Q7TQI3 · OTUB1_MOUSE
- ProteinUbiquitin thioesterase OTUB1
- GeneOtub1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids271 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Hydrolase that can specifically remove compared to 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation (By similarity).
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 (PubMed:14661020).
Acts via its interaction with RNF128/GRAIL (PubMed:14661020).
Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020).
Deubiquitinates estrogen receptor alpha (ESR1) (By similarity).
Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (By similarity).
Not able to cleave di-ubiquitin (By similarity).
Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (By similarity).
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 (PubMed:14661020).
Acts via its interaction with RNF128/GRAIL (PubMed:14661020).
Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020).
Deubiquitinates estrogen receptor alpha (ESR1) (By similarity).
Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (By similarity).
Not able to cleave di-ubiquitin (By similarity).
Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (By similarity).
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.
Catalytic activity
Activity regulation
By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.
Features
Showing features for active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 88 | |||||
Sequence: D | ||||||
Active site | 91 | Nucleophile | ||||
Sequence: C | ||||||
Site | 221 | Interacts with free ubiquitin | ||||
Sequence: I | ||||||
Site | 235 | Interacts with free ubiquitin | ||||
Sequence: Y | ||||||
Site | 237 | Interacts with free ubiquitin | ||||
Sequence: D | ||||||
Site | 261 | Interacts with free ubiquitin | ||||
Sequence: Y | ||||||
Active site | 265 | |||||
Sequence: H | ||||||
Site | 266 | Interacts with free ubiquitin | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | cysteine-type deubiquitinase activity | |
Molecular Function | deNEDDylase activity | |
Molecular Function | deubiquitinase activity | |
Molecular Function | ubiquitin binding | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | ubiquitin-protein transferase inhibitor activity | |
Biological Process | adaptive immune response | |
Biological Process | DNA damage response | |
Biological Process | DNA repair | |
Biological Process | negative regulation of double-strand break repair | |
Biological Process | positive regulation of TORC1 signaling | |
Biological Process | protein deubiquitination | |
Biological Process | protein K48-linked deubiquitination | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin thioesterase OTUB1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ7TQI3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000221009 | 2-271 | Ubiquitin thioesterase OTUB1 | |||
Sequence: AAEEPQQQKQEPLGSDSEGVNCLAYDEAIMAQQDRIQQEIAVQNPLVSERLELSVLYKEYAEDDNIYQQKIKDLHKKYSYIRKTRPDGNCFYRAFGFSHLEALLDDSKELQRFKAVSAKSKEDLVSQGFTEFTIEDFHNTFMDLIEQVEKQTSVADLLASFNDQSTSDYLVVYLRLLTSGYLQRESKFFEHFIEGGRTVKEFCQQEVEPMCKESDHIHIIALAQALSVSIQVEYMDRGEGGTTNPHVFPEGSEPKVYLLYRPGHYDILYK | ||||||
Modified residue | 16 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 26 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylation at Tyr-26 by SRC and SRMS promotes deubiquitination of RPTOR via a non-catalytic process.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 80-271 | OTU | ||||
Sequence: SYIRKTRPDGNCFYRAFGFSHLEALLDDSKELQRFKAVSAKSKEDLVSQGFTEFTIEDFHNTFMDLIEQVEKQTSVADLLASFNDQSTSDYLVVYLRLLTSGYLQRESKFFEHFIEGGRTVKEFCQQEVEPMCKESDHIHIIALAQALSVSIQVEYMDRGEGGTTNPHVFPEGSEPKVYLLYRPGHYDILYK | ||||||
Region | 130-138 | Ubiquitin-conjugating enzyme E2 binding | ||||
Sequence: FTEFTIEDF | ||||||
Region | 169-177 | Ubiquitin-conjugating enzyme E2 binding | ||||
Sequence: DYLVVYLRL | ||||||
Region | 189-195 | Free ubiquitin binding | ||||
Sequence: FFEHFIE | ||||||
Region | 206-213 | Ubiquitin-conjugating enzyme E2 binding | ||||
Sequence: QEVEPMCK | ||||||
Region | 214-221 | Free ubiquitin binding | ||||
Sequence: ESDHIHII | ||||||
Region | 245-251 | Free ubiquitin binding | ||||
Sequence: NPHVFPE |
Sequence similarities
Belongs to the peptidase C65 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length271
- Mass (Da)31,270
- Last updated2004-03-01 v2
- Checksum32F78EE1DC5FD679
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 186 | in Ref. 1; BAE20433 | ||||
Sequence: E → D |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK027996 EMBL· GenBank· DDBJ | BAE20433.1 EMBL· GenBank· DDBJ | mRNA | ||
AK140070 EMBL· GenBank· DDBJ | BAE24227.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145273 EMBL· GenBank· DDBJ | BAE26339.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145970 EMBL· GenBank· DDBJ | BAE26795.1 EMBL· GenBank· DDBJ | mRNA | ||
BC022575 EMBL· GenBank· DDBJ | AAH22575.1 EMBL· GenBank· DDBJ | mRNA | ||
BC054410 EMBL· GenBank· DDBJ | AAH54410.1 EMBL· GenBank· DDBJ | mRNA |