Tchem USP28 Ubiquitin carboxyl-terminal hydrolase 28

Protein Summary

Description

Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306). The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

Uniprot Accession IDs

• Q96RU2
• B0YJC0
• B0YJC1
• Q6NZX9
• Q9P213

Gene Name

• USP28

Ensembl ID

• ENST00000003302
• ENSP00000003302
• ENSG00000048028
• ENST00000537706
• ENSP00000445743

Symbol

• KIAA1515

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.8
histone modification site profile	0.74
protein domain	0.73
transcription factor perturbation	0.68
cell line	0.66

Protein Classes

PANTHER Classes

Protein / ... / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 28

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 28

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: 52.26   (req: < 5)

Gene RIFs: 42   (req: <= 3)

Antibodies: 255   (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: 52.26   (req: >= 5)

Gene RIFs: 42   (req: > 3)

Antibodies: 255   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

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

Active Ligands: 118

Tclin

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

Active Drug: 0