{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q13107","secondaryAccessions":["A8K6Y0","C9IY91","O43452","O43453","Q08AK8"],"uniProtkbId":"UBP4_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2006-10-17","entryVersion":216,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Ubiquitin carboxyl-terminal hydrolase 4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16339847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22347420"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25404403"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28604766"}],"value":"3.4.19.12"}]},"alternativeNames":[{"fullName":{"value":"Deubiquitinating enzyme 4"}},{"fullName":{"value":"Ubiquitin thioesterase 4"}},{"fullName":{"value":"Ubiquitin-specific-processing protease 4"}},{"fullName":{"value":"Ubiquitous nuclear protein homolog"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"30514904"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:12627"}],"value":"USP4"},"synonyms":[{"value":"UNP"},{"value":"UNPH"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16339847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22347420"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25404403"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28604766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30514904"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39589880"}],"value":"Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16339847, PubMed:16472766, PubMed:20595234, PubMed:22347420, PubMed:25404403, PubMed:28604766, PubMed:30514904). Deubiquitinates PDPK1 (PubMed:22347420). Deubiquitinates TRIM21 (PubMed:16316627). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847). Deubiquitinates HAS2 (PubMed:28604766). Deubiquitinates MAVs leading to maintain MAVS protein stability, resulting in increased production of type I interferons (IFN-I) and enhanced antiviral innate immune responses against viral infections (PubMed:39589880). Deubiquitinates RHEB in response to EGF signaling, promoting mTORC1 signaling (PubMed:30514904). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234). May also play a role in the regulation of quality control in the ER (PubMed:16339847)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).","ecNumber":"3.4.19.12","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16339847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22347420"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25404403"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28604766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30514904"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25404403"}],"value":"The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":0.15,"unit":"uM","substrate":"ubiquitin-rhodamine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25404403"}]}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P35123"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11571652"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16339847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"}],"value":"Interacts with RB1 (both dephosphorylated and hypophosphorylated forms) (PubMed:11571652). Interacts with RBL1 and RBL2 (By similarity). Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct (PubMed:16339847). Interacts with SART3; recruits USP4 to its substrate PRPF3 (PubMed:20595234)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q13107","intActId":"EBI-723290"},"interactantTwo":{"uniProtKBAccession":"P29274","geneName":"ADORA2A","intActId":"EBI-2902702"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13107","intActId":"EBI-723290"},"interactantTwo":{"uniProtKBAccession":"Q7Z6Z7","geneName":"HUWE1","intActId":"EBI-625934"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13107","intActId":"EBI-723290"},"interactantTwo":{"uniProtKBAccession":"Q13546","geneName":"RIPK1","intActId":"EBI-358507"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13107","intActId":"EBI-723290"},"interactantTwo":{"uniProtKBAccession":"Q13107","geneName":"USP4","intActId":"EBI-723290"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13107-1","intActId":"EBI-723305"},"interactantTwo":{"uniProtKBAccession":"P19474","geneName":"TRIM21","intActId":"EBI-81290"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"}],"value":"Shuttles between the nucleus and cytoplasm. 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The relative amounts found in the nucleus and cytoplasm vary according to the cell type"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16316627"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20595234"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"UnpEL"}],"isoformIds":["Q13107-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"UnpES"}],"isoformIds":["Q13107-2"],"sequenceIds":["VSP_005258"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q13107-3"],"sequenceIds":["VSP_044814","VSP_044815"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16339847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7784062"}],"value":"Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). 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The cristal structure in the paper was correct and was republished later (PubMed:25404403)"}],"commentType":"CAUTION"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":963,"modifier":"EXACT"}},"description":"Ubiquitin carboxyl-terminal hydrolase 4","featureId":"PRO_0000080621"},{"type":"Domain","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":122,"modifier":"EXACT"}},"description":"DUSP","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00613"}]},{"type":"Domain","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":226,"modifier":"EXACT"}},"description":"Ubiquitin-like 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