UBP11 (YKR098C) is one of the ~16-17 ubiquitin-specific proteases (UBP/USP, peptidase C19 family) of budding yeast. It is a 717-residue cysteine-type deubiquitinating enzyme (DUB, EC 3.4.19.12) with a single C-terminal USP catalytic domain (residues ~298-707) bearing an intact catalytic dyad — a nucleophilic cysteine (Cys307) in the Cys box and a proton-acceptor histidine (His649) in the His box — so it is a catalytically competent deubiquitinase that hydrolyzes the bonds formed by the C-terminal glycine of ubiquitin, releasing ubiquitin from conjugates and precursors. Purified/recombinant Ubp11p cleaves ubiquitin fusions in vitro. Beyond this enzymatic activity, its cellular role is largely uncharacterized: no physiological substrate, no specific biological process, and no non-redundant in vivo function have been established, and single deletion causes no strong growth phenotype. UBP11 has a whole-genome-duplication paralog, UBP7, with which it is likely functionally redundant.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004843 cysteine-type deubiquitinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of the deubiquitinase molecular function across the USP/peptidase-C19 family. This is the correct core molecular function for UBP11 and is independently supported by direct in vitro assay (see the IDA row) and by the intact USP catalytic dyad (Cys307/His649). Supporting Evidence: PMID:11076031 14 of the 17 Dubs have now been shown to have file:yeast/UBP11/UBP11-bioinformatics/RESULTS.md the USP catalytic dyad (Cys307/His649) is intact within a 410-aa peptidase C19 domain |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear localization is an IBA propagation from the USP family, not an experimental observation for UBP11. Many yeast UBPs are cytosolic and/or nucleocytoplasmic, and SGD lists UBP11's cellular component as unknown; no UBP11-specific localization study exists. Retained as a plausible but unverified, non-core location — the true site of action is undetermined. Reason: IBA-only; no experimental localization data for UBP11 itself. Where the enzyme acts in vivo is a genuine knowledge gap. |
| GO:0031647 regulation of protein stability | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Broad, family-level biological-process propagation (IBA): deubiquitinases as a class influence protein stability by removing degradative ubiquitin marks. This is a reasonable generic consequence of DUB activity but is not demonstrated for UBP11 specifically, and it names no substrate or pathway. Kept as non-core; the specific process UBP11 acts in is unknown. Reason: Generic DUB-class inference (IBA), not UBP11-specific; no substrate or pathway established. The actual biological process is a knowledge gap. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytosolic localization is an IBA propagation from the USP family. It is a plausible location for a soluble DUB but has not been experimentally determined for UBP11 (SGD lists cellular component as unknown). Retained as a non-core, unverified location. Reason: IBA-only; no experimental localization for UBP11. Plausible but unverified. |
| GO:0004843 cysteine-type deubiquitinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA) assignment of the deubiquitinase activity from InterPro (peptidase C19 signatures IPR001394/IPR018200) and the EC 3.4.19.12 mapping. Redundant with the IBA and IDA rows for the same term but correct and well grounded in the domain; the catalytic residues are intact. Supporting Evidence: file:yeast/UBP11/UBP11-bioinformatics/RESULTS.md Both members of the catalytic dyad expected for a USP/peptidase-C19 cysteine protease (nucleophilic Cys + proton-acceptor His) are present |
| GO:0016579 protein deubiquitination | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic (IEA, InterPro) assignment of the protein-deubiquitination biological process, the direct process counterpart of the DUB molecular function. This is the most defensible process term for UBP11: it follows necessarily from the demonstrated deubiquitinase activity without over-claiming a specific downstream pathway or substrate. Supporting Evidence: PMID:10527495 Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | MARK AS OVER ANNOTATED | Summary: This term comes from a genome-wide computational reconstruction (RCA) of the yeast zinc proteome (domain + motif prediction), not a direct measurement of zinc binding by UBP11. Some USP-family DUBs contain a zinc-finger/Zn-ribbon subdomain, so the prediction is plausible, but UniProt annotates no zinc-binding site in UBP11 and no experimental evidence exists. Marked as over-annotated: a predicted, non-core property that adds little to the functional picture and is not experimentally supported. Reason: RCA (computational proteome-wide prediction) only; no experimental zinc-binding data and no UniProt zinc-binding site for UBP11. Not a demonstrated function. |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:10527495 Chemically synthesized ubiquitin extension proteins detect d... | ACCEPT | Summary: Direct assay (IDA): recombinant Ubp11p was among the yeast UBPs expressed in E. coli and tested against synthetic ubiquitin substrates, cleaving ubiquitin from fusions. This is the primary experimental evidence for the deubiquitinase molecular function and is the core function of UBP11. Note the study found isopeptidase (ubiquitin-epsilonN-lysine) cleavage only for a different subset of DUBs, so UBP11's physiological linkage specificity remains undefined — but its deubiquitinase activity is established. Supporting Evidence: PMID:10527495 Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: Root cellular_component term with ND (no data) evidence — an explicit SGD record that no experimental localization has been determined for UBP11. This honestly reflects the CC knowledge gap and should be retained as-is; it is not an assertion of function. Reason: ND placeholder correctly documenting absence of localization data; keep. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process term with ND (no data) evidence — an explicit SGD record that no specific biological process has been experimentally assigned to UBP11. This honestly reflects the BP-dark status of the gene and should be retained as-is. Reason: ND placeholder correctly documenting absence of a specific process; keep. |
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Download this section (compressed HTML)Q: What are the physiological substrates of UBP11 in S. cerevisiae, and which ubiquitin-chain linkages does it preferentially cleave?
Q: How is deubiquitinase function partitioned between UBP11 and its WGD paralog UBP7, and does the ubp7 ubp11 double mutant reveal a phenotype masked by redundancy?
Experiment: Perform quantitative ubiquitylome (diGly) proteomics comparing wild type, ubp11 deletion, ubp7 deletion, and the ubp7 ubp11 double mutant to identify substrates whose ubiquitylation increases specifically when both DUBs are removed.
Hypothesis: UBP11 acts redundantly with UBP7 on a shared set of ubiquitylated substrates.
Type: quantitative diGly ubiquitylome mass spectrometry
Experiment: Assay recombinant Ubp11p (and a catalytic Cys307 mutant control) against a panel of defined K6/K11/K27/K29/K33/K48/K63/M1-linked di- and tetra-ubiquitin chains to determine linkage preference in vitro.
Hypothesis: Purified Ubp11p has a defined ubiquitin-linkage specificity.
Type: in vitro deubiquitinase linkage-specificity assay
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The physiological substrate(s), ubiquitin-linkage specificity, biological process, and non-redundant in vivo role of UBP11 are unknown. It is established that Ubp11p is a catalytically competent deubiquitinase, but not what it deubiquitinates, in which pathway, or what distinguishes its function from its whole-genome-duplication paralog UBP7 and the wider yeast UBP family.
OPEN BIOLOGYCURATION BP_DARK
What is known: Known: UBP11 is a 717-aa peptidase C19 (USP) enzyme with an intact catalytic dyad (Cys307/His649); recombinant Ubp11p cleaves ubiquitin fusions in vitro, and 14 of the 17 yeast DUBs (Ubp11p included) have demonstrated ubiquitin-cleaving activity. Unknown/absent: a single ubp11 deletion is not lethal or strongly growth-defective under standard conditions, SGD lists both its biological process and cellular component as unknown, no in vivo substrate has been identified, and the isopeptidase specificity assay placed UBP11 outside the isopeptidase-positive DUB subset, leaving its linkage preference undefined.
Significance: UBP11 is a representative of the large, mostly uncharacterized yeast UBP family — most of whose cellular functions remain undiscovered. Assigning a substrate and pathway would both illuminate this specific enzyme and help resolve why the yeast genome maintains ~16-17 partly redundant deubiquitinases, distinguishing genuine functional specialization from WGD-derived redundancy.
What would resolve it: Identify in vivo substrates by comparing the ubiquitylome of ubp11 deletion (and the ubp7 ubp11 double mutant, to bypass paralog redundancy) with wild type; test linkage specificity of purified Ubp11p against defined di-/poly- ubiquitin chains; determine subcellular localization of tagged Ubp11p; and phenotype the double mutant across stress/condition panels.
Provenance (the field's own admissions):
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