnlkhkqyqi lavegalsle eklarrqasq vftaekip
- ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability. Haahr P, et al. Mol Cell, 2018 Apr 5. PMID 29576528. Deubiquitylating enzymes (DUBs) enhance the dynamics of the versatile ubiquitin (Ub) code by reversing and regulating cellular ubiquitylation processes at multiple levels. Here we discovered that the uncharacterized human protein ZUFSP (zinc finger with UFM1-specific peptidase domain protein/C6orf113/ZUP1), which has been annotated as a potentially inactive UFM1 protease, and its fission yeast homolog Mug105 define a previously unrecognized class of evolutionarily conserved cysteine protease DUBs. Human ZUFSP selectively interacts with and cleaves long K63-linked poly-Ub chains by means of tandem Ub-binding domains, whereas it displays poor activity toward mono- or di-Ub substrates. In cells, ZUFSP is recruited to and regulates K63-Ub conjugates at genotoxic stress sites, promoting chromosome stability upon replication stress in a manner dependent on its catalytic activity. Our findings establish ZUFSP as a new type of linkage-selective cysteine peptidase DUB with a role in genome maintenance pathways.
- A family of unconventional deubiquitinases with modular chain specificity determinants. Hermanns T, et al. Nat Commun, 2018 Feb 23. PMID 29476094, Free PMC Article. 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.
- Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes. Hewings DS, et al. Nat Commun, 2018 Mar 21. PMID 29563501, Free PMC Article. Activity-based probes (ABPs) are widely used to monitor the activity of enzyme families in biological systems. Inferring enzyme activity from probe reactivity requires that the probe reacts with the enzyme at its active site; however, probe-labeling sites are rarely verified. Here we present an enhanced chemoproteomic approach to evaluate the activity and probe reactivity of deubiquitinase enzymes, using bioorthogonally tagged ABPs and a sequential on-bead digestion protocol to enhance the identification of probe-labeling sites. We confirm probe labeling of deubiquitinase catalytic Cys residues and reveal unexpected labeling of deubiquitinases on non-catalytic Cys residues and of non-deubiquitinase proteins. In doing so, we identify ZUFSP (ZUP1) as a previously unannotated deubiquitinase with high selectivity toward cleaving K63-linked chains. ZUFSP interacts with and modulates ubiquitination of the replication protein A (RPA) complex. Our reactive-site-centric chemoproteomics method is broadly applicable for identifying the reaction sites of covalent molecules, which may expand our understanding of enzymatic mechanisms.,
GeneRIFs: Gene References Into Functions
- ZUFSP is recruited to and regulates K63-Ub conjugates at genotoxic stress sites, promoting chromosome stability upon replication stress in a manner dependent on its catalytic activity.
- Identify two 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.
- ZUFSP,the singular human member of this family, which contains multiple ubiquitin-binding domains responsible for the specific action on K63-linked chains.
- ZUFSP (ZUP1) is a K63-specific deubiquitinating enzyme that is distantly related to proteases for the ubiquitin-like modifiers Ufm1 and Atg8. ZUFSP does not have any activity on these modifiers. ZUFSP specifically cleaves long K63-linked poly-ubiquitin chains in an ""endo"" mode, i.e. cleavage takes place in the middle of a chain rather than by removing the terminal ubiquitin from a chain.
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