ID:UBP25_HUMAN DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 25; EC=3.4.19.12; AltName: Full=Deubiquitinating enzyme 25; AltName: Full=USP on chromosome 21; AltName: Full=Ubiquitin thioesterase 25; AltName: Full=Ubiquitin-specific-processing protease 25; FUNCTION: Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains. FUNCTION: The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function. CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). SUBUNIT: Homodimer or oligomer. Interacts with ACTA1 (via its C- terminus); the interaction occurs for all isoforms but is strongest for isoform USP25m in muscle differentiating cells. Interacts (isoform USP25m only) with MYBPC1; the interaction prevents proteasomal degradation of MYBPC1. Interacts (isoform USP25m only) with FLNC (via filament repeats 17-18, 20-21 and 24). Interacts with GAPDH. Interacts with SUMO3; the interaction sumoylates efficiently USP25. Interacts with SUMO2; the interaction sumoylates efficiently USP25. Interacts with SUMO1; the interaction only weakly sumoylates USP25. Interacts with SYK; phosphorylates USP25 and regulates USP25 intracellular levels. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Isoform USP25m: Cytoplasm (By similarity). Nucleus (By similarity). Note=Some transient punctuate nuclear location in myotubes during myocyte development (By similarity). TISSUE SPECIFICITY: Isoform USB25a is found in most adult and fetal tissues; expression is moderately high in testis, pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, but very low in peripheral blood, colon, small intestine, ovary, prostate, thymus and spleen. Isoform USB25b is found in all tissues except heart and skeletal muscle. Isoform USB25m is heart and skeletal muscle specific. INDUCTION: The muscle-specific isoform (USP25m) is up-regulated during myocyte differentiation. Levels increase up to 100-fold towards completion of differentiation. PTM: Acetylated. PTM: Sumoylation impairs binding to and hydrolysis of ubiquitin chains. Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1. Regulated by ubiquitination on the same residue. PTM: Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions. PTM: Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels. SIMILARITY: Belongs to the peptidase C19 family. SIMILARITY: Contains 1 UBA-like domain. SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UHP3
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006464 cellular protein modification process GO:0006508 proteolysis GO:0006511 ubiquitin-dependent protein catabolic process GO:0016579 protein deubiquitination GO:0070536 protein K63-linked deubiquitination GO:0071108 protein K48-linked deubiquitination GO:1904293 negative regulation of ERAD pathway