OTUB1
entrez
55611
canonical
uniprot
Q96FW1
canonical
ensembl
ENSG00000167770
resolver
ensp
ENSP00000444357
resolver
genesymbol
OTUB1
resolver
genesymbol_syn
OTB1
resolver
genesymbol_syn
OTU1
resolver
hgnc
HGNC:23077
resolver
uniprot
B3KUV5
resolver
uniprot
Q32Q78
resolver
uniprot
Q96II3
resolver
uniprot
Q9NXQ4
resolver
uniprot
Q9P0B8
resolver
uniprot_entry
B3KUV5_HUMAN
resolver
uniprot_entry
OTUB1_HUMAN
resolver
uniprot_sec
Q32Q78
resolver
uniprot_sec
Q96II3
resolver
uniprot_sec
Q9NXQ4
resolver
uniprot_sec
Q9P0B8
resolver
activity_regulation
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. {ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539}.
uniprot
proteins
amino_acid_sequence
MAAEEPQQQKQEPLGSDSEGVNCLAYDEAIMAQQDRIQQEIAVQNPLVSERLELSVLYKEYAEDDNIYQQKIKDLHKKYSYIRKTRPDGNCFYRAFGFSHLEALLDDSKELQRFKAVSAKSKEDLVSQGFTEFTIEDFHNTFMDLIEQVEKQTSVADLLASFNDQSTSDYLVVYLRLLTSGYLQRESKFFEHFIEGGRTVKEFCQQEVEPMCKESDHIHIIALAQALSVSIQVEYMDRGEGGTTNPHIFPEGSEPKVYLLYRPGHYDILYK
uniprot
proteins
ec_number
3.4.19.12
uniprot
proteins
function
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 (PubMed:12401499, PubMed:12704427, PubMed:14661020, PubMed:23827681). 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, a crucial inductor of CD4 T-cell anergy (PubMed:14661020). Isoform 1 destabilizes RNF128, leading to prevent anergy (PubMed:14661020). In contrast, isoform 2 stabilizes RNF128 and promotes anergy (PubMed:14661020). Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020). Deubiquitinates estrogen receptor alpha (ESR1) (PubMed:19383985). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (PubMed:18954305, PubMed:19211026, PubMed:23827681). Not able to cleave di-ubiquitin (PubMed:18954305, PubMed:23827681). Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (PubMed:18954305, PubMed:23827681). {ECO:0000269|PubMed:12401499, ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:18954305, ECO:0000269|PubMed:19211026, ECO:0000269|PubMed:19383985, ECO:0000269|PubMed:23827681}.; 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 (PubMed:20725033, PubMed:22325355). 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 (PubMed:20725033, PubMed:22325355). 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 (PubMed:20725033, PubMed:22325355). The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain (PubMed:20725033, PubMed:22325355). Acts as a regulator of mTORC1 and mTORC2 complexes (PubMed:29382726, PubMed:35927303). 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 (PubMed:35927303). Can also act as an inhibitor of the mTORC1 and mTORC2 complexes in response to amino acids by mediating non-catalytic deubiquitination of DEPTOR (PubMed:29382726). {ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:35927303}.
uniprot
proteins
mass_dalton
31284
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="C->A: Abolishes only ubiquitin-vinylsulfone adduct formation."; /evidence="ECO:0000269|PubMed:19211026"; MUTAGEN 23; /note="C->S: Does not affect ability to deubiquitinate DEPTOR."; /evidence="ECO:0000269|PubMed:29382726"; MUTAGEN 26; /note="Y->A: Abolished ability to deubiquitinate RPTOR."; /evidence="ECO:0000269|PubMed:35927303"; MUTAGEN 33; /note="Q->R: Impairs inhibition of UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 37; /note="I->T: Impairs inhibition of UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 39; /note="Q->L: Does not affect activity in DNA repair and ability to inhibit UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 87; /note="P->G: Slightly improves ability to cleave 'K63'-linked ubiquitin."; /evidence="ECO:0000269|PubMed:18954305"; MUTAGEN 88; /note="D->A: Abolished ability to deubiquitinate DEPTOR. Does not affect ability to deubiquitinate RPTOR; when associated with A-91 and A-265."; /evidence="ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:35927303"; MUTAGEN 88; /note="D->E: Abolishes hydrolase activity in vitro. Abolishes ability to inhibit RNF168; when associated with S-91 and A-265."; /evidence="ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:20725033"; MUTAGEN 91; /note="C->A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. Does not affect ability to deubiquitinate RPTOR; when associated with A-88 and A-265."; /evidence="ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:18954305, ECO:0000269|PubMed:19211026, ECO:0000269|PubMed:19383985, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:35927303"; MUTAGEN 91; /note="C->S: Abolishes hydrolase activity in vitro. Does not affect ability to inhibit RNF168. Does not affect ability to deubiquitinate DEPTOR. Abolishes ability to inhibit RNF168; when associated with E-88 and A-265."; /evidence="ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:18954305, ECO:0000269|PubMed:19211026, ECO:0000269|PubMed:19383985, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:29382726"; MUTAGEN 116; /note="A->T: Does not affect ability to inhibit UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 134; /note="T->R: Impairs inhibition of UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 137; /note="D->G: Impairs inhibition of UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 176; /note="R->L: No effect on RNF128."; /evidence="ECO:0000269|PubMed:14661020"; MUTAGEN 190; /note="F->S: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 212; /note="C->A: No effect on RNF128."; /evidence="ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:19211026"; MUTAGEN 261; /note="Y->H: Impairs inhibition of UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 263; /note="P->L: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:22325355"; MUTAGEN 265; /note="H->A: Abolishes ability to inhibit RNF168; when associated with A-88 and S-91. Does not affect ability to deubiquitinate RPTOR; when associated with A-88 and A-91."; /evidence="ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:35927303"; MUTAGEN 265; /note="H->R: Abolishes hydrolase activity in vitro."; /evidence="ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:20725033
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Tyr-26 by SRC and SRMS promotes deubiquitination of RPTOR via a non-catalytic process. {ECO:0000269|PubMed:35927303}.
uniprot
proteins
protein_family
Peptidase C65 family
uniprot
proteins
pubmed
11042152
uniprot
proteins
pubmed
12401499
uniprot
proteins
pubmed
12704427
uniprot
proteins
pubmed
14661020
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18954305
uniprot
proteins
pubmed
19211026
uniprot
proteins
pubmed
19383985
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20725033
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22325355
uniprot
proteins
pubmed
22367539
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23827681
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
29382726
uniprot
proteins
pubmed
35927303
uniprot
proteins
sequence_length
271
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:B2RYG6}.
uniprot
proteins