OTUB1
Description
The OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) is a protein-coding gene located on chromosome 11.
Ubiquitin thioesterase OTUB1, also known as otubain-1, is an enzyme that in humans is encoded by the OTUB1 gene. Alternative splicing results in multiple transcript variants.
== Function == Otubain-1 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, being specific for lysine48 -linked polyubiquitin but not lysine63 -linked polyubiquitin. It interacts with another ubiquitin protease and an E3 ubiquitin ligase that inhibits cytokine gene transcription in the immune system. It is proposed to function in specific ubiquitin-dependent pathways, possibly by providing an editing function for polyubiquitin chain growth.
== Interactions == OTUB1 has been shown to interact with RNF128 and GNB2L1.
OTUB1 is a hydrolase that specifically removes 'Lys-48'-linked conjugated ubiquitin from proteins, playing a crucial role in regulating protein turnover by preventing degradation. It regulates T-cell anergy, a state where T-cells become unresponsive to antigens, by interacting with RNF128/GRAIL, a key inducer of CD4 T-cell anergy. OTUB1's two isoforms have opposing effects on RNF128: isoform 1 destabilizes RNF128, preventing anergy, while isoform 2 stabilizes RNF128, promoting anergy. Interestingly, OTUB1 regulates RNF128-mediated ubiquitination without directly deubiquitinating polyubiquitinated RNF128. OTUB1 also deubiquitinates estrogen receptor alpha (ESR1). It specifically removes 'Lys-48'-linked polyubiquitin chains but not 'Lys-63'-linked chains, and is unable to cleave di-ubiquitin. While OTUB1 can remove NEDD8 from NEDD8 conjugates, it shows a much lower preference compared to 'Lys-48'-linked ubiquitin.
OTUB1 is also known as HSPC263, OTB1, OTU1.
