Tchem USP8 Ubiquitin carboxyl-terminal hydrolase 8

Protein Summary

Description

Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-medaited APP cleavage and amyloid-beta formation (PubMed:27302062). This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Uniprot Accession IDs

• P40818
• B4DKA8
• Q2TB31
• Q7Z3U2
• Q86VA0
• Q8IWI7

Gene Name

• USP8

Ensembl ID

• ENST00000307179
• ENSP00000302239
• ENSG00000138592
• ENST00000396444
• ENSP00000379721
• ENST00000425032
• ENSP00000412682

Symbol

• KIAA0055
• UBPY
• UBPY
• PITA4
• SPG59
• HumORF8

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
interacting protein	0.85
histone modification site profile	0.79
cellular component	0.78
transcription factor binding site profile	0.75

Protein Classes

PANTHER Classes

Protein / ... / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 8

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 8

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: 136.79   (req: < 5)

Gene RIFs: 83   (req: <= 3)

Antibodies: 252   (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: 136.79   (req: >= 5)

Gene RIFs: 83   (req: > 3)

Antibodies: 252   (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: 1

Tclin

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

Active Drug: 0