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. 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. Alternative splicing results in multiple transcript variants.
Full Name
OTUB1
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.
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.
Biological Process
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
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
Cellular Location
Cytoplasm
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Anti-OTUB1 antibodies
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Target: OTUB1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey, Hamster, Cattle, Dog
Clone: D8F7
Application*: WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: 5F7
Application*: P, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: 1A6
Application*: F, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 2H1
Application*: IF, P, WB
Target: OTUB1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Mouse, Rat, Human
Clone: CBXO-0129
Application*: WB, IP
Target: OTUB1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Mouse, Rat, Human
Clone: CBXO-0128
Application*: WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: CBXO-0093
Application*: WB, E, IF
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 5B8
Application*: F, P, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 5F6
Application*: F, IF, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBXO-0413
Application*: E, F, IF, WB
Target: OTUB1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey, Hamster, Cattle, Dog
Clone: CBXO-0426
Application*: WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 1C12
Application*: E, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: CBXO-0469
Application*: WB, F, E, IF
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: 9BA29
Application*: E, WB
Target: OTUB1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 9BA27
Application*: E, WB
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For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
- AActivation
- AGAgonist
- APApoptosis
- BBlocking
- BABioassay
- BIBioimaging
- CImmunohistochemistry-Frozen Sections
- CIChromatin Immunoprecipitation
- CTCytotoxicity
- CSCostimulation
- DDepletion
- DBDot Blot
- EELISA
- ECELISA(Cap)
- EDELISA(Det)
- ESELISpot
- EMElectron Microscopy
- FFlow Cytometry
- FNFunction Assay
- GSGel Supershift
- IInhibition
- IAEnzyme Immunoassay
- ICImmunocytochemistry
- IDImmunodiffusion
- IEImmunoelectrophoresis
- IFImmunofluorescence
- IGImmunochromatography
- IHImmunohistochemistry
- IMImmunomicroscopy
- IOImmunoassay
- IPImmunoprecipitation
- ISIntracellular Staining for Flow Cytometry
- LALuminex Assay
- LFLateral Flow Immunoassay
- MMicroarray
- MCMass Cytometry/CyTOF
- MDMeDIP
- MSElectrophoretic Mobility Shift Assay
- NNeutralization
- PImmunohistologyp-Paraffin Sections
- PAPeptide Array
- PEPeptide ELISA
- PLProximity Ligation Assay
- RRadioimmunoassay
- SStimulation
- SESandwich ELISA
- SHIn situ hybridization
- TCTissue Culture
- WBWestern Blot
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