OTUB1 Hydrolase that can specifically remove '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, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. 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. 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. Belongs to the peptidase C65 family. Isoform 1 is ubiquitous. Isoform 2 is expressed only in lymphoid tissues such as tonsils, lymph nodes and spleen, as well as peripheral blood mononuclear cells. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 3.4.19.12; Protease; Ubiquitin conjugating system; Ubiquitin-specific protease
Chromosomal Location of Human Ortholog: 11q13.1
Cellular Component:  cytosol; nucleoplasm
Molecular Function:  NEDD8-specific protease activity; protein binding; thiol-dependent ubiquitin-specific protease activity; ubiquitin binding; ubiquitin protein ligase binding
Biological Process:  adaptive immune response; cellular response to DNA damage stimulus; cellular response to interleukin-1; DNA repair; negative regulation of double-strand break repair; negative regulation of histone H2A K63-linked ubiquitination; protein deubiquitination; protein K48-linked deubiquitination
Reference #:  Q96FW1 (UniProtKB)
Alt. Names/Synonyms: Deubiquitinating enzyme OTUB1; FLJ20113; FLJ40710; hOTU1; HSPC263; MGC111158; MGC4584; OTB1; OTU domain, ubiquitin aldehyde binding 1; OTU domain-containing ubiquitin aldehyde-binding protein 1; OTU-domain Ubal-binding 1; OTU1; OTUB1; Otubain-1; Ubiquitin thioesterase OTUB1; ubiquitin-specific protease otubain 1; Ubiquitin-specific-processing protease OTUB1
Gene Symbols: OTUB1
Molecular weight: 31,284 Da
Basal Isoelectric point: 4.85  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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OTUB1

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene