UBP11 (YKR098C / P36026) research notes

S. cerevisiae ubiquitin-specific protease 11. An understudied ("dark") gene: the
molecular activity is clear (a cysteine-type deubiquitinase), but its physiological
substrate, biological process, non-redundant role, and localization are essentially
unknown. These notes record what is KNOWN vs NOT-KNOWN with provenance.

Identity and domain architecture (KNOWN)

• UniProt P36026, UBP11_YEAST, systematic name YKR098C, chromosome XI; 717 aa,
  ~82.7 kDa. RecName "Ubiquitin carboxyl-terminal hydrolase 11"; EC 3.4.19.12
  (thiol-dependent hydrolysis of ubiquitin C-terminal ester/thioester/amide/peptide/
  isopeptide bonds). (UBP11-uniprot.txt)
• Belongs to the peptidase C19 family (USP / ubiquitin-specific protease); single
  USP catalytic domain spanning residues 298–707 (~410 aa). Two annotated catalytic
  ACT_SITE residues: Cys307 (nucleophile) and His649 (proton acceptor).
  PROSITE USP signatures PS00972 (USP_1, Cys box), PS00973 (USP_2, His box) and PS50235
  (USP_3 profile) all match. (UBP11-uniprot.txt)
• Bioinformatics check (this repo, UBP11-bioinformatics/RESULTS.md): the catalytic dyad
  Cys307/His649 is present and intact → catalytically competent DUB by domain, not a
  degenerate pseudo-DUB. The catalytic Cys sits in the canonical Cys box (NPCNTC…).

Molecular function: deubiquitinase (KNOWN)

• Ubp11p was assayed directly for deubiquitinating activity. In the synthetic-substrate
  study, yeast Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p were "expressed in
  Escherichia coli" and their catalytic capacities assessed against ubiquitin fusions
  PMID:10527495. This is the basis
  of the SGD IDA annotation to GO:0004843 (cysteine-type deubiquitinase activity).
• Nuance on specificity: in that same study, isopeptidase activity
  (cleavage of ubiquitin-(εN)-lysine) was "only associated with Yuh1p, Unp,
  Ubp1p, and Ubp2p" PMID:10527495. UBP11 was NOT in the
  isopeptidase-positive set — i.e., its in vitro activity profile against these
  particular synthetic substrates was limited. This does not negate the deubiquitinase
  MF (it cleaves ubiquitin fusions / linear extensions) but flags that the physiological
  linkage/substrate specificity is undefined.
• Family-level confirmation: of the 17 potential yeast DUB genes, "14 of the 17 Dubs have
  now been shown to have ubiquitin-cleaving activity" including Ubp11p
  PMID:11076031.

Biological process / phenotype / localization (NOT KNOWN)

• No specific biological process is established for UBP11. SGD lists its biological
  process and cellular component as unknown despite the clear enzymatic function
  (https://www.yeastgenome.org/locus/S000001806, accessed 2026-07).
• Amerik, Li & Hochstrasser systematically deleted each of the 17 yeast DUB genes:
  "none of the mutants is lethal or strongly growth defective under standard conditions,
  although a number have detectable abnormalities"
  PMID:11076031. So ubp11Δ has no strong single-mutant phenotype — the classic
  signature of a redundant / condition-specific DUB.
• The GOA localization terms (nucleus GO:0005634, cytosol GO:0005829) are IBA only
  (phylogenetic propagation from the USP family), not experimentally determined for
  UBP11 itself. SGD marks localization unknown.
• GOA also carries an SGD ND (no data) row for both cellular_component and
  biological_process, which correctly reflects the absence of experimental evidence.

Paralogy and redundancy (KNOWN structure, UNKNOWN functional division)

• UBP11 has a paralog, UBP7 (YIL156W), that arose from the whole-genome duplication
  (WGD); both single nulls are viable (SGD). This is the most likely explanation for the
  lack of a ubp11Δ phenotype, but the functional division of labour between UBP11 and
  UBP7 (and vs the broader 16-17 member yeast UBP family) has not been dissected.
• Family context: the yeast genome encodes ~16-17 UBPs; they are "largely divergent in
  primary sequence except in two short motifs, the Cys and His boxes"; and "the cellular
  functions of most of the UBPs have not yet been discovered" (family reviews /
  Amerik et al. 2000, PMID:11076031).

Candidate pathway lead (WEAK / genetic, not in GOA) — Rsp5 endosomal network

• The falcon deep research surfaces a candidate-pathway lead worth recording but NOT
  strong enough to annotate: Tardiff et al. 2013 (Science, doi:10.1126/science.1245321,
  "Yeast reveal a druggable Rsp5/Nedd4 network that ameliorates α-synuclein toxicity")
  place UBP7 and UBP11 in an Rsp5-centered ubiquitin-dependent endosomal transport
  network as "two proteins that can deubiquitinate Rsp5 substrates," where
  overexpression of UBP7/UBP11 partially compromised NAB2-mediated rescue of
  α-synuclein toxicity.
• Why this stays a lead, not an annotation: the same study found that deletion of
  UBP7 and UBP11, singly or as the ubp7Δ ubp11Δ double, had no effect on NAB2 rescue,
  i.e. UBP11 is not the central target and any role is redundant/context-dependent. This
  is genetic/chemical-genetic association, no direct in vivo UBP11 substrate, and the
  paper is not in our publications cache (would need fetching + verbatim-quote checking
  before any YAML citation). So the review keeps the conservative "BP-dark, substrate
  unknown" stance; Rsp5/endosomal trafficking is the leading hypothesis to test, and is
  reflected in the knowledge_gaps resolution (paralog-aware ubiquitylome of the double
  mutant). Paralog UBP7 has been shown directly to deubiquitinate the endocytic factor
  Ede1 (Weinberg & Drubin 2014), which is consistent with, but does not itself
  demonstrate, an equivalent UBP11 role.

Zinc ion binding annotation (weak / computational)

• GOA has GO:0008270 (zinc ion binding), evidence RCA, from PMID:30358795 (Wang et al.,
  yeast zinc proteome). This is a proteome-wide bioinformatic prediction of zinc-binding
  proteins (domain + motif search), NOT a direct measurement of zinc binding by UBP11.
  Many USP-family DUBs contain a zinc-finger/Zn-ribbon subdomain, so the prediction is
  plausible, but it is a computational reconstruction (RCA), not experimental. The UniProt
  record does NOT annotate a zinc-binding site in UBP11.

Summary: what is the gap?

• MF known (competent cysteine-type deubiquitinase, by domain + in vitro assay).
• BP dark: no physiological process; no in vivo substrate; no non-redundant role
  distinguished from paralog UBP7 or the wider UBP family.
• CC uncertain: nucleus/cytosol are IBA propagations, not UBP11-specific data.
• This is a BIOLOGY gap (primary) + CURATION note: the deubiquitinase MF is real but
  the "for what?" is genuinely undetermined, and a single-gene deletion has no strong
  phenotype because of paralog redundancy.

References used

• PMID:10527495 — Layfield et al. 1999, Anal Biochem. Synthetic ubiquitin substrates;
  Ubp11p among yeast DUBs assayed. (abstract only in cache)
• PMID:11076031 — Amerik, Li & Hochstrasser 2000, Biol Chem. Systematic deletion of all
  17 yeast DUB genes; none lethal/strongly growth-defective; 14/17 have Ub-cleaving
  activity. (abstract only in cache)
• PMID:30358795 — Wang et al. 2018, Metallomics. Yeast zinc proteome; source of the RCA
  zinc-ion-binding annotation. (abstract only in cache)
• SGD locus page S000001806 (UBP11) — paralog UBP7/WGD; BP & CC unknown.
• file:yeast/UBP11/UBP11-bioinformatics/RESULTS.md — catalytic-dyad integrity check.