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)

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 - does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu - 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

General

oligomerizing protein phosphoprotein ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme zinc finger protein

Properties

SIZE: entity length = 942 aa MW = 107 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Zinc finger NAME: Zinc finger SITE: 59-123 EFFECTOR-BOUND: Zn+2 cysteine residue {C194} Ser phosphorylation site {S439} histidine residue {H673} DUSP 1 {717-810} DUSP 2 {818-921}

Database Correlations

UniProt Q8TEY7 PFAM correlations Entrez Gene 23032 Kegg hsa:23032 ENZYME 3.4.19.12

References

UniProt :accession Q8TEY7