OTUB1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0002250Biological processadaptive immune response
GO_0006974Biological processDNA damage response
GO_0071108Biological processprotein K48-linked deubiquitination
GO_0006281Biological processDNA repair
GO_1904263Biological processpositive regulation of TORC1 signaling
GO_2000780Biological processnegative regulation of double-strand break repair
GO_0006508Biological processproteolysis
GO_0016579Biological processprotein deubiquitination
GO_0070062Cellular componentextracellular exosome
GO_0005654Cellular componentnucleoplasm
GO_0005829Cellular componentcytosol
GO_0055105Molecular functionubiquitin-protein transferase inhibitor activity
GO_0019784Molecular functiondeNEDDylase activity
GO_0031625Molecular functionubiquitin protein ligase binding
GO_0005515Molecular functionprotein binding
GO_0004843Molecular functioncysteine-type deubiquitinase activity
GO_0043130Molecular functionubiquitin binding

IV. Literature review

[source]
Gene nameOTUB1
Protein nameUbiquitin thioesterase (EC 3.4.19.12)
Ubiquitin thioesterase OTUB1 (EC 3.4.19.12) (Deubiquitinating enzyme OTUB1) (OTU domain-containing ubiquitin aldehyde-binding protein 1) (Otubain-1) (hOTU1) (Ubiquitin-specific-processing protease OTUB1)
ubiquitinyl hydrolase 1 (EC 3.4.19.12)
SynonymsOTB1
HSPC263
OTU1
DescriptionFUNCTION: 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 . .; FUNCTION: 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 . .

AccessionsENST00000538426.6 [Q96FW1-1]
F5GYN4
ENST00000535140.1
ENST00000541478.5
ENST00000428192.6 [Q96FW1-1]
Q96FW1
ENST00000535715.5
ENST00000543988.1
F5H4F3
ENST00000543004.5
F5H3F0
F5GYJ8
F5H6Q1