Existing Annotations Review

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-κB 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-κB 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-κB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS
GO:0006974 DNA damage response	IMP PMID:25861989 TRAF Family Member-associated NF-κB 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-κB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS
GO:0016579 protein deubiquitination	IMP PMID:25861989 TRAF Family Member-associated NF-κB 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-κB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS
GO:0043124 negative regulation of canonical NF-kappaB signal transduction	IMP PMID:25861989 TRAF Family Member-associated NF-κB 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-κB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS
GO:0071347 cellular response to interleukin-1	IMP PMID:25861989 TRAF Family Member-associated NF-κB 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-κB activation upon DNA damage PMID:25861989 TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS
GO:0005515 protein binding	IPI PMID:25861989 TRAF Family Member-associated NF-κB 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-κB 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

Core Functions

USP10 is a ubiquitin-specific cysteine deubiquitinase that removes ubiquitin from protein substrates. This broad catalytic function underlies its p53, CFTR, LC3B/Beclin1, NF-kappaB, MAVS, and ribosome-quality-control activities.

Molecular Function:

cysteine-type deubiquitinase activity

Directly Involved In:

protein deubiquitination monoubiquitinated protein deubiquitination rescue of stalled cytosolic ribosome

Cellular Locations:

cytoplasm cytosol cytosolic ribosome nucleus nucleoplasm early endosome

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
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
PMID:33577797
LC3B ubiquitination is reversed by the action of the deubiquitinating enzyme USP10

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:19398555

The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells.

PMID:19615732

Defining the human deubiquitinating enzyme interaction landscape.

PMID:20096447

USP10 regulates p53 localization and stability by deubiquitinating p53.

PMID:21455491

A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.

PMID:21962518

Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:22681889

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.

PMID:23279204

Both G3BP1 and G3BP2 contribute to stress granule formation.

PMID:24270572

USP10 inhibits genotoxic NF-κB activation by MCPIP1-facilitated deubiquitination of NEMO.

PMID:24845384

Deubiquitination and stabilization of T-bet by USP10.

PMID:24981860

Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25861989

TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase.

PMID:27022092

G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits.

PMID:29892012

An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:31981475

The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiquitinated 40S Subunits of Ribosomes Stalled in Translation from Lysosomal Degradation.

PMID:32011234

Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32302570

Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33495715

SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble stress granules and facilitate viral production.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34348161

The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation.

PMID:34469731

iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation.

PMID:34799561

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities.

PMID:34901782

SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenuates stress granules to impair host stress response.

PMID:35156780

CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:36012204

Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

PMID:36279435

Yin and yang regulation of stress granules by Caprin-1.

PMID:37023208

Immune evasion strategy involving propionylation by the KSHV interferon regulatory factor 1 (vIRF1).

PMID:37582970

MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Reactome:R-HSA-110313

Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template

Reactome:R-HSA-5653766

USP10 binds monoUb:K164,ISG:K164,ISG:K168-PCNA

Reactome:R-HSA-5653770

USP10 deubiquitinates monoUb:K164,ISG:K164,ISG:K168-PCNA

Reactome:R-HSA-5688426

Deubiquitination

Reactome:R-HSA-5689973

USP10,USP24,USP42 deubiquitinate TP53

Reactome:R-HSA-6781779

USP13 deubiquitinates BECN1,USP10

Reactome:R-HSA-6782106

USP10 deubiquitinates SNX3, CFTR

PMID:33577797

The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity.

Suggested Experiments

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

📚 Additional Documentation

Notes

(USP10-notes.md)

USP10 notes

Review started from just fetch-gene human USP10. The proteostasis network places USP10 in ATG8/LC3 deubiquitination, ribosome-associated quality control, and USP-family deubiquitinase contexts.

Falcon deep research was requested with just deep-research-falcon human USP10. The provider returned a 503 retry and timed out after 600 seconds, so no usable USP10-deep-research-falcon.md was generated. The review below is based on cached UniProt/GOA/Reactome/publication evidence and the PMID-resolved PN LC3B source.

USP10 is a ubiquitin-specific cysteine deubiquitinase. UniProt names it "Ubiquitin carboxyl-terminal hydrolase 10" and lists EC 3.4.19.12; multiple experimental publications support catalytic deubiquitinase activity. A general Reactome entry states that "Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways" [Reactome:R-HSA-5688426 "Deubiquitination"], while substrate-specific papers show USP10 removing ubiquitin from p53, CFTR, ribosomal proteins, and LC3B.

The p53 axis is a well-supported but substrate/context-specific USP10 function. Yuan et al. report that "USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53" and that after DNA damage "a fraction of USP10 translocates to the nucleus to activate p53" PMID:20096447. This supports cysteine-type deubiquitinase activity, protein deubiquitination, p53 binding, cytoplasm/nucleus localization, and p53-class DNA damage signaling, but the core molecular function remains DUB activity rather than generic DNA damage response.

USP10 has a direct early-endosome/channel trafficking substrate in CFTR. Bomberger et al. found that "USP10 is located in early endosomes and regulates the deubiquitination of CFTR" and that knockdown increased ubiquitinated CFTR, lysosomal degradation, and decreased chloride secretion PMID:19398555. The same paper states that USP10 facilitates "the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR" PMID:19398555. This supports early endosome localization and a specific transporter-binding/substrate context, but not a broad transporter function.

Autophagy regulation is supported through Beclin1 and LC3B substrates. Liu et al. report that spautin-1 inhibits "two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes" and that "Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities" PMID:21962518. More directly for the PN ATG8 context, Jia et al. report that "LC3B ubiquitination is reversed by the action of the deubiquitinating enzyme USP10"; USP10 silencing reduces LC3B-I and LC3B-II through increased ubiquitination/proteasomal degradation, and "LC3B and autophagic activity are controlled through cycles of LC3B ubiquitination and deubiquitination" PMID:33577797. Current GO can capture this only as broad protein deubiquitination or regulation of autophagy; a more specific ATG8-family protein deubiquitination term would be useful.

USP10 has a direct ribosome-associated quality-control function on ubiquitinated 40S subunits. Meyer et al. report that "G3BP1-family-USP10 complexes are required for deubiquitination of RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed degradation" PMID:31981475. Garzia et al. similarly state that impeded ribosomes are tagged on the 40S subunit "for subsequent programmed degradation unless rescued by USP10" PMID:34348161. Garshott et al. identify "the deubiquitylating enzyme USP10 as the key" enzyme for uS3/uS5 ribosomal ubiquitylation and state that loss of USP10 causes enhanced uS3/uS5 ubiquitylation, while USP10 overexpression removes observable ribosomal ubiquitylation in an activity-dependent manner PMID:34469731. These support cytosolic ribosome, monoubiquitinated protein deubiquitination, and rescue of stalled cytosolic ribosome as direct proteostasis functions.

USP10 is linked to stress-granule regulation through G3BP binding rather than a broad catalytic autophagy mechanism. Kedersha et al. report that "Caprin binding promotes, but USP10 binding inhibits, SG formation" and that G3BP interacts with 40S subunits through its RGG motif PMID:27022092. Yang et al. model stress granule and P-body organization as RNA/protein networks in which "competitive binding of unconnected proteins disengages networks and prevents LLPS" PMID:32302570. These support negative regulation of stress granule assembly and molecular function inhibitor activity as non-core, context-specific roles. Generic protein binding should remain over-annotated.

The NF-kappaB/IL-1 annotations are also supported but non-core. Wang et al. show that TANK forms a complex with MCPIP1/ZC3H12A and USP10 and that this was essential for "USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-kappaB activation upon DNA damage" PMID:25861989. The same abstract reports that the TANK-MCPIP1-USP10 complex decreased TRAF6 ubiquitination in cells treated with IL-1beta or LPS and that USP10 depletion enhanced NF-kappaB activation PMID:25861989. This supports non-core negative regulation of canonical NF-kappaB signaling, cellular response to IL-1, protein complex participation, and DNA-damage-linked signaling.

Innate immune annotations should be handled carefully. The GOA-seeded annotation cites the KSHV vIRF1/SIRT6 paper, where vIRF1 blocks "SIRT6's interaction with ubiquitin-specific peptidase 10 (USP10)" leading to SIRT6 degradation PMID:37023208. That is indirect for USP10 as an innate immune effector. However, a separate MAVS paper provides direct USP10 immune evidence: "USP10 as a direct DUB that removes unanchored K63-linked polyubiquitin chains from MAVS" and attenuates RIG-I-mediated MAVS aggregation and type I interferon production PMID:37582970. I will keep innate immune response as a non-core regulatory context with this caveat rather than making it a core function.

The high-throughput RNA-binding annotations (PMID:22658674 and PMID:22681889) are broad RBP-atlas style evidence. USP10 has G3BP/40S/stress-granule contexts, but the current evidence does not make RNA binding a core USP10 molecular function. Treat RNA binding as non-core or over-annotated depending on validation consistency; do not use it as a core function.

Annotation stance:
- Core molecular function: cysteine-type deubiquitinase activity (GO:0004843), directly involved in protein deubiquitination (GO:0016579).
- Direct proteostasis processes to accept: monoubiquitinated protein deubiquitination (GO:0035520) and rescue of stalled cytosolic ribosome (GO:0072344), supported by 40S/RQC papers.
- Direct cellular locations/activity sites: cytoplasm/cytosol, nucleus/nucleoplasm for p53/Reactome contexts, early endosome for CFTR, and cytosolic ribosome for RQC.
- Non-core but supported contexts: regulation of autophagy (Beclin1/LC3B), p53-class DNA damage response, translesion synthesis/PCNA deubiquitination, stress-granule inhibition, NF-kappaB/IL-1 regulation, MAVS/RLR innate immune regulation, p53 binding, CFTR/transporter binding, RNA binding.
- Modify cysteine-type endopeptidase activity (GO:0004197) to cysteine-type deubiquitinase activity (GO:0004843).
- Mark generic protein binding (GO:0005515) as over-annotated; when meaningful, capture the specific substrate/context in notes and replacement questions rather than keeping a generic MF term.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording framed USP10's most direct roles in the Proteostasis Network as protein deubiquitination, rescue of ubiquitinated stalled 40S ribosomal subunits, and non-core regulation of autophagy/stress-granule signaling through LC3B, Beclin1, and G3BP contexts.

Pn Notes

(USP10-pn-notes.md)

USP10 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q14694
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/USP10/USP10-ai-review.yaml
AIGR review HTML: present - genes/human/USP10/USP10-ai-review.html
Gene notes: present - genes/human/USP10/USP10-notes.md
GOA TSV: present - genes/human/USP10/USP10-goa.tsv
UniProt record: present - genes/human/USP10/USP10-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/USP10.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/USP10.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 45; KEEP_AS_NON_CORE: 16; MARK_AS_OVER_ANNOTATED: 28; MODIFY: 1

PN Consistency Summary

Consistency: Consistent across all three branches. Notes, review, and PN agree on a core cysteine-type DUB (GO:0004843) acting on p53, CFTR, LC3B, and 40S ribosomal proteins, with RQC and ATG8 as direct substrate contexts. Review accepts the RQC story strongly (GO:0072344 rescue of stalled cytosolic ribosome, GO:0035520 monoubiquitinated protein deubiquitination, GO:0022626 cytosolic ribosome) and keeps autophagy/LC3B as KEEP_AS_NON_CORE.
PN story / NEW pressure: The RQC group's GO:0006515 (verified real, non-obsolete) is new_to_goa and the dossier rationale notes GO lacks a dedicated ribosome-associated-QC term. The review instead captures RQC via the more specific, already-curatable GO:0072344 + GO:0035520 (both in GOA, IDA-supported). So the function is captured at finer grain than the PN projection; GO:0006515 would be a defensible but broader add. Verdict: already captured (more specifically) — GO:0006515 is broader than the review's RQC terms.
Evidence alignment: PN RQC row has no titled reference; ALP cites PMID:33577797 (USP10 deubiquitinates LC3B) — present in review (non-core autophagy). UPS row cites "19734957/rev". Review's RQC evidence: PMID:31981475, 34348161, 34469731 (40S/iRQC) — richer than PN. Strong overlap on the LC3B paper.
Verdict: Consistent; RQC and ATG8 stories captured (RQC more specifically than the PN's GO:0006515, which is broader). No NEW term needed.

Full Consistency Review

UniProt: Q14694 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: TR Cytosolic translation|Ribosome-associated QC|Deubiquitination; ALP …|ATG8 homolog processing, direct|Deubiquitination of ATG8 homologs; UPS DUBs and UBL demodifiers|USP|Ataxin-2, C term|other ; PN-node mapping: RQC type→GO:0101005 deubiquitinase activity; RQC group→GO:0006515 protein QC for misfolded/incompletely synthesized proteins (new_to_goa); ALP type→GO:0016579 protein deubiquitination (already_in_goa); UPS group→GO:0101005.
Consistency: Consistent across all three branches. Notes, review, and PN agree on a core cysteine-type DUB (GO:0004843) acting on p53, CFTR, LC3B, and 40S ribosomal proteins, with RQC and ATG8 as direct substrate contexts. Review accepts the RQC story strongly (GO:0072344 rescue of stalled cytosolic ribosome, GO:0035520 monoubiquitinated protein deubiquitination, GO:0022626 cytosolic ribosome) and keeps autophagy/LC3B as KEEP_AS_NON_CORE.
PN story / NEW pressure: The RQC group's GO:0006515 (verified real, non-obsolete) is new_to_goa and the dossier rationale notes GO lacks a dedicated ribosome-associated-QC term. The review instead captures RQC via the more specific, already-curatable GO:0072344 + GO:0035520 (both in GOA, IDA-supported). So the function is captured at finer grain than the PN projection; GO:0006515 would be a defensible but broader add. Verdict: already captured (more specifically) — GO:0006515 is broader than the review's RQC terms.
Mapping strategy: USP10 supports the RQC node well. The PN-projected GO:0006515 is broader than the review's GO:0072344/GO:0035520 — a precedent-style "broader than review" case (cf. TOMM20/HSPA8). MF granularity note: PN projects GO:0101005 deubiquitinase activity while GOA/review use child GO:0004843; entailed_by_goa_closure is correct, no conflict. ALP→GO:0016579 matches.
Evidence alignment: PN RQC row has no titled reference; ALP cites PMID:33577797 (USP10 deubiquitinates LC3B) — present in review (non-core autophagy). UPS row cites "19734957/rev". Review's RQC evidence: PMID:31981475, 34348161, 34469731 (40S/iRQC) — richer than PN. Strong overlap on the LC3B paper.
Verdict: Consistent; RQC and ATG8 stories captured (RQC more specifically than the PN's GO:0006515, which is broader). No NEW term needed.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/USP10/USP10-ai-review.yaml
PN workbook rows: 3

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | Deubiquitination

UniProt: Q14694
In branches: TR, ALP, UPS
PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome-associated QC|Deubiquitination
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0101005 deubiquitinase activity]
  rationale: This PN RQC type denotes deubiquitinases acting in ribosome-associated quality control. Deubiquitinase activity is the shared molecular-function target.
- [group] Translation|Cytosolic translation|Ribosome-associated QC
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
  rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 2: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | ATG8 homolog processing, direct | Deubiquitination of ATG8 homologs

UniProt: Q14694
In branches: TR, ALP, UPS
Notes: Deubiquitinase that removes ubiquitin from LC3, thereby increasing autophagy.
PN references (titles):
- The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels and autophagic activity - ScienceDirect
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, direct|Deubiquitination of ATG8 homologs
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0016579 protein deubiquitination]
  rationale: This PN type denotes deubiquitination of ATG8-family proteins within the autophagy pathway. GO does not currently provide an ATG8-specific deubiquitination term, so the defensible target is the broader parent process protein deubiquitination.
- [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, direct
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Ubiquitin Proteasome System | DUBs and UBL demodifiers | USP | Ataxin-2, C term | other

UniProt: Q14694
In branches: TR, ALP, UPS
Signature domains: IPR028889
Auxiliary domains: IPR009818
PN references (titles):
- 19734957 / rev
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|DUBs and UBL demodifiers|USP|Ataxin-2, C term|other
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower active DUB family/domain subdivision already covered by the curated parent DUB-family mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|DUBs and UBL demodifiers|USP|Ataxin-2, C term
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower active DUB family/domain subdivision already covered by the curated parent DUB-family mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|DUBs and UBL demodifiers|USP
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0101005 deubiquitinase activity]
  rationale: This PN group is an active deubiquitinase family bucket. The shared molecular-function assertion is deubiquitinase activity.
- [class] Ubiquitin Proteasome System|DUBs and UBL demodifiers
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (4)

GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
GO:0101005 deubiquitinase activity | scope=ok_for_propagation_to_go | goa_status=entailed_by_goa_closure | from=Translation|Cytosolic translation|Ribosome-associated QC|Deubiquitination
GO:0016579 protein deubiquitination | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, direct|Deubiquitination of ATG8 homologs
GO:0101005 deubiquitinase activity | scope=ok_for_propagation_to_go | goa_status=entailed_by_goa_closure | from=Ubiquitin Proteasome System|DUBs and UBL demodifiers|USP

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q14694
gene_symbol: USP10
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q14694-1
- name: '2'
  id: Q14694-2
  sequence_note: VSP_038869
- name: '3'
  id: Q14694-3
  sequence_note: VSP_038868
existing_annotations:
- term:
    id: GO:0010506
    label: regulation of autophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: USP10 regulates autophagy through Beclin1/Vps34 complexes and LC3B 
      deubiquitination, but this is one substrate pathway of the broader DUB function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:21962518
    - PMID:33577797
    supported_by:
    - &id024
      reference_id: PMID:21962518
      supporting_text: two ubiquitin-specific peptidases, USP10 and USP13, that target 
        the Beclin1 subunit of Vps34 complexes
    - &id025
      reference_id: PMID:33577797
      supporting_text: LC3B ubiquitination is reversed by the action of the 
        deubiquitinating enzyme USP10
    - &id026
      reference_id: PMID:33577797
      supporting_text: LC3B and autophagic activity are controlled through cycles of 
        LC3B ubiquitination and deubiquitination
- term:
    id: GO:0030330
    label: DNA damage response, signal transduction by p53 class mediator
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: USP10 activates p53 signaling after DNA damage by 
      deubiquitinating/stabilizing p53 and translocating to the nucleus.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The annotation is supported but represents a 
      substrate-specific signaling outcome of USP10 DUB activity.
    additional_reference_ids:
    - PMID:20096447
    supported_by:
    - &id001
      reference_id: PMID:20096447
      supporting_text: USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates
        p53
    - &id002
      reference_id: PMID:20096447
      supporting_text: After DNA damage, USP10 is stabilized, and a fraction of USP10 
        translocates to the nucleus to activate p53
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and 
      supports endocytic recycling.
    action: ACCEPT
    reason: Accept as a supported active compartment for a direct USP10 substrate 
      context.
    additional_reference_ids:
    - PMID:19398555
    - Reactome:R-HSA-6782106
    supported_by:
    - &id003
      reference_id: PMID:19398555
      supporting_text: USP10 is located in early endosomes and regulates the 
        deubiquitination of CFTR
    - &id004
      reference_id: PMID:19398555
      supporting_text: facilitating the deubiquitination of CFTR in early endosomes and 
        thereby enhancing the endocytic recycling of CFTR
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - &id005
      reference_id: Reactome:R-HSA-5688426
      supporting_text: Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and 
        regulate Ub-mediated pathways
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: USP10 translocates to or acts in the nucleus in p53 and T-bet 
      substrate-stability contexts.
    action: ACCEPT
    reason: Accept as a supported location, while treating the specific nuclear 
      signaling outputs as substrate/context-specific rather than the sole core 
      function.
    additional_reference_ids:
    - PMID:20096447
    - PMID:24845384
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts 
      occur in the cytoplasm.
    action: ACCEPT
    reason: Accept as a supported cellular location for USP10 deubiquitination, 
      including p53 homeostasis, RQC, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    - PMID:37582970
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and 
      supports endocytic recycling.
    action: ACCEPT
    reason: Accept as a supported active compartment for a direct USP10 substrate 
      context.
    additional_reference_ids:
    - PMID:19398555
    - Reactome:R-HSA-6782106
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id005
    - *id001
    - *id003
    - &id006
      reference_id: PMID:31981475
      supporting_text: G3BP1-family-USP10 complexes are required for deubiquitination of
        RPS2, RPS3, and RPS10 to rescue modified 40S subunits from programmed 
        degradation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19615732
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21455491
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24270572
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24981860
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33495715
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34799561
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34901782
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:23279204
  qualifier: located_in
  review:
    summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts 
      occur in the cytoplasm.
    action: ACCEPT
    reason: Accept as a supported cellular location for USP10 deubiquitination, 
      including p53 homeostasis, RQC, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    - PMID:37582970
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IPI
  original_reference_id: PMID:31981475
  qualifier: located_in
  review:
    summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts 
      occur in the cytoplasm.
    action: ACCEPT
    reason: Accept as a supported cellular location for USP10 deubiquitination, 
      including p53 homeostasis, RQC, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    - PMID:37582970
    supported_by:
    - *id006
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IDA
  original_reference_id: PMID:34469731
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id006
    - &id007
      reference_id: PMID:34348161
      supporting_text: These impeded ribosomes are tagged by ubiquitin at their 40S 
        subunit for subsequent programmed degradation unless rescued by USP10
    - &id008
      reference_id: PMID:34469731
      supporting_text: USP10 as the deubiquitylating enzyme responsible for removing 
        ubiquitin from uS3 and uS5
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: NAS
  original_reference_id: PMID:34469731
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0062030
    label: negative regulation of stress granule assembly
  evidence_type: IDA
  original_reference_id: PMID:27022092
  qualifier: involved_in
  review:
    summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated
      condensate context.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. This is a supported stress-granule regulatory role but not
      the core catalytic DUB activity.
    additional_reference_ids:
    - PMID:27022092
    - PMID:32302570
    supported_by:
    - &id009
      reference_id: PMID:27022092
      supporting_text: Caprin binding promotes, but USP10 binding inhibits, SG formation
    - &id010
      reference_id: PMID:27022092
      supporting_text: G3BP interacts with 40S ribosomal subunits through its RGG motif
    - &id011
      reference_id: PMID:32302570
      supporting_text: competitive binding of unconnected proteins disengages networks 
        and prevents LLPS
- term:
    id: GO:0062030
    label: negative regulation of stress granule assembly
  evidence_type: NAS
  original_reference_id: PMID:27022092
  qualifier: involved_in
  review:
    summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated
      condensate context.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. This is a supported stress-granule regulatory role but not
      the core catalytic DUB activity.
    additional_reference_ids:
    - PMID:27022092
    - PMID:32302570
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 
      deubiquitination Reactome contexts.
    action: ACCEPT
    reason: Accept as a nuclear subcompartment location for substrate-specific USP10 
      activities.
    additional_reference_ids:
    - Reactome:R-HSA-5653766
    - Reactome:R-HSA-5653770
    - Reactome:R-HSA-5689973
    supported_by:
    - &id012
      reference_id: Reactome:R-HSA-5653766
      supporting_text: Ubiquitin protease USP10 binds doubly ISGylated and 
        monoubiquitinated PCNA
    - &id013
      reference_id: Reactome:R-HSA-5653770
      supporting_text: USP10 acts as a ubiquitin protease to remove ubiquitin from 
        lysine K164 residue of doubly ISGylated PCNA
    - &id014
      reference_id: Reactome:R-HSA-5653770
      supporting_text: Deubiquitination of PCNA by USP10 causes dissociation of Y family
        DNA damage bypass polymerases
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and 
      substrate regulation.
    action: ACCEPT
    reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 
      regulation and ribosome-quality-control evidence are consistent with this 
      assignment.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    supported_by:
    - *id001
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5688426
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id005
    - *id001
    - *id003
    - *id006
- term:
    id: GO:0019985
    label: translesion synthesis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-110313
  qualifier: involved_in
  review:
    summary: Reactome places USP10 in the PCNA deubiquitination step that 
      terminates/limits translesion synthesis.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. This is a specific nuclear DNA-damage-bypass substrate 
      context, not the defining USP10 function.
    additional_reference_ids:
    - Reactome:R-HSA-110313
    - Reactome:R-HSA-5653766
    - Reactome:R-HSA-5653770
    supported_by:
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5653770
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5689973
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - &id023
      reference_id: Reactome:R-HSA-5689973
      supporting_text: USP10 specifically deubiquitinate p53 and not MDM2
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6782106
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - &id022
      reference_id: Reactome:R-HSA-6782106
      supporting_text: USP10 deubiquitinates CFTR in early endosomes thereby enhancing 
        its endocytic recycling
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: EXP
  original_reference_id: PMID:32011234
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id005
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:37582970
  qualifier: located_in
  review:
    summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts 
      occur in the cytoplasm.
    action: ACCEPT
    reason: Accept as a supported cellular location for USP10 deubiquitination, 
      including p53 homeostasis, RQC, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    - PMID:37582970
    supported_by:
    - &id015
      reference_id: PMID:37582970
      supporting_text: USP10 as a direct DUB that removes unanchored K63-linked 
        polyubiquitin chains from MAVS
    - &id016
      reference_id: PMID:37582970
      supporting_text: USP10 attenuates RIG-I-mediated MAVS aggregation and the 
        production of type I interferon
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IDA
  original_reference_id: PMID:37023208
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:37582970
    supported_by:
    - *id015
    - *id016
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IDA
  original_reference_id: PMID:31981475
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IDA
  original_reference_id: PMID:34348161
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IDA
  original_reference_id: PMID:34469731
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:34348161
  qualifier: is_active_in
  review:
    summary: USP10 acts at cytosolic 40S ribosomal subunits during ribosome-associated 
      quality control.
    action: ACCEPT
    reason: Accept as an active site/context for the ribosomal deubiquitination 
      function.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:34469731
  qualifier: is_active_in
  review:
    summary: USP10 acts at cytosolic 40S ribosomal subunits during ribosome-associated 
      quality control.
    action: ACCEPT
    reason: Accept as an active site/context for the ribosomal deubiquitination 
      function.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0035520
    label: monoubiquitinated protein deubiquitination
  evidence_type: IDA
  original_reference_id: PMID:34348161
  qualifier: involved_in
  review:
    summary: USP10 directly removes monoubiquitin from 40S ribosomal proteins in 
      ribosome quality-control contexts.
    action: ACCEPT
    reason: Accept as a direct proteostasis function. RPS2/RPS3/RPS10 deubiquitination 
      rescues modified 40S subunits from degradation.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0035520
    label: monoubiquitinated protein deubiquitination
  evidence_type: IDA
  original_reference_id: PMID:34469731
  qualifier: involved_in
  review:
    summary: USP10 directly removes monoubiquitin from 40S ribosomal proteins in 
      ribosome quality-control contexts.
    action: ACCEPT
    reason: Accept as a direct proteostasis function. RPS2/RPS3/RPS10 deubiquitination 
      rescues modified 40S subunits from degradation.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:31981475
  qualifier: involved_in
  review:
    summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits 
      from programmed degradation.
    action: ACCEPT
    reason: Accept as a direct ribosome-associated quality-control role in the 
      proteostasis network.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:34348161
  qualifier: involved_in
  review:
    summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits 
      from programmed degradation.
    action: ACCEPT
    reason: Accept as a direct ribosome-associated quality-control role in the 
      proteostasis network.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:34469731
  qualifier: involved_in
  review:
    summary: USP10-containing G3BP complexes rescue ubiquitinated stalled 40S subunits 
      from programmed degradation.
    action: ACCEPT
    reason: Accept as a direct ribosome-associated quality-control role in the 
      proteostasis network.
    additional_reference_ids:
    - PMID:31981475
    - PMID:34348161
    - PMID:34469731
    supported_by:
    - *id006
    - *id007
    - *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27022092
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32302570
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36279435
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0062030
    label: negative regulation of stress granule assembly
  evidence_type: IDA
  original_reference_id: PMID:32302570
  qualifier: involved_in
  review:
    summary: USP10 binding to G3BP inhibits stress granule formation in a 40S-associated
      condensate context.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. This is a supported stress-granule regulatory role but not
      the core catalytic DUB activity.
    additional_reference_ids:
    - PMID:27022092
    - PMID:32302570
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0140678
    label: molecular function inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:27022092
  qualifier: enables
  review:
    summary: USP10 acts as an inhibitor in the G3BP stress-granule assembly network.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:27022092
    - PMID:32302570
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0140678
    label: molecular function inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:32302570
  qualifier: enables
  review:
    summary: USP10 acts as an inhibitor in the G3BP stress-granule assembly network.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:27022092
    - PMID:32302570
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23279204
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24845384
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:24845384
  qualifier: located_in
  review:
    summary: USP10 translocates to or acts in the nucleus in p53 and T-bet 
      substrate-stability contexts.
    action: ACCEPT
    reason: Accept as a supported location, while treating the specific nuclear 
      signaling outputs as substrate/context-specific rather than the sole core 
      function.
    additional_reference_ids:
    - PMID:20096447
    - PMID:24845384
    supported_by:
    - &id017
      reference_id: PMID:24845384
      supporting_text: USP10, a carboxyl-terminal ubiquitin-processing protease, could 
        interact with T-bet in the nucleus
    - &id018
      reference_id: PMID:24845384
      supporting_text: Overexpression of USP10 directly inhibited T-bet ubiquitination 
        and increased the expression of T-bet
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IMP
  original_reference_id: PMID:24845384
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id017
    - *id018
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IMP
  original_reference_id: PMID:25861989
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - &id019
      reference_id: PMID:25861989
      supporting_text: TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a 
        deubiquitinase, USP10
    - &id020
      reference_id: PMID:25861989
      supporting_text: USP10-dependent deubiquitination of TRAF6 and the resolution of 
        genotoxic NF-κB activation upon DNA damage
    - &id021
      reference_id: PMID:25861989
      supporting_text: TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in 
        cells treated with IL-1β or LPS
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IMP
  original_reference_id: PMID:25861989
  qualifier: involved_in
  review:
    summary: USP10 participates in DNA-damage-linked signaling through p53 and NF-kappaB
      pathway substrate deubiquitination.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The cited evidence supports DNA-damage-response 
      modulation, but the direct molecular role is deubiquitination of signaling 
      proteins.
    additional_reference_ids:
    - PMID:20096447
    - PMID:25861989
    supported_by:
    - *id019
    - *id020
    - *id021
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IMP
  original_reference_id: PMID:25861989
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id019
    - *id020
    - *id021
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:25861989
  qualifier: involved_in
  review:
    summary: USP10 promotes TRAF6/NEMO deubiquitination in a TANK-MCPIP1 complex to 
      dampen canonical NF-kappaB signaling.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The signaling effect is supported but is substrate- and 
      pathway-specific.
    additional_reference_ids:
    - PMID:25861989
    supported_by:
    - *id019
    - *id020
    - *id021
- term:
    id: GO:0071347
    label: cellular response to interleukin-1
  evidence_type: IMP
  original_reference_id: PMID:25861989
  qualifier: involved_in
  review:
    summary: USP10 participates in the IL-1beta/LPS NF-kappaB response through TRAF6 
      deubiquitination in the TANK-MCPIP1-USP10 complex.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. This is a supported immune-signaling response context, not
      the core DUB function itself.
    additional_reference_ids:
    - PMID:25861989
    supported_by:
    - *id019
    - *id020
    - *id021
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25861989
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:25861989
  qualifier: part_of
  review:
    summary: USP10 participates in a TANK-MCPIP1-USP10 complex, but GO:0032991 is too 
      generic to be an informative gene-level annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. The evidence supports a specific complex context for
      NF-kappaB signaling, not the broad term protein-containing complex.
    additional_reference_ids:
    - PMID:25861989
    supported_by:
    - *id019
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6781779
  qualifier: located_in
  review:
    summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and 
      substrate regulation.
    action: ACCEPT
    reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 
      regulation and ribosome-quality-control evidence are consistent with this 
      assignment.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    supported_by:
    - reference_id: Reactome:R-HSA-6781779
      supporting_text: USP13 can deubiquitinate USP10, an essential regulator of TP53 
        stability
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6782106
  qualifier: located_in
  review:
    summary: Cytosol is a supported compartment for USP10 deubiquitinase activity and 
      substrate regulation.
    action: ACCEPT
    reason: Accept as a supported cytosolic location for USP10 activity; cytosolic p53 
      regulation and ribosome-quality-control evidence are consistent with this 
      assignment.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    supported_by:
    - *id022
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5653766
  qualifier: located_in
  review:
    summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 
      deubiquitination Reactome contexts.
    action: ACCEPT
    reason: Accept as a nuclear subcompartment location for substrate-specific USP10 
      activities.
    additional_reference_ids:
    - Reactome:R-HSA-5653766
    - Reactome:R-HSA-5653770
    - Reactome:R-HSA-5689973
    supported_by:
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5653770
  qualifier: located_in
  review:
    summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 
      deubiquitination Reactome contexts.
    action: ACCEPT
    reason: Accept as a nuclear subcompartment location for substrate-specific USP10 
      activities.
    additional_reference_ids:
    - Reactome:R-HSA-5653766
    - Reactome:R-HSA-5653770
    - Reactome:R-HSA-5689973
    supported_by:
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5689973
  qualifier: located_in
  review:
    summary: Nucleoplasm is a supported location for USP10 in PCNA/TLS and TP53 
      deubiquitination Reactome contexts.
    action: ACCEPT
    reason: Accept as a nuclear subcompartment location for substrate-specific USP10 
      activities.
    additional_reference_ids:
    - Reactome:R-HSA-5653766
    - Reactome:R-HSA-5653770
    - Reactome:R-HSA-5689973
    supported_by:
    - *id023
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IMP
  original_reference_id: PMID:21962518
  qualifier: enables
  review:
    summary: The cited Beclin1/spautin-1 study supports ubiquitin-specific peptidase 
      activity, not a generic cysteine-type endopeptidase function.
    action: MODIFY
    reason: Modify to the more specific and biologically correct cysteine-type 
      deubiquitinase activity term.
    proposed_replacement_terms:
    - id: GO:0004843
      label: cysteine-type deubiquitinase activity
    additional_reference_ids:
    - PMID:21962518
    supported_by:
    - *id024
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IDA
  original_reference_id: PMID:21962518
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id024
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21962518
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0010506
    label: regulation of autophagy
  evidence_type: IDA
  original_reference_id: PMID:21962518
  qualifier: involved_in
  review:
    summary: USP10 regulates autophagy through Beclin1/Vps34 complexes and LC3B 
      deubiquitination, but this is one substrate pathway of the broader DUB function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:21962518
    - PMID:33577797
    supported_by:
    - *id024
    - *id025
    - *id026
- term:
    id: GO:0002039
    label: p53 binding
  evidence_type: IPI
  original_reference_id: PMID:20096447
  qualifier: enables
  review:
    summary: USP10 binds p53 as part of its p53 deubiquitination/stabilization pathway.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. p53 binding is substrate-specific and informative, but 
      USP10 core function is catalytic deubiquitination.
    additional_reference_ids:
    - PMID:20096447
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IMP
  original_reference_id: PMID:19398555
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  evidence_type: IDA
  original_reference_id: PMID:20096447
  qualifier: enables
  review:
    summary: USP10 is a ubiquitin-specific cysteine deubiquitinase; this MF captures the
      core catalytic activity even though individual papers test different substrates.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:34469731
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19398555
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for USP10 and obscures more 
      specific substrate/context annotations.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20096447
  qualifier: located_in
  review:
    summary: USP10 translocates to or acts in the nucleus in p53 and T-bet 
      substrate-stability contexts.
    action: ACCEPT
    reason: Accept as a supported location, while treating the specific nuclear 
      signaling outputs as substrate/context-specific rather than the sole core 
      function.
    additional_reference_ids:
    - PMID:20096447
    - PMID:24845384
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20096447
  qualifier: located_in
  review:
    summary: USP10 is a cytoplasmic/cytosolic DUB and several core substrate contexts 
      occur in the cytoplasm.
    action: ACCEPT
    reason: Accept as a supported cellular location for USP10 deubiquitination, 
      including p53 homeostasis, RQC, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:31981475
    - PMID:37582970
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:19398555
  qualifier: located_in
  review:
    summary: USP10 localizes to early endosomes where it deubiquitinates CFTR and 
      supports endocytic recycling.
    action: ACCEPT
    reason: Accept as a supported active compartment for a direct USP10 substrate 
      context.
    additional_reference_ids:
    - PMID:19398555
    - Reactome:R-HSA-6782106
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IMP
  original_reference_id: PMID:19398555
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0016579
    label: protein deubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20096447
  qualifier: involved_in
  review:
    summary: Protein deubiquitination is the broad biological process that best 
      summarizes USP10 catalytic action across multiple substrates.
    action: ACCEPT
    reason: Accept as core. Substrate-specific evidence supports deubiquitination of 
      p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
    additional_reference_ids:
    - PMID:20096447
    - PMID:19398555
    - PMID:31981475
    - PMID:33577797
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0030330
    label: DNA damage response, signal transduction by p53 class mediator
  evidence_type: IMP
  original_reference_id: PMID:20096447
  qualifier: involved_in
  review:
    summary: USP10 activates p53 signaling after DNA damage by 
      deubiquitinating/stabilizing p53 and translocating to the nucleus.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The annotation is supported but represents a 
      substrate-specific signaling outcome of USP10 DUB activity.
    additional_reference_ids:
    - PMID:20096447
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IDA
  original_reference_id: PMID:19398555
  qualifier: enables
  review:
    summary: USP10 binds/regulates the transmembrane transporter CFTR in early 
      endosomes.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The annotation reflects a supported CFTR substrate 
      context, not broad transporter-binding specificity.
    additional_reference_ids:
    - PMID:19398555
    - Reactome:R-HSA-6782106
    supported_by:
    - *id003
    - *id004
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location 
    vocabulary mapping, accompanied by conservative changes to GO terms applied by 
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19398555
  title: The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of 
    cystic fibrosis transmembrane conductance regulator in airway epithelial cells.
  findings: []
- id: PMID:19615732
  title: Defining the human deubiquitinating enzyme interaction landscape.
  findings: []
- id: PMID:20096447
  title: USP10 regulates p53 localization and stability by deubiquitinating p53.
  findings: []
- id: PMID:21455491
  title: A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic 
    system.
  findings: []
- id: PMID:21962518
  title: Beclin1 controls the levels of p53 by regulating the deubiquitination activity 
    of USP10 and USP13.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding 
    transcripts.
  findings: []
- id: PMID:23279204
  title: Both G3BP1 and G3BP2 contribute to stress granule formation.
  findings: []
- id: PMID:24270572
  title: USP10 inhibits genotoxic NF-κB activation by MCPIP1-facilitated 
    deubiquitination of NEMO.
  findings: []
- id: PMID:24845384
  title: Deubiquitination and stabilization of T-bet by USP10.
  findings: []
- id: PMID:24981860
  title: Human-chromatin-related protein interactions identify a demethylase complex 
    required for chromosome segregation.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25861989
  title: TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear
    Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination
    of TRAF6 Ligase.
  findings: []
- id: PMID:27022092
  title: G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate 
    with 40S subunits.
  findings: []
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations 
    for developmental disorders.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the 
    allele frequency spectrum in human populations.
  findings: []
- id: PMID:31981475
  title: The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiquitinated 40S 
    Subunits of Ribosomes Stalled in Translation from Lysosomal Degradation.
  findings: []
- id: PMID:32011234
  title: Distinct regulatory ribosomal ubiquitylation events are reversible and 
    hierarchically organized.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32302570
  title: Competing Protein-RNA Interaction Networks Control Multiphase Intracellular 
    Organization.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins 
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33495715
  title: SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble 
    stress granules and facilitate viral production.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human 
    interactome.
  findings: []
- id: PMID:34348161
  title: The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes 
    compromised in translation.
  findings: []
- id: PMID:34469731
  title: iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA 
    translation initiation.
  findings: []
- id: PMID:34799561
  title: Large scale discovery of coronavirus-host factor protein interaction motifs 
    reveals SARS-CoV-2 specific mechanisms and vulnerabilities.
  findings: []
- id: PMID:34901782
  title: SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenuates stress granules
    to impair host stress response.
  findings: []
- id: PMID:35156780
  title: CFTR interactome mapping using the mammalian membrane two-hybrid 
    high-throughput screening system.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment
    in Multiple SLC Transporters.
  findings: []
- id: PMID:36279435
  title: Yin and yang regulation of stress granules by Caprin-1.
  findings: []
- id: PMID:37023208
  title: Immune evasion strategy involving propionylation by the KSHV interferon 
    regulatory factor 1 (vIRF1).
  findings: []
- id: PMID:37582970
  title: MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the 
    RIG-I-MAVS signaling cascade.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: Reactome:R-HSA-110313
  title: Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA 
    template
  findings: []
- id: Reactome:R-HSA-5653766
  title: USP10 binds monoUb:K164,ISG:K164,ISG:K168-PCNA
  findings: []
- id: Reactome:R-HSA-5653770
  title: USP10 deubiquitinates monoUb:K164,ISG:K164,ISG:K168-PCNA
  findings: []
- id: Reactome:R-HSA-5688426
  title: Deubiquitination
  findings: []
- id: Reactome:R-HSA-5689973
  title: USP10,USP24,USP42 deubiquitinate TP53
  findings: []
- id: Reactome:R-HSA-6781779
  title: USP13 deubiquitinates BECN1,USP10
  findings: []
- id: Reactome:R-HSA-6782106
  title: USP10 deubiquitinates SNX3, CFTR
  findings: []
- id: PMID:33577797
  title: The ubiquitin isopeptidase USP10 deubiquitinates LC3B to increase LC3B levels 
    and autophagic activity.
  findings: []
core_functions:
- molecular_function:
    id: GO:0004843
    label: cysteine-type deubiquitinase activity
  description: USP10 is a ubiquitin-specific cysteine deubiquitinase that removes 
    ubiquitin from protein substrates. This broad catalytic function underlies its p53, 
    CFTR, LC3B/Beclin1, NF-kappaB, MAVS, and ribosome-quality-control activities.
  directly_involved_in:
  - id: GO:0016579
    label: protein deubiquitination
  - id: GO:0035520
    label: monoubiquitinated protein deubiquitination
  - id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005829
    label: cytosol
  - id: GO:0022626
    label: cytosolic ribosome
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0005769
    label: early endosome
  supported_by:
  - *id005
  - *id001
  - *id003
  - *id006
  - *id007
  - *id008
  - *id025
proposed_new_terms:
- proposed_name: ATG8-family protein deubiquitination
  proposed_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.
  proposed_parent:
    id: GO:0016579
    label: protein deubiquitination
  supported_by:
  - *id025
  - *id026
- proposed_name: 40S ribosomal protein deubiquitination during ribosome quality control
  proposed_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.
  proposed_parent:
    id: GO:0035520
    label: monoubiquitinated protein deubiquitination
  supported_by:
  - *id006
  - *id007
  - *id008
suggested_questions:
- question: Should USP10 and UCHL1 be annotated to a shared ATG8-family protein 
    deubiquitination term for LC3/ATG8 substrate deubiquitination?
  experts:
  - GO autophagy editors
  - Juan S. Bonifacino
  - Ai Yamamoto
- question: Should 40S ribosomal protein deubiquitination during ribosome quality 
    control be represented as a substrate-specific child of monoubiquitinated protein 
    deubiquitination?
  experts:
  - Eric J. Bennett
  - Judith Frydman
  - GO proteostasis editors
- question: Which USP10 substrate contexts should remain non-core gene-level annotations
    versus annotation extensions on the core deubiquitinase activity?
  experts:
  - GO ubiquitin editors
  - GO-CAM editors
suggested_experiments:
- description: 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.
  experiment_type: substrate mapping and catalytic rescue assay
  hypothesis: USP10 directly deubiquitinates LC3-family ATG8 proteins to preserve LC3 
    abundance and stress-induced autophagy.
- description: Use ribosome profiling, ribosomal-protein ubiquitinomics, and 40S 
    turnover assays in USP10 catalytic mutants to separate elongation RQC from 
    initiation RQC substrates.
  experiment_type: ribosome quality-control ubiquitinomics
  hypothesis: USP10 rescues distinct classes of ubiquitinated 40S subunits by removing 
    substrate-specific mono-ubiquitin marks from RPS2/RPS3/RPS10.
- description: 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.
  experiment_type: curation-focused comparative substrate model
  hypothesis: Most USP10 biological-process annotations are substrate-context outputs of
    a single core DUB activity rather than independent core functions.

USP10

Gene Description

Proposed New Ontology Terms

ATG8-family protein deubiquitination

40S ribosomal protein deubiquitination during ribosome quality control