{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9Y4E8","secondaryAccessions":["Q08AL5","Q9H8G9","Q9HCA6","Q9UNP0","Q9Y5B5"],"uniProtkbId":"UBP15_HUMAN","entryAudit":{"firstPublicDate":"2000-12-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-02-12","entryVersion":229,"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":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Ubiquitin carboxyl-terminal hydrolase 15"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10444327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16005295"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21947082"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22344298"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24852371"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27368102"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33093067"}],"value":"3.4.19.12"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10444327"}],"value":"Deubiquitinating enzyme 15"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10444327"}],"value":"Ubiquitin thioesterase 15"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10444327"}],"value":"Ubiquitin-specific-processing protease 15"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.9"}],"value":"Unph-2"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.1"}],"value":"Unph4"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10444327"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:12613"}],"value":"USP15"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9628581"}],"value":"KIAA0529"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16005295"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17318178"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19576224"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19826004"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21947082"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22344298"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24526689"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24852371"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27368102"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33093067"}],"value":"Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004, PubMed:21947082, PubMed:22344298, PubMed:24852371). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9 (PubMed:33093067)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19553310"}],"value":"(Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway"}],"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":"10444327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16005295"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21947082"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22344298"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27368102"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33093067"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16005295"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21750715"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21947082"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22001210"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22344298"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24526689"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24852371"}],"value":"A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (PubMed:22001210). Identified in a complex with the COP9 signalosome complex (CSN) (PubMed:16005295). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct (PubMed:21947082). Forms a complex with SMURF2 and SMAD7 (PubMed:22344298). Interacts with TGFBR1 (PubMed:22344298). Interacts with SART3; the interaction is direct (PubMed:24526689). May interact with RNF20 and RNF40 (PubMed:24526689). May interact with PRKN (PubMed:24852371). Interacts with INCA1 (PubMed:21750715)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19553310"}],"value":"(Microbial infection) Interacts with human papillomavirus type 16 protein 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