UniProtKB - Q96G74 (OTUD5_HUMAN)
OTU domain-containing protein 5
OTUD5
Functioni
Deubiquitinating enzyme that functions as negative regulator of the innate immune system. Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production. Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro). Controls neuroectodermal differentiation through cleaving 'Lys-48'-linked ubiquitin chains to counteract degradation of select chromatin regulators such as ARID1A, HDAC2 and HCF1 (PubMed:33523931).
4 PublicationsCatalytic 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 |
---|---|---|---|---|
Active sitei | 221 | Sequence analysis | 1 | |
Active sitei | 224 | Nucleophile1 Publication | 1 | |
Active sitei | 334 | 1 Publication | 1 |
GO - Molecular functioni
- deubiquitinase activity Source: MGI
- Lys48-specific deubiquitinase activity Source: MGI
- Lys63-specific deubiquitinase activity Source: MGI
- thiol-dependent deubiquitinase Source: UniProtKB
GO - Biological processi
- negative regulation of canonical Wnt signaling pathway Source: FlyBase
- negative regulation of type I interferon production Source: Reactome
- neural crest cell differentiation Source: UniProtKB
- positive regulation of TORC1 signaling Source: FlyBase
- positive regulation of TORC2 signaling Source: FlyBase
- protein deubiquitination Source: MGI
- protein K48-linked deubiquitination Source: UniProtKB
- protein K63-linked deubiquitination Source: UniProtKB
- response to lipopolysaccharide Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q96G74 |
Reactomei | R-HSA-5689896, Ovarian tumor domain proteases R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling |
SignaLinki | Q96G74 |
SIGNORi | Q96G74 |
Protein family/group databases
MEROPSi | C85.001 |
Names & Taxonomyi
Protein namesi | Recommended name: OTU domain-containing protein 5Curated (EC:3.4.19.121 Publication)Alternative name(s): Deubiquitinating enzyme A Short name: DUBA |
Gene namesi | Name:OTUD5Imported |
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:25402, OTUD5 |
MIMi | 300713, gene |
neXtProti | NX_Q96G74 |
VEuPathDBi | HostDB:ENSG00000068308 |
Pathology & Biotechi
Involvement in diseasei
Multiple congenital anomalies-neurodevelopmental syndrome, X-linked (MCAND)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_085336 | 161 – 163 | Missing in MCAND; reduced cleavage activity towards 'K-48'-chains but not 'K-63'-chains; no effect on phosphorylation. 1 Publication | 3 | |
Natural variantiVAR_085337 | 256 | D → N in MCAND; reduced cleavage activity towards 'K-63'- and 'K-48'-chains; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085338 | 274 | R → W in MCAND; partial mislocation at the cytoplasm; reduced cleavage activity towards 'K-63'- and 'K-48'-chains; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085339 | 352 | L → P in MCAND; in mice embryo the mutation is lethal; reduced cleavage activity towards 'K-48'-chains but not 'K-63'-chains; no effect on nuclear location; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085340 | 404 | R → W in MCAND; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_085341 | 494 | G → S in MCAND; decreased mRNA and protein levels; no effect on cleavage activity towards 'K-48'-chains but not 'K-63'-chains; in mice embryo the mutation is lethal; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085342 | 520 | R → W in MCAND; unknown pathological significance. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 177 | S → D or E: Loss of deubiquitinase activity. Abolishes activation by protein kinases. 1 Publication | 1 | |
Mutagenesisi | 224 | C → S: Loss of deubiquitinase activity. Loss of suppression of IFN production. No effect on nuclear location. 3 Publications | 1 | |
Mutagenesisi | 542 | L → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-549. 1 Publication | 1 | |
Mutagenesisi | 549 | S → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-542. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Mental retardationOrganism-specific databases
DisGeNETi | 55593 |
MalaCardsi | OTUD5 |
MIMi | 301056, phenotype |
OpenTargetsi | ENSG00000068308 |
PharmGKBi | PA142671217 |
Miscellaneous databases
Pharosi | Q96G74, Tbio |
Genetic variation databases
BioMutai | OTUD5 |
DMDMi | 74731791 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000278223 | 1 – 571 | OTU domain-containing protein 5Add BLAST | 571 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 64 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 165 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 175 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 177 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 452 | PhosphoserineCombined sources | 1 | |
Modified residuei | 507 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q96G74 |
jPOSTi | Q96G74 |
MassIVEi | Q96G74 |
MaxQBi | Q96G74 |
PaxDbi | Q96G74 |
PeptideAtlasi | Q96G74 |
PRIDEi | Q96G74 |
ProteomicsDBi | 33910 4133 76598 [Q96G74-1] 76599 [Q96G74-2] 76600 [Q96G74-3] |
TopDownProteomicsi | Q96G74-2 [Q96G74-2] |
PTM databases
GlyGeni | Q96G74, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q96G74 |
PhosphoSitePlusi | Q96G74 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000068308, Expressed in quadriceps femoris and 217 other tissues |
ExpressionAtlasi | Q96G74, baseline and differential |
Genevisiblei | Q96G74, HS |
Organism-specific databases
HPAi | ENSG00000068308, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with TRAF3.
2 PublicationsProtein-protein interaction databases
BioGRIDi | 120738, 47 interactors |
DIPi | DIP-53541N |
IntActi | Q96G74, 23 interactors |
MINTi | Q96G74 |
STRINGi | 9606.ENSP00000156084 |
Miscellaneous databases
RNActi | Q96G74, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96G74 |
SMRi | Q96G74 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 213 – 341 | OTUPROSITE-ProRule annotationAdd BLAST | 129 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 111 | DisorderedSequence analysisAdd BLAST | 111 | |
Regioni | 146 – 175 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 218 – 224 | Cys-loopBy similarity | 7 | |
Regioni | 273 – 283 | Variable-loopBy similarityAdd BLAST | 11 | |
Regioni | 329 – 334 | His-loopBy similarity | 6 | |
Regioni | 418 – 502 | DisorderedSequence analysisAdd BLAST | 85 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 30 | Pro residuesSequence analysisAdd BLAST | 30 | |
Compositional biasi | 93 – 108 | Pro residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 420 – 460 | Polar residuesSequence analysisAdd BLAST | 41 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2605, Eukaryota |
GeneTreei | ENSGT00940000158963 |
HOGENOMi | CLU_021938_0_1_1 |
InParanoidi | Q96G74 |
OMAi | REDKHFE |
OrthoDBi | 1448656at2759 |
PhylomeDBi | Q96G74 |
TreeFami | TF326812 |
Family and domain databases
InterProi | View protein in InterPro IPR031084, OTU5 IPR003323, OTU_dom IPR038765, Papain-like_cys_pep_sf |
PANTHERi | PTHR12419:SF4, PTHR12419:SF4, 1 hit |
Pfami | View protein in Pfam PF02338, OTU, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 1 potential isoform that is 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
MTILPKKKPP PPDADPANEP PPPGPMPPAP RRGGGVGVGG GGTGVGGGDR
60 70 80 90 100
DRDSGVVGAR PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP
110 120 130 140 150
PPCGGPGGPG GGPGDALGAA AAGVGAAGVV VGVGGAVGVG GCCSGPGHSK
160 170 180 190 200
RRRQAPGVGA VGGGSPEREE VGAGYNSEDE YEAAAARIEA MDPATVEQQE
210 220 230 240 250
HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH EVVRKHCMDY
260 270 280 290 300
LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ
310 320 330 340 350
YSTGTSAVEP INTFHGIHQN EDEPIRVSYH RNIHYNSVVN PNKATIGVGL
360 370 380 390 400
GLPSFKPGFA EQSLMKNAIK TSEESWIEQQ MLEDKKRATD WEATNEAIEE
410 420 430 440 450
QVARESYLQW LRDQEKQARQ VRGPSQPRKA SATCSSATAA ASSGLEEWTS
460 470 480 490 500
RSPRQRSSAS SPEHPELHAE LGMKPPSPGT VLALAKPPSP CAPGTSSQFS
510 520 530 540 550
AGADRATSPL VSLYPALECR ALIQQMSPSA FGLNDWDDDE ILASVLAVSQ
560 570
QEYLDSMKKN KVHRDPPPDK S
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH7BZQ3 | H7BZQ3_HUMAN | Ubiquitinyl hydrolase 1 | OTUD5 | 444 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_085336 | 161 – 163 | Missing in MCAND; reduced cleavage activity towards 'K-48'-chains but not 'K-63'-chains; no effect on phosphorylation. 1 Publication | 3 | |
Natural variantiVAR_085337 | 256 | D → N in MCAND; reduced cleavage activity towards 'K-63'- and 'K-48'-chains; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085338 | 274 | R → W in MCAND; partial mislocation at the cytoplasm; reduced cleavage activity towards 'K-63'- and 'K-48'-chains; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085339 | 352 | L → P in MCAND; in mice embryo the mutation is lethal; reduced cleavage activity towards 'K-48'-chains but not 'K-63'-chains; no effect on nuclear location; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085340 | 404 | R → W in MCAND; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_085341 | 494 | G → S in MCAND; decreased mRNA and protein levels; no effect on cleavage activity towards 'K-48'-chains but not 'K-63'-chains; in mice embryo the mutation is lethal; no effect on phosphorylation. 1 Publication | 1 | |
Natural variantiVAR_085342 | 520 | R → W in MCAND; unknown pathological significance. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045185 | 1 – 217 | Missing in isoform 4. 1 PublicationAdd BLAST | 217 | |
Alternative sequenceiVSP_023195 | 17 – 40 | Missing in isoform 2. 1 PublicationAdd BLAST | 24 | |
Alternative sequenceiVSP_023192 | 304 – 308 | Missing in isoform 2, isoform 3, isoform 4 and isoform 5. 3 Publications | 5 | |
Alternative sequenceiVSP_023193 | 563 – 566 | HRDP → PCRC in isoform 3. 1 Publication | 4 | |
Alternative sequenceiVSP_023194 | 567 – 571 | Missing in isoform 3. 1 Publication | 5 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK022612 mRNA Translation: BAB14131.1 Different initiation. AK026260 mRNA Translation: BAB15416.1 Different initiation. AK294590 mRNA Translation: BAG57778.1 AF207550 Genomic DNA No translation available. CH471224 Genomic DNA Translation: EAW50724.1 BC009917 mRNA Translation: AAH09917.1 BC028225 mRNA Translation: AAH28225.1 BC098440 mRNA Translation: AAH98440.1 AL137509 mRNA Translation: CAB70778.1 |
CCDSi | CCDS14313.1 [Q96G74-1] CCDS48104.1 [Q96G74-5] CCDS48105.1 [Q96G74-4] |
PIRi | T46265 |
RefSeqi | NP_001129629.1, NM_001136157.1 [Q96G74-5] NP_001129630.1, NM_001136158.1 [Q96G74-5] NP_001129631.1, NM_001136159.1 [Q96G74-4] NP_060072.1, NM_017602.3 [Q96G74-1] XP_006724600.1, XM_006724537.2 [Q96G74-1] |
Genome annotation databases
Ensembli | ENST00000156084.8; ENSP00000156084.4; ENSG00000068308.15 ENST00000376488.8; ENSP00000365671.3; ENSG00000068308.15 [Q96G74-5] ENST00000396743.7; ENSP00000379969.3; ENSG00000068308.15 [Q96G74-5] ENST00000428668.2; ENSP00000401629.2; ENSG00000068308.15 [Q96G74-4] |
GeneIDi | 55593 |
KEGGi | hsa:55593 |
MANE-Selecti | ENST00000376488.8; ENSP00000365671.3; NM_001136157.2; NP_001129629.1 [Q96G74-5] |
UCSCi | uc004dlt.5, human [Q96G74-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK022612 mRNA Translation: BAB14131.1 Different initiation. AK026260 mRNA Translation: BAB15416.1 Different initiation. AK294590 mRNA Translation: BAG57778.1 AF207550 Genomic DNA No translation available. CH471224 Genomic DNA Translation: EAW50724.1 BC009917 mRNA Translation: AAH09917.1 BC028225 mRNA Translation: AAH28225.1 BC098440 mRNA Translation: AAH98440.1 AL137509 mRNA Translation: CAB70778.1 |
CCDSi | CCDS14313.1 [Q96G74-1] CCDS48104.1 [Q96G74-5] CCDS48105.1 [Q96G74-4] |
PIRi | T46265 |
RefSeqi | NP_001129629.1, NM_001136157.1 [Q96G74-5] NP_001129630.1, NM_001136158.1 [Q96G74-5] NP_001129631.1, NM_001136159.1 [Q96G74-4] NP_060072.1, NM_017602.3 [Q96G74-1] XP_006724600.1, XM_006724537.2 [Q96G74-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3PFY | X-ray | 1.70 | A | 172-344 | [»] | |
3TMO | X-ray | 2.20 | A | 172-351 | [»] | |
3TMP | X-ray | 1.91 | A/C/E/G | 172-351 | [»] | |
AlphaFoldDBi | Q96G74 | |||||
SMRi | Q96G74 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120738, 47 interactors |
DIPi | DIP-53541N |
IntActi | Q96G74, 23 interactors |
MINTi | Q96G74 |
STRINGi | 9606.ENSP00000156084 |
Protein family/group databases
MEROPSi | C85.001 |
PTM databases
GlyGeni | Q96G74, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q96G74 |
PhosphoSitePlusi | Q96G74 |
Genetic variation databases
BioMutai | OTUD5 |
DMDMi | 74731791 |
Proteomic databases
EPDi | Q96G74 |
jPOSTi | Q96G74 |
MassIVEi | Q96G74 |
MaxQBi | Q96G74 |
PaxDbi | Q96G74 |
PeptideAtlasi | Q96G74 |
PRIDEi | Q96G74 |
ProteomicsDBi | 33910 4133 76598 [Q96G74-1] 76599 [Q96G74-2] 76600 [Q96G74-3] |
TopDownProteomicsi | Q96G74-2 [Q96G74-2] |
Protocols and materials databases
Antibodypediai | 409, 169 antibodies from 33 providers |
DNASUi | 55593 |
Genome annotation databases
Ensembli | ENST00000156084.8; ENSP00000156084.4; ENSG00000068308.15 ENST00000376488.8; ENSP00000365671.3; ENSG00000068308.15 [Q96G74-5] ENST00000396743.7; ENSP00000379969.3; ENSG00000068308.15 [Q96G74-5] ENST00000428668.2; ENSP00000401629.2; ENSG00000068308.15 [Q96G74-4] |
GeneIDi | 55593 |
KEGGi | hsa:55593 |
MANE-Selecti | ENST00000376488.8; ENSP00000365671.3; NM_001136157.2; NP_001129629.1 [Q96G74-5] |
UCSCi | uc004dlt.5, human [Q96G74-1] |
Organism-specific databases
CTDi | 55593 |
DisGeNETi | 55593 |
GeneCardsi | OTUD5 |
HGNCi | HGNC:25402, OTUD5 |
HPAi | ENSG00000068308, Low tissue specificity |
MalaCardsi | OTUD5 |
MIMi | 300713, gene 301056, phenotype |
neXtProti | NX_Q96G74 |
OpenTargetsi | ENSG00000068308 |
PharmGKBi | PA142671217 |
VEuPathDBi | HostDB:ENSG00000068308 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2605, Eukaryota |
GeneTreei | ENSGT00940000158963 |
HOGENOMi | CLU_021938_0_1_1 |
InParanoidi | Q96G74 |
OMAi | REDKHFE |
OrthoDBi | 1448656at2759 |
PhylomeDBi | Q96G74 |
TreeFami | TF326812 |
Enzyme and pathway databases
PathwayCommonsi | Q96G74 |
Reactomei | R-HSA-5689896, Ovarian tumor domain proteases R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling |
SignaLinki | Q96G74 |
SIGNORi | Q96G74 |
Miscellaneous databases
BioGRID-ORCSi | 55593, 105 hits in 721 CRISPR screens |
ChiTaRSi | OTUD5, human |
GenomeRNAii | 55593 |
Pharosi | Q96G74, Tbio |
PROi | PR:Q96G74 |
RNActi | Q96G74, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000068308, Expressed in quadriceps femoris and 217 other tissues |
ExpressionAtlasi | Q96G74, baseline and differential |
Genevisiblei | Q96G74, HS |
Family and domain databases
InterProi | View protein in InterPro IPR031084, OTU5 IPR003323, OTU_dom IPR038765, Papain-like_cys_pep_sf |
PANTHERi | PTHR12419:SF4, PTHR12419:SF4, 1 hit |
Pfami | View protein in Pfam PF02338, OTU, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | OTUD5_HUMAN | |
Accessioni | Q96G74Primary (citable) accession number: Q96G74 Secondary accession number(s): B4DGG7 Q9NT65 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 20, 2007 |
Last sequence update: | December 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 154 of the entry and version 1 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, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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