ZRANB1
Domain
The RanBP2-type zinc fingers, also called NZFs, mediate the interaction with ubiquitin and determine linkage specificity (PubMed:25752577). RanBP2-type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin (PubMed:25752573, PubMed:25752577). RanBP2-type zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin chains but it does not interact with 'Lys-29'-linked chains (PubMed:25752573).
The OTU domain mediates the deubiquitinating activity.
The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity.
Function
Ubiquitin thioesterase, which specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin (PubMed:22157957, PubMed:23827681, PubMed:25752573, PubMed:25752577). Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones (PubMed:18281465). Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription (PubMed:18281465). Acts as a regulator of autophagy by mediating deubiquitination of PIK3C3/VPS34, thereby promoting autophagosome maturation (PubMed:33637724). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). Required in the stress fiber dynamics and cell migration (PubMed:21834987).
Sequence Similarities
Belongs to the peptidase C64 family.
Tissue Specificity
Widely expressed.
Cellular localization
- Cytoplasm
- Nucleus
- Enriched in punctate localization in the cytoplasm.
Alternative names
TRABID, ZRANB1, Ubiquitin thioesterase ZRANB1, TRAF-binding domain-containing protein, Zinc finger Ran-binding domain-containing protein 1, hTrabid