Summary

Name USP15
Full Name Ubiquitin carboxyl-terminal hydrolase 15
Synonyms Deubiquitinating enzyme 15, Ubiquitin thioesterase 15, Ubiquitin-specific-processing protease 15, Unph-2, Unph4 | KIAA0529
Primary ID Q9Y4E8
Links - -
Type protein
Relations 3
Function 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 (PubMed:21947082). 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 (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). 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 (PubMed:24852371). 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 (PubMed:27368102). Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9 (PubMed:33093067).

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Relations

Regulator Mechanism target score
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination USP15 0.27
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png deubiquitination BRAP 0.27
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png deubiquitination SQSTM1 0.263
Publications: 1 Organism: Homo Sapiens