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Protein

OTU domain-containing protein 5

Gene

OTUD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • Lys48-specific deubiquitinase activity Source: MGI
  • Lys63-specific deubiquitinase activity Source: MGI
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • ubiquitinyl hydrolase activity Source: MGI

GO - Biological processi

  • negative regulation of type I interferon production Source: Reactome
  • protein deubiquitination Source: MGI
  • protein K48-linked deubiquitination Source: UniProtKB
  • protein K63-linked deubiquitination Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS12191-MONOMER.
ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-936440. Negative regulators of RIG-I/MDA5 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

HGNCiHGNC:25402. OTUD5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
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.
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. 22 interactors.
DIPiDIP-53541N.
IntActiQ96G74. 16 interactors.
MINTiMINT-1408843.
STRINGi9606.ENSP00000156084.

Structurei

Secondary structure

1571
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi178 – 180Combined sources3
Helixi181 – 186Combined sources6
Helixi193 – 211Combined sources19
Beta strandi214 – 216Combined sources3
Helixi224 – 234Combined sources11
Helixi237 – 239Combined sources3
Helixi240 – 253Combined sources14
Helixi255 – 258Combined sources4
Helixi259 – 261Combined sources3
Helixi266 – 273Combined sources8
Helixi282 – 292Combined sources11
Beta strandi296 – 301Combined sources6
Beta strandi303 – 305Combined sources3
Beta strandi311 – 314Combined sources4
Beta strandi325 – 330Combined sources6
Turni331 – 333Combined sources3
Beta strandi334 – 339Combined sources6

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...

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
Contains 1 OTU domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR031084. OTU5/OTLD1.
IPR003323. OTU_dom.
[Graphical view]
PANTHERiPTHR12419:SF4. PTHR12419:SF4. 1 hit.
PfamiPF02338. OTU. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

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

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

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

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. 22 interactors.
DIPiDIP-53541N.
IntActiQ96G74. 16 interactors.
MINTiMINT-1408843.
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.
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.
GeneCardsiOTUD5.
HGNCiHGNC:25402. OTUD5.
HPAiHPA017375.
MIMi300713. gene.
neXtProtiNX_Q96G74.
OpenTargetsiENSG00000068308.
PharmGKBiPA142671217.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS12191-MONOMER.
ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

ChiTaRSiOTUD5. human.
GenomeRNAii55593.
PROiQ96G74.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068308.
CleanExiHS_OTUD5.
ExpressionAtlasiQ96G74. baseline and differential.
GenevisibleiQ96G74. HS.

Family and domain databases

InterProiIPR031084. OTU5/OTLD1.
IPR003323. OTU_dom.
[Graphical view]
PANTHERiPTHR12419:SF4. PTHR12419:SF4. 1 hit.
PfamiPF02338. OTU. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTUD5_HUMAN
AccessioniPrimary (citable) accession number: Q96G74
Secondary accession number(s): B4DGG7
, G5E9D7, Q4KMN9, Q8N6T5, Q9H650, Q9H9U0, Q9NT65
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 123 of the entry and version 1 of the sequence. [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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.