Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation.
|Gene References into Functions
- None of the genitourinary pseudosarcomatous myofibroblastic proliferations was found to harbour USP6 (0/12), ROS1 (0/8) or ETV6 (0/7) rearrangements PMID: 29617048
- we identified seven novel fusion partners for USP6 in nodular fasciitis, highlighting the importance of USP6 expression and promoter-swapping fusions in the etiology of this neoplasm PMID: 28752842
- Report the presence of USP6 rearrangements in a subset of cellular fibroma of tendon sheath. PMID: 27125357
- our studies highlight Jak1 as the first identified substrate for USP6, and they offer a mechanistic rationale for the clinical investigation of Jak and STAT3 inhibitors as therapeutics for the treatment of bone and soft tissue tumors along with other neoplasms driven by USP6 overexpression PMID: 27440725
- Molecular analyses revealed the presence and amplification of the novel PPPR6-USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of Nodular fasciitis PMID: 27113271
- It was shown that TRE17 activates the classical NF-kappa B pathway through an atypical mechanism that does not involve IkappaB degradation. Optimal activation of NF-kappa B by TRE17 required both catalytic subunits of IkappaB kinase. PMID: 22081069
- USP6 fluorescence in-situ hybridization is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration. PMID: 27271298
- the deubiquitylase ubiquitin-specific protease 6 (USP6) as a potent activator of Wnt signaling. USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance. PMID: 27162353
- TRE17/USP6 regulates ubiquitylation and trafficking of cargo proteins that enter cells by clathrin-independent endocytosis PMID: 25179595
- 8 of the 9 giant cell reparative granulomas from hands and feet showed rearrangements of the USP6 gene compared with none of 8 gnathic lesions PMID: 24742829
- we discuss the clinicopathologic features, molecular pathology, and pathogenesis of ABC and nodular fasciitis in relation to USP6 PMID: 23769422
- identification of a USP6 gene rearrangement is helpful in making a diagnosis of nodular fasciitis. PMID: 23748914
- manipulating USP6 expression levels alters the ability of cells to migrate and to divide. Cell proliferation and progression through cytokinesis depend on USP6 expression PMID: 22188517
- TRE17 is sufficient to initiate tumorigenesis, identify MMPs as novel TRE17 effectors that likely contribute to aneurysmal bone cyst pathogenesis. PMID: 20418905
- TRE17 coprecipitated specifically with the active forms of Cdc42 and Rac1 in vivo. TRE17 is part of a novel effector complex for Cdc42 and Rac1, potentially contributing to their effects on actin remodeling. PMID: 12612085
- Complementation tests in yeasts indicate that Tre2 codes for a nonfunctional RabGAP. PMID: 14521938
- Deregulated USP6 transcription is associated with aneurysmal bone cyst PMID: 15026324
- primary aneurysmal bone cysts are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements PMID: 15509545
- TRE17 associates directly with Arf6 in its GDP- but not GTP-bound state. PMID: 15509780
- Tre2 oncogene seems to encode a nonfunctional Rab GAP. As regions flanking the TBC domain may be crucial for catalytic activity PMID: 16099424
- Ca2+/CaM has a role in regulating ubiquitination through direct interaction with TRE17 PMID: 16127172
- The lack of secondary structure of the region flanking the TBC domain in TRE2 may explain why this region plays a role in the lack of GAP activity, even when a potentially functional TBC domain is present. PMID: 17701273
- No USP6 rearrangements were found in cherubism or brown tumors. USP6 rearrangements were identified in 2 patients with myositis ossificans. PMID: 18265974
|Involvement in disease
||A chromosomal aberration involving USP6 is a common genetic feature of aneurysmal bone cyst, a benign osseous neoplasm. Translocation t(16;17)(q22;p13) with CDH11. The translocation generates a fusion gene in which the strong CDH11 promoter is fused to the entire USP6 coding sequence, resulting in USP6 transcriptional up-regulation (PubMed:15026324).
||Cell membrane. Cytoplasm. Endosome. Note=Localizes to the plasma membrane and to filamentous structures within the cell corresponding to ARF6 regulated tubular endosomes. Activation of RAC1 and CDC42 can direct the relocalization of USP6 to the plasma membrane in a manner that depends on the integrity of the actin cytoskeleton.
||Peptidase C19 family
||Testis specific. Expressed in various cancer cell lines.