| IED ID | IndEnz0002012825 |
| Enzyme Type ID | protease012825 |
| Protein Name |
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 hVDU1 |
| Gene Name | USP33 KIAA1097 VDU1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MTGSNSHITILTLKVLPHFESLGKQEKIPNKMSAFRNHCPHLDSVGEITKEDLIQKSLGTCQDCKVQGPNLWACLENRCSYVGCGESQVDHSTIHSQETKHYLTVNLTTLRVWCYACSKEVFLDRKLGTQPSLPHVRQPHQIQENSVQDFKIPSNTTLKTPLVAVFDDLDIEADEEDELRARGLTGLKNIGNTCYMNAALQALSNCPPLTQFFLDCGGLARTDKKPAICKSYLKLMTELWHKSRPGSVVPTTLFQGIKTVNPTFRGYSQQDAQEFLRCLMDLLHEELKEQVMEVEEDPQTITTEETMEEDKSQSDVDFQSCESCSNSDRAENENGSRCFSEDNNETTMLIQDDENNSEMSKDWQKEKMCNKINKVNSEGEFDKDRDSISETVDLNNQETVKVQIHSRASEYITDVHSNDLSTPQILPSNEGVNPRLSASPPKSGNLWPGLAPPHKKAQSASPKRKKQHKKYRSVISDIFDGTIISSVQCLTCDRVSVTLETFQDLSLPIPGKEDLAKLHSSSHPTSIVKAGSCGEAYAPQGWIAFFMEYVKRFVVSCVPSWFWGPVVTLQDCLAAFFARDELKGDNMYSCEKCKKLRNGVKFCKVQNFPEILCIHLKRFRHELMFSTKISTHVSFPLEGLDLQPFLAKDSPAQIVTYDLLSVICHHGTASSGHYIAYCRNNLNNLWYEFDDQSVTEVSESTVQNAEAYVLFYRKSSEEAQKERRRISNLLNIMEPSLLQFYISRQWLNKFKTFAEPGPISNNDFLCIHGGVPPRKAGYIEDLVLMLPQNIWDNLYSRYGGGPAVNHLYICHTCQIEAEKIEKRRKTELEIFIRLNRAFQKEDSPATFYCISMQWFREWESFVKGKDGDPPGPIDNTKIAVTKCGNVMLRQGADSGQISEETWNFLQSIYGGGPEVILRPPVVHVDPDILQAEEKIEVETRSL |
| Enzyme Length | 942 |
| Uniprot Accession Number | Q8TEY7 |
| Absorption | |
| Active Site | ACT_SITE 194; /note="Nucleophile"; ACT_SITE 673; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | 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. {ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:23486064}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (4); Beta strand (5); Chain (1); Compositional bias (2); Domain (3); Erroneous initiation (1); Helix (3); Metal binding (12); Modified residue (2); Mutagenesis (2); Region (2); Sequence conflict (5); Turn (4); Zinc finger (1) |
| Keywords | 3D-structure;Alternative splicing;Cytoplasm;Cytoskeleton;Endocytosis;Golgi apparatus;Hydrolase;Metal-binding;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q13228 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000269|PubMed:19118533}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23486064}. Note=Associates with centrosomes predominantly in S and G2 phases but less in G1 phase (PubMed:23486064). {ECO:0000269|PubMed:23486064}.; SUBCELLULAR LOCATION: [Isoform 3]: Golgi apparatus {ECO:0000269|PubMed:21801292}. |
| Modified Residue | MOD_RES 377; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 439; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:18669648 |
| Post Translational Modification | PTM: Ubiquitinated via a VHL-dependent pathway for proteasomal degradation. {ECO:0000269|PubMed:11739384}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1) |
| Cross Reference PDB | 2UZG; |
| Mapped Pubmed ID | 16169070; 19615732; 19684588; 19706539; 20724312; 24056301; 24855649; 24981056; 25242263; 26304236; 27835898; 28506875; 29533940; 29802710; 30896071; 31432739; 32835698; 33792613; 33936086; |
| Motif | |
| Gene Encoded By | |
| Mass | 106,727 |
| Kinetics | |
| Metal Binding | METAL 39; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 41; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 61; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 64; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 74; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 79; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 84; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 91; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 95; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 101; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 114; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 117; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502 |
| Rhea ID | |
| Cross Reference Brenda |