ID UBP20_HUMAN Reviewed; 914 AA. AC Q9Y2K6; Q541F1; Q8IXQ1; Q96LG5; Q9UQN8; Q9UQP0; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 203. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 20; DE EC=3.4.19.12 {ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:35063767}; DE AltName: Full=Deubiquitinating enzyme 20; DE AltName: Full=Ubiquitin thioesterase 20; DE AltName: Full=Ubiquitin-specific-processing protease 20; DE AltName: Full=VHL-interacting deubiquitinating enzyme 2; DE Short=hVDU2; GN Name=USP20; Synonyms=KIAA1003, LSFR3A, VDU2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, UBIQUITINATION, AND INTERACTION WITH RP VHL. RX PubMed=12056827; DOI=10.1016/s0006-291x(02)00534-x; RA Li Z., Wang D., Na X., Schoen S.R., Messing E.M., Wu G.; RT "Identification of a deubiquitinating enzyme subfamily as substrates of the RT von Hippel-Lindau tumor suppressor."; RL Biochem. Biophys. Res. Commun. 294:700-709(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-803 AND 839-914. RX PubMed=10369878; DOI=10.1093/hmg/8.7.1313; RA Gilley J., Fried M.; RT "Extensive gene order differences within regions of conserved synteny RT between the Fugu and human genomes: implications for chromosomal evolution RT and the cloning of disease genes."; RL Hum. Mol. Genet. 8:1313-1320(1999). RN [7] RP FUNCTION, INTERACTION WITH DIO2, AND SUBCELLULAR LOCATION. RX PubMed=12865408; DOI=10.1172/jci18348; RA Curcio-Morelli C., Zavacki A.M., Christofollete M., Gereben B., RA de Freitas B.C., Harney J.W., Li Z., Wu G., Bianco A.C.; RT "Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau RT protein-interacting deubiquitinating enzymes regulates thyroid hormone RT activation."; RL J. Clin. Invest. 112:189-196(2003). RN [8] RP FUNCTION, AND INTERACTION WITH HIF1A. RX PubMed=15776016; DOI=10.1038/sj.embor.7400377; RA Li Z., Wang D., Messing E.M., Wu G.; RT "VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and RT stabilizes HIF-1alpha."; RL EMBO Rep. 6:373-378(2005). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-134, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-377 AND SER-413, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP FUNCTION, INTERACTION WITH ADRB2, AND MUTAGENESIS OF CYS-154 AND HIS-643. RX PubMed=19424180; DOI=10.1038/emboj.2009.128; RA Berthouze M., Venkataramanan V., Li Y., Shenoy S.K.; RT "The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor RT recycling and resensitization."; RL EMBO J. 28:1684-1696(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-134, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [14] RP INTERACTION WITH ADRB2. RX PubMed=23166351; DOI=10.1083/jcb.201208192; RA Han S.O., Xiao K., Kim J., Wu J.H., Wisler J.W., Nakamura N., RA Freedman N.J., Shenoy S.K.; RT "MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound RT beta(2)-adrenergic receptors."; RL J. Cell Biol. 199:817-830(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-132; SER-134; RP SER-305; THR-377; SER-408 AND SER-413, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CCP110. RX PubMed=23486064; DOI=10.1038/nature11941; RA Li J., D'Angiolella V., Seeley E.S., Kim S., Kobayashi T., Fu W., RA Campos E.I., Pagano M., Dynlacht B.D.; RT "USP33 regulates centrosome biogenesis via deubiquitination of the RT centriolar protein CP110."; RL Nature 495:255-259(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-134, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=26839314; DOI=10.1074/jbc.m115.687129; RA Jean-Charles P.Y., Zhang L., Wu J.H., Han S.O., Brian L., Freedman N.J., RA Shenoy S.K.; RT "Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of beta- RT Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor kappaB (NFkappaB) RT Activation."; RL J. Biol. Chem. 291:7450-7464(2016). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH USP18. RX PubMed=27801882; DOI=10.1038/cr.2016.125; RA Zhang M., Zhang M.X., Zhang Q., Zhu G.F., Yuan L., Zhang D.E., Zhu Q., RA Yao J., Shu H.B., Zhong B.; RT "USP18 recruits USP20 to promote innate antiviral response through RT deubiquitinating STING/MITA."; RL Cell Res. 26:1302-1319(2016). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-154 AND HIS-643. RX PubMed=29487085; DOI=10.15252/embr.201744378; RA Kim J.H., Seo D., Kim S.J., Choi D.W., Park J.S., Ha J., Choi J., Lee J.H., RA Jung S.M., Seo K.W., Lee E.W., Lee Y.S., Cheong H., Choi C.Y., Park S.H.; RT "The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy RT initiation."; RL EMBO Rep. 19:0-0(2018). RN [21] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32354117; DOI=10.3390/ijms21093116; RA Ha J., Kim M., Seo D., Park J.S., Lee J., Lee J., Park S.H.; RT "The Deubiquitinating Enzyme USP20 Regulates the TNFalpha-Induced NF-kappaB RT Signaling Pathway through Stabilization of p62."; RL Int. J. Mol. Sci. 21:0-0(2020). RN [22] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=33792613; DOI=10.1083/jcb.202004086; RA Culver J.A., Mariappan M.; RT "Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane RT proteins."; RL J. Cell Biol. 220:0-0(2021). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-154. RX PubMed=35063767; DOI=10.1016/j.bbrc.2022.01.019; RA Feng J., Liu P., Li X., Zhang D., Lin H., Hou Z., Guo C., Niu Y., Dai B., RA Wang O., Qi M., Wang H., Zhou H.; RT "The deubiquitinating enzyme USP20 regulates the stability of the MCL1 RT protein."; RL Biochem. Biophys. Res. Commun. 593:122-128(2022). CC -!- FUNCTION: Deubiquitinating enzyme that plays a role in many cellular CC processes including autophagy, cellular antiviral response or membrane CC protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4- CC mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 CC and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes CC cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'- CC linked ubiquitination of STING1 leading to its stabilization CC (PubMed:27801882). Plays an essential role in autophagy induction by CC regulating the ULK1 stability through deubiquitination of ULK1 CC (PubMed:29487085). Acts as a positive regulator for NF-kappa-B CC activation by TNF-alpha through deubiquitinating 'Lys-48'-linked CC polyubiquitination of SQSTM1, leading to its increased stability CC (PubMed:32354117). Acts as a regulator of G-protein coupled receptor CC (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic CC receptor (ADRB2)(PubMed:19424180). Plays a central role in ADRB2 CC recycling and resensitization after prolonged agonist stimulation by CC constitutively binding ADRB2, mediating deubiquitination of ADRB2 and CC inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is CC probably transferred to the translocated beta-arrestins, possibly CC leading to beta-arrestins deubiquitination and disengagement from ADRB2 CC (PubMed:19424180). This suggests the existence of a dynamic exchange CC between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby CC regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading CC to stabilize HIF1A and enhance HIF1A-mediated activity CC (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti- CC apoptotic Bcl-2 protein family to regulate its stability CC (PubMed:35063767). Within the endoplasmic reticulum, participates with CC USP33 in the rescue of post-translationally targeted membrane proteins CC that are inappropriately ubiquitinated by the cytosolic protein quality CC control in the cytosol (PubMed:33792613). {ECO:0000269|PubMed:12056827, CC ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:15776016, CC ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:26839314, CC ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, CC ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:33792613, CC ECO:0000269|PubMed:35063767}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:26839314, CC ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, CC ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:35063767}; CC -!- SUBUNIT: Interacts with VHL, leading to its ubiquitination and CC subsequent degradation (PubMed:12056827). Interacts with CCP110 CC (PubMed:23486064). Interacts with DIO2 (PubMed:12865408). Interacts CC with HIF1A (PubMed:15776016). Interacts with ADRB2 (PubMed:19424180, CC PubMed:23166351). Interacts with USP18 (PubMed:27801882). CC {ECO:0000269|PubMed:12056827, ECO:0000269|PubMed:12865408, CC ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:19424180, CC ECO:0000269|PubMed:23166351, ECO:0000269|PubMed:23486064, CC ECO:0000269|PubMed:27801882}. CC -!- INTERACTION: CC Q9Y2K6; P13196: ALAS1; NbExp=3; IntAct=EBI-2511991, EBI-3905054; CC Q9Y2K6; Q7L4P6: BEND5; NbExp=3; IntAct=EBI-2511991, EBI-724373; CC Q9Y2K6; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-2511991, EBI-10181188; CC Q9Y2K6; Q969F0: FATE1; NbExp=3; IntAct=EBI-2511991, EBI-743099; CC Q9Y2K6; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2511991, EBI-8638439; CC Q9Y2K6; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-2511991, EBI-10178634; CC Q9Y2K6; Q99750: MDFI; NbExp=3; IntAct=EBI-2511991, EBI-724076; CC Q9Y2K6; O43597: SPRY2; NbExp=3; IntAct=EBI-2511991, EBI-742487; CC Q9Y2K6; P36406: TRIM23; NbExp=3; IntAct=EBI-2511991, EBI-740098; CC Q9Y2K6; O95292: VAPB; NbExp=3; IntAct=EBI-2511991, EBI-1188298; CC Q9Y2K6; Q53XM7: VAPB; NbExp=3; IntAct=EBI-2511991, EBI-10178947; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8C6M1}. CC Endoplasmic reticulum {ECO:0000269|PubMed:12865408, CC ECO:0000269|PubMed:33792613}. Cytoplasm, perinuclear region CC {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, CC centrosome {ECO:0000269|PubMed:23486064}. CC -!- DOMAIN: The UBP-type zinc finger binds 3 zinc ions. However, it does CC not bind ubiquitin, probably because the conserved Arg in position 55 CC is replaced by a Glu residue (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated via a VHL-dependent pathway for proteasomal CC degradation. {ECO:0000269|PubMed:12056827}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76847.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY074877; AAL79676.1; -; mRNA. DR EMBL; AB023220; BAA76847.2; ALT_INIT; mRNA. DR EMBL; AL158207; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87914.1; -; Genomic_DNA. DR EMBL; BC039593; AAH39593.1; -; mRNA. DR EMBL; Y17457; CAB44350.1; -; Genomic_DNA. DR EMBL; Y17459; CAB44352.1; -; Genomic_DNA. DR CCDS; CCDS43892.1; -. DR RefSeq; NP_001008563.2; NM_001008563.4. DR RefSeq; NP_001103773.2; NM_001110303.3. DR RefSeq; NP_006667.3; NM_006676.7. DR RefSeq; XP_005251722.1; XM_005251665.3. DR RefSeq; XP_011516463.1; XM_011518161.2. DR RefSeq; XP_011516464.1; XM_011518162.2. DR PDB; 6KCZ; NMR; -; A=1-99. DR PDBsum; 6KCZ; -. DR AlphaFoldDB; Q9Y2K6; -. DR SMR; Q9Y2K6; -. DR BioGRID; 116077; 146. DR IntAct; Q9Y2K6; 56. DR MINT; Q9Y2K6; -. DR STRING; 9606.ENSP00000313811; -. DR BindingDB; Q9Y2K6; -. DR ChEMBL; CHEMBL3232682; -. DR MEROPS; C19.025; -. DR iPTMnet; Q9Y2K6; -. DR PhosphoSitePlus; Q9Y2K6; -. DR SwissPalm; Q9Y2K6; -. DR BioMuta; USP20; -. DR DMDM; 116242837; -. DR EPD; Q9Y2K6; -. DR jPOST; Q9Y2K6; -. DR MassIVE; Q9Y2K6; -. DR MaxQB; Q9Y2K6; -. DR PaxDb; 9606-ENSP00000313811; -. DR PeptideAtlas; Q9Y2K6; -. DR ProteomicsDB; 85826; -. DR Pumba; Q9Y2K6; -. DR Antibodypedia; 1730; 350 antibodies from 32 providers. DR DNASU; 10868; -. DR Ensembl; ENST00000315480.9; ENSP00000313811.4; ENSG00000136878.14. DR Ensembl; ENST00000358355.5; ENSP00000351122.1; ENSG00000136878.14. DR Ensembl; ENST00000372429.8; ENSP00000361506.3; ENSG00000136878.14. DR GeneID; 10868; -. DR KEGG; hsa:10868; -. DR MANE-Select; ENST00000372429.8; ENSP00000361506.3; NM_001110303.4; NP_001103773.2. DR UCSC; uc004byr.4; human. DR AGR; HGNC:12619; -. DR CTD; 10868; -. DR DisGeNET; 10868; -. DR GeneCards; USP20; -. DR HGNC; HGNC:12619; USP20. DR HPA; ENSG00000136878; Low tissue specificity. DR MIM; 615143; gene. DR neXtProt; NX_Q9Y2K6; -. DR OpenTargets; ENSG00000136878; -. DR PharmGKB; PA37245; -. DR VEuPathDB; HostDB:ENSG00000136878; -. DR eggNOG; KOG1870; Eukaryota. DR GeneTree; ENSGT00940000158829; -. DR HOGENOM; CLU_004896_0_0_1; -. DR InParanoid; Q9Y2K6; -. DR OMA; IDQDDEC; -. DR OrthoDB; 227085at2759; -. DR PhylomeDB; Q9Y2K6; -. DR TreeFam; TF352179; -. DR PathwayCommons; Q9Y2K6; -. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR SignaLink; Q9Y2K6; -. DR SIGNOR; Q9Y2K6; -. DR BioGRID-ORCS; 10868; 11 hits in 1195 CRISPR screens. DR ChiTaRS; USP20; human. DR GeneWiki; USP20; -. DR GenomeRNAi; 10868; -. DR Pharos; Q9Y2K6; Tbio. DR PRO; PR:Q9Y2K6; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9Y2K6; Protein. DR Bgee; ENSG00000136878; Expressed in granulocyte and 145 other cell types or tissues. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IC:UniProt. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB. DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProt. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB. DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR CDD; cd02674; Peptidase_C19R; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 2. DR Gene3D; 3.30.2230.10; DUSP-like; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR035927; DUSP-like_sf. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR006615; Pept_C19_DUSP. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR018200; USP_CS. DR InterPro; IPR028889; USP_dom. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR001607; Znf_UBP. DR PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF13; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 20; 1. DR Pfam; PF06337; DUSP; 2. DR Pfam; PF00443; UCH; 1. DR Pfam; PF02148; zf-UBP; 1. DR SMART; SM00695; DUSP; 2. DR SMART; SM00290; ZnF_UBP; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF143791; DUSP-like; 2. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51283; DUSP; 2. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR PROSITE; PS50271; ZF_UBP; 1. DR Genevisible; Q9Y2K6; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Cytoskeleton; Endocytosis; Endoplasmic reticulum; KW Hydrolase; Metal-binding; Phosphoprotein; Protease; Reference proteome; KW Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1..914 FT /note="Ubiquitin carboxyl-terminal hydrolase 20" FT /id="PRO_0000080647" FT DOMAIN 145..685 FT /note="USP" FT DOMAIN 687..780 FT /note="DUSP 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613" FT DOMAIN 789..892 FT /note="DUSP 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613" FT ZN_FING 6..111 FT /note="UBP-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT REGION 257..347 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 360..415 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 262..289 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 317..335 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 154 FT /note="Nucleophile" FT ACT_SITE 643 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT BINDING 8 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 10 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 30 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 33 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 43 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 48 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 53 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 60 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 64 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 70 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 83 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT BINDING 86 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502" FT MOD_RES 112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 258 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 305 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 368 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8C6M1" FT MOD_RES 377 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 408 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VARIANT 103 FT /note="S -> Y (in dbSNP:rs36086252)" FT /id="VAR_051529" FT VARIANT 444 FT /note="V -> I (in dbSNP:rs36055332)" FT /id="VAR_051530" FT MUTAGEN 154 FT /note="C->S: Abolishes deubiquitinating activity. Does not FT inhibit lysosomal trafficking of ADRB2; when associated FT with Q-643." FT /evidence="ECO:0000269|PubMed:19424180, FT ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:35063767" FT MUTAGEN 643 FT /note="H->Q: Abolishes deubiquitinating activity. Does not FT inhibit lysosomal trafficking of ADRB2; when associated FT with S-154." FT /evidence="ECO:0000269|PubMed:19424180, FT ECO:0000269|PubMed:29487085" FT CONFLICT 320 FT /note="A -> V (in Ref. 1; AAL79676 and 2; BAA76847)" FT /evidence="ECO:0000305" FT CONFLICT 359 FT /note="Missing (in Ref. 1; AAL79676, 2; BAA76847, 4; FT EAW87914 and 5; AAH39593)" FT /evidence="ECO:0000305" FT CONFLICT 776 FT /note="H -> Q (in Ref. 6; CAB44350)" FT /evidence="ECO:0000305" FT CONFLICT 794 FT /note="R -> M (in Ref. 6; CAB44350)" FT /evidence="ECO:0000305" FT STRAND 4..7 FT /evidence="ECO:0007829|PDB:6KCZ" FT TURN 10..13 FT /evidence="ECO:0007829|PDB:6KCZ" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:6KCZ" FT TURN 31..33 FT /evidence="ECO:0007829|PDB:6KCZ" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:6KCZ" FT TURN 55..58 FT /evidence="ECO:0007829|PDB:6KCZ" FT HELIX 60..67 FT /evidence="ECO:0007829|PDB:6KCZ" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:6KCZ" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:6KCZ" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:6KCZ" FT TURN 84..87 FT /evidence="ECO:0007829|PDB:6KCZ" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:6KCZ" SQ SEQUENCE 914 AA; 102003 MW; DC094570A396D20E CRC64; MGDSRDLCPH LDSIGEVTKE DLLLKSKGTC QSCGVTGPNL WACLQVACPY VGCGESFADH STIHAQAKKH NLTVNLTTFR LWCYACEKEV FLEQRLAAPL LGSSSKFSEQ DSPPPSHPLK AVPIAVADEG ESESEDDDLK PRGLTGMKNL GNSCYMNAAL QALSNCPPLT QFFLECGGLV RTDKKPALCK SYQKLVSEVW HKKRPSYVVP TSLSHGIKLV NPMFRGYAQQ DTQEFLRCLM DQLHEELKEP VVATVALTEA RDSDSSDTDE KREGDRSPSE DEFLSCDSSS DRGEGDGQGR GGGSSQAETE LLIPDEAGRA ISEKERMKDR KFSWGQQRTN SEQVDEDADV DTAMAALDDQ PAEAQPPSPR SSSPCRTPEP DNDAHLRSSS RPCSPVHHHE GHAKLSSSPP RASPVRMAPS YVLKKAQVLS AGSRRRKEQR YRSVISDIFD GSILSLVQCL TCDRVSTTVE TFQDLSLPIP GKEDLAKLHS AIYQNVPAKP GACGDSYAAQ GWLAFIVEYI RRFVVSCTPS WFWGPVVTLE DCLAAFFAAD ELKGDNMYSC ERCKKLRNGV KYCKVLRLPE ILCIHLKRFR HEVMYSFKIN SHVSFPLEGL DLRPFLAKEC TSQITTYDLL SVICHHGTAG SGHYIAYCQN VINGQWYEFD DQYVTEVHET VVQNAEGYVL FYRKSSEEAM RERQQVVSLA AMREPSLLRF YVSREWLNKF NTFAEPGPIT NQTFLCSHGG IPPHKYHYID DLVVILPQNV WEHLYNRFGG GPAVNHLYVC SICQVEIEAL AKRRRIEIDT FIKLNKAFQA EESPGVIYCI SMQWFREWEA FVKGKDNEPP GPIDNSRIAQ VKGSGHVQLK QGADYGQISE ETWTYLNSLY GGGPEIAIRQ SVAQPLGPEN LHGEQKIEAE TRAV //