Tbio USP15 Ubiquitin carboxyl-terminal hydrolase 15

Protein Summary

Description

Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). (Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]

Uniprot Accession IDs

• Q9Y4E8
• Q08AL5
• Q9H8G9
• Q9HCA6
• Q9UNP0
• Q9Y5B5

Gene Name

• USP15

Ensembl ID

• ENST00000280377
• ENSP00000280377
• ENSG00000135655
• ENST00000312635
• ENSP00000309240
• ENST00000353364
• ENSP00000258123

Symbol

• KIAA0529
• UNPH4
• UNPH-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	0.93
protein domain	0.92
interacting protein	0.91
transcription factor binding site profile	0.91
transcription factor perturbation	0.88

Protein Classes

PANTHER Classes

Protein / ... / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 15

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Carboxyl-terminal Hydrolase 15

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: 75.22   (req: < 5)

Gene RIFs: 56   (req: <= 3)

Antibodies: 298   (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: 75.22   (req: >= 5)

Gene RIFs: 56   (req: > 3)

Antibodies: 298   (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 Ligand: 0

Tclin

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

Active Drug: 0