USP33

This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

Ubiquitin Specific Peptidase 33

Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.

Biological Process axon guidance Source:UniProtKB
Biological Process cell migration Source:UniProtKB
Biological Process cellular response to starvation Source:UniProtKB1 Publication
Biological Process centrosome duplication Source:UniProtKB1 Publication
Biological Process endocytosis Source:UniProtKB-KW
Biological Process negative regulation of protein binding Source:UniProtKB1 Publication
Biological Process positive regulation of protein binding Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB4 Publications
Biological Process protein K48-linked deubiquitination Source:UniProtKB1 Publication
Biological Process protein K63-linked deubiquitination Source:UniProtKB1 Publication
Biological Process protein stabilization Source:CACAO1 Publication
Biological Process regulation of autophagy Source:UniProtKB1 Publication
Biological Process regulation of G protein-coupled receptor signaling pathway Source:UniProtKB2 Publications
Biological Process ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication

Cytoplasm, perinuclear region
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Associates with centrosomes predominantly in S and G2 phases but less in G1 phase (PubMed:23486064).
Isoform 3
Golgi apparatus

Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.