The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
UBP11 (systematic name YKR098C; UniProt P36026) encodes ubiquitin carboxyl-terminal hydrolase 11 (also known as deubiquitinating enzyme 11, ubiquitin thioesterase 11, or ubiquitin-specific-processing protease 11) in Saccharomyces cerevisiae (strain ATCC 204508 / S288c). The protein is 717 amino acids in length and belongs to the peptidase C19 family of cysteine proteases, classified under EC 3.4.19.12 (suresh2020thestructureand pages 4-5, suresh2020thestructureand pages 2-3). Ubp11 is one of 16 USP/UBP (ubiquitin-specific protease) family members in budding yeast, which together constitute the largest family of deubiquitinases (DUBs) among the 22 total putative DUBs encoded by the yeast genome (suresh2020thestructureand pages 3-4).
The following table summarizes the key properties of UBP11:
| Property | Summary | Source |
|---|---|---|
| Gene name | UBP11 | (suresh2020thestructureand pages 4-5) |
| Systematic name | YKR098C | (suresh2020thestructureand pages 4-5) |
| UniProt ID | P36026 | (suresh2020thestructureand pages 4-5) |
| Protein length | 717 aa | (suresh2020thestructureand pages 2-3) |
| EC number | EC 3.4.19.12 (ubiquitin carboxyl-terminal hydrolase / deubiquitinating enzyme) | (suresh2020thestructureand pages 4-5, suresh2020thestructureand pages 3-4) |
| Protein family | Member of the USP/UBP (ubiquitin-specific protease) family; yeast has 16 USP/UBP DUBs within 22 total putative DUBs | (suresh2020thestructureand pages 3-4) |
| Key domains | Catalytic USP domain / USP catalytic core characteristic of peptidase C19 family DUBs; USP/UBP enzymes share a conserved catalytic domain with finger, palm, and thumb subdomains for ubiquitin recognition | (suresh2020thestructureand pages 3-4) |
| Subcellular localization | Reported as cytoplasm in a systematic snapshot of budding-yeast DUBs | (suresh2020thestructureand pages 4-5) |
| Enzymatic activity | Predicted/annotated cysteine protease deubiquitinase that hydrolyzes Ub–substrate or Ub–Ub isopeptide bonds; direct substrate-level biochemical characterization for Ubp11 itself is limited | (suresh2020thestructureand pages 1-2, suresh2020thestructureand pages 3-4) |
| Known functional associations | Genetic/chemical-genetic evidence places UBP11 in an Rsp5-centered endosomal transport network; UBP11 and UBP7 were described as proteins that can deubiquitinate Rsp5 substrates | (tardiff2013yeastreveala pages 3-4) |
| Endocytosis / trafficking context | In α-synuclein/NAB2 studies, overexpression of UBP11 (and UBP7) partially compromised NAB2-mediated rescue of α-syn toxicity, consistent with Ubp11 antagonizing Rsp5-driven ubiquitin-dependent endosomal trafficking | (tardiff2013yeastreveala pages 3-4) |
| Deletion phenotype | No strong standalone phenotype was highlighted in the retrieved literature; in the NAB2 study, no deletion, including ubp7Δ ubp11Δ, produced more than partial resistance to NAB2, arguing UBP11 is involved but not itself the central NAB2 target; available evidence therefore suggests a subtle or context-dependent loss-of-function phenotype | (tardiff2013yeastreveala pages 3-4) |
| Closest functional paralogs | UBP7 is the closest experimentally supported functional paralog based on shared placement with UBP11 as deubiquitinases of Rsp5 substrates in the same endocytic/endosomal transport network; direct redundancy is suggested but not fully resolved | (tardiff2013yeastreveala pages 3-4, bohm2016thebuddingyeast pages 2-3) |
| Current evidence strength | Undercharacterized relative to other yeast DUBs: strong family/domain assignment and pathway association exist, but direct biochemical substrate specificity, chain-linkage preference, and dedicated deletion-phenotype studies for Ubp11 remain sparse in the retrieved literature | (suresh2020thestructureand pages 3-4, suresh2020thestructureand pages 4-5, tardiff2013yeastreveala pages 3-4) |
Table: This table summarizes the core annotated and literature-supported properties of the yeast deubiquitinase UBP11/YKR098C, including structure, localization, catalytic class, and the best-supported functional association with the Rsp5-endocytosis network. It is useful as a compact evidence map because UBP11 appears to be relatively undercharacterized compared with other budding-yeast DUBs.
As a member of the USP/UBP family, Ubp11 is predicted to function as a cysteine protease that hydrolyzes isopeptide bonds between ubiquitin and substrate proteins, or between ubiquitin moieties in polyubiquitin chains. The USP/UBP catalytic domain adopts a highly conserved structure resembling a right hand with three subdomains: a finger, palm, and thumb. The catalytic center is formed in a cleft between the palm and thumb, with the catalytic cysteine residing in the thumb and the catalytic histidine in the palm, while the finger subdomain interacts with ubiquitin to facilitate its positioning in the catalytic center (suresh2020thestructureand pages 3-4). The catalytic triad typical of cysteine protease DUBs comprises Cys, His, and Asp/Asn residues, where the nearby His residue lowers the pKa of the catalytic Cys, facilitating a nucleophilic attack on the isopeptide bond (suresh2020thestructureand pages 3-4).
Substrate recognition by USP/UBP family members typically involves either their variable sequence regions or scaffolds and substrate adaptors within multi-protein complexes (suresh2020thestructureand pages 3-4). Many USP/UBP DUBs utilize additional protein-protein interaction (PPI) domains to bind target proteins, enabling them to cleave ubiquitin chains from specific targets regardless of chain architecture (suresh2020thestructureand pages 3-4). It should be noted that direct biochemical characterization of Ubp11's substrate specificity and ubiquitin-chain linkage preference has not been reported in the available literature; the enzyme's activity is inferred primarily from its domain architecture and family membership.
Systematic localization studies of budding yeast DUBs indicate that Ubp11 localizes to the cytoplasm (suresh2020thestructureand pages 4-5). This localization is consistent with a role in cytosolic deubiquitination processes, including the regulation of ubiquitinated substrates involved in endosomal and vesicular trafficking pathways.
The strongest functional evidence for Ubp11 comes from a landmark chemical-genetic study by Tardiff et al. (2013, Science). In this study, a small molecule called NAB2 was identified as a compound that rescues α-synuclein toxicity in yeast by promoting Rsp5-dependent ubiquitin-mediated endosomal transport. A comprehensive genetic screen revealed a highly connected network of functionally related genes underlying NAB2 activity. This network included the E3 ubiquitin ligase RSP5 (a HECT domain ligase that catalyzes K63-linked ubiquitination of diverse membrane proteins to regulate endosomal trafficking), endocytic proteins (SLA1, VRP1), the multivesicular body sorting deubiquitinase DOA4, an Rsp5 adaptor (BUL1), known and potential Rsp5 substrates (BAP2, BAP3, MMP1), VPS23 (which directs Rsp5 substrates for vacuolar degradation), and critically, two proteins that can deubiquitinate Rsp5 substrates: UBP7 and UBP11 (tardiff2013yeastreveala pages 3-4).
In this context, overexpression of UBP7 and UBP11 partially compromised the ability of NAB2 to rescue α-synuclein toxicity, consistent with a model in which these deubiquitinases counteract Rsp5-driven ubiquitination of endocytic cargo and/or the endocytic machinery itself (tardiff2013yeastreveala pages 3-4). Conversely, deletion of UBP7 and UBP11, either singly or in combination (ubp7Δ ubp11Δ double mutant), had no effect on NAB2's rescue of α-synuclein toxicity, and no deletion (including the double deletion) conferred more than partial resistance to NAB2 (tardiff2013yeastreveala pages 3-4). This indicates that while Ubp11 participates in the Rsp5-dependent endosomal pathway, it is not the central target of NAB2 and likely acts redundantly with other DUBs.
Ubp7 is the closest characterized functional paralog of Ubp11 based on their shared placement in the Rsp5 endosomal transport network (tardiff2013yeastreveala pages 3-4). Ubp7 has been independently characterized as a late-arriving component of endocytic sites that, together with Ubp2, regulates clathrin-mediated endocytosis by deubiquitinating endocytic machinery proteins, most notably the early endocytic protein Ede1 (weinberg2014regulationofclathrinmediated pages 3-5, weinberg2014regulationofclathrinmediated pages 5-7). The dynamic ubiquitination and deubiquitination of Ede1 by Rsp5 (E3 ligase) and Ubp2/Ubp7 (DUBs) regulates endocytic coat assembly and disassembly at the plasma membrane (weinberg2014regulationofclathrinmediated pages 3-5, weinberg2014regulationofclathrinmediated pages 5-7). While Ubp7 has been directly demonstrated to deubiquitinate Ede1 in vitro (weinberg2014regulationofclathrinmediated pages 3-5), no equivalent in vitro experiment has been reported for Ubp11. Nevertheless, the genetic evidence places Ubp11 in the same functional pathway.
Additionally, Ubp7 has been shown to have a role in S phase progression and the DNA damage response, with evolutionary rate covariation analysis linking it to homologous recombination and nucleotide excision repair pathways (bohm2016thebuddingyeast pages 1-2, bohm2016thebuddingyeast pages 2-3). Whether Ubp11 shares these additional roles remains untested.
The yeast ubiquitin system employs DUBs across multiple cellular compartments and processes. Several other UBP family members have well-characterized roles: Ubp6 and the JAMM family DUB Rpn11 function at the proteasome; Doa4 recycles ubiquitin at multivesicular bodies; Ubp8 deubiquitinates histone H2B as part of the SAGA complex; Ubp3 plays pleiotropic roles in protein quality control, ribophagy, and stress response; and Ubp2/Ubp15 regulate the ART/Rsp5 ubiquitin ligase complex (suresh2020thestructureand pages 8-9, suresh2020thestructureand pages 5-6, suresh2020thestructureand pages 9-10). In the context of ER-associated degradation, the related DUB Ubp1 (not to be confused with Ubp11) specifically antagonizes the Doa10 E3 ligase and regulates the ERAD ubiquitin ligase Hrd1 through cycles of autoubiquitination and deubiquitination (peterson2019cyclesofautoubiquitination pages 2-3). When 23 different DUBs were tested for their ability to increase Hrd1 levels, Ubp1 showed the strongest and most specific effect, suggesting that most other DUBs including Ubp11 do not play a major role in ERAD (peterson2019cyclesofautoubiquitination pages 2-3).
Notably, Ubp11 was not among the nine DUBs selected for proteome-wide protein expression profiling in the systematic study by Isasa et al. (2015), which focused on UBP3, DOA4, UBP6, UBP8, UBP10, UBP14, UBP15, OTU1, and OTU2 (isasa2015multiplexedproteomewideprotein pages 1-2, isasa2015multiplexedproteomewideprotein pages 3-4). This omission reflects the relative lack of characterized phenotypes associated with UBP11 deletion, consistent with the general observation that many yeast DUBs exhibit functional redundancy.
The deletion of UBP11, either alone or in combination with UBP7, does not cause severe growth defects under standard laboratory conditions (tardiff2013yeastreveala pages 3-4). This is consistent with the high degree of functional redundancy observed among yeast DUBs, where individual deletions often have subtle or condition-specific phenotypes. The observation that even the ubp7Δ ubp11Δ double deletion confers only partial effects on the Rsp5/endocytosis pathway suggests that additional DUBs (such as Ubp2) can compensate for the loss of these enzymes.
Ubp11 is a 717 amino acid protein containing the characteristic USP catalytic domain with the Cys-His catalytic dyad common to peptidase C19 family members (suresh2020thestructureand pages 2-3). The protein contains the USP_CS (ubiquitin-specific protease cysteine signature) motif (InterPro: IPR018200) and the broader USP domain (InterPro: IPR028889), both hallmarks of ubiquitin-specific proteases. Unlike some other yeast USPs, Ubp11 does not appear to have a clearly annotated human orthologue based on the domain architecture comparison in Suresh et al. (2020), in contrast to DUBs like Ubp6/USP14, Ubp8/USP22, or Ubp14/ISOT, which have well-established human counterparts (suresh2020thestructureand pages 2-3). This suggests that Ubp11 may represent a yeast-specific or clade-restricted DUB, or one whose human orthologue has diverged sufficiently to preclude straightforward assignment.
UBP11 encodes a relatively undercharacterized member of the USP/UBP cysteine protease family of deubiquitinating enzymes in S. cerevisiae. Its primary function, based on genetic and chemical-genetic evidence, is to deubiquitinate substrates of the Rsp5 E3 ubiquitin ligase, thereby modulating ubiquitin-dependent endosomal and vesicular transport processes. Ubp11 localizes to the cytoplasm and appears to function redundantly with Ubp7 (and potentially other DUBs such as Ubp2) in regulating the ubiquitination status of endocytic machinery and cargo proteins. The enzyme catalyzes the hydrolysis of ubiquitin-protein isopeptide bonds (EC 3.4.19.12) via a cysteine protease mechanism involving a conserved Cys-His-Asp/Asn catalytic triad within the USP domain. Despite clear pathway-level evidence linking Ubp11 to the Rsp5/endocytosis network, direct biochemical characterization of its substrate specificity, ubiquitin chain-linkage preference, and specific protein substrates remains an important gap in the field.
References
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(suresh2020thestructureand pages 8-9): Harsha Garadi Suresh, Natasha Pascoe, and Brenda Andrews. The structure and function of deubiquitinases: lessons from budding yeast. Oct 2020. URL: https://doi.org/10.1098/rsob.200279, doi:10.1098/rsob.200279. This article has 62 citations and is from a peer-reviewed journal.
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