COMPARTMENTS

USP15 [ENSP00000280377]

Ubiquitin carboxyl-terminal hydrolase 15; Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes . According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal . Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B . Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys- 48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy . Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery . ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689,

Synonyms:  USP15,  USP15p,  hUSP15,  F8VVY7,  F8VZG8 ...

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