| IED ID | IndEnz0002009258 |
| Enzyme Type ID | protease009258 |
| Protein Name |
Ubiquitin thioesterase OTUB1 EC 3.4.19.12 Deubiquitinating enzyme OTUB1 OTU domain-containing ubiquitin aldehyde-binding protein 1 Otubain-1 Ubiquitin-specific-processing protease OTUB1 |
| Gene Name | Otub1 |
| Organism | Mus musculus (Mouse) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAAEEPQQQKQEPLGSDSEGVNCLAYDEAIMAQQDRIQQEIAVQNPLVSERLELSVLYKEYAEDDNIYQQKIKDLHKKYSYIRKTRPDGNCFYRAFGFSHLEALLDDSKELQRFKAVSAKSKEDLVSQGFTEFTIEDFHNTFMDLIEQVEKQTSVADLLASFNDQSTSDYLVVYLRLLTSGYLQRESKFFEHFIEGGRTVKEFCQQEVEPMCKESDHIHIIALAQALSVSIQVEYMDRGEGGTTNPHVFPEGSEPKVYLLYRPGHYDILYK |
| Enzyme Length | 271 |
| Uniprot Accession Number | Q7TQI3 |
| Absorption | |
| Active Site | ACT_SITE 88; /evidence=ECO:0000250|UniProtKB:Q96FW1; ACT_SITE 91; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q96FW1; ACT_SITE 265; /evidence=ECO:0000250|UniProtKB:Q96FW1 |
| Activity Regulation | ACTIVITY REGULATION: By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1. {ECO:0000250}. |
| 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; Evidence={ECO:0000250|UniProtKB:Q96FW1}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Hydrolase that can specifically remove compared to 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin. {ECO:0000269|PubMed:14661020}.; FUNCTION: Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain (By similarity). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Domain (1); Initiator methionine (1); Modified residue (2); Region (6); Sequence conflict (1); Site (5) |
| Keywords | Acetylation;Adaptive immunity;Cytoplasm;DNA damage;DNA repair;Direct protein sequencing;Hydrolase;Immunity;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:Q96FW1; MOD_RES 16; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q96FW1 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 14610273; 15618518; 15741177; 16615898; 18799693; 18973680; 19455133; 21311561; 22174793; 22988430; 24194600; 26514267; 26811477; 27626380; 28083634; 28114324; 29559747; 30091036; 30282802; 30908891; 30944096; 31086255; 31182807; 31386800; 34793600; |
| Motif | |
| Gene Encoded By | |
| Mass | 31,270 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |