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. Homooligomer. 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. Down-regulated by cisplatin. Expressed in mesangial cells of the kidney and in different types of glomerulonephritides. Cleavage is inhibited by ubiquitin in a dosage- dependent manner. Cleavage is blocked by ubiquitin aldehyde. Belongs to the peptidase C19 family. USP2 subfamily. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Protease; Ubiquitin-specific protease; EC 184.108.40.206
Cellular Component: centrosome; perinuclear region of cytoplasm; cytoplasm; cell cortex; nucleus
Molecular Function: identical protein binding; protein binding; cyclin binding; metal ion binding; cysteine-type endopeptidase activity; ubiquitin protein ligase binding; ubiquitin-specific protease activity
Biological Process: locomotor rhythm; proteasomal ubiquitin-dependent protein catabolic process; negative regulation of skeletal muscle development; muscle development; protein deubiquitination; protein stabilization; negative regulation of transcription from RNA polymerase II promoter; circadian regulation of gene expression; positive regulation of skeletal muscle development; positive regulation of mitotic cell cycle; cell cycle; circadian behavior; entrainment of circadian clock by photoperiod
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.