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O88623

- UBP2_MOUSE

UniProt

O88623 - UBP2_MOUSE

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Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene

Usp2

Organism
Mus musculus (Mouse)
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. 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).By similarity

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. Cleavage is blocked by ubiquitin aldehyde (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei284 – 2841NucleophilePROSITE-ProRule annotation
Metal bindingi433 – 4331ZincBy similarity
Metal bindingi436 – 4361ZincBy similarity
Metal bindingi484 – 4841ZincBy similarity
Metal bindingi487 – 4871ZincBy similarity
Active sitei565 – 5651Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. identical protein binding Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. ubiquitin-specific protease activity Source: Ensembl
  4. 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: Ensembl
  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: Ensembl
  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
Gene namesi
Name:Usp2
Synonyms:Ubp41
ORF Names:MNCb-0190
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1858178. Usp2.

Subcellular locationi

Cytoplasm 1 Publication. 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
Isoform 2 : Nucleus By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 613613Ubiquitin carboxyl-terminal hydrolase 2PRO_0000080617Add
BLAST

Proteomic databases

MaxQBiO88623.
PRIDEiO88623.

PTM databases

PhosphoSiteiO88623.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

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

Gene expression databases

BgeeiO88623.
CleanExiMM_USP2.
ExpressionAtlasiO88623. baseline and differential.
GenevestigatoriO88623.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

BioGridi207299. 12 interactions.

Structurei

3D structure databases

ProteinModelPortaliO88623.
SMRiO88623. Positions 271-608.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini275 – 607333USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 207207Necessary for interaction with MDM4By similarityAdd
BLAST
Regioni411 – 511101Necessary 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 4 are not essential for their catalytic activity (By similarity).By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00760000119208.
HOGENOMiHOG000231498.
HOVERGENiHBG011164.
InParanoidiO88623.
KOiK11833.
OMAiSASHRSY.
OrthoDBiEOG7FR7GN.
PhylomeDBiO88623.
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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O88623-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MSQLSSTLKR YTESSRYTDA PYAKPGYGTY TPSSYGANLA ASFLEKEKLG
60 70 80 90 100
FKPVSPTSFL PRPRTYGPSS ILDCDRGRPL LRSDIIGSSK RSESQTRGNE
110 120 130 140 150
RPSGSGLNGG SGFSYGVSSN SLSYLPMNAR DQGVTLSQKK SNSQSDLARD
160 170 180 190 200
FSSLRTSDGY RTSEGFRIDP GNLGRSPMLA RTRKELCALQ GLYQAASRSE
210 220 230 240 250
YLTDYLENYG RKGSAPQVLT QAPPPSRVPE VLSPTYRPSG RYTLWEKSKG
260 270 280 290 300
QASGPSRSSS PGRDTMNSKS AQGLAGLRNL GNTCFMNSIL QCLSNTRELR
310 320 330 340 350
DYCLQRLYMR DLGHTSSAHT ALMEEFAKLI QTIWTSSPND VVSPSEFKTQ
360 370 380 390 400
IQRYAPRFMG YNQQDAQEFL RFLLDGLHNE VNRVAARPKA SPETLDHLPD
410 420 430 440 450
EEKGRQMWRK YLEREDSRIG DLFVGQLKSS LTCTDCGYCS TVFDPFWDLS
460 470 480 490 500
LPIAKRGYPE VTLMDCMRLF TKEDILDGDE KPTCCRCRAR KRCIKKFSVQ
510 520 530 540 550
RFPKILVLHL KRFSESRIRT SKLTTFVNFP LRDLDLREFA SENTNHAVYN
560 570 580 590 600
LYAVSNHSGT TMGGHYTAYC RSPVTGEWHT FNDSSVTPMS SSQVRTSDAY
610
LLFYELASPP SRM
Length:613
Mass (Da):68,845
Last modified:September 5, 2006 - v2
Checksum:i7B5DD3594A42C445
GO
Isoform 2 (identifier: O88623-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:396
Mass (Da):45,238
Checksum:i14CC674DC08FFF93
GO
Isoform 3 (identifier: O88623-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     154-154: L → LRTSDGY

Show »
Length:619
Mass (Da):69,525
Checksum:i93A6F2B9269316F8
GO
Isoform 4 (identifier: O88623-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:393
Mass (Da):44,908
Checksum:iF4715ABDE436573B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Isoform 2 (identifier: O88623-2)
Sequence conflicti44 – 441L → M in AAC28393. 1 PublicationCurated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 220220Missing in isoform 4. 1 PublicationVSP_020130Add
BLAST
Alternative sequencei1 – 217217Missing in isoform 2. 2 PublicationsVSP_020131Add
BLAST
Alternative sequencei154 – 1541L → LRTSDGY in isoform 3. 3 PublicationsVSP_020132
Alternative sequencei218 – 26649VLTQA…GRDTM → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2. 2 PublicationsVSP_020133Add
BLAST
Alternative sequencei221 – 26848QAPPP…DTMNS → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKA in isoform 4. 1 PublicationVSP_020134Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS23094.1. [O88623-3]
CCDS23095.1. [O88623-2]
RefSeqiNP_058088.2. NM_016808.2. [O88623-3]
NP_932759.1. NM_198091.2. [O88623-2]
NP_932760.2. NM_198092.2. [O88623-3]
XP_006510543.1. XM_006510480.1. [O88623-3]
XP_006510544.1. XM_006510481.1. [O88623-3]
XP_006510545.1. XM_006510482.1. [O88623-3]
XP_006510546.1. XM_006510483.1. [O88623-3]
UniGeneiMm.272770.

Genome annotation databases

EnsembliENSMUST00000034508; ENSMUSP00000034508; ENSMUSG00000032010. [O88623-3]
ENSMUST00000065461; ENSMUSP00000070264; ENSMUSG00000032010. [O88623-2]
ENSMUST00000114830; ENSMUSP00000110479; ENSMUSG00000032010. [O88623-3]
ENSMUST00000176416; ENSMUSP00000135482; ENSMUSG00000032010. [O88623-4]
ENSMUST00000177054; ENSMUSP00000135018; ENSMUSG00000032010. [O88623-3]
GeneIDi53376.
KEGGimmu:53376.
UCSCiuc009pbn.1. mouse. [O88623-3]
uc009pbp.1. mouse. [O88623-2]
uc012grp.1. mouse. [O88623-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS23094.1. [O88623-3 ]
CCDS23095.1. [O88623-2 ]
RefSeqi NP_058088.2. NM_016808.2. [O88623-3 ]
NP_932759.1. NM_198091.2. [O88623-2 ]
NP_932760.2. NM_198092.2. [O88623-3 ]
XP_006510543.1. XM_006510480.1. [O88623-3 ]
XP_006510544.1. XM_006510481.1. [O88623-3 ]
XP_006510545.1. XM_006510482.1. [O88623-3 ]
XP_006510546.1. XM_006510483.1. [O88623-3 ]
UniGenei Mm.272770.

3D structure databases

ProteinModelPortali O88623.
SMRi O88623. Positions 271-608.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 207299. 12 interactions.

Protein family/group databases

MEROPSi C19.013.

PTM databases

PhosphoSitei O88623.

Proteomic databases

MaxQBi O88623.
PRIDEi O88623.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000034508 ; ENSMUSP00000034508 ; ENSMUSG00000032010 . [O88623-3 ]
ENSMUST00000065461 ; ENSMUSP00000070264 ; ENSMUSG00000032010 . [O88623-2 ]
ENSMUST00000114830 ; ENSMUSP00000110479 ; ENSMUSG00000032010 . [O88623-3 ]
ENSMUST00000176416 ; ENSMUSP00000135482 ; ENSMUSG00000032010 . [O88623-4 ]
ENSMUST00000177054 ; ENSMUSP00000135018 ; ENSMUSG00000032010 . [O88623-3 ]
GeneIDi 53376.
KEGGi mmu:53376.
UCSCi uc009pbn.1. mouse. [O88623-3 ]
uc009pbp.1. mouse. [O88623-2 ]
uc012grp.1. mouse. [O88623-4 ]

Organism-specific databases

CTDi 9099.
MGIi MGI:1858178. Usp2.

Phylogenomic databases

eggNOGi COG5533.
GeneTreei ENSGT00760000119208.
HOGENOMi HOG000231498.
HOVERGENi HBG011164.
InParanoidi O88623.
KOi K11833.
OMAi SASHRSY.
OrthoDBi EOG7FR7GN.
PhylomeDBi O88623.
TreeFami TF106277.

Miscellaneous databases

NextBioi 310185.
PROi O88623.
SOURCEi Search...

Gene expression databases

Bgeei O88623.
CleanExi MM_USP2.
ExpressionAtlasi O88623. baseline and differential.
Genevestigatori O88623.

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. "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.
    , 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.

Entry informationi

Entry nameiUBP2_MOUSE
AccessioniPrimary (citable) accession number: O88623
Secondary accession number(s): Q6X4T9
, Q6X4U1, Q8VD74, Q9JJ87
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 5, 2006
Last modified: November 26, 2014
This is version 106 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3