UCHL5 (UCH37) is a ubiquitin C-terminal hydrolase (peptidase C12, UCH family) cysteine protease that removes ubiquitin from polyubiquitin chains. A UCH catalytic domain with a Cys88/His164 dyad is followed by a C-terminal ULD/KEKE region that autoinhibits the enzyme and mediates partner binding. In the cytoplasm and nucleus UCHL5 docks onto the 19S regulatory particle of the 26S proteasome through the DEUBAD domain of ADRM1/RPN13, which relieves autoinhibition. Proteasome-bound UCHL5 trims K48-linked chains from the distal end and preferentially debranches K48-containing branched chains. This can either rescue poorly ubiquitinated substrates from degradation or promote degradation and proteasome recycling, depending on the substrate. In the nucleus UCHL5 is also a subunit of the INO80 chromatin-remodeling complex. There the related DEUBAD domain of NFRKB (INO80G) binds the same C-terminal region and holds the enzyme inactive, though transient contact with the proteasome can activate it. Reported substrates include Smoothened, which UCHL5 deubiquitinates and stabilises to support Hedgehog signalling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: RNA binding from HeLa mRNA interactome capture. Reason: The only support is a single proteome-wide UV-crosslinking screen. UCHL5 has no recognised RNA-binding domain, and no study has examined RNA binding by UCHL5 or a role for it in UCHL5 function. The claim is not refuted, but it is not part of the characterised biology of this deubiquitinase. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria |
| GO:0004843 cysteine-type deubiquitinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cysteine-type deubiquitinase activity propagated from PTN000063280. Reason: The PAINT node PTN000063280 spans the UCH family, whose members are thiol proteases acting at the ubiquitin C terminus; UCHL5 itself is among the experimental seeds. The human protein retains the catalytic residues and has direct biochemical evidence. UCHL5 is a peptidase C12 (UCH) cysteine protease with a Cys88/His164 catalytic dyad; purified and proteasome-bound UCH37 hydrolyses ubiquitin-AMC and disassembles K48-linked polyubiquitin, and the C88A mutant is inactive. This is the core activity of the gene, experimentally established for the human protein (PMID:16906146, PMID:18922472, PMID:33156996). Supporting Evidence: PMID:16906146 We show that Uch37 is responsible for the ubiquitin isopeptidase activity in the PA700 (19S) proteasome regulatory complex. file:human/UCHL5/UCHL5-uniprot.txt C->A: Abolishes enzymatic activity. |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: Deubiquitinase activity of UCH37, activated by proteasome binding and inhibited in INO80. Reason: UCHL5 is a peptidase C12 (UCH) cysteine protease with a Cys88/His164 catalytic dyad; purified and proteasome-bound UCH37 hydrolyses ubiquitin-AMC and disassembles K48-linked polyubiquitin, and the C88A mutant is inactive. This is the core activity of the gene, experimentally established for the human protein (PMID:16906146, PMID:18922472, PMID:33156996). Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. |
| GO:0004843 cysteine-type deubiquitinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Deubiquitinase activity from InterPro/EC mapping. Reason: Consistent with the experimental rows: UCHL5 carries the peptidase C12 UCH catalytic domain. UCHL5 is a peptidase C12 (UCH) cysteine protease with a Cys88/His164 catalytic dyad; purified and proteasome-bound UCH37 hydrolyses ubiquitin-AMC and disassembles K48-linked polyubiquitin, and the C88A mutant is inactive. This is the core activity of the gene, experimentally established for the human protein (PMID:16906146, PMID:18922472, PMID:33156996). Supporting Evidence: PMID:16906146 We show that Uch37 is responsible for the ubiquitin isopeptidase activity in the PA700 (19S) proteasome regulatory complex. |
| GO:0004843 cysteine-type deubiquitinase activity | IMP PMID:28992318 The deubiquitinase UCHL5/UCH37 positively regulates Hedgehog... | ACCEPT | Summary: UCH37 deubiquitinates Smoothened, stabilising it. Reason: The study shows UCHL5/UCH37 deubiquitinates Smo in Drosophila and human cells. Smo is one substrate; the activity itself is the gene's core function. UCHL5 is a peptidase C12 (UCH) cysteine protease with a Cys88/His164 catalytic dyad; purified and proteasome-bound UCH37 hydrolyses ubiquitin-AMC and disassembles K48-linked polyubiquitin, and the C88A mutant is inactive. This is the core activity of the gene, experimentally established for the human protein (PMID:16906146, PMID:18922472, PMID:33156996). Supporting Evidence: PMID:28992318 we find that the mammalian counterpart of UCHL5, UCH37, plays the same role in the regulation of Hh signaling by modulating hSmo ubiquitination and stability. |
| GO:0004866 endopeptidase inhibitor activity | IMP PMID:18162577 Relative structural and functional roles of multiple deubiqu... | REMOVE | Summary: Endopeptidase inhibitor activity inferred from UCH37 RNAi accelerating cellular protein degradation. Reason: The cited abstract itself reports that UCH37 knockdown had no detectable effect on proteasome proteolytic capacity; what changed was the cellular rate of protein degradation. An inhibitor of the proteasome's peptidase activity would alter proteolytic capacity. UCHL5 is a deubiquitinase that edits substrate ubiquitin chains, and the degradation effect is captured as regulation of proteasomal protein catabolic process (GO:0061136) from the same paper. Later work shows UCHL5 can also promote degradation by debranching chains (PMID:33156996), which is inconsistent with an intrinsic protease inhibitor function. Supporting Evidence: PMID:18162577 In contrast, RNAi of Uch37 or Usp14 had no detectable effect on cell growth, proteasome structure or proteolytic capacity, but accelerated cellular protein degradation. |
| GO:0005515 protein binding | IPI PMID:11163772 Identification of two proteins, S14 and UIP1, that interact ... | REMOVE | Summary: Interaction of UCHL5 with UIP1 (HAUS7) reported in PMID:11163772. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. UIP1 was identified in a yeast two-hybrid screen and competes with proteasome binding in vitro; no specific UCHL5 activity toward it is established. |
| GO:0005515 protein binding | IPI PMID:16990800 A novel proteasome interacting protein recruits the deubiqui... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMA6 reported in PMID:16990800. Reason: Bare protein binding is uninformative. PSMA6 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16990800 hRpn13 recruits UCH37, a deubiquitinating enzyme known to associate with 26 proteasomes. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:16990800 A novel proteasome interacting protein recruits the deubiqui... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:16990800. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16990800 hRpn13 recruits UCH37, a deubiquitinating enzyme known to associate with 26 proteasomes. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:16990800 A novel proteasome interacting protein recruits the deubiqui... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:16990800. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16990800 hRpn13 recruits UCH37, a deubiquitinating enzyme known to associate with 26 proteasomes. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:17139257 hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds ... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:17139257. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:17139257 The C-terminal half of hRpn13 binds directly to the proteasome-associated deubiquitinating enzyme, UCH37 PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:17139257 hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds ... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:17139257. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:17139257 The C-terminal half of hRpn13 binds directly to the proteasome-associated deubiquitinating enzyme, UCH37 PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | REMOVE | Summary: Interaction of UCHL5 with TFPT (INO80F) reported in PMID:18922472. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. TFPT (INO80F) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:18922472. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMA6 reported in PMID:18922472. Reason: Bare protein binding is uninformative. PSMA6 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:18922472. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:18922472. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | REMOVE | Summary: Interaction of UCHL5 with NFRKB (INO80G) reported in PMID:18922472. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. NFRKB (INO80G) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. Supporting Evidence: PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | REMOVE | Summary: Interaction of UCHL5 with INO80E reported in PMID:18922472. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. INO80E is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | REMOVE | Summary: Interaction of UCHL5 with ACTR8 (ARP8) reported in PMID:18922472. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. ACTR8 (ARP8) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:19490896 Assembly pathway of the Mammalian proteasome base subcomplex... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:19490896. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19490896 Assembly pathway of the Mammalian proteasome base subcomplex... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMA6 reported in PMID:19490896. Reason: Bare protein binding is uninformative. PSMA6 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19490896 Assembly pathway of the Mammalian proteasome base subcomplex... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:19490896. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19490896 Assembly pathway of the Mammalian proteasome base subcomplex... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:19490896. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Interaction of UCHL5 with TFPT (INO80F) reported in PMID:19615732. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. TFPT (INO80F) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:19615732. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:19615732. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:19615732. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Interaction of UCHL5 with NFRKB (INO80G) reported in PMID:19615732. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. NFRKB (INO80G) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. Supporting Evidence: PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Interaction of UCHL5 with INO80E reported in PMID:19615732. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. INO80E is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:21303910 Subunit organization of the human INO80 chromatin remodeling... | REMOVE | Summary: Interaction of UCHL5 with INO80E reported in PMID:21303910. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. INO80E is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:21516116. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Interaction of UCHL5 with ZBED1 reported in PMID:25416956. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. This is a single high-throughput binary interaction with no functional follow-up. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:25416956. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Interaction of UCHL5 with NFRKB (INO80G) reported in PMID:25416956. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. NFRKB (INO80G) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. Supporting Evidence: PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:31515488. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of UCHL5 with TFPT (INO80F) reported in PMID:33961781. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. TFPT (INO80F) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:33961781. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:33961781. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:33961781. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of UCHL5 with NFRKB (INO80G) reported in PMID:33961781. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. NFRKB (INO80G) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. Supporting Evidence: PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of UCHL5 with INO80E reported in PMID:33961781. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. INO80E is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of UCHL5 with ACTR8 (ARP8) reported in PMID:33961781. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. ACTR8 (ARP8) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD4/RPN10 reported in PMID:35271311. Reason: Bare protein binding is uninformative. PSMD4/RPN10 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMA6 reported in PMID:35271311. Reason: Bare protein binding is uninformative. PSMA6 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:35271311. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction of UCHL5 with TFPT (INO80F) reported in PMID:40205054. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. TFPT (INO80F) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit PSMD2/RPN1 reported in PMID:40205054. Reason: Bare protein binding is uninformative. PSMD2/RPN1 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Interaction of UCHL5 with the 26S proteasome subunit ADRM1/RPN13 reported in PMID:40205054. Reason: Bare protein binding is uninformative. ADRM1/RPN13 is a subunit of the 26S proteasome, and the interaction reflects UCHL5 docking onto the 19S regulatory particle, which is recruited by the ADRM1/RPN13 DEUBAD domain binding the UCHL5 C-terminal ULD (PMID:16906146, PMID:17139257, PMID:16990800). The informative function is proteasome binding (GO:0070628), which this gene already carries by IDA. The interaction itself is not in doubt. Proposed replacements: proteasome binding Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction of UCHL5 with NFRKB (INO80G) reported in PMID:40205054. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. NFRKB (INO80G) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. Supporting Evidence: PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction of UCHL5 with INO80E reported in PMID:40205054. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. INO80E is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction of UCHL5 with ACTR8 (ARP8) reported in PMID:40205054. Reason: Bare protein binding (GO:0005515) carries no functional information and is removed under the protein-binding policy; removal does not mean the reported interaction is false. ACTR8 (ARP8) is an INO80 complex subunit; UCHL5 membership of INO80 is captured by the Ino80 complex (GO:0031011) annotations, and NFRKB binding inhibits rather than enables UCHL5 activity (PMID:25702872), so there is no informative UCHL5 molecular function to substitute. |
| GO:0005634 nucleus | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: Nuclear UCH37 associated with hINO80. Reason: UCHL5 is found in the nucleus, where it is a subunit of the INO80 complex; nuclear proteasomes also carry it. Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state file:human/UCHL5/UCHL5-uniprot.txt Cytoplasm {ECO:0000269|PubMed:18922472}. Nucleus {ECO:0000269|PubMed:18922472}. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus from UniProt subcellular location mapping. Reason: Consistent with the experimental nuclear localisation and INO80 membership (PMID:18922472). Supporting Evidence: file:human/UCHL5/UCHL5-uniprot.txt Cytoplasm {ECO:0000269|PubMed:18922472}. Nucleus {ECO:0000269|PubMed:18922472}. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm from HPA immunofluorescence. Reason: Nucleoplasmic signal agrees with UCHL5 membership of the nuclear INO80 chromatin-remodeling complex. Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689544 | ACCEPT | Summary: Reactome: UCHL5 binds the INO80 complex in the nucleoplasm. Reason: Consistent with the INO80 association described in PMID:18922472. Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleolus from HPA immunofluorescence. Reason: Supported only by an antibody-based HPA image; no study links UCHL5 activity to the nucleolus. It is a plausible sub-nuclear signal for a protein that is both nuclear and proteasome-associated, but it is peripheral to the characterised functions. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm propagated from PTN000063280. Reason: UCH-family enzymes, including UCHL5 itself (a seed of the node), are cytoplasmic; UCHL5 associates with the 19S proteasome in the cytoplasm. Supporting Evidence: file:human/UCHL5/UCHL5-uniprot.txt Cytoplasm {ECO:0000269|PubMed:18922472}. Nucleus {ECO:0000269|PubMed:18922472}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm from UniProt subcellular location mapping. Reason: Consistent with the IDA and IBA evidence. Supporting Evidence: file:human/UCHL5/UCHL5-uniprot.txt Cytoplasm {ECO:0000269|PubMed:18922472}. Nucleus {ECO:0000269|PubMed:18922472}. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol from HPA immunofluorescence. Reason: Cytosolic signal agrees with UCHL5 association with cytosolic 26S proteasomes. Supporting Evidence: PMID:16906146 We show that Uch37 is responsible for the ubiquitin isopeptidase activity in the PA700 (19S) proteasome regulatory complex. |
| GO:0005829 cytosol | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: Cytoplasmic UCH37 associated with proteasomes. Reason: UCH37 associates with the 19S proteasome in the cytoplasm. Supporting Evidence: file:human/UCHL5/UCHL5-uniprot.txt Cytoplasm {ECO:0000269|PubMed:18922472}. Nucleus {ECO:0000269|PubMed:18922472}. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5665854 | ACCEPT | Summary: Reactome: ADRM1:26S proteasome binds UCHL5 in the cytosol. Reason: Consistent with ADRM1-mediated recruitment of UCHL5 to cytosolic proteasomes (PMID:16906146). Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:0006275 regulation of DNA replication | IMP PMID:25016522 The mammalian INO80 chromatin remodeling complex is required... | MARK AS OVER ANNOTATED | Summary: Regulation of DNA replication from INO80 knockdown under replication stress. Reason: The cached full text of this paper reports esiRNA knockdown of the Ino80 ATPase and Arp8 and does not mention UCH37/UCHL5. Even if UCHL5 was assayed in material we cannot see, the phenotype belongs to the INO80 remodeler; UCHL5 sits in the metazoan-specific module that is not required for nucleosome remodeling and is held catalytically inactive in INO80 (PMID:21303910, PMID:18922472). No UCHL5 activity in DNA replication is established. Supporting Evidence: PMID:21303910 These modules include (i) one that is composed of the N terminus of the hIno80 protein and all of the metazoan-specific subunits and is not required for ATP-dependent nucleosome remodeling |
| GO:0006338 chromatin remodeling | IDA PMID:21303910 Subunit organization of the human INO80 chromatin remodeling... | MARK AS OVER ANNOTATED | Summary: Chromatin remodeling by the hINO80 complex, of which UCHL5 is a subunit. Reason: UCHL5 is a genuine INO80 subunit (accepted as Ino80 complex), but this paper places it in the module assembled on the Ino80 N terminus with the metazoan-specific subunits, and shows that module is not required for ATP-dependent nucleosome remodeling, which the conserved core catalyses. UCHL5 is inhibited by NFRKB in this complex. UCHL5 therefore does not do the remodeling work. Supporting Evidence: PMID:21303910 These modules include (i) one that is composed of the N terminus of the hIno80 protein and all of the metazoan-specific subunits and is not required for ATP-dependent nucleosome remodeling PMID:25702872 NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Ubiquitin-dependent protein catabolic process from InterPro mapping. Reason: Correct but general. UCHL5 acts at the 26S proteasome, where its debranching of K48 chains promotes degradation of ubiquitinated substrates; the specific supported descendant is proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161). Proposed replacements: proteasome-mediated ubiquitin-dependent protein catabolic process Supporting Evidence: PMID:33156996 Using reconstituted proteasome complexes, we find that chain debranching promotes degradation of substrates modified with branched chains under multi-turnover conditions. PMID:34761751 In cultured human cells under conditions of proteolytic stress, we show that substrate clearance by the proteasome is promoted by both binding and deubiquitination of branched polyubiquitin by UCH37. |
| GO:0016579 protein deubiquitination | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: Protein deubiquitination by UCH37. Reason: UCHL5 removes ubiquitin from polyubiquitin chains and substrates; this is the process its core activity executes. Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. |
| GO:0016579 protein deubiquitination | IEA GO_REF:0000002 | ACCEPT | Summary: Protein deubiquitination from InterPro mapping. Reason: Consistent with the experimental row. Supporting Evidence: PMID:16906146 PA700 isopeptidase disassembles Lys 48-linked polyubiquitin specifically from the distal end of the chain |
| GO:0031011 Ino80 complex | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: UCH37 co-purifies with hINO80. Reason: UCHL5 is a stable INO80 subunit (PMID:18922472, PMID:21303910), recruited via NFRKB/INO80G (PMID:25702872, PMID:25702870). Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state |
| GO:0031011 Ino80 complex | IDA PMID:21303910 Subunit organization of the human INO80 chromatin remodeling... | ACCEPT | Summary: UCHL5 is a subunit of the hINO80 N-terminal module. Reason: Subunit mapping places UCHL5 in the module assembled on the Ino80 N terminus with the metazoan-specific subunits. Supporting Evidence: PMID:21303910 These modules include (i) one that is composed of the N terminus of the hIno80 protein and all of the metazoan-specific subunits and is not required for ATP-dependent nucleosome remodeling |
| GO:0031011 Ino80 complex | IEA GO_REF:0000002 | ACCEPT | Summary: Ino80 complex from InterPro UCH37 signature mapping. Reason: Consistent with the experimental rows. Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:23770237 Insulin/IGF-1 signaling regulates proteasome activity throug... | KEEP AS NON CORE | Summary: Knockdown of UCHL5 in mammalian cells increased degradation of proteotoxic proteins. Reason: The mammalian knockdown result supports a context in which UCHL5 restrains proteasomal degradation, consistent with the editing model in which distal-end chain trimming rescues poorly ubiquitinated substrates (PMID:9034192, PMID:16906146). Other studies show the opposite for substrates carrying branched K48 chains (PMID:33156996, PMID:35451368). The net effect on degradation is substrate-dependent, so this regulatory claim is kept as non-core. Supporting Evidence: PMID:23770237 we demonstrate that proteasome activation through downregulation of the ubh-4 human ortholog uchl5 increases degradation of proteotoxic proteins in mammalian cells. |
| GO:0033044 regulation of chromosome organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of chromosome organization propagated from PTN000834083 (Eumetazoa). Reason: The node is seeded only by mammalian UCHL5 (human, and MGI:1914848), and the human seed is the INO80 knockdown study PMID:26340092. The PAINT placement on the metazoan UCHL5 branch is coherent with INO80 membership being an animal UCHL5 property. However, the underlying evidence is a remodeler-level phenotype, and UCHL5 is held inactive in INO80 in a module not needed for remodeling, so its own contribution is unknown. Kept as non-core rather than removed. Supporting Evidence: PMID:18922472 Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state |
| GO:0033044 regulation of chromosome organization | IMP PMID:26340092 Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin... | KEEP AS NON CORE | Summary: INO80 complex knockdown caused abnormal chromosome stability. Reason: Abstract-only. The abstract describes knockdown of the INO80 complex; the curators presumably saw UCHL5-specific knockdown data in the full text, which we cannot check. The phenotype reflects the INO80 remodeler and UCHL5's own role in it is undefined, so the claim is kept as non-core. Supporting Evidence: PMID:26340092 RNAi knockdown strategies of INO80 not only led to prolonged progression of cell cycle phase G2/M to G1, but it also resulted in abnormal chromosome stability. |
| GO:0045880 positive regulation of smoothened signaling pathway | IMP PMID:28992318 The deubiquitinase UCHL5/UCH37 positively regulates Hedgehog... | KEEP AS NON CORE | Summary: UCHL5/UCH37 positively regulates Hedgehog signaling by deubiquitinating and stabilising Smoothened. Reason: The human data show UCH37 deubiquitinates and stabilises hSmo, a direct substrate-level mechanism, so the regulation claim is reasonable. It is one substrate-specific outcome of the general deubiquitinase activity, not the core function. Supporting Evidence: PMID:28992318 we find that the mammalian counterpart of UCHL5, UCH37, plays the same role in the regulation of Hh signaling by modulating hSmo ubiquitination and stability. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:27641337 INO80 is required for oncogenic transcription and tumor grow... | MARK AS OVER ANNOTATED | Summary: INO80 required for oncogenic transcription in NSCLC. Reason: Abstract-only; the abstract concerns the Ino80 ATPase and Ino80B. If UCHL5 knockdown was included, the outcome still reflects INO80 remodeler occupancy at enhancers, and UCHL5 is held inactive in INO80 in a module not required for remodeling (PMID:21303910). UCHL5 is not shown to perform any step in transcriptional activation. Supporting Evidence: PMID:27641337 Here we show that the INO80 chromatin remodeling complex is required for oncogenic transcription |
| GO:0051726 regulation of cell cycle | IMP PMID:26340092 Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin... | MARK AS OVER ANNOTATED | Summary: INO80 complex knockdown prolonged G2/M progression. Reason: A broad downstream cell-cycle phenotype of INO80 depletion; no UCHL5 activity acting in cell-cycle control is described. Supporting Evidence: PMID:26340092 RNAi knockdown strategies of INO80 not only led to prolonged progression of cell cycle phase G2/M to G1, but it also resulted in abnormal chromosome stability. |
| GO:0060382 regulation of DNA strand elongation | IMP PMID:25016522 The mammalian INO80 chromatin remodeling complex is required... | MARK AS OVER ANNOTATED | Summary: Regulation of DNA strand elongation from INO80 knockdown. Reason: As for regulation of DNA replication from the same paper: the cached full text reports Ino80 and Arp8 knockdown and does not mention UCHL5, and the phenotype is a property of the INO80 remodeler, not of UCHL5 activity. Supporting Evidence: PMID:21303910 These modules include (i) one that is composed of the N terminus of the hIno80 protein and all of the metazoan-specific subunits and is not required for ATP-dependent nucleosome remodeling |
| GO:0061136 regulation of proteasomal protein catabolic process | IMP PMID:18162577 Relative structural and functional roles of multiple deubiqu... | ACCEPT | Summary: UCH37 RNAi altered the rate of cellular protein degradation. Reason: UCHL5 is an intrinsic proteasome-associated DUB whose chain editing and debranching set the fate of ubiquitinated substrates at the proteasome; depletion changes degradation rates in both directions depending on substrate (PMID:18162577, PMID:33156996). Regulation of proteasomal protein catabolism is the right level for this core role. Supporting Evidence: PMID:18162577 In contrast, RNAi of Uch37 or Usp14 had no detectable effect on cell growth, proteasome structure or proteolytic capacity, but accelerated cellular protein degradation. PMID:35451368 By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. |
| GO:0070628 proteasome binding | IDA PMID:18162577 Relative structural and functional roles of multiple deubiqu... | ACCEPT | Summary: Uch37 is a constituent DUB of the mammalian 26S proteasome. Reason: UCHL5 binds the 19S regulatory particle through ADRM1/RPN13, which activates it (PMID:16906146, PMID:17139257). Supporting Evidence: PMID:18162577 Three deubiquitylating activities were associated with the 26S proteasome: two from constituent subunits, Rpn11/S13 and Uch37, and one from a reversibly associated protein, Usp14. |
| GO:0070628 proteasome binding | IDA PMID:18922472 Distinct modes of regulation of the Uch37 deubiquitinating e... | ACCEPT | Summary: Proteasome binding activates UCH37. Reason: Direct evidence that binding to the proteasome enables UCH37 to process polyubiquitin. Supporting Evidence: PMID:18922472 Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. |
| GO:0070628 proteasome binding | IEA GO_REF:0000002 | ACCEPT | Summary: Proteasome binding from InterPro UCH37 signature mapping. Reason: Consistent with the experimental rows. Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. |
| GO:1990380 K48-linked deubiquitinase activity | IDA PMID:16906146 Proteasome recruitment and activation of the Uch37 deubiquit... | NEW | Summary: UCHL5 disassembles Lys48-linked polyubiquitin from the distal end and debranches K48 chains. Reason: The 19S isopeptidase activity attributable to UCH37 disassembles K48-linked chains from the distal end, and proteasome-bound UCHL5 cleaves K48 linkages in branched chains using a K48-chain-specific binding site. This linkage preference is the defining biochemical property of the human enzyme and refines GO:0004843. Supporting Evidence: PMID:16906146 PA700 isopeptidase disassembles Lys 48-linked polyubiquitin specifically from the distal end of the chain PMID:33156996 we report that UCH37/UCHL5, a proteasome-associated deubiquitinase, cleaves K48 branched chains. PMID:35451368 By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. |
| GO:0005838 proteasome regulatory particle | IDA PMID:16906146 Proteasome recruitment and activation of the Uch37 deubiquit... | NEW | Summary: UCHL5 is a subunit of the 19S (PA700) regulatory particle, docked via ADRM1/RPN13. Reason: UCH37 is the isopeptidase subunit of purified PA700 and binds the 19S through ADRM1, which sits on RPN2. The gene carries proteasome binding but no proteasome component term; comparator 19S DUBs (PSMD14, a lid subunit) carry proteasome complex terms. UCHL5 is substoichiometric and its docking site ADRM1 is itself not present on every proteasome, so the general regulatory particle term is used rather than base or lid. Supporting Evidence: PMID:16906146 Uch37 binds through Adrm1, a previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. PMID:9034192 This enzyme is an intrinsic subunit of PA700, the 19S regulatory complex of the 26S proteasome. |
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Download this section (compressed HTML)Q: Does UCHL5 have any catalytic role within the INO80 complex, given that NFRKB holds it inactive there, or does INO80 act as a nuclear reservoir that hands UCHL5 to proteasomes?
Q: Do the INO80-phenotype annotations to UCHL5 from PMID:25016522, PMID:26340092 and PMID:27641337 rest on UCHL5-specific knockdowns? The cached full text of PMID:25016522 reports only Ino80 and Arp8 knockdowns.
Q: Which substrates does UCHL5 rescue from degradation by distal-end chain editing, and which does it help degrade by debranching? Answering this would reconcile the opposite knockdown effects reported for UCHL5.
Experiment: Separation-of-function UCHL5 alleles that bind NFRKB but not ADRM1, and the reverse, combined with catalytic-dead C88A, to test whether INO80-associated UCHL5 contributes to chromatin remodeling or DNA replication phenotypes independently of the proteasome.
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