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Protein

Ubiquitin carboxyl-terminal hydrolase 20

Gene

USP20

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Deubiquitinating enzyme involved in beta-2 adrenergic receptor (ADRB2) recycling. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). 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. 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. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.4 Publications

Catalytic activityi

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei154Nucleophile1
Active sitei643Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri28 – 92UBP-typePROSITE-ProRule annotationAdd BLAST65

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • G-protein coupled receptor binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: InterPro
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processEndocytosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.025

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 20 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 20
Ubiquitin thioesterase 20
Ubiquitin-specific-processing protease 20
VHL-interacting deubiquitinating enzyme 2
Short name:
hVDU2
Gene namesi
Name:USP20
Synonyms:KIAA1003, LSFR3A, VDU2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000136878.12
HGNCiHGNC:12619 USP20
MIMi615143 gene
neXtProtiNX_Q9Y2K6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi154C → S: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with Q-643. 1 Publication1
Mutagenesisi643H → Q: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with S-154. 1 Publication1

Organism-specific databases

DisGeNETi10868
OpenTargetsiENSG00000136878
PharmGKBiPA37245

Chemistry databases

ChEMBLiCHEMBL3232682

Polymorphism and mutation databases

DMDMi116242837

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806471 – 914Ubiquitin carboxyl-terminal hydrolase 20Add BLAST914

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei112PhosphoserineCombined sources1
Modified residuei132PhosphoserineCombined sources1
Modified residuei134PhosphoserineCombined sources1
Modified residuei258PhosphothreonineCombined sources1
Modified residuei305PhosphoserineCombined sources1
Modified residuei368PhosphoserineBy similarity1
Modified residuei377PhosphothreonineCombined sources1
Modified residuei408PhosphoserineCombined sources1
Modified residuei413PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y2K6
MaxQBiQ9Y2K6
PaxDbiQ9Y2K6
PeptideAtlasiQ9Y2K6
PRIDEiQ9Y2K6
ProteomicsDBi85826

PTM databases

iPTMnetiQ9Y2K6
PhosphoSitePlusiQ9Y2K6

Expressioni

Gene expression databases

BgeeiENSG00000136878 Expressed in 187 organ(s), highest expression level in lower esophagus muscularis layer
CleanExiHS_USP20
GenevisibleiQ9Y2K6 HS

Organism-specific databases

HPAiHPA006287
HPA007008

Interactioni

Subunit structurei

Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with CCP110, DIO2 and HIF1A.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116077, 75 interactors
IntActiQ9Y2K6, 50 interactors
STRINGi9606.ENSP00000313811

Chemistry databases

BindingDBiQ9Y2K6

Structurei

Secondary structure

1914
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y2K6
SMRiQ9Y2K6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini145 – 685USPAdd BLAST541
Domaini687 – 780DUSP 1PROSITE-ProRule annotationAdd BLAST94
Domaini789 – 892DUSP 2PROSITE-ProRule annotationAdd BLAST104

Domaini

The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue (By similarity).By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri28 – 92UBP-typePROSITE-ProRule annotationAdd BLAST65

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1870 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000286031
HOVERGENiHBG054196
InParanoidiQ9Y2K6
KOiK11848
OMAiLHGEQKI
OrthoDBiEOG091G02UV
PhylomeDBiQ9Y2K6
TreeFamiTF352179

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR035927 DUSP-like_sf
IPR038765 Papain_like_cys_pep_sf
IPR006615 Pept_C19_DUSP
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF06337 DUSP, 2 hits
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SMARTiView protein in SMART
SM00695 DUSP, 2 hits
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF143791 SSF143791, 2 hits
SSF54001 SSF54001, 3 hits
PROSITEiView protein in PROSITE
PS51283 DUSP, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit

Sequencei

Sequence statusi: Complete.

Q9Y2K6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGDSRDLCPH LDSIGEVTKE DLLLKSKGTC QSCGVTGPNL WACLQVACPY
60 70 80 90 100
VGCGESFADH STIHAQAKKH NLTVNLTTFR LWCYACEKEV FLEQRLAAPL
110 120 130 140 150
LGSSSKFSEQ DSPPPSHPLK AVPIAVADEG ESESEDDDLK PRGLTGMKNL
160 170 180 190 200
GNSCYMNAAL QALSNCPPLT QFFLECGGLV RTDKKPALCK SYQKLVSEVW
210 220 230 240 250
HKKRPSYVVP TSLSHGIKLV NPMFRGYAQQ DTQEFLRCLM DQLHEELKEP
260 270 280 290 300
VVATVALTEA RDSDSSDTDE KREGDRSPSE DEFLSCDSSS DRGEGDGQGR
310 320 330 340 350
GGGSSQAETE LLIPDEAGRA ISEKERMKDR KFSWGQQRTN SEQVDEDADV
360 370 380 390 400
DTAMAALDDQ PAEAQPPSPR SSSPCRTPEP DNDAHLRSSS RPCSPVHHHE
410 420 430 440 450
GHAKLSSSPP RASPVRMAPS YVLKKAQVLS AGSRRRKEQR YRSVISDIFD
460 470 480 490 500
GSILSLVQCL TCDRVSTTVE TFQDLSLPIP GKEDLAKLHS AIYQNVPAKP
510 520 530 540 550
GACGDSYAAQ GWLAFIVEYI RRFVVSCTPS WFWGPVVTLE DCLAAFFAAD
560 570 580 590 600
ELKGDNMYSC ERCKKLRNGV KYCKVLRLPE ILCIHLKRFR HEVMYSFKIN
610 620 630 640 650
SHVSFPLEGL DLRPFLAKEC TSQITTYDLL SVICHHGTAG SGHYIAYCQN
660 670 680 690 700
VINGQWYEFD DQYVTEVHET VVQNAEGYVL FYRKSSEEAM RERQQVVSLA
710 720 730 740 750
AMREPSLLRF YVSREWLNKF NTFAEPGPIT NQTFLCSHGG IPPHKYHYID
760 770 780 790 800
DLVVILPQNV WEHLYNRFGG GPAVNHLYVC SICQVEIEAL AKRRRIEIDT
810 820 830 840 850
FIKLNKAFQA EESPGVIYCI SMQWFREWEA FVKGKDNEPP GPIDNSRIAQ
860 870 880 890 900
VKGSGHVQLK QGADYGQISE ETWTYLNSLY GGGPEIAIRQ SVAQPLGPEN
910
LHGEQKIEAE TRAV
Length:914
Mass (Da):102,003
Last modified:October 17, 2006 - v2
Checksum:iDC094570A396D20E
GO

Sequence cautioni

The sequence BAA76847 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti320A → V in AAL79676 (PubMed:12056827).Curated1
Sequence conflicti320A → V in BAA76847 (PubMed:10231032).Curated1
Sequence conflicti359Missing in AAL79676 (PubMed:12056827).Curated1
Sequence conflicti359Missing in BAA76847 (PubMed:10231032).Curated1
Sequence conflicti359Missing in EAW87914 (Ref. 4) Curated1
Sequence conflicti359Missing in AAH39593 (PubMed:15489334).Curated1
Sequence conflicti776H → Q in CAB44350 (PubMed:10369878).Curated1
Sequence conflicti794R → M in CAB44350 (PubMed:10369878).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051529103S → Y. Corresponds to variant dbSNP:rs36086252Ensembl.1
Natural variantiVAR_051530444V → I. Corresponds to variant dbSNP:rs36055332Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY074877 mRNA Translation: AAL79676.1
AB023220 mRNA Translation: BAA76847.2 Different initiation.
AL158207 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87914.1
BC039593 mRNA Translation: AAH39593.1
Y17457 Genomic DNA Translation: CAB44350.1
Y17459 Genomic DNA Translation: CAB44352.1
CCDSiCCDS43892.1
RefSeqiNP_001008563.2, NM_001008563.4
NP_001103773.2, NM_001110303.3
NP_006667.3, NM_006676.7
XP_005251722.1, XM_005251665.3
XP_011516463.1, XM_011518161.2
XP_011516464.1, XM_011518162.2
UniGeneiHs.5452

Genome annotation databases

EnsembliENST00000315480; ENSP00000313811; ENSG00000136878
ENST00000358355; ENSP00000351122; ENSG00000136878
ENST00000372429; ENSP00000361506; ENSG00000136878
GeneIDi10868
KEGGihsa:10868
UCSCiuc004byr.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBP20_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2K6
Secondary accession number(s): Q541F1
, Q8IXQ1, Q96LG5, Q9UQN8, Q9UQP0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: October 17, 2006
Last modified: September 12, 2018
This is version 170 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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