USP6

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.

Full Name

ubiquitin specific peptidase 6 (Tre-2 oncogene)

Function

Biological Process

Biological Process activation of GTPase activity Source:GO_Central1 Publication
Biological Process protein deubiquitination Source:UniProtKB1 Publication
Biological Process protein modification process Source:UniProtKB1 Publication
Biological Process regulation of vesicle-mediated transport Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Cell membrane
Cytoplasm
Endosome
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.

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).

PTM

Monubiquitinated; ubiquitination is calmodulin and calcium dependent.