Tbio USP2 Ubiquitin carboxyl-terminal hydrolase 2

Protein Summary

Description

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 ARNTL/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 Ca(2+) 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 Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine. 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]

Uniprot Accession IDs

• O75604
• B0YJB8
• E9PPM2
• Q8IUM2
• Q8IW04
• Q96MB9
• Q9BQ21

Gene Name

• USP2

Ensembl ID

• ENST00000260187
• ENSP00000260187
• ENSG00000036672
• ENST00000455332
• ENSP00000407842
• ENST00000525735
• ENSP00000436952

Symbol

• UBP41
• USP9
• UBP41

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.88
biological process	0.86
histone modification site profile	0.84
transcription factor	0.74
molecular function	0.73

Protein Classes

PANTHER Classes

Protein / ... / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 2

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 146.33   (req: < 5)

Gene RIFs: 47   (req: <= 3)

Antibodies: 393   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 146.33   (req: >= 5)

Gene RIFs: 47   (req: > 3)

Antibodies: 393   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0