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Q5U349

- UBP2_RAT

UniProt

Q5U349 - UBP2_RAT

Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene

Usp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 71 (01 Oct 2014)
      Sequence version 1 (07 Dec 2004)
      Previous versions | rss
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    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.By similarity2 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.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei289 – 2891Nucleophile
    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 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

    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
    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.

    GO - Cellular componenti

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

    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 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.By similarity

    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.

    Sequence similaritiesi

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

    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

    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:
    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

    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: October 1, 2014
    This is version 71 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