Uch2 is the fission-yeast UCH37/UCHL5-family cysteine deubiquitinase associated with the 26S proteasome. Its UCH catalytic domain processes ubiquitin conjugates, while a C-terminal extension promotes proteasome association and concentration at the nuclear periphery. It contributes to proteasome-associated ubiquitin-chain processing, with functional redundancy explaining viability of deletion mutants. Purified Uch2 also cleaves the artificial NEDD8-AMC substrate, although its physiological contribution to deconjugating NEDD8 from proteins remains less well established.
IDA PMID:23496905 Nedd8 processing enzymes in Schizosaccharomyces pombe.
MARK AS OVER ANNOTATED
Summary: The full paper directly demonstrates cleavage of NEDD8-AMC by purified GST-Uch2 and tests NEDD8-precursor processing genetically.
Reason: The full paper directly demonstrates cleavage of NEDD8-AMC by purified GST-Uch2 and tests NEDD8-precursor processing genetically. It does not isolate Uch2-dependent hydrolysis of an isopeptide-linked NEDD8-protein conjugate. The current deNEDDylase definition specifically requires deconjugation from a target protein, so this specificity exceeds the assay; retain the real NEDD8-processing observation in the biological description.
While incubation with GST alone does not result in cleavage of Nedd8-AMC, GST-Uch1, GST-Uch2, GST-Nep1 and GST-Nep2 can all cleave Nedd8-AMC (n = 5, S.E.M. shown as error bars).
HDA PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
ACCEPT
Summary: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome.
Reason: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome. Proteomic purification recovers the proteasome, supporting membership and participation in proteasomal protein turnover rather than independent proteolysis of entire substrates.
Rpn11 and Uch2 co-purified all of the 26S proteasome subunits (19S regulatory particle and 20S core particle) in quantities similar to those of the bait (Table S1)
NAS PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
ACCEPT
Summary: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome.
Reason: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome. Proteomic purification recovers the proteasome, supporting membership and participation in proteasomal protein turnover rather than independent proteolysis of entire substrates.
Rpn11 and Uch2 co-purified all of the 26S proteasome subunits (19S regulatory particle and 20S core particle) in quantities similar to those of the bait (Table S1)
Summary: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439).
Reason: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439). The full census study classifies UCH enzymes as cysteine proteases (PMID:20838651).
Summary: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439).
Reason: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439). The full census study classifies UCH enzymes as cysteine proteases (PMID:20838651).
IGI PMID:28765280 The exocyst subunit Sec3 is regulated by a protein quality c...
ACCEPT
Summary: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439).
Reason: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439). The full census study classifies UCH enzymes as cysteine proteases (PMID:20838651).
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome.
Reason: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome. The broad nuclear term and the more specific nuclear periphery are compatible.
HDA PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
ACCEPT
Summary: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome.
Reason: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome. The broad nuclear term and the more specific nuclear periphery are compatible.
Summary: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome.
Reason: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome. The broad nuclear term and the more specific nuclear periphery are compatible.
Summary: The PAINT assertion represents inferred ancestral cytoplasmic residence, but the target localization study reports an exclusively nuclear signal under the tested conditions.
Reason: The PAINT assertion represents inferred ancestral cytoplasmic residence, but the target localization study reports an exclusively nuclear signal under the tested conditions. Conditional cytoplasmic pools are not excluded. The relevant ancestral node, assay conditions and possible target divergence require examination before accepting or rejecting the broader inheritance claim.
Ubp6, Ubp8, Ubp14, Ubp16, Rpn11, and Uch2 are exclusively nuclear (Figure 2A and 2B)
GO:0006511 ubiquitin-dependent protein catabolic process
IEA GO_REF:0000002
ACCEPT
Summary: Proteasome-associated deubiquitination is a function within ubiquitin-dependent protein catabolism, established in studies directly characterizing fission-yeast Uch2.
Reason: Proteasome-associated deubiquitination is a function within ubiquitin-dependent protein catabolism, established in studies directly characterizing fission-yeast Uch2. Viability and a subtle deletion phenotype reflect redundancy rather than absence of pathway participation.
NAS PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
ACCEPT
Summary: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome.
Reason: Uch2 is directly characterized as the major deubiquitinating enzyme associated with the fission-yeast 26S proteasome. Proteomic purification recovers the proteasome, supporting membership and participation in proteasomal protein turnover rather than independent proteolysis of entire substrates.
Rpn11 and Uch2 co-purified all of the 26S proteasome subunits (19S regulatory particle and 20S core particle) in quantities similar to those of the bait (Table S1)
Summary: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439).
Reason: Uch2 has a UCH-family cysteine-protease catalytic domain and directly established proteasome-associated deubiquitination activity (PMID:15533439). The full census study classifies UCH enzymes as cysteine proteases (PMID:20838651).
IDA PMID:23496905 Nedd8 processing enzymes in Schizosaccharomyces pombe.
MARK AS OVER ANNOTATED
Summary: The full paper directly demonstrates cleavage of NEDD8-AMC by purified GST-Uch2 and tests NEDD8-precursor processing genetically.
Reason: The full paper directly demonstrates cleavage of NEDD8-AMC by purified GST-Uch2 and tests NEDD8-precursor processing genetically. It does not isolate Uch2-dependent hydrolysis of an isopeptide-linked NEDD8-protein conjugate. The current deNEDDylase definition specifically requires deconjugation from a target protein, so this specificity exceeds the assay; retain the real NEDD8-processing observation in the biological description.
While incubation with GST alone does not result in cleavage of Nedd8-AMC, GST-Uch1, GST-Uch2, GST-Nep1 and GST-Nep2 can all cleave Nedd8-AMC (n = 5, S.E.M. shown as error bars).
HDA PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
ACCEPT
Summary: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome.
Reason: Target imaging shows nuclear and predominantly nuclear-peripheral localization, consistent with association of Uch2 with the fission-yeast proteasome. The broad nuclear term and the more specific nuclear periphery are compatible.
As shown previously, Rpn11 and Uch2 localize primarily to the nuclear envelope (Figure 2B), where they interact with the proteasome [31],[32].
GO:0071629 cytoplasm protein quality control by the ubiquitin-proteasome system
IGI PMID:28765280 The exocyst subunit Sec3 is regulated by a protein quality c...
UNDECIDED
Summary: The accessible abstract of the cited Sec3 study establishes a cytosolic quality-control pathway and highlights Ubp3, but does not identify the Uch2 result.
Reason: The accessible abstract of the cited Sec3 study establishes a cytosolic quality-control pathway and highlights Ubp3, but does not identify the Uch2 result. This does not imply paralog confusion: the full experimental screen may include Uch2. Until the relevant full-text or supplementary target result is available, this specific physiological assignment remains unresolved.
HDA PMID:20838651 A global census of fission yeast deubiquitinating enzyme loc...
MODIFY
Summary: The full census paper identifies Uch2 as a UCH-family DUB and explicitly distinguishes cysteine-protease UCH domains from JAMM metalloproteases.
Reason: The full census paper identifies Uch2 as a UCH-family DUB and explicitly distinguishes cysteine-protease UCH domains from JAMM metalloproteases. Uch2 co-purifies with Rpn11 and the proteasome, so activity of the purified complex does not establish a metal-dependent catalytic mechanism intrinsic to Uch2. The supported molecular function is cysteine-type deubiquitinase activity.
Rpn11 and Uch2 co-purified all of the 26S proteasome subunits (19S regulatory particle and 20S core particle) in quantities similar to those of the bait (Table S1)
Core Functions
Proteasome-associated cysteine deubiquitinase that processes ubiquitin chains and conjugates during protein turnover.
Q: Which physiological NEDD8-conjugated proteins, if any, are direct Uch2 substrates, as distinct from cleavage of NEDD8 precursors or NEDD8-AMC in vitro?
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Review rationale: Fission-yeast Uch2 is directly characterized as the major deubiquitinating enzyme associated with the 26S proteasome, and proteomic work recovers its association with the proteasome. Processing ubiquitin conjugates at this complex is a function in ubiquitin-dependent protein turnover even though the DUB removes ubiquitin rather than degrading the substrate polypeptide itself. The supported, more precise proteasomal protein catabolic process annotation GO:0010498 is already present. Thus the general catabolic-process prediction is correct but less precise; weak deletion phenotypes reflect redundancy and do not negate pathway participation.
Supporting Evidence:
PMID:15533439: "We report that the subunit Uch2/Uch37 is the major deubiquitinating enzyme associated with the fission yeast 26S proteasome."
PMID:20838651: "Rpn11 and Uch2 co-purified all of the 26S proteasome subunits (19S regulatory particle and 20S core particle) in quantities similar to those of the bait (Table S1)"