O88623 · UBP2_MOUSE

  • Protein
    Ubiquitin carboxyl-terminal hydrolase 2
  • Gene
    Usp2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (By similarity).
Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity).
Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (By similarity).
Has no deubiquitinase activity against p53/TP53 (By similarity).
Prevents MDM2-mediated degradation of MDM4 (By similarity).
Plays a role in the G1/S cell-cycle progression in normal and cancer cells (By similarity).
Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity).
Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (PubMed:23213472, PubMed:25238854, PubMed:26756164).
Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (PubMed:23213472).
Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and BMAL1 (PubMed:25238854).

Isoform 2

Circadian clock output effector that regulates Ca2+ absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca2+ membrane permeability mediated by the Ca2+ channel TRPV6 in the intestine.

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).
    EC:3.4.19.12 (UniProtKB | ENZYME | Rhea)

Activity regulation

Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde.

Features

Showing features for active site, binding site.

TypeIDPosition(s)Description
Active site290Nucleophile
Binding site439Zn2+ (UniProtKB | ChEBI)
Binding site442Zn2+ (UniProtKB | ChEBI)
Binding site490Zn2+ (UniProtKB | ChEBI)
Binding site493Zn2+ (UniProtKB | ChEBI)
Active site571Proton acceptor

GO annotations

AspectTerm
Cellular Componentcentrosome
Cellular Componentcytoplasm
Cellular Componentmembrane
Cellular Componentnucleus
Cellular Componentperinuclear region of cytoplasm
Molecular Functioncyclin binding
Molecular Functioncysteine-type deubiquitinase activity
Molecular Functionidentical protein binding
Molecular Functionmetal ion binding
Molecular Functionubiquitin protein ligase binding
Biological Processcircadian behavior
Biological Processcircadian regulation of gene expression
Biological Processentrainment of circadian clock by photoperiod
Biological Processlocomotor rhythm
Biological Processmuscle organ development
Biological Processnegative regulation of calcium ion transport
Biological Processnegative regulation of skeletal muscle tissue development
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processpositive regulation of mitotic cell cycle
Biological Processpositive regulation of skeletal muscle tissue development
Biological Processprotein deubiquitination
Biological Processprotein stabilization
Biological Processproteolysis

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Ubiquitin carboxyl-terminal hydrolase 2
  • EC number
  • Alternative names
    • 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

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O88623
  • Secondary accessions
    • Q6X4T9
    • Q6X4U1
    • Q8VD74
    • Q9JJ87

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Note: Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane.

Isoform 2

Nucleus
Membrane
; Peripheral membrane protein
Cytoplasm
Note: Predominantly expressed at membranes.

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000806171-619Ubiquitin carboxyl-terminal hydrolase 2

Proteomic databases

PTM databases

Expression

Tissue specificity

Isoform 1: Expressed in heart, liver, kidney, pancreas and to a lower extent in skeletal muscle, brain and testis (at protein level) (PubMed:14686789).
Expressed in testis, brain, heart and skeletal muscle (PubMed:14686789, PubMed:26756164).
Not detected in the small intestine (PubMed:26756164).
Isoform 2: Expressed in the small intestine (PubMed:26756164).

Induction

Isoform 2

Expressed in a circadian manner in the intestine.

Developmental stage

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

Gene expression databases

Interaction

Subunit

Found in trimeric complex with MDM2 and MDM4 and USP2. 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 and PER1 (By similarity).
Homooligomer. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores plasma membrane localization of KCNQ1 (By similarity).
Isoform 2: Interacts with NHERF4 and CLTC (PubMed:26756164).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region1-23Disordered
Region1-213Necessary for interaction with MDM4
Region54-112Disordered
Compositional bias87-112Polar residues
Compositional bias133-164Polar residues
Region133-175Disordered
Region221-275Disordered
Compositional bias255-275Polar residues
Domain281-613USP
Region417-517Necessary for interaction with MDM4

Domain

The different N-terminus extensions of isoform 1 and isoform 2 determine their respective subcellular localization and differential 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.

Sequence similarities

Belongs to the peptidase C19 family. USP2 subfamily.

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

O88623-3

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.

  • Length
    619
  • Mass (Da)
    69,525
  • Last updated
    2022-12-14 v3
  • Checksum
    93A6F2B9269316F8
MSQLSSTLKRYTESSRYTDAPYAKPGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDIIGSSKRSESQTRGNERPSGSGLNGGSGFSYGVSSNSLSYLPMNARDQGVTLSQKKSNSQSDLARDFSSLRTSDGYRTSDGYRTSEGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLENYGRKGSAPQVLTQAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTMNSKSAQGLAGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLGHTSSAHTALMEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFMGYNQQDAQEFLRFLLDGLHNEVNRVAARPKASPETLDHLPDEEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDILDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPVTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELASPPSRM

O88623-2

  • Name
    2
  • Synonyms
    Usp2-45
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-223: Missing
    • 224-272: VLTQAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTM → MRTSYTVTLPEEPPAAHFPALAKELRPRSPLSPSLLLSTFVGLLLNKAK

O88623-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-226: Missing
    • 227-274: QAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTMNS → MRTSYTVTLPEEPPAAHFPALAKELRPRSPLSPSLLLSTFVGLLLNKA

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
H3BLN9H3BLN9_MOUSEUsp2174
H3BLH3H3BLH3_MOUSEUsp243

Features

Showing features for alternative sequence, sequence conflict, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0617461-223in isoform 2
Alternative sequenceVSP_0617451-226in isoform 4
Sequence conflict44In isoform O88623-2; in Ref. 5; AAC28393
Compositional bias87-112Polar residues
Compositional bias133-164Polar residues
Sequence conflict164-169in Ref. 1; AAQ83303
Alternative sequenceVSP_061747224-272in isoform 2
Alternative sequenceVSP_061748227-274in isoform 4
Compositional bias255-275Polar residues
Sequence conflict267in Ref. 5; AAC28393

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY255637
EMBL· GenBank· DDBJ
AAQ83301.1
EMBL· GenBank· DDBJ
mRNA
AY255638
EMBL· GenBank· DDBJ
AAQ83302.1
EMBL· GenBank· DDBJ
mRNA
AY255639
EMBL· GenBank· DDBJ
AAQ83303.1
EMBL· GenBank· DDBJ
mRNA
AY255640
EMBL· GenBank· DDBJ
AAQ83304.1
EMBL· GenBank· DDBJ
mRNA
AB041799
EMBL· GenBank· DDBJ
BAA95110.1
EMBL· GenBank· DDBJ
mRNA
AK138799
EMBL· GenBank· DDBJ
BAE23782.1
EMBL· GenBank· DDBJ
mRNA
BC017517
EMBL· GenBank· DDBJ
AAH17517.1
EMBL· GenBank· DDBJ
mRNA
AF079565
EMBL· GenBank· DDBJ
AAC28393.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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