OTUB1 — OTU deubiquitinase, ubiquitin aldehyde binding 1
OTUB1 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
OTUB1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Cellular biosynthesis Housekeeping | CCDC32, CTSB, HDGF, MEA1, MESD, MFSD6, MRPS11, MTHFD2 +9 more | View in SCUBA |
| Gamma-delta T cells | Basal Cell Maintenance Housekeeping | ARHGDIB, CYB561D2, DNAJC8, GPAA1, INO80E, LMF2, MIF4GD, PCYT2 +9 more | |
| Innate lymphoid cells | Cellular Metabolic Maintenance Metabolism | ADIPOR1, APH1A, ARF5, BCAP31, CLIC1, CSNK2B, CYB5R3, DHPS +13 more | View in SCUBA |
| Macrophages | Protein Biogenesis Housekeeping | ATP6V0D1, B3GAT3, BUD23, C11orf58, CHD4, CNPY2, DAZAP1, DDX46 +23 more | View in SCUBA |
About the gene
| Synonyms | FLJ20113, FLJ40710 |
|---|---|
| Chromosome | 11: 63985853-64001811 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Enzymes, Plasma proteins, Predicted intracellular proteins |
| Molecular function | Hydrolase, Protease, Thiol protease |
| Biological process | Adaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway |
Function
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. Acts as a regulator of mTORC1 and mTORC2 complexes. When phosphorylated at Tyr-26, acts as an activator of the mTORC1 complex by mediating deubiquitination of RPTOR via a non- catalytic process: acts by binding and inhibiting the activity of the ubiquitin-conjugating enzyme E2 (UBE2D1/UBCH5A, UBE2W/UBC16 and UBE2N/UBC13), thereby preventing ubiquitination of RPTOR. Can also act as an inhibitor of the mTORC1 and mTORC2 complexes in response to amino acids by mediating non-catalytic deubiquitination of DEPTOR.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.