Mouse Anti-OTUB1 Antibody (9BA27) (CBMAB-1474CQ)

OTUB1

The product of this gene is a member of the OTU (ovarian tumor) superfamily of predicted cysteine proteases. The encoded protein is a highly specific ubiquitin iso-peptidase, and cleaves ubiquitin from branched poly-ubiquitin chains but not from ubiquitinated substrates. 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.

OTB1; OTU1; Deubiquitinating Enzyme OTUB1; Ubiquitin-Specific-Processing Protease OTUB1; OTU Domain-Containing Ubiquitin Aldehyde-Binding; FLJ20113; FLJ40710; Protein 1; OTU-Domain Ubal-Binding 1; Otubain-1; Ubiquitin Thioesterase OTUB1; Ubiquitin specific protease; HOTU1

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.

Adaptive immune responseIEA:UniProtKB-KW
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
DNA repairIEA:UniProtKB-KW
Negative regulation of double-strand break repairManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of histone H2A K63-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K48-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB

Cytoplasm