USP2 Antibody – Rabbit Polyclonal

This gene encodes a member of the family of de-ubiquitinating enzymes, which belongs to the peptidase C19 superfamily. The encoded protein is a ubiquitin-specific protease which is required for TNF-alpha (tumor necrosis factor alpha) -induced NF-kB (nuclear factor kB) signaling. This protein deubiquitinates polyubiquitinated target proteins such as fatty acid synthase, murine double minute 2 (MDM2), MDM4/MDMX and cyclin D1. MDM2 and MDM4 are negative regulators of the p53 tumor suppressor and cyclin D1 is required for cell cycle G1/S transition. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

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. Ref.8 Ref.9 Ref.10

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. Ref.13

Subunit structure: 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. Ref.8 Ref.9 Ref.10

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.Isoform 4: Nucleus

By similarity.

Tissue specificity: Expressed in mesangial cells of the kidney and in different types of glomerulonephritides (at protein level). Ref.11

Induction: Down-regulated by cisplatin (at protein level). Ref.10 Ref.13

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.

Sequence similarities: Belongs to the peptidase C19 family. USP2 subfamily.