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Protein

OTU domain-containing protein 5

Gene

OTUD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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).3 Publications

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

Activity regulationi

Inhibited by N-ethyl-maleimide (NEM).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei221Sequence analysis1
Active sitei224Nucleophile1 Publication1
Active sitei3341 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-5689896 Ovarian tumor domain proteases
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling

Protein family/group databases

MEROPSiC85.001

Names & Taxonomyi

Protein namesi
Recommended name:
OTU domain-containing protein 5 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme A
Short name:
DUBA
Gene namesi
Name:OTUD5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000068308.13
HGNCiHGNC:25402 OTUD5
MIMi300713 gene
neXtProtiNX_Q96G74

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi177S → D or E: Loss of deubiquitinase activity. Abolishes activation by protein kinases. 1 Publication1
Mutagenesisi224C → S: Loss of deubiquitinase activity. Loss of suppression of IFN production. 2 Publications1
Mutagenesisi542L → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-549. 1 Publication1
Mutagenesisi549S → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-542. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000068308
PharmGKBiPA142671217

Polymorphism and mutation databases

BioMutaiOTUD5
DMDMi74731791

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002782231 – 571OTU domain-containing protein 5Add BLAST571

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei64PhosphoserineCombined sources1 Publication1
Modified residuei165PhosphoserineCombined sources1 Publication1
Modified residuei175Phosphotyrosine1 Publication1
Modified residuei177PhosphoserineCombined sources1 Publication1
Modified residuei452PhosphoserineCombined sources1
Modified residuei507Phosphothreonine1 Publication1

Post-translational modificationi

Phosphorylation at Ser-177 is required for deubiquitinating activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96G74
MaxQBiQ96G74
PaxDbiQ96G74
PeptideAtlasiQ96G74
PRIDEiQ96G74
ProteomicsDBi76598
76599 [Q96G74-2]
76600 [Q96G74-3]
TopDownProteomicsiQ96G74-2 [Q96G74-2]

PTM databases

iPTMnetiQ96G74
PhosphoSitePlusiQ96G74

Expressioni

Tissue specificityi

Expressed in various tissues, including the liver and placenta, as well as in peripheral blood leukocytes.1 Publication

Inductioni

Up-regulated by bacterial lipopolysaccharide (LPS) in bone marrow-derived macrophages.1 Publication

Gene expression databases

BgeeiENSG00000068308 Expressed in 203 organ(s), highest expression level in islet of Langerhans
CleanExiHS_OTUD5
ExpressionAtlasiQ96G74 baseline and differential
GenevisibleiQ96G74 HS

Organism-specific databases

HPAiHPA017375

Interactioni

Subunit structurei

Interacts with TRAF3.2 Publications

Protein-protein interaction databases

BioGridi120738, 25 interactors
DIPiDIP-53541N
IntActiQ96G74, 18 interactors
STRINGi9606.ENSP00000156084

Structurei

Secondary structure

1571
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96G74
SMRiQ96G74
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini213 – 341OTUPROSITE-ProRule annotationAdd BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni218 – 224Cys-loopBy similarity7
Regioni273 – 283Variable-loopBy similarityAdd BLAST11
Regioni329 – 334His-loopBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi5 – 113Pro-richAdd BLAST109
Compositional biasi33 – 174Gly-richAdd BLAST142

Sequence similaritiesi

Belongs to the peptidase C85 family.Curated

Phylogenomic databases

eggNOGiKOG2605 Eukaryota
ENOG410XNYW LUCA
GeneTreeiENSGT00530000063508
HOGENOMiHOG000231360
HOVERGENiHBG060214
InParanoidiQ96G74
KOiK12655
OMAiDSMKHQS
OrthoDBiEOG091G0NE6
PhylomeDBiQ96G74
TreeFamiTF326812

Family and domain databases

InterProiView protein in InterPro
IPR031084 OTU5/OTLD1
IPR003323 OTU_dom
IPR038765 Papain_like_cys_pep_sf
PANTHERiPTHR12419:SF4 PTHR12419:SF4, 1 hit
PfamiView protein in Pfam
PF02338 OTU, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96G74-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:571
Mass (Da):60,626
Last modified:December 1, 2001 - v1
Checksum:iF4B2B385B84ABC46
GO
Isoform 2 (identifier: Q96G74-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     17-40: Missing.
     304-308: Missing.

Note: No experimental confirmation available. Dubious isoform produced through aberrant splice sites.
Show »
Length:542
Mass (Da):58,007
Checksum:iFB641E44937EC3F2
GO
Isoform 3 (identifier: Q96G74-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-308: Missing.
     563-566: HRDP → PCRC
     567-571: Missing.

Note: No experimental confirmation available. Dubious isoform produced through aberrant splice sites.
Show »
Length:561
Mass (Da):59,640
Checksum:i9C931880385CF8CB
GO
Isoform 4 (identifier: Q96G74-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     304-308: Missing.

Note: No experimental confirmation available.
Show »
Length:349
Mass (Da):39,185
Checksum:i555902ECCA9C52E4
GO
Isoform 5 (identifier: Q96G74-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-308: Missing.

Show »
Length:566
Mass (Da):60,210
Checksum:i46EBC6634CD55DA2
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BZQ3H7BZQ3_HUMAN
OTU domain-containing protein 5
OTUD5
444Annotation score:
A0A087WXV6A0A087WXV6_HUMAN
OTU domain-containing protein 5
OTUD5
542Annotation score:

Sequence cautioni

The sequence BAB14131 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15416 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0451851 – 217Missing in isoform 4. 1 PublicationAdd BLAST217
Alternative sequenceiVSP_02319517 – 40Missing in isoform 2. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_023192304 – 308Missing in isoform 2, isoform 3, isoform 4 and isoform 5. 3 Publications5
Alternative sequenceiVSP_023193563 – 566HRDP → PCRC in isoform 3. 1 Publication4
Alternative sequenceiVSP_023194567 – 571Missing in isoform 3. 1 Publication5

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
CCDSiCCDS14313.1 [Q96G74-1]
CCDS48104.1 [Q96G74-5]
CCDS48105.1 [Q96G74-4]
PIRiT46265
RefSeqiNP_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]
UniGeneiHs.496098

Genome annotation databases

EnsembliENST00000156084; ENSP00000156084; ENSG00000068308 [Q96G74-1]
ENST00000376488; ENSP00000365671; ENSG00000068308 [Q96G74-5]
ENST00000396743; ENSP00000379969; ENSG00000068308 [Q96G74-5]
ENST00000428668; ENSP00000401629; ENSG00000068308 [Q96G74-4]
GeneIDi55593
KEGGihsa:55593
UCSCiuc004dlt.5 human [Q96G74-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS14313.1 [Q96G74-1]
CCDS48104.1 [Q96G74-5]
CCDS48105.1 [Q96G74-4]
PIRiT46265
RefSeqiNP_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]
UniGeneiHs.496098

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3PFYX-ray1.70A172-344[»]
3TMOX-ray2.20A172-351[»]
3TMPX-ray1.91A/C/E/G172-351[»]
ProteinModelPortaliQ96G74
SMRiQ96G74
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120738, 25 interactors
DIPiDIP-53541N
IntActiQ96G74, 18 interactors
STRINGi9606.ENSP00000156084

Protein family/group databases

MEROPSiC85.001

PTM databases

iPTMnetiQ96G74
PhosphoSitePlusiQ96G74

Polymorphism and mutation databases

BioMutaiOTUD5
DMDMi74731791

Proteomic databases

EPDiQ96G74
MaxQBiQ96G74
PaxDbiQ96G74
PeptideAtlasiQ96G74
PRIDEiQ96G74
ProteomicsDBi76598
76599 [Q96G74-2]
76600 [Q96G74-3]
TopDownProteomicsiQ96G74-2 [Q96G74-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000156084; ENSP00000156084; ENSG00000068308 [Q96G74-1]
ENST00000376488; ENSP00000365671; ENSG00000068308 [Q96G74-5]
ENST00000396743; ENSP00000379969; ENSG00000068308 [Q96G74-5]
ENST00000428668; ENSP00000401629; ENSG00000068308 [Q96G74-4]
GeneIDi55593
KEGGihsa:55593
UCSCiuc004dlt.5 human [Q96G74-1]

Organism-specific databases

CTDi55593
EuPathDBiHostDB:ENSG00000068308.13
GeneCardsiOTUD5
HGNCiHGNC:25402 OTUD5
HPAiHPA017375
MIMi300713 gene
neXtProtiNX_Q96G74
OpenTargetsiENSG00000068308
PharmGKBiPA142671217
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2605 Eukaryota
ENOG410XNYW LUCA
GeneTreeiENSGT00530000063508
HOGENOMiHOG000231360
HOVERGENiHBG060214
InParanoidiQ96G74
KOiK12655
OMAiDSMKHQS
OrthoDBiEOG091G0NE6
PhylomeDBiQ96G74
TreeFamiTF326812

Enzyme and pathway databases

ReactomeiR-HSA-5689896 Ovarian tumor domain proteases
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling

Miscellaneous databases

ChiTaRSiOTUD5 human
GenomeRNAii55593
PROiPR:Q96G74
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068308 Expressed in 203 organ(s), highest expression level in islet of Langerhans
CleanExiHS_OTUD5
ExpressionAtlasiQ96G74 baseline and differential
GenevisibleiQ96G74 HS

Family and domain databases

InterProiView protein in InterPro
IPR031084 OTU5/OTLD1
IPR003323 OTU_dom
IPR038765 Papain_like_cys_pep_sf
PANTHERiPTHR12419:SF4 PTHR12419:SF4, 1 hit
PfamiView protein in Pfam
PF02338 OTU, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiOTUD5_HUMAN
AccessioniPrimary (citable) accession number: Q96G74
Secondary accession number(s): B4DGG7
, G5E9D7, Q4KMN9, Q8N6T5, Q9H650, Q9H9U0, Q9NT65
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: December 1, 2001
Last modified: November 7, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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