Q9Y2K6 (UBP20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	USP20
Synonyms:	KIAA1003, LSFR3A, VDU2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	914 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.7 Ref.8 Ref.12
Catalytic activity	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).
Subunit structure	Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with DIO2 and HIF1A. Ref.1 Ref.7 Ref.8 Ref.12
Subcellular location	Cytoplasm › perinuclear region By similarity. Note: According to Ref.7, it localizes in the endoplasmic reticulum; however the relevance of such result is unclear.
Domain	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.
Post-translational modification	Ubiquitinated via a VHL-dependent pathway for proteasomal degradation. Ref.1
Sequence similarities	Belongs to the peptidase C19 family. USP20/USP33 subfamily. Contains 2 DUSP domains. Contains 1 UBP-type zinc finger.
Sequence caution	The sequence BAA76847.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Endocytosis Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW protein K48-linked deubiquitination Inferred from direct assay Ref.12. Source: UniProtKB protein K63-linked deubiquitination Inferred from direct assay Ref.12. Source: UniProtKB regulation of G-protein coupled receptor protein signaling pathway Inferred from mutant phenotype Ref.12. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase activity Inferred from mutant phenotype Ref.12. Source: UniProtKB ubiquitin thiolesterase activity Inferred from direct assay Ref.12. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 914	914	Ubiquitin carboxyl-terminal hydrolase 20		PRO_0000080647
Regions
	Domain	687 – 780	94	DUSP 1
	Domain	789 – 892	104	DUSP 2
	Zinc finger	28 – 92	65	UBP-type
Sites
	Active site	154	1	Nucleophile
	Active site	643	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	132	1	Phosphoserine Ref.10 Ref.13
	Modified residue	134	1	Phosphoserine Ref.10 Ref.13
	Modified residue	258	1	Phosphothreonine Ref.9
	Modified residue	377	1	Phosphothreonine Ref.11
	Modified residue	413	1	Phosphoserine Ref.11
Natural variations
	Natural variant	103	1	S → Y. Corresponds to variant rs36086252 [ dbSNP | Ensembl ].		VAR_051529
	Natural variant	444	1	V → I. Corresponds to variant rs36055332 [ dbSNP | Ensembl ].		VAR_051530
Experimental info
	Mutagenesis	154	1	C → S: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with Q-643. Ref.12
	Mutagenesis	643	1	H → Q: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with S-154. Ref.12
	Sequence conflict	320	1	A → V in AAL79676. Ref.1
	Sequence conflict	320	1	A → V in BAA76847. Ref.2
	Sequence conflict	359	1	Missing in AAL79676. Ref.1
	Sequence conflict	359	1	Missing in BAA76847. Ref.2
	Sequence conflict	359	1	Missing in EAW87914. Ref.4
	Sequence conflict	359	1	Missing in AAH39593. Ref.5
	Sequence conflict	776	1	H → Q in CAB44350. Ref.6
	Sequence conflict	794	1	R → M in CAB44350. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9Y2K6 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: DC094570A396D20E	FASTA	914	102,003
	10 20 30 40 50 60 MGDSRDLCPH LDSIGEVTKE DLLLKSKGTC QSCGVTGPNL WACLQVACPY VGCGESFADH 70 80 90 100 110 120 STIHAQAKKH NLTVNLTTFR LWCYACEKEV FLEQRLAAPL LGSSSKFSEQ DSPPPSHPLK 130 140 150 160 170 180 AVPIAVADEG ESESEDDDLK PRGLTGMKNL GNSCYMNAAL QALSNCPPLT QFFLECGGLV 190 200 210 220 230 240 RTDKKPALCK SYQKLVSEVW HKKRPSYVVP TSLSHGIKLV NPMFRGYAQQ DTQEFLRCLM 250 260 270 280 290 300 DQLHEELKEP VVATVALTEA RDSDSSDTDE KREGDRSPSE DEFLSCDSSS DRGEGDGQGR 310 320 330 340 350 360 GGGSSQAETE LLIPDEAGRA ISEKERMKDR KFSWGQQRTN SEQVDEDADV DTAMAALDDQ 370 380 390 400 410 420 PAEAQPPSPR SSSPCRTPEP DNDAHLRSSS RPCSPVHHHE GHAKLSSSPP RASPVRMAPS 430 440 450 460 470 480 YVLKKAQVLS AGSRRRKEQR YRSVISDIFD GSILSLVQCL TCDRVSTTVE TFQDLSLPIP 490 500 510 520 530 540 GKEDLAKLHS AIYQNVPAKP GACGDSYAAQ GWLAFIVEYI RRFVVSCTPS WFWGPVVTLE 550 560 570 580 590 600 DCLAAFFAAD ELKGDNMYSC ERCKKLRNGV KYCKVLRLPE ILCIHLKRFR HEVMYSFKIN 610 620 630 640 650 660 SHVSFPLEGL DLRPFLAKEC TSQITTYDLL SVICHHGTAG SGHYIAYCQN VINGQWYEFD 670 680 690 700 710 720 DQYVTEVHET VVQNAEGYVL FYRKSSEEAM RERQQVVSLA AMREPSLLRF YVSREWLNKF 730 740 750 760 770 780 NTFAEPGPIT NQTFLCSHGG IPPHKYHYID DLVVILPQNV WEHLYNRFGG GPAVNHLYVC 790 800 810 820 830 840 SICQVEIEAL AKRRRIEIDT FIKLNKAFQA EESPGVIYCI SMQWFREWEA FVKGKDNEPP 850 860 870 880 890 900 GPIDNSRIAQ VKGSGHVQLK QGADYGQISE ETWTYLNSLY GGGPEIAIRQ SVAQPLGPEN 910 LHGEQKIEAE TRAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a deubiquitinating enzyme subfamily as substrates of the von Hippel-Lindau tumor suppressor." Li Z., Wang D., Na X., Schoen S.R., Messing E.M., Wu G. Biochem. Biophys. Res. Commun. 294:700-709(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, UBIQUITINATION, INTERACTION WITH VHL.
[2]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[6]	"Extensive gene order differences within regions of conserved synteny between the Fugu and human genomes: implications for chromosomal evolution and the cloning of disease genes." Gilley J., Fried M. Hum. Mol. Genet. 8:1313-1320(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-803 AND 839-914.
[7]	"Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation." Curcio-Morelli C., Zavacki A.M., Christofollete M., Gereben B., de Freitas B.C., Harney J.W., Li Z., Wu G., Bianco A.C. J. Clin. Invest. 112:189-196(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DIO2.
[8]	"VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha." Li Z., Wang D., Messing E.M., Wu G. EMBO Rep. 6:373-378(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HIF1A.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-258, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-134, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-377 AND SER-413, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization." Berthouze M., Venkataramanan V., Li Y., Shenoy S.K. EMBO J. 28:1684-1696(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ADRB2, MUTAGENESIS OF CYS-154 AND HIS-643.
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-134, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY074877 mRNA. Translation: AAL79676.1. AB023220 mRNA. Translation: BAA76847.2. Different initiation. AL158207 Genomic DNA. Translation: CAC88170.1. CH471090 Genomic DNA. Translation: EAW87914.1. BC039593 mRNA. Translation: AAH39593.1. Y17457 Genomic DNA. Translation: CAB44350.1. Y17459 Genomic DNA. Translation: CAB44352.1.
IPI	IPI00328285.
RefSeq	NP_001008563.2. NM_001008563.4. NP_001103773.2. NM_001110303.3. NP_006667.3. NM_006676.7.
UniGene	Hs.5452.
3D structure databases
ProteinModelPortal	Q9Y2K6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2K6. 40 interactions.
STRING	9606.ENSP00000313811.
Protein family/group databases
MEROPS	C19.025.
PTM databases
PhosphoSite	Q9Y2K6.
Polymorphism databases
DMDM	116242837.
Proteomic databases
PaxDb	Q9Y2K6.
PRIDE	Q9Y2K6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315480; ENSP00000313811; ENSG00000136878. ENST00000358355; ENSP00000351122; ENSG00000136878. ENST00000372429; ENSP00000361506; ENSG00000136878.
GeneID	10868.
KEGG	hsa:10868.
UCSC	uc004byr.2. human.
Organism-specific databases
CTD	10868.
GeneCards	GC09P132596.
H-InvDB	HIX0008459.
HGNC	HGNC:12619. USP20.
HPA	HPA006287.
neXtProt	NX_Q9Y2K6.
PharmGKB	PA37245.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5560.
HOGENOM	HOG000286031.
HOVERGEN	HBG054196.
InParanoid	Q9Y2K6.
KO	K11848.
OMA	ADYGQIS.
OrthoDB	EOG4D52WZ.
PhylomeDB	Q9Y2K6.
Gene expression databases
ArrayExpress	Q9Y2K6.
Bgee	Q9Y2K6.
CleanEx	HS_USP20.
Genevestigator	Q9Y2K6.
GermOnline	ENSG00000136878. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR006615. Pept_C19_DUSP. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Pfam	PF06337. DUSP. 1 hit. PF00443. UCH. 1 hit. PF02148. zf-UBP. 1 hit. [Graphical view]
SMART	SM00695. DUSP. 2 hits. [Graphical view]
PROSITE	PS51283. DUSP. 2 hits. PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50271. ZF_UBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	USP20. human.
GenomeRNAi	10868.
NextBio	41265.

Entry information

Entry name

UBP20_HUMAN

Accession

Primary (citable) accession number: Q9Y2K6
Secondary accession number(s): Q541F1 , Q8IXQ1, Q96LG5, Q9UQN8, Q9UQP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.