USP2

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.

Full Name

Ubiquitin Specific Peptidase 2

Function

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19917254, PubMed:19838211).
Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity).
Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211).
Has no deubiquitinase activity against p53/TP53 (PubMed:17290220).
Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220).
Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254).
Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity).
Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity).
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 (By similarity).
Isoform 4
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.

Biological Process

Biological Process cell cycle Source:UniProtKB-KW
Biological Process circadian behavior Source:UniProtKB
Biological Process circadian regulation of gene expression Source:UniProtKB
Biological Process entrainment of circadian clock by photoperiod Source:UniProtKB
Biological Process locomotor rhythm Source:UniProtKB
Biological Process muscle organ development Source:UniProtKB-KW
Biological Process negative regulation of transcription by RNA polymerase II Source:UniProtKB1 Publication
Biological Process positive regulation of mitotic cell cycle Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB2 Publications
Biological Process protein stabilization Source:UniProtKB1 Publication
Biological Process regulation of signal transduction by p53 class mediator Source:Reactome
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Cytoplasm
Cytoplasm, perinuclear region
Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane.
Isoform 4
Nucleus
Membrane
Cytoplasm
Predominantly expressed at membranes.