Protein: Ubiquitin carboxyl-terminal hydrolase 33 (EC 3.4.19.12) (Deubiquitinating enzyme 33) (Ubiquitin thioesterase 33) (Ubiquitin-specific-processing protease 33) (VHL-interacting deubiquitinating enzyme 1) (Q8R5K2)
Organism: Mus musculus (Mouse)
Function: 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.
Subcellular location: Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q8TEY7}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q8TEY7}. Note=Associates with centrosomes predominantly in S and G2 phases but less in G1 phase (By similarity). {ECO:0000250|UniProtKB:Q8TEY7}.
Sequence: MTTFRNHCPHLDSVGEITKEDLIQKSLGACQDCKVRGPNLWACLENRCSYVGCGESQVDHSTIHSQETKHYLTVNLTTLRVWCYACSKEVFLDRKLGTPPSLPHVRQPQQTQENSVQDFKIPSNPALKTPMVAVSEDLDIEVEEEDELKARGLTGLKNIGNTCYMNAALQALSNCPPLTQFFLDCGGLARTDKKPAICKSYLKLMTELWHKSRPGSVVPANLFQGIKTVNPTFRGYSQQDAQEFLRCLMDLLHEELKEQVMEMEEEPQTLTSEETVEEEKSQSDVDFQSCESCSSSEKAENESGSKGFPEDSNETTMLIQDEDDLEMAKDWQKEKVCNKINKANADVELDKDRDTVCETVDLNSQETVKVQIHGRASESITDVHLNDLATSQILPSNESVSPRLSASPPKLGSLWPGLSPPHKKAQSTSAKRKKQHKKYRSVISDIFDGTVISSVQCLTCDRVSITLETFQDLSLPIPGKEDLAKLHSSSHPTIVKAGSCGEAYAPQGWIAFFMEYVKRFVVSCVPSWFWGPVVTLQDCLAAFFARDELKGDNMYSCEKCKKLRNGVKFCKVQKFPEILCIHLKRFRHELMFSTKISTHVSFPLEGLDLQPFLAKDSPAQIVTYDLLSVICHHGTASSGHYIAYCRNNLNNLWYEFDDQSVTEVSESTVQNAEAYVLFYRKSSEEAQKERRRISNLLNIMEPSLLQFYISRQWLNKFKTFAEPGPISNNDFLCIHGGIPPRKASYIEDLVLMLPQNIWDNLYSRYGGGPAVNHLYICHTCQIELEKIEKRRKTELEIFIRLNRAFQEEDSPATFYCISMQWFREWESFVKGKDGDPPGPIDNTKIAVTKCGSVMLKQGADSGQISEETWNFLQSIYGGGPEVILRPPVVHVDPDVLQAEEKIEVETRSL
InterPro domains: - IPR035927: DUSP-like superfamily (homologous_superfamily) [678-904]
- IPR018200: Ubiquitin specific protease, conserved site (conserved_site) [155-641]
- IPR001394: Peptidase C19, ubiquitin carboxyl-terminal hydrolase (domain) [154-679]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [3-99]
- IPR006615: Peptidase C19, ubiquitin-specific peptidase, DUSP domain (domain) [684-891]
- IPR001607: Zinc finger, UBP-type (domain) [6-109]
- IPR038765: Papain-like cysteine peptidase superfamily (homologous_superfamily) [152-681]
- IPR028889: Ubiquitin specific protease UPS, catalytic domain (domain) [154-682]
- IPR050185: Ubiquitin carboxyl-terminal hydrolase (family) [74-681]
Interaction partners: - Centriolar coiled-coil protein of 110 kDa
- Beta-2 adrenergic receptor
- Roundabout homolog 1
- von Hippel-Lindau disease tumor suppressor
- Beta-arrestin-2
- WD repeat and SOCS box-containing protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010646 (regulation of cell communication), GO:0009966 (regulation of signal transduction), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0006508 (proteolysis), GO:0008277 (regulation of G protein-coupled receptor signaling pathway), GO:0070646 (protein modification by small protein removal), GO:0070647 (protein modification by small protein conjugation or removal), GO:0016579 (protein deubiquitination), GO:0070536 (protein K63-linked deubiquitination), GO:0071108 (protein K48-linked deubiquitination)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:1902494 (catalytic complex), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm), GO:0140535 (intracellular protein-containing complex), GO:1990234 (transferase complex), GO:0000151 (ubiquitin ligase complex)