ubiquitin carboxyl-terminal hydrolase 2; 41 kD ubiquitin-specific protease; deubiquitinating enzyme 2; ubiquitin thiolesterase 2; ubiquitin-specific-processing protease 2 (USP2, UBP41)

^[1]^[2]

Function

deubiquitinates polyubiquitinated target proteins including as MDM2, MDM4 & CCND1
isoforms 1 & 4 possess both ubiquitin-specific peptidase & isopeptidase activities
deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination & thus indirectly promotes p53/TP53 degradation & 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 & cancer cells
plays a role in the regulation of myogenic differentiation of embryonic muscle cells
thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
cleavage is inhibited by ubiquitin (dose-dependent)
cleavage is blocked by ubiquitin aldehyde
found in trimeric complex with MDM2 & MDM4 & UPB2
interacts with CCND1; the interaction is direct & promotes its stabilization by antagonizing ubiquitin-dependent degradation
interacts (via N-terminus & C-terminus) with MDM2
interacts with MDM4

homooligomer (putative).
the different N-terminus extensions of isoforms 1 & 4 determine their respective subcellular localization & differential effect on myoblast fusion & accumulation of muscle-specific proteins
the different N-terminus extensions of isoforms 1 & 4 are not essential for their catalytic activity
belongs to the peptidase C19 family, USP2 subfamily

cytoplasm, perinuclear region (putative)
localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane & the plasma membrane
isoform 4: nucleus (putative)

expressed in mesangial cells of the kidney & in different types of glomerulonephritis (at protein level)
down-regulated by cisplatin (at protein level)