UniProtKB - Q96FW1 (OTUB1_HUMAN)
Ubiquitin thioesterase OTUB1
OTUB1
Functioni
Miscellaneous
Catalytic activityi
- Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication EC:3.4.19.12
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 23 | Required for proximal ubiquitin-binding1 Publication | 1 | |
Active sitei | 88 | Combined sources1 Publication | 1 | |
Active sitei | 91 | Nucleophile1 Publication1 Publication | 1 | |
Sitei | 221 | Interacts with free ubiquitin1 Publication | 1 | |
Sitei | 235 | Interacts with free ubiquitin1 Publication | 1 | |
Sitei | 237 | Interacts with free ubiquitin1 Publication | 1 | |
Sitei | 261 | Interacts with free ubiquitin1 Publication | 1 | |
Active sitei | 265 | 1 Publication1 Publication | 1 | |
Sitei | 266 | Interacts with free ubiquitinCombined sources2 Publications | 1 |
GO - Molecular functioni
- NEDD8-specific protease activity Source: UniProtKB
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
- ubiquitin binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- cellular response to DNA damage stimulus Source: UniProtKB
- DNA repair Source: UniProtKB-KW
- negative regulation of double-strand break repair Source: UniProtKB
- negative regulation of histone H2A K63-linked ubiquitination Source: UniProtKB
- protein deubiquitination Source: Reactome
- protein K48-linked deubiquitination Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Adaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q96FW1 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases |
SIGNORi | Q96FW1 |
Protein family/group databases
MEROPSi | C65.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin thioesterase OTUB1 (EC:3.4.19.121 Publication)Alternative name(s): Deubiquitinating enzyme OTUB1 OTU domain-containing ubiquitin aldehyde-binding protein 1 Otubain-1 Short name: hOTU1 Ubiquitin-specific-processing protease OTUB1 |
Gene namesi | Name:OTUB1 Synonyms:OTB1, OTU1 ORF Names:HSPC263 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23077, OTUB1 |
MIMi | 608337, gene |
neXtProti | NX_Q96FW1 |
VEuPathDBi | HostDB:ENSG00000167770.11 |
Subcellular locationi
Other locations
- Cytoplasm By similarity
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 23 | C → A: Abolishes only ubiquitin-vinylsulfone adduct formation. 1 Publication | 1 | |
Mutagenesisi | 33 | Q → R: Impairs inhibition of UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 37 | I → T: Impairs inhibition of UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 39 | Q → L: Does not affect activity in DNA repair and ability to inhibit UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 87 | P → G: Slightly improves ability to cleave 'K63'-linked ubiquitin. 1 Publication | 1 | |
Mutagenesisi | 88 | D → E: Abolishes hydrolase activity in vitro. Abolishes ability to inhibit RNF168; when associated with S-91 and A-265. 2 Publications | 1 | |
Mutagenesisi | 91 | C → A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. 7 Publications | 1 | |
Mutagenesisi | 91 | C → S: Abolishes hydrolase activity in vitro. Does not affect ability to inhibit RNF168. Abolishes ability to inhibit RNF168; when associated with A-88 and A-265. 7 Publications | 1 | |
Mutagenesisi | 116 | A → T: Does not affect ability to inhibit UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 134 | T → R: Impairs inhibition of UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 137 | D → G: Impairs inhibition of UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 176 | R → L: No effect on RNF128. 1 Publication | 1 | |
Mutagenesisi | 190 | F → S: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 212 | C → A: No effect on RNF128. 2 Publications | 1 | |
Mutagenesisi | 261 | Y → H: Impairs inhibition of UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 263 | P → L: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication | 1 | |
Mutagenesisi | 265 | H → A: Abolishes ability to inhibit RNF168; when associated with A-88 and S-91. 2 Publications | 1 | |
Mutagenesisi | 265 | H → R: Abolishes hydrolase activity in vitro. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 55611 |
OpenTargetsi | ENSG00000167770 |
PharmGKBi | PA134988141 |
Miscellaneous databases
Pharosi | Q96FW1, Tbio |
Genetic variation databases
BioMutai | OTUB1 |
DMDMi | 44888286 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000221008 | 2 – 271 | Ubiquitin thioesterase OTUB1Add BLAST | 270 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 16 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-244 CPTAC-245 |
EPDi | Q96FW1 |
jPOSTi | Q96FW1 |
MassIVEi | Q96FW1 |
MaxQBi | Q96FW1 |
PaxDbi | Q96FW1 |
PeptideAtlasi | Q96FW1 |
PRIDEi | Q96FW1 |
ProteomicsDBi | 76566 [Q96FW1-1] 76567 [Q96FW1-2] |
PTM databases
iPTMneti | Q96FW1 |
MetOSitei | Q96FW1 |
PhosphoSitePlusi | Q96FW1 |
SwissPalmi | Q96FW1 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000167770, Expressed in anterior cingulate cortex and 246 other tissues |
ExpressionAtlasi | Q96FW1, baseline and differential |
Genevisiblei | Q96FW1, HS |
Organism-specific databases
HPAi | ENSG00000167770, Low tissue specificity |
Interactioni
Subunit structurei
Isoform 1 and isoform 2 interact with RNF128. Isoform 1 forms a ternary complex with RNF128 and USP8.
Isoform 1 interacts with the C-terminal UCH catalytic domain of USP8. Isoform 2 does not associate with USP8.
Interacts with FUS, ESR1 and RACK1.
Interacts with UBE2N/UBC13.
6 PublicationsBinary interactionsi
Q96FW1
Isoform 1 [Q96FW1-1]
With | #Exp. | IntAct |
---|---|---|
UBE2N [P61088] | 5 | EBI-15972141,EBI-1052908 |
GO - Molecular functioni
- ubiquitin binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 120751, 240 interactors |
CORUMi | Q96FW1 |
DIPi | DIP-41158N |
IntActi | Q96FW1, 371 interactors |
MINTi | Q96FW1 |
STRINGi | 9606.ENSP00000444357 |
Miscellaneous databases
RNActi | Q96FW1, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q96FW1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96FW1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 80 – 271 | OTUPROSITE-ProRule annotationAdd BLAST | 192 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 130 – 138 | Ubiquitin-conjugating enzyme E2 binding1 Publication | 9 | |
Regioni | 169 – 177 | Ubiquitin-conjugating enzyme E2 binding1 Publication | 9 | |
Regioni | 189 – 195 | Free ubiquitin bindingCombined sources2 Publications | 7 | |
Regioni | 206 – 213 | Ubiquitin-conjugating enzyme E2 bindingCombined sources2 Publications | 8 | |
Regioni | 214 – 221 | Free ubiquitin bindingCombined sources2 Publications | 8 | |
Regioni | 245 – 251 | Free ubiquitin bindingCombined sources2 Publications | 7 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3991, Eukaryota |
GeneTreei | ENSGT00390000006979 |
InParanoidi | Q96FW1 |
PhylomeDBi | Q96FW1 |
TreeFami | TF314145 |
Family and domain databases
Gene3Di | 1.20.1300.20, 1 hit 3.30.200.60, 1 hit |
InterProi | View protein in InterPro IPR003323, OTU_dom IPR030298, OTUB1 IPR016615, Otubain IPR038765, Papain-like_cys_pep_sf IPR019400, Peptidase_C65_otubain IPR042468, Peptidase_C65_otubain_sub1 IPR042467, Peptidase_C65_otubain_sub2 |
PANTHERi | PTHR12931, PTHR12931, 1 hit PTHR12931:SF19, PTHR12931:SF19, 1 hit |
Pfami | View protein in Pfam PF10275, Peptidase_C65, 1 hit |
PIRSFi | PIRSF013503, Ubiquitin_thioesterase_Otubain, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE
60 70 80 90 100
RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH
110 120 130 140 150
LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE
160 170 180 190 200
KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV
210 220 230 240 250
KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHIFP
260 270
EGSEPKVYLL YRPGHYDILY K
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3KR44 | J3KR44_HUMAN | Ubiquitin thioesterase | OTUB1 | 272 | Annotation score: | ||
F5H6Q1 | F5H6Q1_HUMAN | Ubiquitin thioesterase | OTUB1 | 280 | Annotation score: | ||
F5GYN4 | F5GYN4_HUMAN | Ubiquitinyl hydrolase 1 | OTUB1 | 241 | Annotation score: | ||
F5GYJ8 | F5GYJ8_HUMAN | Ubiquitinyl hydrolase 1 | OTUB1 | 286 | Annotation score: | ||
F5H3F0 | F5H3F0_HUMAN | Ubiquitinyl hydrolase 1 | OTUB1 | 170 | Annotation score: | ||
F5H4F3 | F5H4F3_HUMAN | Ubiquitin thioesterase OTUB1 | OTUB1 | 102 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 61 | Y → C in AAH10368 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 151 | K → R in BAA90956 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_009464 | 1 – 112 | MAAEE…SKELQ → MMKPSWLSRTEFSKRLLCRT LWCQSGWSSRSYTRSMLKMT TSINRRSRTSTKSTRTSARP GLTATVSIGLSDSPTWRHCW MTARSCSGEKGGHWAPRQVG VYLLPGRVGCVSSRVSPSFP GDGLDSGLARRGSAVSALAS GLVEEPMLGPPFHPTP in isoform 2. 1 PublicationAdd BLAST | 112 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY177200 mRNA Translation: AAO27702.1 AF161381 mRNA Translation: AAF28941.1 Different initiation. AK000120 mRNA Translation: BAA90956.1 AP000721 Genomic DNA No translation available. BC007519 mRNA Translation: AAH07519.1 BC010368 mRNA Translation: AAH10368.1 BC107701 mRNA Translation: AAI07702.1 |
CCDSi | CCDS8055.1 [Q96FW1-1] |
RefSeqi | NP_060140.2, NM_017670.2 [Q96FW1-1] |
Genome annotation databases
Ensembli | ENST00000428192; ENSP00000402551; ENSG00000167770 [Q96FW1-1] ENST00000538426; ENSP00000444357; ENSG00000167770 [Q96FW1-1] |
GeneIDi | 55611 |
KEGGi | hsa:55611 |
UCSCi | uc001nyf.2, human [Q96FW1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY177200 mRNA Translation: AAO27702.1 AF161381 mRNA Translation: AAF28941.1 Different initiation. AK000120 mRNA Translation: BAA90956.1 AP000721 Genomic DNA No translation available. BC007519 mRNA Translation: AAH07519.1 BC010368 mRNA Translation: AAH10368.1 BC107701 mRNA Translation: AAI07702.1 |
CCDSi | CCDS8055.1 [Q96FW1-1] |
RefSeqi | NP_060140.2, NM_017670.2 [Q96FW1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ZFY | X-ray | 1.69 | A | 40-271 | [»] | |
3VON | X-ray | 3.15 | A/H/O/V/c/j | 45-271 | [»] | |
4DDG | X-ray | 3.30 | A/B/C/J/K/L | 25-271 | [»] | |
4DDI | X-ray | 3.80 | A/B/C | 25-271 | [»] | |
4DHZ | X-ray | 3.11 | A | 1-45 | [»] | |
4I6L | X-ray | 2.49 | A | 45-271 | [»] | |
4LDT | X-ray | 1.90 | A | 1-45 | [»] | |
SMRi | Q96FW1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120751, 240 interactors |
CORUMi | Q96FW1 |
DIPi | DIP-41158N |
IntActi | Q96FW1, 371 interactors |
MINTi | Q96FW1 |
STRINGi | 9606.ENSP00000444357 |
Protein family/group databases
MEROPSi | C65.001 |
PTM databases
iPTMneti | Q96FW1 |
MetOSitei | Q96FW1 |
PhosphoSitePlusi | Q96FW1 |
SwissPalmi | Q96FW1 |
Genetic variation databases
BioMutai | OTUB1 |
DMDMi | 44888286 |
Proteomic databases
CPTACi | CPTAC-244 CPTAC-245 |
EPDi | Q96FW1 |
jPOSTi | Q96FW1 |
MassIVEi | Q96FW1 |
MaxQBi | Q96FW1 |
PaxDbi | Q96FW1 |
PeptideAtlasi | Q96FW1 |
PRIDEi | Q96FW1 |
ProteomicsDBi | 76566 [Q96FW1-1] 76567 [Q96FW1-2] |
Protocols and materials databases
Antibodypediai | 29104, 451 antibodies |
CPTCi | Q96FW1, 3 antibodies |
DNASUi | 55611 |
Genome annotation databases
Ensembli | ENST00000428192; ENSP00000402551; ENSG00000167770 [Q96FW1-1] ENST00000538426; ENSP00000444357; ENSG00000167770 [Q96FW1-1] |
GeneIDi | 55611 |
KEGGi | hsa:55611 |
UCSCi | uc001nyf.2, human [Q96FW1-1] |
Organism-specific databases
CTDi | 55611 |
DisGeNETi | 55611 |
GeneCardsi | OTUB1 |
HGNCi | HGNC:23077, OTUB1 |
HPAi | ENSG00000167770, Low tissue specificity |
MIMi | 608337, gene |
neXtProti | NX_Q96FW1 |
OpenTargetsi | ENSG00000167770 |
PharmGKBi | PA134988141 |
VEuPathDBi | HostDB:ENSG00000167770.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3991, Eukaryota |
GeneTreei | ENSGT00390000006979 |
InParanoidi | Q96FW1 |
PhylomeDBi | Q96FW1 |
TreeFami | TF314145 |
Enzyme and pathway databases
PathwayCommonsi | Q96FW1 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases |
SIGNORi | Q96FW1 |
Miscellaneous databases
BioGRID-ORCSi | 55611, 27 hits in 881 CRISPR screens |
ChiTaRSi | OTUB1, human |
EvolutionaryTracei | Q96FW1 |
GeneWikii | OTUB1 |
GenomeRNAii | 55611 |
Pharosi | Q96FW1, Tbio |
PROi | PR:Q96FW1 |
RNActi | Q96FW1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167770, Expressed in anterior cingulate cortex and 246 other tissues |
ExpressionAtlasi | Q96FW1, baseline and differential |
Genevisiblei | Q96FW1, HS |
Family and domain databases
Gene3Di | 1.20.1300.20, 1 hit 3.30.200.60, 1 hit |
InterProi | View protein in InterPro IPR003323, OTU_dom IPR030298, OTUB1 IPR016615, Otubain IPR038765, Papain-like_cys_pep_sf IPR019400, Peptidase_C65_otubain IPR042468, Peptidase_C65_otubain_sub1 IPR042467, Peptidase_C65_otubain_sub2 |
PANTHERi | PTHR12931, PTHR12931, 1 hit PTHR12931:SF19, PTHR12931:SF19, 1 hit |
Pfami | View protein in Pfam PF10275, Peptidase_C65, 1 hit |
PIRSFi | PIRSF013503, Ubiquitin_thioesterase_Otubain, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | OTUB1_HUMAN | |
Accessioni | Q96FW1Primary (citable) accession number: Q96FW1 Secondary accession number(s): Q32Q78 Q9P0B8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 1, 2004 |
Last sequence update: | March 1, 2004 | |
Last modified: | February 10, 2021 | |
This is version 179 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries