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.