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Q5U349

- UBP2_RAT

UniProt

Q5U349 - UBP2_RAT

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Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene
Usp2, Ubp41, Ubp69
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.2 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

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei289 – 2891Nucleophile
Metal bindingi438 – 4381Zinc By similarity
Metal bindingi441 – 4411Zinc By similarity
Metal bindingi489 – 4891Zinc By similarity
Metal bindingi492 – 4921Zinc By similarity
Active sitei570 – 5701Proton acceptor By similarity

GO - Molecular functioni

  1. cysteine-type peptidase activity Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. muscle organ development Source: UniProtKB-KW
  3. negative regulation of skeletal muscle tissue development Source: UniProtKB
  4. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  5. positive regulation of mitotic cell cycle Source: UniProtKB
  6. positive regulation of skeletal muscle tissue development Source: UniProtKB
  7. protein deubiquitination Source: UniProtKB
  8. protein stabilization Source: UniProtKB
  9. ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

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 1 Publication
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.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.3 Publications

Gene expression databases

GenevestigatoriQ5U349.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ5U349.
SMRiQ5U349. Positions 276-613.

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 MDM4 By similarityAdd
BLAST
Regioni416 – 516101Necessary for interaction with MDM4 By 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.

Sequence similaritiesi

Contains 1 USP domain.

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00750000117710.
HOGENOMiHOG000231498.
HOVERGENiHBG011164.
InParanoidiQ9R083.
KOiK11833.
OMAiALELVWQ.
OrthoDBiEOG7FR7GN.
PhylomeDBiQ5U349.
TreeFamiTF106277.

Family and domain databases

InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[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

MSQLSSTLKR YTESSRYTDA PYAKSGYGTY TPSSYGANLA ASFLEKEKLG    50
FKPVSPTSFL PRPRTYGPSS ILDCDRGRPL LRSDITGGSK RSESQTRGNE 100
RPSGSGLNGG SGFPYGVTSN SLSYLPMNAR DQGVTLGQKK SNSQSDLARD 150
FSSLRTSDSY RTSDGYRASD GFRIDPGNLG RSPMLARTRK ELCALQGLYQ 200
AASRSEYLTD YLENYGRKGS APQVLTQAPP SRVPEVLSPT YRPSGRYTLW 250
EKNKGQASGP SRSTSPGRDT MNSKSAQGLA GLRNLGNTCF MNSILQCLSN 300
TRELRDYCLQ RLYMRDLGHT SSAHTALMEE FAKLIQTIWT SSPNDVVSPS 350
EFKTQIQRYA PRFVGYNQQD AQEFLRFLLD GLHNEVNRVA ARPKPSPESL 400
DHLPDEEKGR QMWRKYLERE DSRIGDLFVG QLKSSLTCTD CGYCSTVFDP 450
FWDLSLPIAK RGYPEVTLMD CMRLFTKEDV LDGDEKPTCC RCRARKRCIK 500
KFSVQRFPKI LVLHLKRFSE SRIRTSKLTT FVNFPLRDLD LREFASENTN 550
HAVYNLYAVS NHSGTTMGGH YTAYCRSPVT GEWHTFNDSS VTPMSSSQVR 600
TSDAYLLFYE LASPPSRM 618

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 271271MSQLS…GRDTM → MRTSYTVTLPEEPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2. VSP_039561Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti172 – 1721F → S in AAF17574. 1 Publication
Sequence conflicti202 – 2021A → T in AAF14190. 1 Publication
Sequence conflicti260 – 2601P → A in AAF17574. 1 Publication
Sequence conflicti607 – 6071L → F in AAF14189. 1 Publication
Sequence conflicti607 – 6071L → F in AAF14190. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006242861.1. [Q5U349-1]
XP_006242924.1. XM_006242862.1. [Q5U349-1]
XP_006242925.1. XM_006242863.1. [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:
EMBL
GenBank
DDBJ
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 .
RefSeqi NP_446226.2. NM_053774.2.
XP_006242923.1. XM_006242861.1. [Q5U349-1 ]
XP_006242924.1. XM_006242862.1. [Q5U349-1 ]
XP_006242925.1. XM_006242863.1. [Q5U349-2 ]
UniGenei Rn.168987.
Rn.203590.

3D structure databases

ProteinModelPortali Q5U349.
SMRi Q5U349. Positions 276-613.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 250433. 2 interactions.
DIPi DIP-48683N.
STRINGi 10116.ENSRNOP00000009975.

Protein family/group databases

MEROPSi C19.013.

Proteomic databases

PaxDbi Q5U349.
PRIDEi Q5U349.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000009975 ; ENSRNOP00000009975 ; ENSRNOG00000006663 . [Q5U349-1 ]
ENSRNOT00000036051 ; ENSRNOP00000030257 ; ENSRNOG00000006663 . [Q5U349-2 ]
GeneIDi 115771.
KEGGi rno:115771.
UCSCi RGD:621073. rat. [Q5U349-1 ]

Organism-specific databases

CTDi 9099.
RGDi 621073. Usp2.

Phylogenomic databases

eggNOGi COG5533.
GeneTreei ENSGT00750000117710.
HOGENOMi HOG000231498.
HOVERGENi HBG011164.
InParanoidi Q9R083.
KOi K11833.
OMAi ALELVWQ.
OrthoDBi EOG7FR7GN.
PhylomeDBi Q5U349.
TreeFami TF106277.

Miscellaneous databases

NextBioi 618951.
PROi Q5U349.

Gene expression databases

Genevestigatori Q5U349.

Family and domain databases

InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view ]
Pfami PF00443. UCH. 1 hit.
[Graphical view ]
PROSITEi PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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.
    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.

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: May 14, 2014
This is version 70 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