Q5U349 · UBP2_RAT
- ProteinUbiquitin carboxyl-terminal hydrolase 2
- GeneUsp2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids618 (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 (PubMed:12107281).
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).
Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (PubMed:23213472).
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 (By similarity).
Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (PubMed:12107281).
Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities (PubMed:12107281).
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).
Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (PubMed:23213472).
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 (By similarity).
Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (PubMed:12107281).
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 (By similarity).
Cleavage is blocked by ubiquitin aldehyde
Cleavage is blocked by ubiquitin aldehyde
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 289 | Nucleophile | ||||
Sequence: C | ||||||
Binding site | 438 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 441 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 489 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 492 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Active site | 570 | 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 > Rattus
Accessions
- Primary accessionQ5U349
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
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
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 289 | Loss of enzymatic activity. Reduces both membrane fusion during myogenesis and accumulation of muscle-specific proteins. | ||||
Sequence: C → S |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000395966 | 1-618 | Ubiquitin carboxyl-terminal hydrolase 2 | |||
Sequence: MSQLSSTLKRYTESSRYTDAPYAKSGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDITGGSKRSESQTRGNERPSGSGLNGGSGFPYGVTSNSLSYLPMNARDQGVTLGQKKSNSQSDLARDFSSLRTSDSYRTSDGYRASDGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLENYGRKGSAPQVLTQAPPSRVPEVLSPTYRPSGRYTLWEKNKGQASGPSRSTSPGRDTMNSKSAQGLAGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLGHTSSAHTALMEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFVGYNQQDAQEFLRFLLDGLHNEVNRVAARPKPSPESLDHLPDEEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDVLDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPVTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELASPPSRM |
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Induction
Up-regulated by IL-1. Isoform 1 is up-regulated with any signal for withdrawal from the cell cycle such as serum deprivation.
Gene expression databases
Interaction
Subunit
Homooligomer. 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 (By similarity).
Interacts with PER1. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores plasma membrane localization of KCNQ1 (By similarity).
Isoform 4: Interacts with NHERF4 and CLTC (By similarity).
Interacts with PER1. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores plasma membrane localization of KCNQ1 (By similarity).
Isoform 4: Interacts with NHERF4 and CLTC (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-213 | Necessary for interaction with MDM4 | ||||
Sequence: MSQLSSTLKRYTESSRYTDAPYAKSGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDITGGSKRSESQTRGNERPSGSGLNGGSGFPYGVTSNSLSYLPMNARDQGVTLGQKKSNSQSDLARDFSSLRTSDSYRTSDGYRASDGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLE | ||||||
Region | 54-112 | Disordered | ||||
Sequence: VSPTSFLPRPRTYGPSSILDCDRGRPLLRSDITGGSKRSESQTRGNERPSGSGLNGGSG | ||||||
Compositional bias | 87-112 | Polar residues | ||||
Sequence: GGSKRSESQTRGNERPSGSGLNGGSG | ||||||
Region | 246-274 | Disordered | ||||
Sequence: RYTLWEKNKGQASGPSRSTSPGRDTMNSK | ||||||
Compositional bias | 254-274 | Polar residues | ||||
Sequence: KGQASGPSRSTSPGRDTMNSK | ||||||
Domain | 280-612 | USP | ||||
Sequence: AGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLGHTSSAHTALMEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFVGYNQQDAQEFLRFLLDGLHNEVNRVAARPKPSPESLDHLPDEEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDVLDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPVTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELA | ||||||
Region | 416-516 | Necessary for interaction with MDM4 | ||||
Sequence: YLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDVLDGDEKPTCCRCRARKRCIKKFSVQRFPKILVLHLK |
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 2 are not essential for their catalytic activity.
Sequence similarities
Belongs to the peptidase C19 family. USP2 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q5U349-1
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.
- Name1
- SynonymsUbp69, Ubp-t2
- NoteStimulates both membrane fusion during myogenesis and accumulation of muscle-specific proteins.
- Length618
- Mass (Da)69,363
- Last updated2004-12-07 v1
- ChecksumB8B2091192CA4944
Q5U349-2
- Name2
- SynonymsUbp45, Ubp-t1
- NoteInhibits both membrane fusion during myogenesis and accumulation of muscle-specific proteins.
- Differences from canonical
- 1-271: MSQLSSTLKRYTESSRYTDAPYAKSGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDITGGSKRSESQTRGNERPSGSGLNGGSGFPYGVTSNSLSYLPMNARDQGVTLGQKKSNSQSDLARDFSSLRTSDSYRTSDGYRASDGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLENYGRKGSAPQVLTQAPPSRVPEVLSPTYRPSGRYTLWEKNKGQASGPSRSTSPGRDTM → MRTSYTVTLPEEPPAAPFPALAKELRPRSPLSPSLLLSTFVGLLLNKAK
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2Q4I7 | A0A8L2Q4I7_RAT | Usp2 | 612 |
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_039561 | 1-271 | in isoform 2 | |||
Sequence: MSQLSSTLKRYTESSRYTDAPYAKSGYGTYTPSSYGANLAASFLEKEKLGFKPVSPTSFLPRPRTYGPSSILDCDRGRPLLRSDITGGSKRSESQTRGNERPSGSGLNGGSGFPYGVTSNSLSYLPMNARDQGVTLGQKKSNSQSDLARDFSSLRTSDSYRTSDGYRASDGFRIDPGNLGRSPMLARTRKELCALQGLYQAASRSEYLTDYLENYGRKGSAPQVLTQAPPSRVPEVLSPTYRPSGRYTLWEKNKGQASGPSRSTSPGRDTM → MRTSYTVTLPEEPPAAPFPALAKELRPRSPLSPSLLLSTFVGLLLNKAK | ||||||
Compositional bias | 87-112 | Polar residues | ||||
Sequence: GGSKRSESQTRGNERPSGSGLNGGSG | ||||||
Sequence conflict | 172 | in Ref. 1; AAF17574 | ||||
Sequence: F → S | ||||||
Sequence conflict | 202 | in Ref. 2; AAF14190 | ||||
Sequence: A → T | ||||||
Compositional bias | 254-274 | Polar residues | ||||
Sequence: KGQASGPSRSTSPGRDTMNSK | ||||||
Sequence conflict | 260 | in Ref. 1; AAF17574 | ||||
Sequence: P → A | ||||||
Sequence conflict | 607 | in Ref. 2; AAF14189/AAF14190 | ||||
Sequence: L → F |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF202453 EMBL· GenBank· DDBJ | AAF17574.1 EMBL· GenBank· DDBJ | mRNA | ||
AF202454 EMBL· GenBank· DDBJ | AAF17575.1 EMBL· GenBank· DDBJ | mRNA | ||
AF106658 EMBL· GenBank· DDBJ | AAF14189.1 EMBL· GenBank· DDBJ | mRNA | ||
AF106659 EMBL· GenBank· DDBJ | AAF14190.1 EMBL· GenBank· DDBJ | mRNA | ||
CH473975 EMBL· GenBank· DDBJ | EDL95274.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH473975 EMBL· GenBank· DDBJ | EDL95276.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH473975 EMBL· GenBank· DDBJ | EDL95277.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC085719 EMBL· GenBank· DDBJ | AAH85719.1 EMBL· GenBank· DDBJ | mRNA |