ubiquitin carboxyl-terminal hydrolase 33; deubiquitinating enzyme 33; ubiquitin thiolesterase 33; ubiquitin-specific-processing protease 33; VHL-interacting deubiquitinating enzyme 1; hVDU1 (USP33, KIAA1097, VDU1)
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Function
- deubiquitinating enzyme with roles in:
- cellular migration
- beta-2 adrenergic receptor (ADRB2) recycling
- role in cell migration via interaction with the intracellular domain of ROBO1, leading to regulate Slit signaling
- role in commissural axon guidance cross the ventral midline of the neural tube (Slit-dependent) possibly by mediating deubiquitination of ROBO1
- acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating deubiquitination of beta-arrestins (ARRB1 & ARRB2) & beta-2 adrenergic receptor (ADRB2)
- role in ADRB2 recycling & resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 & inhibiting lysosomal trafficking of ADRB2
- upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination & disengagement from ADRB2
- this suggests a dynamic exchange between the ADRB2 & beta-arrestins
- deubiquitinates DIO2, thereby regulating thyroid hormones
- mediates deubiquitination of both Lys-48- & Lys-63- linked polyubiquitin chains
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
- ubiquitinated via a VHL-dependent pathway for proteasomal degradation
- interacts with VHL, leading to its ubiquitination & subsequent degradation
- interacts with ARRB1, ARRB2, ADRB2, DIO2 & ROBO1
- interacts with SELENBP1 (selenium-dependent)
Structure
- UBP-type Zn+2 finger binds 3 Zn+2
- belongs to the peptidase C19 family, USP20/USP33 subfamily
- contains 2 DUSP domains
- contains 1 UBP-type Zn+2 finger
Compartment
- cytoplasm, perinuclear region, endoplasmic reticulum ?
Alternative splicing
named isoforms=3
Expression
widely expressed