USP10 encodes a ubiquitin-specific cysteine deubiquitinase that removes ubiquitin from selected substrates including p53/TP53, CFTR, Beclin1-complex components, LC3B, and 40S ribosomal proteins. Its direct roles in protein homeostasis include protein deubiquitination, rescue of ubiquitinated stalled 40S ribosomal subunits, and regulation of autophagy/stress-granule signaling through LC3B, Beclin1, and G3BP contexts.
Definition: A protein deubiquitination process in which ubiquitin is removed from an ATG8-family protein, thereby modulating ATG8 protein stability, lipidated ATG8 abundance, or autophagic activity.
Justification: USP10 directly deubiquitinates LC3B and regulates LC3B abundance/autophagic activity, but current GOA can only capture broad protein deubiquitination or regulation of autophagy.
Parent term: protein deubiquitination
Supporting Evidence:
Definition: A monoubiquitinated protein deubiquitination process in which ubiquitin is removed from proteins of a cytosolic 40S ribosomal subunit during ribosome-associated quality control, preventing or reversing programmed degradation of the modified 40S subunit.
Justification: USP10 removes ubiquitin from RPS2/uS5, RPS3/uS3, and RPS10/eS10 in stalled or compromised 40S ribosomal-subunit contexts. Existing GO terms capture either broad monoubiquitinated protein deubiquitination or rescue of stalled cytosolic ribosome, but not the substrate-specific deubiquitination event.
Parent term: monoubiquitinated protein deubiquitination
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0010506 regulation of autophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: USP10 regulates autophagy through Beclin1/Vps34 complexes and LC3B deubiquitination, but this is one substrate pathway of the broader DUB function. Reason: Keep as non-core. The process is well supported and relevant to the PN ATG8 context, but the molecular function should remain protein deubiquitination rather than a generic autophagy-regulator identity. Supporting Evidence: PMID:21962518 two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes PMID:33577797 LC3B ubiquitination is reversed by the action of the deubiquitinating enzyme USP10 PMID:33577797 LC3B and autophagic activity are controlled through cycles of LC3B ubiquitination and deubiquitination |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: USP10 activates p53 signaling after DNA damage by deubiquitinating/stabilizing p53 and translocating to the nucleus. Reason: Keep as non-core. The annotation is supported but represents a substrate-specific signaling outcome of USP10 DUB activity. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and supports endocytic recycling. Reason: Accept as a supported active compartment for a direct USP10 substrate context. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
| GO:0004843 cysteine-type deubiquitinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: Reactome:R-HSA-5688426 Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: USP10 translocates to or acts in the nucleus in p53 and T-bet substrate-stability contexts. Reason: Accept as a supported location, while treating the specific nuclear signaling outputs as substrate/context-specific rather than the sole core function. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts occur in the cytoplasm. Reason: Accept as a supported cellular location for USP10 deubiquitination, including p53 homeostasis, RQC, and immune-signaling substrates. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and supports endocytic recycling. Reason: Accept as a supported active compartment for a direct USP10 substrate context. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
| GO:0016579 protein deubiquitination | IEA GO_REF:0000002 | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: Reactome:R-HSA-5688426 Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:21455491 A Pseudomonas aeruginosa toxin that hijacks the host ubiquit... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:24270572 USP10 inhibits genotoxic NF-ΞΊB activation by MCPIP1-facilita... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:33495715 SARS-CoV-2 nucleocapsid protein phase separates with G3BPs t... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:34799561 Large scale discovery of coronavirus-host factor protein int... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:34901782 SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenua... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005737 cytoplasm | NAS PMID:23279204 Both G3BP1 and G3BP2 contribute to stress granule formation. | ACCEPT | Summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts occur in the cytoplasm. Reason: Accept as a supported cellular location for USP10 deubiquitination, including p53 homeostasis, RQC, and immune-signaling substrates. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005737 cytoplasm | IPI PMID:31981475 The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiqui... | ACCEPT | Summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts occur in the cytoplasm. Reason: Accept as a supported cellular location for USP10 deubiquitination, including p53 homeostasis, RQC, and immune-signaling substrates. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation |
| GO:0016579 protein deubiquitination | IDA PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0016579 protein deubiquitination | NAS PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0062030 negative regulation of stress granule assembly | IDA PMID:27022092 G3BP-Caprin1-USP10 complexes mediate stress granule condensa... | KEEP AS NON CORE | Summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated condensate context. Reason: Keep as non-core. This is a supported stress-granule regulatory role but not the core catalytic DUB activity. Supporting Evidence: PMID:27022092 Caprin binding promotes, but USP10 binding inhibits, SG formation PMID:27022092 G3BP interacts with 40S ribosomal subunits through its RGG motif PMID:32302570 competitive binding of unconnected proteins disengages networks and prevents LLPS |
| GO:0062030 negative regulation of stress granule assembly | NAS PMID:27022092 G3BP-Caprin1-USP10 complexes mediate stress granule condensa... | KEEP AS NON CORE | Summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated condensate context. Reason: Keep as non-core. This is a supported stress-granule regulatory role but not the core catalytic DUB activity. Supporting Evidence: PMID:27022092 Caprin binding promotes, but USP10 binding inhibits, SG formation PMID:27022092 G3BP interacts with 40S ribosomal subunits through its RGG motif PMID:32302570 competitive binding of unconnected proteins disengages networks and prevents LLPS |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 deubiquitination Reactome contexts. Reason: Accept as a nuclear subcompartment location for substrate-specific USP10 activities. Supporting Evidence: Reactome:R-HSA-5653766 Ubiquitin protease USP10 binds doubly ISGylated and monoubiquitinated PCNA Reactome:R-HSA-5653770 USP10 acts as a ubiquitin protease to remove ubiquitin from lysine K164 residue of doubly ISGylated PCNA Reactome:R-HSA-5653770 Deubiquitination of PCNA by USP10 causes dissociation of Y family DNA damage bypass polymerases |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and substrate regulation. Reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 regulation and ribosome-quality-control evidence are consistent with this assignment. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 |
| GO:0016579 protein deubiquitination | TAS Reactome:R-HSA-5688426 | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: Reactome:R-HSA-5688426 Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation |
| GO:0019985 translesion synthesis | TAS Reactome:R-HSA-110313 | KEEP AS NON CORE | Summary: Reactome places USP10 in the PCNA deubiquitination step that terminates/limits translesion synthesis. Reason: Keep as non-core. This is a specific nuclear DNA-damage-bypass substrate context, not the defining USP10 function. Supporting Evidence: Reactome:R-HSA-5653766 Ubiquitin protease USP10 binds doubly ISGylated and monoubiquitinated PCNA Reactome:R-HSA-5653770 USP10 acts as a ubiquitin protease to remove ubiquitin from lysine K164 residue of doubly ISGylated PCNA Reactome:R-HSA-5653770 Deubiquitination of PCNA by USP10 causes dissociation of Y family DNA damage bypass polymerases |
| GO:0004843 cysteine-type deubiquitinase activity | TAS Reactome:R-HSA-5653770 | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: Reactome:R-HSA-5653766 Ubiquitin protease USP10 binds doubly ISGylated and monoubiquitinated PCNA Reactome:R-HSA-5653770 USP10 acts as a ubiquitin protease to remove ubiquitin from lysine K164 residue of doubly ISGylated PCNA Reactome:R-HSA-5653770 Deubiquitination of PCNA by USP10 causes dissociation of Y family DNA damage bypass polymerases |
| GO:0004843 cysteine-type deubiquitinase activity | TAS Reactome:R-HSA-5689973 | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: Reactome:R-HSA-5689973 USP10 specifically deubiquitinate p53 and not MDM2 |
| GO:0004843 cysteine-type deubiquitinase activity | TAS Reactome:R-HSA-6782106 | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: Reactome:R-HSA-6782106 USP10 deubiquitinates CFTR in early endosomes thereby enhancing its endocytic recycling |
| GO:0004843 cysteine-type deubiquitinase activity | EXP PMID:32011234 Distinct regulatory ribosomal ubiquitylation events are reve... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: Reactome:R-HSA-5688426 Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways |
| GO:0005737 cytoplasm | EXP PMID:37582970 MAVS-loaded unanchored Lys63-linked polyubiquitin chains act... | ACCEPT | Summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts occur in the cytoplasm. Reason: Accept as a supported cellular location for USP10 deubiquitination, including p53 homeostasis, RQC, and immune-signaling substrates. Supporting Evidence: PMID:37582970 USP10 as a direct DUB that removes unanchored K63-linked polyubiquitin chains from MAVS PMID:37582970 USP10 attenuates RIG-I-mediated MAVS aggregation and the production of type I interferon |
| GO:0045087 innate immune response | IDA PMID:37023208 Immune evasion strategy involving propionylation by the KSHV... | KEEP AS NON CORE | Summary: USP10 modulates innate immune signaling by removing unanchored K63-linked ubiquitin chains from MAVS; the seeded KSHV/SIRT6 paper is indirect for this term. Reason: Keep as non-core with added MAVS evidence. USP10 has a real RLR/MAVS immune-regulatory role, but the original reference mainly describes viral interference with SIRT6-USP10 regulation. Supporting Evidence: PMID:37582970 USP10 as a direct DUB that removes unanchored K63-linked polyubiquitin chains from MAVS PMID:37582970 USP10 attenuates RIG-I-mediated MAVS aggregation and the production of type I interferon |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:31981475 The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiqui... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:34348161 The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunit... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0022626 cytosolic ribosome | IDA PMID:34348161 The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunit... | ACCEPT | Summary: USP10 acts at cytosolic 40S ribosomal subunits during ribosome-associated quality control. Reason: Accept as an active site/context for the ribosomal deubiquitination function. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0022626 cytosolic ribosome | IDA PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: USP10 acts at cytosolic 40S ribosomal subunits during ribosome-associated quality control. Reason: Accept as an active site/context for the ribosomal deubiquitination function. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0035520 monoubiquitinated protein deubiquitination | IDA PMID:34348161 The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunit... | ACCEPT | Summary: USP10 directly removes monoubiquitin from 40S ribosomal proteins in ribosome quality-control contexts. Reason: Accept as a direct proteostasis function. RPS2/RPS3/RPS10 deubiquitination rescues modified 40S subunits from degradation. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0035520 monoubiquitinated protein deubiquitination | IDA PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: USP10 directly removes monoubiquitin from 40S ribosomal proteins in ribosome quality-control contexts. Reason: Accept as a direct proteostasis function. RPS2/RPS3/RPS10 deubiquitination rescues modified 40S subunits from degradation. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:31981475 The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiqui... | ACCEPT | Summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits from programmed degradation. Reason: Accept as a direct ribosome-associated quality-control role in the proteostasis network. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:34348161 The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunit... | ACCEPT | Summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits from programmed degradation. Reason: Accept as a direct ribosome-associated quality-control role in the proteostasis network. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:34469731 iRQC, a surveillance pathway for 40S ribosomal quality contr... | ACCEPT | Summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits from programmed degradation. Reason: Accept as a direct ribosome-associated quality-control role in the proteostasis network. Supporting Evidence: PMID:31981475 G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation PMID:34348161 These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10 PMID:34469731 USP10 as the deubiquitylating enzyme responsible for removing ubiquitin from uS3 and uS5 |
| GO:0005515 protein binding | IPI PMID:27022092 G3BP-Caprin1-USP10 complexes mediate stress granule condensa... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:32302570 Competing Protein-RNA Interaction Networks Control Multiphas... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:36279435 Yin and yang regulation of stress granules by Caprin-1. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0062030 negative regulation of stress granule assembly | IDA PMID:32302570 Competing Protein-RNA Interaction Networks Control Multiphas... | KEEP AS NON CORE | Summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated condensate context. Reason: Keep as non-core. This is a supported stress-granule regulatory role but not the core catalytic DUB activity. Supporting Evidence: PMID:27022092 Caprin binding promotes, but USP10 binding inhibits, SG formation PMID:27022092 G3BP interacts with 40S ribosomal subunits through its RGG motif PMID:32302570 competitive binding of unconnected proteins disengages networks and prevents LLPS |
| GO:0140678 molecular function inhibitor activity | IDA PMID:27022092 G3BP-Caprin1-USP10 complexes mediate stress granule condensa... | KEEP AS NON CORE | Summary: USP10 acts as an inhibitor in the G3BP stress-granule assembly network. Reason: Keep as non-core. The MF-inhibitor annotation captures a real G3BP regulatory effect, but the more informative biological-process annotation is negative regulation of stress granule assembly. Supporting Evidence: PMID:27022092 Caprin binding promotes, but USP10 binding inhibits, SG formation PMID:27022092 G3BP interacts with 40S ribosomal subunits through its RGG motif PMID:32302570 competitive binding of unconnected proteins disengages networks and prevents LLPS |
| GO:0140678 molecular function inhibitor activity | IDA PMID:32302570 Competing Protein-RNA Interaction Networks Control Multiphas... | KEEP AS NON CORE | Summary: USP10 acts as an inhibitor in the G3BP stress-granule assembly network. Reason: Keep as non-core. The MF-inhibitor annotation captures a real G3BP regulatory effect, but the more informative biological-process annotation is negative regulation of stress granule assembly. Supporting Evidence: PMID:27022092 Caprin binding promotes, but USP10 binding inhibits, SG formation PMID:27022092 G3BP interacts with 40S ribosomal subunits through its RGG motif PMID:32302570 competitive binding of unconnected proteins disengages networks and prevents LLPS |
| GO:0005515 protein binding | IPI PMID:23279204 Both G3BP1 and G3BP2 contribute to stress granule formation. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005515 protein binding | IPI PMID:24845384 Deubiquitination and stabilization of T-bet by USP10. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005634 nucleus | IDA PMID:24845384 Deubiquitination and stabilization of T-bet by USP10. | ACCEPT | Summary: USP10 translocates to or acts in the nucleus in p53 and T-bet substrate-stability contexts. Reason: Accept as a supported location, while treating the specific nuclear signaling outputs as substrate/context-specific rather than the sole core function. Supporting Evidence: PMID:24845384 USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus PMID:24845384 Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet |
| GO:0016579 protein deubiquitination | IMP PMID:24845384 Deubiquitination and stabilization of T-bet by USP10. | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:24845384 USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus PMID:24845384 Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet |
| GO:0004843 cysteine-type deubiquitinase activity | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1Ξ² or LPS |
| GO:0006974 DNA damage response | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: USP10 participates in DNA-damage-linked signaling through p53 and NF-kappaB pathway substrate deubiquitination. Reason: Keep as non-core. The cited evidence supports DNA-damage-response modulation, but the direct molecular role is deubiquitination of signaling proteins. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1Ξ² or LPS |
| GO:0016579 protein deubiquitination | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1Ξ² or LPS |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: USP10 promotes TRAF6/NEMO deubiquitination in a TANK-MCPIP1 complex to dampen canonical NF-kappaB signaling. Reason: Keep as non-core. The signaling effect is supported but is substrate- and pathway-specific. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1Ξ² or LPS |
| GO:0071347 cellular response to interleukin-1 | IMP PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | KEEP AS NON CORE | Summary: USP10 participates in the IL-1beta/LPS NF-kappaB response through TRAF6 deubiquitination in the TANK-MCPIP1-USP10 complex. Reason: Keep as non-core. This is a supported immune-signaling response context, not the core DUB function itself. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 PMID:25861989 USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-ΞΊB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1Ξ² or LPS |
| GO:0005515 protein binding | IPI PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0032991 protein-containing complex | IDA PMID:25861989 TRAF Family Member-associated NF-ΞΊB Activator (TANK) Inhibit... | MARK AS OVER ANNOTATED | Summary: USP10 participates in a TANK-MCPIP1-USP10 complex, but GO:0032991 is too generic to be an informative gene-level annotation. Reason: Mark as over-annotated. The evidence supports a specific complex context for NF-kappaB signaling, not the broad term protein-containing complex. Supporting Evidence: PMID:25861989 TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6781779 | ACCEPT | Summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and substrate regulation. Reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 regulation and ribosome-quality-control evidence are consistent with this assignment. Supporting Evidence: Reactome:R-HSA-6781779 USP13 can deubiquitinate USP10, an essential regulator of TP53 stability |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6782106 | ACCEPT | Summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and substrate regulation. Reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 regulation and ribosome-quality-control evidence are consistent with this assignment. Supporting Evidence: Reactome:R-HSA-6782106 USP10 deubiquitinates CFTR in early endosomes thereby enhancing its endocytic recycling |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: The RNA-binding annotations come from broad high-throughput mRNA-bound-proteome studies and do not establish RNA binding as an informative USP10 function. Reason: Mark as over-annotated. USP10 has G3BP/40S/stress-granule contexts, but the stronger gene-specific evidence supports DUB and ribosome-quality-control roles rather than RNA binding as a core MF. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: The RNA-binding annotations come from broad high-throughput mRNA-bound-proteome studies and do not establish RNA binding as an informative USP10 function. Reason: Mark as over-annotated. USP10 has G3BP/40S/stress-granule contexts, but the stronger gene-specific evidence supports DUB and ribosome-quality-control roles rather than RNA binding as a core MF. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5653766 | ACCEPT | Summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 deubiquitination Reactome contexts. Reason: Accept as a nuclear subcompartment location for substrate-specific USP10 activities. Supporting Evidence: Reactome:R-HSA-5653766 Ubiquitin protease USP10 binds doubly ISGylated and monoubiquitinated PCNA Reactome:R-HSA-5653770 USP10 acts as a ubiquitin protease to remove ubiquitin from lysine K164 residue of doubly ISGylated PCNA Reactome:R-HSA-5653770 Deubiquitination of PCNA by USP10 causes dissociation of Y family DNA damage bypass polymerases |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5653770 | ACCEPT | Summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 deubiquitination Reactome contexts. Reason: Accept as a nuclear subcompartment location for substrate-specific USP10 activities. Supporting Evidence: Reactome:R-HSA-5653766 Ubiquitin protease USP10 binds doubly ISGylated and monoubiquitinated PCNA Reactome:R-HSA-5653770 USP10 acts as a ubiquitin protease to remove ubiquitin from lysine K164 residue of doubly ISGylated PCNA Reactome:R-HSA-5653770 Deubiquitination of PCNA by USP10 causes dissociation of Y family DNA damage bypass polymerases |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689973 | ACCEPT | Summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 deubiquitination Reactome contexts. Reason: Accept as a nuclear subcompartment location for substrate-specific USP10 activities. Supporting Evidence: Reactome:R-HSA-5689973 USP10 specifically deubiquitinate p53 and not MDM2 |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:21962518 Beclin1 controls the levels of p53 by regulating the deubiqu... | MODIFY | Summary: The cited Beclin1/spautin-1 study supports ubiquitin-specific peptidase activity, not a generic cysteine-type endopeptidase function. Reason: Modify to the more specific and biologically correct cysteine-type deubiquitinase activity term. Proposed replacements: cysteine-type deubiquitinase activity Supporting Evidence: PMID:21962518 two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:21962518 Beclin1 controls the levels of p53 by regulating the deubiqu... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:21962518 two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes |
| GO:0005515 protein binding | IPI PMID:21962518 Beclin1 controls the levels of p53 by regulating the deubiqu... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0010506 regulation of autophagy | IDA PMID:21962518 Beclin1 controls the levels of p53 by regulating the deubiqu... | KEEP AS NON CORE | Summary: USP10 regulates autophagy through Beclin1/Vps34 complexes and LC3B deubiquitination, but this is one substrate pathway of the broader DUB function. Reason: Keep as non-core. The process is well supported and relevant to the PN ATG8 context, but the molecular function should remain protein deubiquitination rather than a generic autophagy-regulator identity. Supporting Evidence: PMID:21962518 two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes PMID:33577797 LC3B ubiquitination is reversed by the action of the deubiquitinating enzyme USP10 PMID:33577797 LC3B and autophagic activity are controlled through cycles of LC3B ubiquitination and deubiquitination |
| GO:0002039 p53 binding | IPI PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | KEEP AS NON CORE | Summary: USP10 binds p53 as part of its p53 deubiquitination/stabilization pathway. Reason: Keep as non-core. p53 binding is substrate-specific and informative, but USP10 core function is catalytic deubiquitination. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0004843 cysteine-type deubiquitinase activity | IMP PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
| GO:0004843 cysteine-type deubiquitinase activity | IDA PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | ACCEPT | Summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the core catalytic activity even though individual papers test different substrates. Reason: Accept as the core molecular function. USP10 repeatedly removes ubiquitin from protein substrates including p53, CFTR, LC3B, TRAF6/NEMO contexts, and 40S ribosomal proteins. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005515 protein binding | IPI PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for USP10 and obscures more specific substrate/context annotations. Reason: Mark as over-annotated. Supported specific interactions include p53 binding, CFTR/transporter binding, G3BP stress-granule regulation, and substrate-specific deubiquitination; GO:0005515 should not be retained as a functional conclusion. |
| GO:0005634 nucleus | IDA PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | ACCEPT | Summary: USP10 translocates to or acts in the nucleus in p53 and T-bet substrate-stability contexts. Reason: Accept as a supported location, while treating the specific nuclear signaling outputs as substrate/context-specific rather than the sole core function. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005737 cytoplasm | IDA PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | ACCEPT | Summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts occur in the cytoplasm. Reason: Accept as a supported cellular location for USP10 deubiquitination, including p53 homeostasis, RQC, and immune-signaling substrates. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0005769 early endosome | IDA PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | ACCEPT | Summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and supports endocytic recycling. Reason: Accept as a supported active compartment for a direct USP10 substrate context. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
| GO:0016579 protein deubiquitination | IMP PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
| GO:0016579 protein deubiquitination | IDA PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | ACCEPT | Summary: Protein deubiquitination is the broad biological process that best summarizes USP10 catalytic action across multiple substrates. Reason: Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IMP PMID:20096447 USP10 regulates p53 localization and stability by deubiquiti... | KEEP AS NON CORE | Summary: USP10 activates p53 signaling after DNA damage by deubiquitinating/stabilizing p53 and translocating to the nucleus. Reason: Keep as non-core. The annotation is supported but represents a substrate-specific signaling outcome of USP10 DUB activity. Supporting Evidence: PMID:20096447 USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53 PMID:20096447 After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53 |
| GO:0044325 transmembrane transporter binding | IDA PMID:19398555 The deubiquitinating enzyme USP10 regulates the post-endocyt... | KEEP AS NON CORE | Summary: USP10 binds/regulates the transmembrane transporter CFTR in early endosomes. Reason: Keep as non-core. The annotation reflects a supported CFTR substrate context, not broad transporter-binding specificity. Supporting Evidence: PMID:19398555 USP10 is located in early endosomes and regulates the deubiquitination of CFTR PMID:19398555 facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Should USP10 and UCHL1 be annotated to a shared ATG8-family protein deubiquitination term for LC3/ATG8 substrate deubiquitination?
Suggested experts: GO autophagy editors, Juan S. Bonifacino, Ai Yamamoto
Q: Should 40S ribosomal protein deubiquitination during ribosome quality control be represented as a substrate-specific child of monoubiquitinated protein deubiquitination?
Suggested experts: Eric J. Bennett, Judith Frydman, GO proteostasis editors
Q: Which USP10 substrate contexts should remain non-core gene-level annotations versus annotation extensions on the core deubiquitinase activity?
Suggested experts: GO ubiquitin editors, GO-CAM editors
Experiment: Map endogenous LC3A/LC3B/LC3C ubiquitination sites in USP10 knockout and catalytic-rescue cells, then test whether catalytically inactive USP10 fails to restore LC3 abundance and autophagy flux.
Hypothesis: USP10 directly deubiquitinates LC3-family ATG8 proteins to preserve LC3 abundance and stress-induced autophagy.
Type: substrate mapping and catalytic rescue assay
Experiment: Use ribosome profiling, ribosomal-protein ubiquitinomics, and 40S turnover assays in USP10 catalytic mutants to separate elongation RQC from initiation RQC substrates.
Hypothesis: USP10 rescues distinct classes of ubiquitinated 40S subunits by removing substrate-specific mono-ubiquitin marks from RPS2/RPS3/RPS10.
Type: ribosome quality-control ubiquitinomics
Experiment: Build substrate-specific USP10 GO-CAM models for p53, CFTR, LC3B, TRAF6/NEMO, MAVS, and 40S ribosomal proteins and compare which contexts are conserved across cell types.
Hypothesis: Most USP10 biological-process annotations are substrate-context outputs of a single core DUB activity rather than independent core functions.
Type: curation-focused comparative substrate model
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)