Recombinant Human His6-USP25 Protein, CF

Ubiquitin Specific Peptidase 25 (USP25) is a cytoplasmic, Ubiquitin-specific deconjugating enzyme that belongs to the peptidase C19 family of deubiquitinating enzymes (1). It has been shown to be expressed as three tissue-specific isoforms: USP25a, USP25b, and USP25m (2). The canonical isoform, USP25a, is 1055 amino acids (aa) in length and has a predicted molecular weight of 122.2 kDa (2). Human USP25a shares 94% aa sequence identity with the mouse and rat orthologs. It is widely expressed with the highest levels being observed in fetal brain and adult testis (2). USP25b and USP25m are 1087 aa and 1125 aa in length with predicted molecular weights of 125.8 and 130 kDa, respectively. USP25b is found in all tissues except heart and skeletal muscle, while USP25m is exclusively expressed in heart and skeletal muscle (2). The catalytic domain of USP25 is found at aa 166-654 (3). USP25 also contains a Ubiquitin-associated domain (aa 16-57), a SUMO-interacting motif (aa 77-102) and two Ubiquitin-interacting motifs (aa 97-116 and 123-140), which appear to be required for in vitro hydrolysis of Lys48- and Lys63-linked poly-Ubiquitin chains (3,4). USP25 has been shown to interact with the non-receptor tyrosine kinase SYK, which phosphorylates USP25 on Tyr740, leading to a decrease in its intracellular levels (5). USP25 can also be SUMOylated on Lys99 and Lys141. This inhibits USP25 activity by impeding its binding to poly-Ubiquitin chains (3). USP25m can also be ubiquitinated on Lys99 and is thought to stimulate USP25m activity (6). USP25 has been shown to inhibit the degradation of endoplasmic reticulum proteins and to negatively regulate inflammatory responses induced by IL-17 (4,7). Additionally, USP25 has been found to be overexpressed in Down Syndrome fetal brains (1,2). USP25m is thought to be involved in the regulation of muscular differentiation and function. Its expression is up-regulated during myogenesis, and it has been shown to interact with three sarcomeric proteins critical for muscle differentiation and maintenance, ACTA1, FLNC, and MyBPC1 (8).