motifs/domains
| structured N-terminal Josephin domain (JD)  , folded N-terminal domain (Josephin domain, residues 1-182) |
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nuclear localization signal (NLS) close to the glutamine tract |
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two ubiquitin-interacting motifs that bind polyubiquilated proteins with a strong preference for chains containing four or more ubiquitins and a polyQ-tract, two contiguous but distinct ubiquitin-binding sites |
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a central flexible region (residues 183-291), a poly-glutamine sequence of variable length |
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C-terminal polyglutamine-containing domain (a polyglutamine stretch encoded by 13 to 36 CAG repeats), inhibiting coactivator-dependent transcription and required for binding coactivators, short C-terminal flexible region |
| basic FUNCTION
| cysteine-protease associated factor conferring a higher susceptibility to death on cells in the Golgi phase |
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inducing cell death and formation of intranuclear inclusions in neuronal cells |
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playing a role in ubiquitin-dependent pathways and in transcriptional activation |
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histone-binding with two independent transcriptional corepressor activities, transcriptional regulation involving targeting histones, coactivators, and an independent mode of direct repression of transcription |
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monomeric domain which folds into a globular conformation and possesses ubiquitin protease activity |
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involved in regulation of the endoplasmic reticulum-associated degradation pathway by modulating VCP-dependent extraction of proteins from the ER |
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polyubiquitin binding protein with ubiquitin protease activity and is a striking suppressor of polyglutamine neurodegeneration |
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having autoproteolytic activity, sustained by the same residues responsible for the ubiquitin hydrolase activity (autolytic activity may play a role in pathogenesis, as fragments carrying expanded polyglutamines are thought to be significantly more toxic than the whole protein) |
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cleaves ubiquitin chains through its Josephin domain and binds ubiquitin chains through a C-terminal cluster of ubiquitin interaction motifs neighboring the pathogenic polyglutamine tract |
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deubiquitinating enzymes that edits topologically complex chains |
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displays deneddylase activity against a fluorogenic NEDD8 substrate |
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Josephin domain-containing proteins is a novel family of active de-ubiquitination enzymes with wide phylogenic distribution |
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key role of CSNK2A1-mediated phosphorylation of ATXN3 in MJD pathophysiology |
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acts as a polyubiquitin-binding protein, recruiting poly-ubiquitinated substrates through a carboxy-terminal cluster of ubiquitin interaction motifs |
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cleaves ubiquitin chains through its Josephin domain and thereby facilitates proteasomal degradation |
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plays an important role in regulating the FOXO4-dependent antioxidant stress response via SOD2,suggesting that a decreased antioxidative capacity and increased susceptibility towards oxidative stress contributes to neuronal cell death in MJD |
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UBE2W and ATXN3, participate in initiating, regulating, and terminating the STUB1 ubiquitination cycle |
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potential role of ATXN3 cleavage by calpains in the pathogenesis of MJD |
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plays an important role in regulating the BL2L1-BAX-mediated anti-oxidative response by modulating the interaction between BCL2L1 and BAX |
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