{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9Y2K6","secondaryAccessions":["Q541F1","Q8IXQ1","Q96LG5","Q9UQN8","Q9UQP0"],"uniProtkbId":"UBP20_HUMAN","entryAudit":{"firstPublicDate":"2001-01-24","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2006-10-17","entryVersion":213,"sequenceVersion":2},"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 20"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26839314"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27801882"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29487085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32354117"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35063767"}],"value":"3.4.19.12"}]},"alternativeNames":[{"fullName":{"value":"Deubiquitinating enzyme 20"}},{"fullName":{"value":"Ubiquitin thioesterase 20"}},{"fullName":{"value":"Ubiquitin-specific-processing protease 20"}},{"fullName":{"value":"VHL-interacting deubiquitinating enzyme 2"},"shortNames":[{"value":"hVDU2"}]}]},"genes":[{"geneName":{"value":"USP20"},"synonyms":[{"value":"KIAA1003"},{"value":"LSFR3A"},{"value":"VDU2"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12056827"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12865408"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15776016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19424180"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26839314"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27801882"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29487085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32354117"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33792613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35063767"}],"value":"Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization (PubMed:27801882). Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1 (PubMed:29487085). Acts as a positive regulator for NF-kappa-B activation by TNF through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability (PubMed:32354117). Acts as a regulator of G protein-coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2) (PubMed:19424180). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2 (PubMed:19424180). This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability (PubMed:35063767). Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol (PubMed:33792613)"}],"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":"26839314"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27801882"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29487085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32354117"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35063767"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12056827"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12865408"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15776016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19424180"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23166351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23486064"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27801882"}],"value":"Interacts with VHL, leading to its ubiquitination and subsequent degradation (PubMed:12056827). Interacts with CCP110 (PubMed:23486064). Interacts with DIO2 (PubMed:12865408). Interacts with HIF1A (PubMed:15776016). Interacts with ADRB2 (PubMed:19424180, PubMed:23166351). Interacts with USP18 (PubMed:27801882)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"O95994","geneName":"AGR2","intActId":"EBI-712648"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"P13196","geneName":"ALAS1","intActId":"EBI-3905054"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q99767","geneName":"APBA2","intActId":"EBI-81711"},"numberOfExperiments":17,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q99767-2","geneName":"APBA2","intActId":"EBI-12218351"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q03989","geneName":"ARID5A","intActId":"EBI-948603"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"P50553","geneName":"ASCL1","intActId":"EBI-957042"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"O95670","geneName":"ATP6V1G2","intActId":"EBI-348290"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q7L4P6","geneName":"BEND5","intActId":"EBI-724373"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q8N7W2-2","geneName":"BEND7","intActId":"EBI-10181188"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"P55201-2","geneName":"BRPF1","intActId":"EBI-12065306"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q9BXJ5","geneName":"C1QTNF2","intActId":"EBI-2817707"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q96S94-5","geneName":"CCNL2","intActId":"EBI-12024864"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"O14519","geneName":"CDK2AP1","intActId":"EBI-1052532"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q8TEP8","geneName":"CEP192","intActId":"EBI-2339778"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"P78358","geneName":"CTAG1B","intActId":"EBI-1188472"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q9H0I2","geneName":"ENKD1","intActId":"EBI-744099"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q99814","geneName":"EPAS1","intActId":"EBI-447470"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q969F0","geneName":"FATE1","intActId":"EBI-743099"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q9C0B1-2","geneName":"FTO","intActId":"EBI-18138793"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"O60478","geneName":"GPR137B","intActId":"EBI-18945347"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q96D09","geneName":"GPRASP2","intActId":"EBI-473189"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"Q6PI77","geneName":"GPRASP3","intActId":"EBI-11519926"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y2K6","intActId":"EBI-2511991"},"interactantTwo":{"uniProtKBAccession":"P61296-2","geneName":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