UBP11 (P36026) bioinformatics analysis — USP catalytic-domain integrity

Question

Is S. cerevisiae UBP11 (YKR098C) a catalytically competent ubiquitin-specific
protease, or a degenerate/pseudo-DUB? A competent DUB molecular-function annotation is
only defensible from the domain if the peptidase C19 (USP) catalytic residues are intact.

Method

analyze_ubp11.py parses the local UniProt flat file (../UBP11-uniprot.txt), extracts
the protein sequence and feature table, reports the residues actually present at the two
annotated ACT_SITE positions, checks the peptidase C19 family declaration, and scans
for the PROSITE USP signatures. Nothing is hardcoded; run with uv run python analyze_ubp11.py.

Results

Feature	Value
Length	717 aa
Declared family (UniProt SIMILARITY)	peptidase C19 family
Annotated USP domain	residues 298–707 (410 aa)
Catalytic nucleophile (ACT_SITE)	Cys307 — present (context `NPCCNTC…`, canonical Cys box)
Catalytic proton acceptor (ACT_SITE)	His649 — present (context `NLINGHYTSVV…`, His box)

Both members of the catalytic dyad expected for a USP/peptidase-C19 cysteine protease
(nucleophilic Cys + proton-acceptor His) are present at their annotated positions.
The Cys307 sits in the recognizable Cys box motif and His649 in the His box, the two
short conserved motifs that together form the C19 active site.

Caveats (honest limitations)

The script's simplified in-house PROSITE regexes are approximate: the USP_1/Cys-box
pattern did not produce an exact match and the USP_2/His-box pattern produced a spurious
match upstream of the real His box. The authoritative signature evidence is UniProt's
own PROSITE annotation, which lists PS00972 (USP_1), PS00973 (USP_2) and PS50235
(USP_3 profile) as all matching. The catalytic-residue check (from UniProt ACT_SITE
features) is the load-bearing result here, and it is unambiguous.
This analysis confirms catalytic competence by domain; it says nothing about the
physiological substrate or linkage specificity of UBP11, which remain unknown
(see the gene review's knowledge gaps).

Verdict

Catalytically competent cysteine-type deubiquitinase by domain. The USP catalytic
dyad (Cys307/His649) is intact within a 410-aa peptidase C19 domain, so a
cysteine-type deubiquitinase activity (GO:0004843) molecular function is well supported
at the domain level. This is consistent with the in vitro demonstration of ubiquitin-cleaving
activity for Ubp11p (PMID:10527495) and the family-level survey showing 14/17 yeast DUBs,
Ubp11p included, have ubiquitin-cleaving activity (PMID:11076031).