ID:UBP2_HUMAN DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 2; EC=3.4.19.12; AltName: Full=41 kDa ubiquitin-specific protease; AltName: Full=Deubiquitinating enzyme 2; AltName: Full=Ubiquitin thioesterase 2; AltName: Full=Ubiquitin-specific-processing protease 2; FUNCTION: Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 4 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. 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. ENZYME REGULATION: Cleavage is inhibited by ubiquitin in a dosage- dependent manner. Cleavage is blocked by ubiquitin aldehyde. SUBUNIT: Homooligomer (By similarity). 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. INTERACTION: P19012:KRT15; NbExp=2; IntAct=EBI-743272, EBI-739566; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm, perinuclear 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). SUBCELLULAR LOCATION: Isoform 4: Nucleus (By similarity). TISSUE SPECIFICITY: Expressed in mesangial cells of the kidney and in different types of glomerulonephritides (at protein level). INDUCTION: Down-regulated by cisplatin (at protein level). DOMAIN: The different N-terminus extensions of isoform 1 and isoform 4 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). SIMILARITY: Belongs to the peptidase C19 family. USP2 subfamily.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75604
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004197 cysteine-type endopeptidase activity GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0005515 protein binding GO:0008233 peptidase activity GO:0008234 cysteine-type peptidase activity GO:0016787 hydrolase activity GO:0030332 cyclin binding GO:0031625 ubiquitin protein ligase binding GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0042802 identical protein binding GO:0046872 metal ion binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006508 proteolysis GO:0006511 ubiquitin-dependent protein catabolic process GO:0007049 cell cycle GO:0007517 muscle organ development GO:0016579 protein deubiquitination GO:0032922 circadian regulation of gene expression GO:0043153 entrainment of circadian clock by photoperiod GO:0045475 locomotor rhythm GO:0045931 positive regulation of mitotic cell cycle GO:0048511 rhythmic process GO:0048512 circadian behavior GO:0050821 protein stabilization
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
