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Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene

USP2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Possesses both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells. Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues. Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability. Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1.By similarity

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).

Enzyme regulationi

Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei277NucleophilePROSITE-ProRule annotation1
Metal bindingi426ZincBy similarity1
Metal bindingi429ZincBy similarity1
Metal bindingi477ZincBy similarity1
Metal bindingi480ZincBy similarity1
Active sitei558Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processBiological rhythms, Cell cycle, Myogenesis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-BTA-5357786 TNFR1-induced proapoptotic signaling
R-BTA-5357905 Regulation of TNFR1 signaling
R-BTA-5357956 TNFR1-induced NFkappaB signaling pathway
R-BTA-5689880 Ub-specific processing proteases
R-BTA-6804757 Regulation of TP53 Degradation

Protein family/group databases

MEROPSiC19.013

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 2 (EC:3.4.19.12)
Alternative name(s):
41 kDa ubiquitin-specific protease
Deubiquitinating enzyme 2
Ubiquitin thioesterase 2
Ubiquitin-specific-processing protease 2
Gene namesi
Name:USP2
Synonyms:UBP41
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 15

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003959651 – 606Ubiquitin carboxyl-terminal hydrolase 2Add BLAST606

Proteomic databases

PaxDbiQ2KHV7
PRIDEiQ2KHV7

Expressioni

Gene expression databases

BgeeiENSBTAG00000009749

Interactioni

Subunit structurei

Homooligomer. Found in trimeric complex with MDM2 and MDM4 and USP2. Interacts with CCND1; the interaction is direct and promotes its stabilization by antagonizing ubiquitin-dependent degradation. Interacts (via N-terminus and C-terminus) with MDM2. Interacts with MDM4 and PER1. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores plasma membrane localization of KCNQ1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000012857

Structurei

3D structure databases

ProteinModelPortaliQ2KHV7
SMRiQ2KHV7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini268 – 600USPAdd BLAST333

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 201Necessary for interaction with MDM4By similarityAdd BLAST201
Regioni404 – 504Necessary for interaction with MDM4By similarityAdd BLAST101

Sequence similaritiesi

Belongs to the peptidase C19 family. USP2 subfamily.Curated

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1868 Eukaryota
ENOG410XP8T LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000048720
HOVERGENiHBG011164
InParanoidiQ2KHV7
KOiK11833
OMAiSGRYSLW
OrthoDBiEOG091G0120
TreeFamiTF106277

Family and domain databases

InterProiView protein in InterPro
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequencei

Sequence statusi: Complete.

Q2KHV7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQLSSTLKR YTESARFTDA PFTKSSYGTY TPSSYGTNLA ASFLEKEKFG
60 70 80 90 100
FKPSPPTSYL TRPRTYGPPS ILDYDRGRPL LRPDVIGGGK RAESQTRGTE
110 120 130 140 150
RPSGSGLSGG SGFSYGVTTS SVSYLPVSAR DQGVTLTQKK SNSQSDLARD
160 170 180 190 200
FSSLQTSDSY RLDSGNLGRS PMLARTRKEL CALQGLYQAA SRSEYLADYL
210 220 230 240 250
ENYGRKASAP QVPTPTPPSR APEVLSPTYR PSGRYSLWEK GKGQALVSSR
260 270 280 290 300
SSSPGRDTMN SKSAQGLAGL RNLGNTCFMN SILQCLSNTR ELRDYCLQRL
310 320 330 340 350
YLRDLSHSSR AHTALMEEFA KLIQTIWTSS PNDVVSPSEF KTQIQRYAPR
360 370 380 390 400
FVGYNQQDAQ EFLRFLLDGL HNEVNRVIAR PKSNTENLDH LPDDEKGRQM
410 420 430 440 450
WRKYLEREDS RIGDLFVGQL KSSLTCTDCG YCSTVFDPFW DLSLPITKRG
460 470 480 490 500
YPEVTLMDCM RLFTKEDVLD GDEKPTCCRC RARKRCIKKF SIQRFPKILV
510 520 530 540 550
LHLKRFSESR IRTSKLTAFV NFPLRDLDLR EFASENTNHA VYNLYAVSNH
560 570 580 590 600
SGTTMGGHYT AYCRSPVTGE WHTFNDSSVS PMSSSQVRTS DAYLLFYELA

SPPSRM
Length:606
Mass (Da):68,101
Last modified:March 7, 2006 - v1
Checksum:i4713919E8BDEE909
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC112866 mRNA Translation: AAI12867.1
RefSeqiNP_001039728.1, NM_001046263.1
UniGeneiBt.21721

Genome annotation databases

EnsembliENSBTAT00000012857; ENSBTAP00000012857; ENSBTAG00000009749
GeneIDi522980
KEGGibta:522980

Similar proteinsi

Entry informationi

Entry nameiUBP2_BOVIN
AccessioniPrimary (citable) accession number: Q2KHV7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: March 7, 2006
Last modified: March 28, 2018
This is version 79 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health