ubiquitin carboxyl-terminal hydrolase 25; deubiquitinating enzyme 25; USP on chromosome 21; ubiquitin thiolesterase 25; ubiquitin-specific-processing protease 25 (USP25)
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Function
- deubiquitinating enzyme
- hydrolyzes ubiquitin moieties conjugated to substrates
- functions to
- process newly synthesized ubiquitin
- recycle ubiquitin molecules
- edit polyubiquitin chains
- prevent proteasomal degradation of substrates
- hydrolyzes both Lys-48- & Lys-63-linked tetraubiquitin chains
- the muscle-specific isoform (USP25m) may have a role in regulation of muscular differentiation & function
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
- sumoylation impairs binding to & hydrolysis of ubiquitin chains
- sumoylated preferentially by SUMO2 or SUMO3
- desumoylated by SENP1
- regulated by ubiquitination on the same residue
- preferentially monoubiquitinated but can also be polyubiquitinated
- autodeubiquitinated
- ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions
- phosphorylation in the C-terminal by SYK regulates USP25 cellular levels
- interacts with ACTA1 (via its C-terminus);
- 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 & 24)
- interacts with GAPDH
- interacts with SUMO3;
- the interaction sumoylates USP25
- interacts with SUMO2;
- the interaction sumoylates USP25
- interacts with SUMO1; the interaction weakly sumoylates USP25
- interacts with SYK;
- the interaction phosphorylates USP25 & regulates its intracellular levels
Structure
- homodimer or oligomer
- acetylated
- belongs to the peptidase C19 family
- contains 1 UBA-like domain
- contains 2 UIM (ubiquitin-interacting motif) repeats
Compartment
Alternative splicing
named isoforms=3; USP25a, USP25b, USP25m
Expression
- isoform USB25a
- found in most adult & fetal tissues
- expression is moderately high in testis, pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart
- expression is very low in peripheral blood, colon, small intestine, ovary, prostate, thymus & spleen
- isoform USB25b
- expressed in most tissues
- not expressed heart & skeletal muscle
- isoform USB25m
- heart & skeletal muscle specific
- up-regulated during myocyte differentiation
- levels increase up to 100-fold towards completion of differentiation