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O88623 (UBP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
Gene names
Name:Usp2
Synonyms:Ubp41
ORF Names:MNCb-0190
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length613 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 2 possess 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 By similarity.

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. Cleavage is blocked by ubiquitin aldehyde By similarity.

Subunit structure

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. Homooligomer. Ref.1

Subcellular location

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

Isoform 2: Nucleus By similarity Ref.1.

Tissue specificity

Isoform 1 is expressed in heart, liver, kidney, pancreas and to a lower extent in skeletal muscle, brain and testis (at protein level). Expressed in testis, brain, heart and skeletal muscle. Ref.1

Developmental stage

No stage-dependent developmental pattern of expression is detected. First detected throughout 7.5 dpc embryos. Ref.1

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 4 are not essential for their catalytic activity By similarity.

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 electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

protein deubiquitination

Inferred from sequence or structural similarity. 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 direct assay Ref.1. Source: MGI

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.1. Source: MGI

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functioncysteine-type peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from direct assay Ref.1. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin thiolesterase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88623-1)

Also known as: Usp2-69;

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.
Isoform 2 (identifier: O88623-2)

Also known as: Usp2-45;

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-266: VLTQAPPPSR...RSSSPGRDTM → MRTSYTVTLP...FVGLLLNKAK
Isoform 3 (identifier: O88623-3)

The sequence of this isoform differs from the canonical sequence as follows:
     154-154: L → LRTSDGY
Isoform 4 (identifier: O88623-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-220: Missing.
     221-268: QAPPPSRVPE...SSPGRDTMNS → MRTSYTVTLP...TFVGLLLNKA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 613613Ubiquitin carboxyl-terminal hydrolase 2
PRO_0000080617

Regions

Domain275 – 607333USP
Region1 – 207207Necessary for interaction with MDM4 By similarity
Region411 – 511101Necessary for interaction with MDM4 By similarity

Sites

Active site2841Nucleophile By similarity
Active site5651Proton acceptor By similarity
Metal binding4331Zinc By similarity
Metal binding4361Zinc By similarity
Metal binding4841Zinc By similarity
Metal binding4871Zinc By similarity

Natural variations

Alternative sequence1 – 220220Missing in isoform 4.
VSP_020130
Alternative sequence1 – 217217Missing in isoform 2.
VSP_020131
Alternative sequence1541L → LRTSDGY in isoform 3.
VSP_020132
Alternative sequence218 – 26649VLTQA…GRDTM → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2.
VSP_020133
Alternative sequence221 – 26848QAPPP…DTMNS → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKA in isoform 4.
VSP_020134

Experimental info

Isoform 2:
Sequence conflict441L → M in AAC28393. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Usp2-69) [UniParc].

Last modified September 5, 2006. Version 2.
Checksum: 7B5DD3594A42C445

FASTA61368,845
        10         20         30         40         50         60 
MSQLSSTLKR YTESSRYTDA PYAKPGYGTY TPSSYGANLA ASFLEKEKLG FKPVSPTSFL 

        70         80         90        100        110        120 
PRPRTYGPSS ILDCDRGRPL LRSDIIGSSK RSESQTRGNE RPSGSGLNGG SGFSYGVSSN 

       130        140        150        160        170        180 
SLSYLPMNAR DQGVTLSQKK SNSQSDLARD FSSLRTSDGY RTSEGFRIDP GNLGRSPMLA 

       190        200        210        220        230        240 
RTRKELCALQ GLYQAASRSE YLTDYLENYG RKGSAPQVLT QAPPPSRVPE VLSPTYRPSG 

       250        260        270        280        290        300 
RYTLWEKSKG QASGPSRSSS PGRDTMNSKS AQGLAGLRNL GNTCFMNSIL QCLSNTRELR 

       310        320        330        340        350        360 
DYCLQRLYMR DLGHTSSAHT ALMEEFAKLI QTIWTSSPND VVSPSEFKTQ IQRYAPRFMG 

       370        380        390        400        410        420 
YNQQDAQEFL RFLLDGLHNE VNRVAARPKA SPETLDHLPD EEKGRQMWRK YLEREDSRIG 

       430        440        450        460        470        480 
DLFVGQLKSS LTCTDCGYCS TVFDPFWDLS LPIAKRGYPE VTLMDCMRLF TKEDILDGDE 

       490        500        510        520        530        540 
KPTCCRCRAR KRCIKKFSVQ RFPKILVLHL KRFSESRIRT SKLTTFVNFP LRDLDLREFA 

       550        560        570        580        590        600 
SENTNHAVYN LYAVSNHSGT TMGGHYTAYC RSPVTGEWHT FNDSSVTPMS SSQVRTSDAY 

       610 
LLFYELASPP SRM 

« Hide

Isoform 2 (Usp2-45) [UniParc].

Checksum: 14CC674DC08FFF93
Show »

FASTA39645,238
Isoform 3 [UniParc].

Checksum: 93A6F2B9269316F8
Show »

FASTA61969,525
Isoform 4 [UniParc].

Checksum: F4715ABDE436573B
Show »

FASTA39344,908

References

« Hide 'large scale' references
[1]"Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69."
Gousseva N., Baker R.T.
Gene Expr. 11:163-179(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, SUBUNIT.
Strain: C57BL/6.
Tissue: Kidney and Retina.
[2]"Isolation of full-length cDNA clones from mouse brain cDNA library made by oligo-capping method."
Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Strain: C57BL/6.
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: C57BL/6J.
Tissue: Thymus.
[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 3).
Strain: C57BL/6.
Tissue: Retina.
[5]"Cloning and expression of the human and mouse UBP41."
Gong L., Yeh E.T.H.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 261-613 (ISOFORM 2).
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY255637 mRNA. Translation: AAQ83301.1.
AY255638 mRNA. Translation: AAQ83302.1.
AY255639 mRNA. Translation: AAQ83303.1.
AY255640 mRNA. Translation: AAQ83304.1.
AB041799 mRNA. Translation: BAA95110.1.
AK138799 mRNA. Translation: BAE23782.1.
BC017517 mRNA. Translation: AAH17517.1.
AF079565 mRNA. Translation: AAC28393.1.
RefSeqNP_058088.2. NM_016808.2.
NP_932759.1. NM_198091.2.
NP_932760.2. NM_198092.2.
XP_006510543.1. XM_006510480.1.
XP_006510544.1. XM_006510481.1.
XP_006510545.1. XM_006510482.1.
XP_006510546.1. XM_006510483.1.
UniGeneMm.272770.

3D structure databases

ProteinModelPortalO88623.
SMRO88623. Positions 271-608.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207299. 12 interactions.

Protein family/group databases

MEROPSC19.013.

PTM databases

PhosphoSiteO88623.

Proteomic databases

PRIDEO88623.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034508; ENSMUSP00000034508; ENSMUSG00000032010. [O88623-3]
ENSMUST00000065461; ENSMUSP00000070264; ENSMUSG00000032010. [O88623-2]
ENSMUST00000114830; ENSMUSP00000110479; ENSMUSG00000032010. [O88623-3]
ENSMUST00000176416; ENSMUSP00000135482; ENSMUSG00000032010. [O88623-4]
ENSMUST00000177054; ENSMUSP00000135018; ENSMUSG00000032010. [O88623-3]
GeneID53376.
KEGGmmu:53376.
UCSCuc009pbn.1. mouse. [O88623-3]
uc009pbp.1. mouse. [O88623-2]
uc012grp.1. mouse. [O88623-4]

Organism-specific databases

CTD9099.
MGIMGI:1858178. Usp2.

Phylogenomic databases

eggNOGCOG5533.
GeneTreeENSGT00750000117710.
HOGENOMHOG000231498.
HOVERGENHBG011164.
InParanoidO88623.
KOK11833.
OMASASHRSY.
OrthoDBEOG7FR7GN.
PhylomeDBO88623.
TreeFamTF106277.

Gene expression databases

ArrayExpressO88623.
BgeeO88623.
CleanExMM_USP2.
GenevestigatorO88623.

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

NextBio310185.
PROO88623.
SOURCESearch...

Entry information

Entry nameUBP2_MOUSE
AccessionPrimary (citable) accession number: O88623
Secondary accession number(s): Q6X4T9 expand/collapse secondary AC list , Q6X4U1, Q8VD74, Q9JJ87
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 5, 2006
Last modified: April 16, 2014
This is version 101 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot