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Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene

Usp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. 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 (By similarity). Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities. 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 (PubMed:23213472). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1.By similarity3 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).

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion.By similarity

Enzyme regulationi

Cleavage is inhibited by ubiquitin in a dosage-dependent manner (By similarity). Cleavage is blocked by ubiquitin aldehyde.By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei289 – 2891NucleophilePROSITE-ProRule annotation
Metal bindingi438 – 4381ZincBy similarity
Metal bindingi441 – 4411ZincBy similarity
Metal bindingi489 – 4891ZincBy similarity
Metal bindingi492 – 4921ZincBy similarity
Active sitei570 – 5701Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: GO_Central
  2. metal ion binding Source: UniProtKB-KW
  3. ubiquitin-specific protease activity Source: GO_Central
  4. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. circadian behavior Source: UniProtKB
  3. circadian regulation of gene expression Source: UniProtKB
  4. entrainment of circadian clock by photoperiod Source: UniProtKB
  5. locomotor rhythm Source: UniProtKB
  6. muscle organ development Source: UniProtKB-KW
  7. negative regulation of skeletal muscle tissue development Source: UniProtKB
  8. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  9. positive regulation of mitotic cell cycle Source: UniProtKB
  10. positive regulation of skeletal muscle tissue development Source: UniProtKB
  11. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  12. protein deubiquitination Source: UniProtKB
  13. protein stabilization Source: UniProtKB
  14. regulation of proteasomal protein catabolic process Source: GO_Central
  15. regulation of transcription, DNA-templated Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Biological rhythms, Cell cycle, Myogenesis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

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
Ubiquitin-specific-processing protease testis
Short name:
UBP-t
Gene namesi
Name:Usp2
Synonyms:Ubp41, Ubp69
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 8

Organism-specific databases

RGDi621073. Usp2.

Subcellular locationi

Cytoplasm By similarity
Isoform 1 : Cytoplasmperinuclear region 1 Publication
Note: Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane.1 Publication
Isoform 2 : Nucleus 1 Publication

GO - Cellular componenti

  1. cell cortex Source: Ensembl
  2. centrosome Source: RGD
  3. nucleus Source: UniProtKB
  4. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi289 – 2891C → S: Loss of enzymatic activity. Reduces both membrane fusion during myogenesis and accumulation of muscle-specific proteins. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 618618Ubiquitin carboxyl-terminal hydrolase 2PRO_0000395966Add
BLAST

Proteomic databases

PaxDbiQ5U349.
PRIDEiQ5U349.

Expressioni

Tissue specificityi

Expressed in mesangial cells of the kidney. Isoform 1 and isoform 2 are expressed in elongated spermatids; the shorter form appearing earlier than the longer form (at protein level). Isoform 1 and isoform 2 are expressed in early round spermatids of the testis. Isoform 1 is expressed in muscle and heart. Isoform 2 is expressed in muscle, lung, heart, brain, liver and ovary. During muscle differentiation, isoform 1 expression increases before the onset of membrane fusion and decreases as the myogenic processes proceeded; un counterpart, isoform 2 expression remains low until the burst of membrane fusion but increases thereafter.3 Publications

Inductioni

Up-regulated by IL-1. Isoform 1 is up-regulated with any signal for withdrawal from the cell cycle such as serum deprivation.2 Publications

Gene expression databases

GenevestigatoriQ5U349.

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 (By similarity). Interacts with PER1.By similarity1 Publication

Protein-protein interaction databases

BioGridi250433. 2 interactions.
DIPiDIP-48683N.
STRINGi10116.ENSRNOP00000009975.

Structurei

3D structure databases

ProteinModelPortaliQ5U349.
SMRiQ5U349. Positions 276-613.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini280 – 612333USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 213213Necessary for interaction with MDM4By similarityAdd
BLAST
Regioni416 – 516101Necessary for interaction with MDM4By similarityAdd
BLAST

Domaini

The different N-terminus extensions of isoform 1 and isoform 2 determine their respective subcellular localization and differentiel effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 2 are not essential for their catalytic activity.1 Publication

Sequence similaritiesi

Belongs to the peptidase C19 family. USP2 subfamily.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00780000121880.
HOGENOMiHOG000231498.
HOVERGENiHBG011164.
InParanoidiQ5U349.
KOiK11833.
OMAiSASHRSY.
OrthoDBiEOG7FR7GN.
PhylomeDBiQ5U349.
TreeFamiTF106277.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q5U349-1) [UniParc]FASTAAdd to Basket

Also known as: Ubp69, Ubp-t2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSQLSSTLKR YTESSRYTDA PYAKSGYGTY TPSSYGANLA ASFLEKEKLG
60 70 80 90 100
FKPVSPTSFL PRPRTYGPSS ILDCDRGRPL LRSDITGGSK RSESQTRGNE
110 120 130 140 150
RPSGSGLNGG SGFPYGVTSN SLSYLPMNAR DQGVTLGQKK SNSQSDLARD
160 170 180 190 200
FSSLRTSDSY RTSDGYRASD GFRIDPGNLG RSPMLARTRK ELCALQGLYQ
210 220 230 240 250
AASRSEYLTD YLENYGRKGS APQVLTQAPP SRVPEVLSPT YRPSGRYTLW
260 270 280 290 300
EKNKGQASGP SRSTSPGRDT MNSKSAQGLA GLRNLGNTCF MNSILQCLSN
310 320 330 340 350
TRELRDYCLQ RLYMRDLGHT SSAHTALMEE FAKLIQTIWT SSPNDVVSPS
360 370 380 390 400
EFKTQIQRYA PRFVGYNQQD AQEFLRFLLD GLHNEVNRVA ARPKPSPESL
410 420 430 440 450
DHLPDEEKGR QMWRKYLERE DSRIGDLFVG QLKSSLTCTD CGYCSTVFDP
460 470 480 490 500
FWDLSLPIAK RGYPEVTLMD CMRLFTKEDV LDGDEKPTCC RCRARKRCIK
510 520 530 540 550
KFSVQRFPKI LVLHLKRFSE SRIRTSKLTT FVNFPLRDLD LREFASENTN
560 570 580 590 600
HAVYNLYAVS NHSGTTMGGH YTAYCRSPVT GEWHTFNDSS VTPMSSSQVR
610
TSDAYLLFYE LASPPSRM

Note: Stimulates both membrane fusion during myogenesis and accumulation of muscle-specific proteins.

Length:618
Mass (Da):69,363
Last modified:December 7, 2004 - v1
Checksum:iB8B2091192CA4944
GO
Isoform 2 (identifier: Q5U349-2) [UniParc]FASTAAdd to Basket

Also known as: Ubp45, Ubp-t1

The sequence of this isoform differs from the canonical sequence as follows:
     1-271: MSQLSSTLKR...RSTSPGRDTM → MRTSYTVTLP...FVGLLLNKAK

Note: Inhibits both membrane fusion during myogenesis and accumulation of muscle-specific proteins.

Show »
Length:396
Mass (Da):45,164
Checksum:iED7C91FB5A0964E3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti172 – 1721F → S in AAF17574. (PubMed:10938131)Curated
Sequence conflicti202 – 2021A → T in AAF14190. (PubMed:12107281)Curated
Sequence conflicti260 – 2601P → A in AAF17574. (PubMed:10938131)Curated
Sequence conflicti607 – 6071L → F in AAF14189. (PubMed:12107281)Curated
Sequence conflicti607 – 6071L → F in AAF14190. (PubMed:12107281)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 271271MSQLS…GRDTM → MRTSYTVTLPEEPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2. 2 PublicationsVSP_039561Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF202453 mRNA. Translation: AAF17574.1.
AF202454 mRNA. Translation: AAF17575.1.
AF106658 mRNA. Translation: AAF14189.1.
AF106659 mRNA. Translation: AAF14190.1.
CH473975 Genomic DNA. Translation: EDL95274.1.
CH473975 Genomic DNA. Translation: EDL95276.1.
CH473975 Genomic DNA. Translation: EDL95277.1.
BC085719 mRNA. Translation: AAH85719.1.
RefSeqiNP_446226.2. NM_053774.2.
XP_006242923.1. XM_006242861.2. [Q5U349-1]
XP_006242925.1. XM_006242863.2. [Q5U349-2]
UniGeneiRn.168987.
Rn.203590.

Genome annotation databases

EnsembliENSRNOT00000009975; ENSRNOP00000009975; ENSRNOG00000006663. [Q5U349-1]
ENSRNOT00000036051; ENSRNOP00000030257; ENSRNOG00000006663. [Q5U349-2]
GeneIDi115771.
KEGGirno:115771.
UCSCiRGD:621073. rat. [Q5U349-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF202453 mRNA. Translation: AAF17574.1.
AF202454 mRNA. Translation: AAF17575.1.
AF106658 mRNA. Translation: AAF14189.1.
AF106659 mRNA. Translation: AAF14190.1.
CH473975 Genomic DNA. Translation: EDL95274.1.
CH473975 Genomic DNA. Translation: EDL95276.1.
CH473975 Genomic DNA. Translation: EDL95277.1.
BC085719 mRNA. Translation: AAH85719.1.
RefSeqiNP_446226.2. NM_053774.2.
XP_006242923.1. XM_006242861.2. [Q5U349-1]
XP_006242925.1. XM_006242863.2. [Q5U349-2]
UniGeneiRn.168987.
Rn.203590.

3D structure databases

ProteinModelPortaliQ5U349.
SMRiQ5U349. Positions 276-613.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250433. 2 interactions.
DIPiDIP-48683N.
STRINGi10116.ENSRNOP00000009975.

Protein family/group databases

MEROPSiC19.013.

Proteomic databases

PaxDbiQ5U349.
PRIDEiQ5U349.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000009975; ENSRNOP00000009975; ENSRNOG00000006663. [Q5U349-1]
ENSRNOT00000036051; ENSRNOP00000030257; ENSRNOG00000006663. [Q5U349-2]
GeneIDi115771.
KEGGirno:115771.
UCSCiRGD:621073. rat. [Q5U349-1]

Organism-specific databases

CTDi9099.
RGDi621073. Usp2.

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00780000121880.
HOGENOMiHOG000231498.
HOVERGENiHBG011164.
InParanoidiQ5U349.
KOiK11833.
OMAiSASHRSY.
OrthoDBiEOG7FR7GN.
PhylomeDBiQ5U349.
TreeFamiTF106277.

Miscellaneous databases

NextBioi618951.
PROiQ5U349.

Gene expression databases

GenevestigatoriQ5U349.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Divergent N-terminal sequences target an inducible testis deubiquitinating enzyme to distinct subcellular structures."
    Lin H., Keriel A., Morales C.R., Bedard N., Zhao Q., Hingamp P., Lefrancois S., Combaret L., Wing S.S.
    Mol. Cell. Biol. 20:6568-6578(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
    Tissue: Testis.
  2. "Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69."
    Park K.C., Kim J.H., Choi E.J., Min S.W., Rhee S., Baek S.H., Chung S.S., Bang O., Park D., Chiba T., Tanaka K., Chung C.H.
    Proc. Natl. Acad. Sci. U.S.A. 99:9733-9738(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF CYS-289, TISSUE SPECIFICITY, DOMAIN.
    Tissue: Skeletal muscle.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  4. "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] (ISOFORM 1).
    Tissue: Heart.
  5. "Expression of USP2-69 in mesangial cells in vivo and in vitro."
    Wang S., Wu H., Liu Y., Sun J., Zhao Z., Chen Q., Guo M., Ma D., Zhang Z.
    Pathol. Int. 60:184-192(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION BY IL-1.
  6. "Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2."
    Yang Y., Duguay D., Bedard N., Rachalski A., Baquiran G., Na C.H., Fahrenkrug J., Storch K.F., Peng J., Wing S.S., Cermakian N.
    Biol. Open 1:789-801(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PER1.

Entry informationi

Entry nameiUBP2_RAT
AccessioniPrimary (citable) accession number: Q5U349
Secondary accession number(s): Q9QXL3
, Q9QXL4, Q9R083, Q9R084
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: December 7, 2004
Last modified: February 4, 2015
This is version 75 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.