O88623 · UBP2_MOUSE
- ProteinUbiquitin carboxyl-terminal hydrolase 2
- GeneUsp2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids619 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 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
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 290 | Nucleophile | ||||
Sequence: C | ||||||
Binding site | 439 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 442 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 490 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 493 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Active site | 571 | Proton acceptor | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin carboxyl-terminal hydrolase 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO88623
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
Membrane ; Peripheral membrane protein
Note: Predominantly expressed at membranes.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000080617 | 1-619 | Ubiquitin carboxyl-terminal hydrolase 2 | |||
Sequence: MSQLSSTLKRYTESSRYTDAPYAKPGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDIIGSSKRSESQTRGNERPSGSGLNGGSGFSYGVSSNSLSYLPMNARDQGVTLSQKKSNSQSDLARDFSSLRTSDGYRTSDGYRTSEGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLENYGRKGSAPQVLTQAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTMNSKSAQGLAGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLGHTSSAHTALMEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFMGYNQQDAQEFLRFLLDGLHNEVNRVAARPKASPETLDHLPDEEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDILDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPVTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELASPPSRM |
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).
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-23 | Disordered | ||||
Sequence: MSQLSSTLKRYTESSRYTDAPYA | ||||||
Region | 1-213 | Necessary for interaction with MDM4 | ||||
Sequence: MSQLSSTLKRYTESSRYTDAPYAKPGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDIIGSSKRSESQTRGNERPSGSGLNGGSGFSYGVSSNSLSYLPMNARDQGVTLSQKKSNSQSDLARDFSSLRTSDGYRTSDGYRTSEGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLE | ||||||
Region | 54-112 | Disordered | ||||
Sequence: VSPTSFLPRPRTYGPSSILDCDRGRPLLRSDIIGSSKRSESQTRGNERPSGSGLNGGSG | ||||||
Compositional bias | 87-112 | Polar residues | ||||
Sequence: GSSKRSESQTRGNERPSGSGLNGGSG | ||||||
Compositional bias | 133-164 | Polar residues | ||||
Sequence: GVTLSQKKSNSQSDLARDFSSLRTSDGYRTSD | ||||||
Region | 133-175 | Disordered | ||||
Sequence: GVTLSQKKSNSQSDLARDFSSLRTSDGYRTSDGYRTSEGFRID | ||||||
Region | 221-275 | Disordered | ||||
Sequence: APQVLTQAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTMNSK | ||||||
Compositional bias | 255-275 | Polar residues | ||||
Sequence: KGQASGPSRSSSPGRDTMNSK | ||||||
Domain | 281-613 | USP | ||||
Sequence: AGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLGHTSSAHTALMEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFMGYNQQDAQEFLRFLLDGLHNEVNRVAARPKASPETLDHLPDEEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDILDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPVTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELA | ||||||
Region | 417-517 | Necessary for interaction with MDM4 | ||||
Sequence: YLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDILDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLK |
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
- Sequence statusComplete
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.
- Name3
- Length619
- Mass (Da)69,525
- Last updated2022-12-14 v3
- Checksum93A6F2B9269316F8
O88623-2
- Name2
- SynonymsUsp2-45
O88623-4
- Name4
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_061746 | 1-223 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_061745 | 1-226 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 44 | In isoform O88623-2; in Ref. 5; AAC28393 | ||||
Sequence: L → M | ||||||
Compositional bias | 87-112 | Polar residues | ||||
Sequence: GSSKRSESQTRGNERPSGSGLNGGSG | ||||||
Compositional bias | 133-164 | Polar residues | ||||
Sequence: GVTLSQKKSNSQSDLARDFSSLRTSDGYRTSD | ||||||
Sequence conflict | 164-169 | in Ref. 1; AAQ83303 | ||||
Sequence: Missing | ||||||
Alternative sequence | VSP_061747 | 224-272 | in isoform 2 | |||
Sequence: VLTQAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTM → MRTSYTVTLPEEPPAAHFPALAKELRPRSPLSPSLLLSTFVGLLLNKAK | ||||||
Alternative sequence | VSP_061748 | 227-274 | in isoform 4 | |||
Sequence: QAPPPSRVPEVLSPTYRPSGRYTLWEKSKGQASGPSRSSSPGRDTMNS → MRTSYTVTLPEEPPAAHFPALAKELRPRSPLSPSLLLSTFVGLLLNKA | ||||||
Compositional bias | 255-275 | Polar residues | ||||
Sequence: KGQASGPSRSSSPGRDTMNSK | ||||||
Sequence conflict | 267 | in Ref. 5; AAC28393 | ||||
Sequence: P → M |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |