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Q5U349 (UBP2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Usp2
Synonyms:Ubp41, Ubp69
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length618 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2

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).

Cofactor

Binds 1 zinc ion By similarity.

Enzyme regulation

Cleavage is inhibited by ubiquitin in a dosage-dependent manner By similarity. Cleavage is blocked by ubiquitin aldehyde. Ref.1

Subunit structure

Homooligomer. Found in trimeric complex with MDM2 and MDM4 and UPB2. 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.

Subcellular location

Cytoplasm By similarity Ref.2.

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

Isoform 2: Nucleus Ref.2.

Tissue specificity

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. Ref.1 Ref.2 Ref.5

Induction

Up-regulated by IL-1. Isoform 1 is up-regulated with any signal for withdrawal from the cell cycle such as serum deprivation. Ref.1 Ref.2 Ref.5

Domain

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.

Sequence similarities

Belongs to the peptidase C19 family. USP2 subfamily.

Contains 1 USP domain.

Ontologies

Keywords
   Biological processCell cycle
Myogenesis
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Protease
Thiol protease
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

muscle organ development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of skeletal muscle tissue development

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of skeletal muscle tissue development

Inferred from direct assay Ref.1. Source: UniProtKB

protein deubiquitination

Inferred from direct assay Ref.1. Source: UniProtKB

protein stabilization

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell cortex

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from direct assay Ref.1. Source: RGD

nucleus

Inferred from direct assay Ref.1. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functioncysteine-type peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin thiolesterase activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5U349-1)

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.
Note: Stimulates both membrane fusion during myogenesis and accumulation of muscle-specific proteins.
Isoform 2 (identifier: Q5U349-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 618618Ubiquitin carboxyl-terminal hydrolase 2
PRO_0000395966

Regions

Domain280 – 612333USP
Region1 – 213213Necessary for interaction with MDM4 By similarity
Region416 – 516101Necessary for interaction with MDM4 By similarity

Sites

Active site2891Nucleophile
Active site5701Proton acceptor By similarity
Metal binding4381Zinc By similarity
Metal binding4411Zinc By similarity
Metal binding4891Zinc By similarity
Metal binding4921Zinc By similarity

Natural variations

Alternative sequence1 – 271271MSQLS…GRDTM → MRTSYTVTLPEEPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2.
VSP_039561

Experimental info

Mutagenesis2891C → S: Loss of enzymatic activity. Reduces both membrane fusion during myogenesis and accumulation of muscle-specific proteins. Ref.2
Sequence conflict1721F → S in AAF17574. Ref.1
Sequence conflict2021A → T in AAF14190. Ref.2
Sequence conflict2601P → A in AAF17574. Ref.1
Sequence conflict6071L → F in AAF14189. Ref.2
Sequence conflict6071L → F in AAF14190. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ubp69) (Ubp-t2) [UniParc].

Last modified December 7, 2004. Version 1.
Checksum: B8B2091192CA4944

FASTA61869,363
        10         20         30         40         50         60 
MSQLSSTLKR YTESSRYTDA PYAKSGYGTY TPSSYGANLA ASFLEKEKLG FKPVSPTSFL 

        70         80         90        100        110        120 
PRPRTYGPSS ILDCDRGRPL LRSDITGGSK RSESQTRGNE RPSGSGLNGG SGFPYGVTSN 

       130        140        150        160        170        180 
SLSYLPMNAR DQGVTLGQKK SNSQSDLARD FSSLRTSDSY RTSDGYRASD GFRIDPGNLG 

       190        200        210        220        230        240 
RSPMLARTRK ELCALQGLYQ AASRSEYLTD YLENYGRKGS APQVLTQAPP SRVPEVLSPT 

       250        260        270        280        290        300 
YRPSGRYTLW EKNKGQASGP SRSTSPGRDT MNSKSAQGLA GLRNLGNTCF MNSILQCLSN 

       310        320        330        340        350        360 
TRELRDYCLQ RLYMRDLGHT SSAHTALMEE FAKLIQTIWT SSPNDVVSPS EFKTQIQRYA 

       370        380        390        400        410        420 
PRFVGYNQQD AQEFLRFLLD GLHNEVNRVA ARPKPSPESL DHLPDEEKGR QMWRKYLERE 

       430        440        450        460        470        480 
DSRIGDLFVG QLKSSLTCTD CGYCSTVFDP FWDLSLPIAK RGYPEVTLMD CMRLFTKEDV 

       490        500        510        520        530        540 
LDGDEKPTCC RCRARKRCIK KFSVQRFPKI LVLHLKRFSE SRIRTSKLTT FVNFPLRDLD 

       550        560        570        580        590        600 
LREFASENTN HAVYNLYAVS NHSGTTMGGH YTAYCRSPVT GEWHTFNDSS VTPMSSSQVR 

       610 
TSDAYLLFYE LASPPSRM 

« Hide

Isoform 2 (Ubp45) (Ubp-t1) [UniParc].

Checksum: ED7C91FB5A0964E3
Show »

FASTA39645,164

References

« Hide 'large scale' references
[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.
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_446226.2. NM_053774.2.
XP_006242923.1. XM_006242861.1.
XP_006242924.1. XM_006242862.1.
XP_006242925.1. XM_006242863.1.
UniGeneRn.168987.
Rn.203590.

3D structure databases

ProteinModelPortalQ5U349.
SMRQ5U349. Positions 276-613.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250433. 2 interactions.
DIPDIP-48683N.
STRING10116.ENSRNOP00000009975.

Protein family/group databases

MEROPSC19.013.

Proteomic databases

PaxDbQ5U349.
PRIDEQ5U349.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000009975; ENSRNOP00000009975; ENSRNOG00000006663. [Q5U349-1]
ENSRNOT00000036051; ENSRNOP00000030257; ENSRNOG00000006663. [Q5U349-2]
GeneID115771.
KEGGrno:115771.
UCSCRGD:621073. rat. [Q5U349-1]

Organism-specific databases

CTD9099.
RGD621073. Usp2.

Phylogenomic databases

eggNOGCOG5533.
GeneTreeENSGT00750000117710.
HOGENOMHOG000231498.
HOVERGENHBG011164.
InParanoidQ9R083.
KOK11833.
OMASASHRSY.
OrthoDBEOG7FR7GN.
PhylomeDBQ5U349.
TreeFamTF106277.

Gene expression databases

GenevestigatorQ5U349.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio618951.
PROQ5U349.

Entry information

Entry nameUBP2_RAT
AccessionPrimary (citable) accession number: Q5U349
Secondary accession number(s): Q9QXL3 expand/collapse secondary AC list , Q9QXL4, Q9R083, Q9R084
Entry history
Integrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries