ID UBP20_PONAB Reviewed; 913 AA. AC Q5R5Z6; DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 14-DEC-2022, entry version 89. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 20; DE EC=3.4.19.12; DE AltName: Full=Deubiquitinating enzyme 20; DE AltName: Full=Ubiquitin thioesterase 20; DE AltName: Full=Ubiquitin-specific-processing protease 20; GN Name=USP20; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Deubiquitinating enzyme involved in beta-2 adrenergic CC receptor (ADRB2) recycling. Acts as a regulator of G-protein coupled CC receptor (GPCR) signaling by mediating the deubiquitination beta-2 CC adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling CC 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 CC ADRB2. This suggests the existence of a dynamic exchange between the CC ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating CC thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize CC HIF1A and enhance HIF1A-mediated activity. Mediates deubiquitination of CC both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By CC similarity). {ECO:0000250}. 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; CC -!- SUBUNIT: Interacts with VHL, leading to its ubiquitination and CC subsequent degradation (By similarity). Interacts with CCP110 (By CC similarity). Interacts with DIO2 (By similarity). Interacts with HIF1A CC (By similarity). Interacts with ADRB2 (By similarity). CC {ECO:0000250|UniProtKB:Q9Y2K6}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000250}. 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:0000250}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily. CC {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; CR860704; CAH92820.1; -; mRNA. DR RefSeq; NP_001126647.1; NM_001133175.1. DR AlphaFoldDB; Q5R5Z6; -. DR STRING; 9601.ENSPPYP00000022065; -. DR MEROPS; C19.025; -. DR GeneID; 100173645; -. DR KEGG; pon:100173645; -. DR CTD; 10868; -. DR eggNOG; KOG1870; Eukaryota. DR InParanoid; Q5R5Z6; -. DR OrthoDB; 147564at2759; -. DR Proteomes; UP000001595; Unplaced. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB. DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB. DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. DR Gene3D; 3.30.2230.10; -; 2. DR Gene3D; 3.30.40.10; -; 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 Pfam; PF06337; DUSP; 2. DR Pfam; PF00443; UCH; 2. 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 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. PE 2: Evidence at transcript level; KW Cytoplasm; Cytoskeleton; Endocytosis; Hydrolase; Metal-binding; KW Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..913 FT /note="Ubiquitin carboxyl-terminal hydrolase 20" FT /id="PRO_0000390419" FT DOMAIN 144..684 FT /note="USP" FT DOMAIN 686..779 FT /note="DUSP 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613" FT DOMAIN 788..891 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 256..414 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 261..288 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 316..334 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 374..388 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 153 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT ACT_SITE 642 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 111 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 131 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 133 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 257 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 304 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 367 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8C6M1" FT MOD_RES 376 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" FT MOD_RES 412 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2K6" SQ SEQUENCE 913 AA; 101851 MW; 54CA311FD1D3E626 CRC64; MGDSRDLCPH LDSIGEVTKE DLLLKSMGTC QSCGVTGPNL WACLQVACPY VGCGESFADH STIHAQAKKH NLTVNLTTFR LWCYACEKEV FLEQRLAAPL LGSSKFSEQD SPPPSHPLKA VPIAVADEGE SESEDDDLKP RGLTGMKNLG NSCYMNAALQ ALSNCPPLTQ FFLECGGLVR TDKKPALCKS YQKLVSEVWH KKRPSYVVPT SLSHGIKLVN PMFRGYAQQD TQEFLRCLMD QLHEELKEPV VATVALTEAR DSDSSDTDEK REGDRSPSED EFLSCDSSSD RGEGDGQGRG GGSSQAETEL LIPDEASRAI SEKERMKDRK FSWGQQRTNS EQVDEDADVD TTMAALDDQP AEAQPPSPRS SSPCRTPEPD NDAHLCSSSR PCSPVHHHEG HAKLSSSPPR ASPVRMAPSY VLKKAQVLSA GSRRRKEQRY RSVISDIFDG SILSLVQCLT CDRVSATVET FQDLSLPIPG KEDLAKLHSA IYQNVPAKPG TCGDSYAAQG WLAFIVEYIR RFVVSCTPSW FWGPVVTLED CLAAFFAADE LKGDNMYSCE RCKKLRNGVK YCKVLRLPEI LCIHLKRFRH EVMYSFKINS HVSFPLEGLD LRPFLAKECT SQITTYDLLS VICHHGTAGS GHYIAYCQNV INGQWYEFDD QYVTEVHETV VQNAEGYVLF YRKSSEEAVR ERQQVVSLAA MREPSLLRFY VSREWLNKFN TFAEPGPITN QTFLCSHGGI PPHKYHYIDD LVVILPQNVW EHLYNRFGGG PAVNHLYVCS ICQVEIEALA KRRRIEIDTF IKLNKAFQAE ESPGIIYCIS MQWFREWEAF VKGKDNEPPG PIDNSRIAQV KGSGHVQLKQ GADYGQISEE TWTYLNSLYG GGPEIAIRQS VAQPLGPESL HGEQKIEAEA RAV //