Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

OTU domain-containing protein 4

Gene

OTUD4

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

Functioni

Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111).3 Publications

Caution

When expressed in bacteria, recombinant OTUD4 specifically hydrolyzes 'Lys-48'-linked diubiquitin. The physiological relevance of this activity remains unknown (PubMed:23827681, PubMed:25944111, PubMed:29395066). In vivo deubiquitinates 'Lys-63'-linked ubiquitin chains (PubMed:29395066).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).3 Publications

Activity regulationi

Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei42By similarity1
Active sitei45Nucleophile3 Publications1
Active sitei148By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processImmunity, Innate immunity, Ubl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
OTU domain-containing protein 4 (EC:3.4.19.123 Publications)
Alternative name(s):
HIV-1-induced protein HIN-11 Publication
Gene namesi
Name:OTUD4Imported
Synonyms:HIN-11 Publication, KIAA10461 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164164.15
HGNCiHGNC:24949 OTUD4
MIMi611744 gene
neXtProtiNX_Q01804

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi45C → A: Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. Impairs 'Lys-63'-specific deubiquitinase activity toward MYD88 substrate. 3 Publications1
Mutagenesisi45C → S: Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. 1 Publication1
Mutagenesisi181 – 550Missing : Abolishes interaction with USP7 and USP9X deubiquitinases. 1 PublicationAdd BLAST370
Mutagenesisi202S → A: Decreases 'Lys-63'-specific deubiquitinase activity. Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204. 1 Publication1
Mutagenesisi204S → A: Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204. 1 Publication1
Mutagenesisi273 – 275KRD → AAA: Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate. 1 Publication3
Mutagenesisi279A → R: Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate. 1 Publication1

Organism-specific databases

DisGeNETi54726
OpenTargetsiENSG00000164164
PharmGKBiPA142671216

Polymorphism and mutation databases

DMDMi302393819

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000839791 – 1114OTU domain-containing protein 4Add BLAST1114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei120Phosphotyrosine1 Publication1
Modified residuei126Phosphoserine1 Publication1
Modified residuei128Phosphoserine1 Publication1
Modified residuei131Phosphothreonine1 Publication1
Modified residuei166Phosphoserine1 Publication1
Modified residuei199Phosphoserine1 Publication1
Modified residuei202Phosphoserine1 Publication1
Modified residuei204Phosphoserine1 Publication1
Modified residuei341PhosphoserineCombined sources1
Modified residuei439PhosphotyrosineBy similarity1
Modified residuei443PhosphoserineCombined sources1
Modified residuei460PhosphotyrosineCombined sources1
Modified residuei546PhosphoserineCombined sources1
Modified residuei893PhosphoserineCombined sources1
Modified residuei900PhosphoserineCombined sources1
Modified residuei1006PhosphoserineCombined sources1
Modified residuei1011PhosphoserineBy similarity1
Modified residuei1014PhosphoserineCombined sources1
Modified residuei1023PhosphoserineCombined sources1
Modified residuei1024PhosphoserineCombined sources1
Modified residuei1049PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ01804
MaxQBiQ01804
PaxDbiQ01804
PeptideAtlasiQ01804
PRIDEiQ01804
ProteomicsDBi57988
57990 [Q01804-3]
57991 [Q01804-4]

PTM databases

iPTMnetiQ01804
PhosphoSitePlusiQ01804

Expressioni

Inductioni

By HIV-1 insertion.1 Publication

Gene expression databases

BgeeiENSG00000164164 Expressed in 241 organ(s), highest expression level in sigmoid colon
CleanExiHS_OTUD4
ExpressionAtlasiQ01804 baseline and differential
GenevisibleiQ01804 HS

Organism-specific databases

HPAiHPA036623

Interactioni

Subunit structurei

Interacts with MYD88; the interaction is direct (PubMed:29395066). Interacts with ALKBH3; the interaction is direct (PubMed:25944111). Interacts with USP7; the interaction is direct (PubMed:25944111). Interacts with USP9X; the interaction is direct (PubMed:25944111).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120112, 62 interactors
IntActiQ01804, 38 interactors
MINTiQ01804
STRINGi9606.ENSP00000409279

Structurei

3D structure databases

ProteinModelPortaliQ01804
SMRiQ01804
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 155OTUPROSITE-ProRule annotation1 PublicationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni39 – 45Cys-loopBy similarity7
Regioni94 – 104Variable-loopBy similarityAdd BLAST11
Regioni143 – 148His-loopBy similarity6

Phylogenomic databases

eggNOGiKOG2605 Eukaryota
ENOG410XNYW LUCA
GeneTreeiENSGT00530000063508
HOVERGENiHBG082091
InParanoidiQ01804
KOiK13718
OMAiTEASVNG
OrthoDBiEOG091G00ZF
PhylomeDBiQ01804
TreeFamiTF326812

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR038765 Papain_like_cys_pep_sf
PfamiView protein in Pfam
PF02338 OTU, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q01804-1) [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
MEAAVGVPDG GDQGGAGPRE DATPMDAYLR KLGLYRKLVA KDGSCLFRAV
60 70 80 90 100
AEQVLHSQSR HVEVRMACIH YLRENREKFE AFIEGSFEEY LKRLENPQEW
110 120 130 140 150
VGQVEISALS LMYRKDFIIY REPNVSPSQV TENNFPEKVL LCFSNGNHYD
160 170 180 190 200
IVYPIKYKES SAMCQSLLYE LLYEKVFKTD VSKIVMELDT LEVADEDNSE
210 220 230 240 250
ISDSEDDSCK SKTAAAAADV NGFKPLSGNE QLKNNGNSTS LPLSRKVLKS
260 270 280 290 300
LNPAVYRNVE YEIWLKSKQA QQKRDYSIAA GLQYEVGDKC QVRLDHNGKF
310 320 330 340 350
LNADVQGIHS ENGPVLVEEL GKKHTSKNLK APPPESWNTV SGKKMKKPST
360 370 380 390 400
SGQNFHSDVD YRGPKNPSKP IKAPSALPPR LQHPSGVRQH AFSSHSSGSQ
410 420 430 440 450
SQKFSSEHKN LSRTPSQIIR KPDRERVEDF DHTSRESNYF GLSPEERREK
460 470 480 490 500
QAIEESRLLY EIQNRDEQAF PALSSSSVNQ SASQSSNPCV QRKSSHVGDR
510 520 530 540 550
KGSRRRMDTE ERKDKDSIHG HSQLDKRPEP STLENITDDK YATVSSPSKS
560 570 580 590 600
KKLECPSPAE QKPAEHVSLS NPAPLLVSPE VHLTPAVPSL PATVPAWPSE
610 620 630 640 650
PTTFGPTGVP APIPVLSVTQ TLTTGPDSAV SQAHLTPSPV PVSIQAVNQP
660 670 680 690 700
LMPLPQTLSL YQDPLYPGFP CNEKGDRAIV PPYSLCQTGE DLPKDKNILR
710 720 730 740 750
FFFNLGVKAY SCPMWAPHSY LYPLHQAYLA ACRMYPKVPV PVYPHNPWFQ
760 770 780 790 800
EAPAAQNESD CTCTDAHFPM QTEASVNGQM PQPEIGPPTF SSPLVIPPSQ
810 820 830 840 850
VSESHGQLSY QADLESETPG QLLHADYEES LSGKNMFPQP SFGPNPFLGP
860 870 880 890 900
VPIAPPFFPH VWYGYPFQGF IENPVMRQNI VLPSDEKGEL DLSLENLDLS
910 920 930 940 950
KDCGSVSTVD EFPEARGEHV HSLPEASVSS KPDEGRTEQS SQTRKADTAL
960 970 980 990 1000
ASIPPVAEGK AHPPTQILNR ERETVPVELE PKRTIQSLKE KTEKVKDPKT
1010 1020 1030 1040 1050
AADVVSPGAN SVDSRVQRPK EESSEDENEV SNILRSGRSK QFYNQTYGSR
1060 1070 1080 1090 1100
KYKSDWGYSG RGGYQHVRSE ESWKGQPSRS RDEGYQYHRN VRGRPFRGDR
1110
RRSGMGDGHR GQHT
Note: Gene prediction based on similarity to orthologs and partial EST data.
Length:1,114
Mass (Da):124,045
Last modified:March 19, 2014 - v4
Checksum:iAD8DF5FEAB8CBE32
GO
Isoform 2 (identifier: Q01804-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     231-231: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:1,048
Mass (Da):116,953
Checksum:i5266BAE77822228E
GO
Isoform 3 (identifier: Q01804-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Show »
Length:1,049
Mass (Da):117,082
Checksum:i1DCACF002992C917
GO
Isoform 4 (identifier: Q01804-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     211-1114: Missing.

Note: Predicted from a chimeric transcript isolated from HIV-1-infected cells. The premature stop may be due to intron retention.
Show »
Length:145
Mass (Da):17,036
Checksum:iBEF79BFC3DB34EF1
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RI06D6RI06_HUMAN
OTU domain-containing protein 4
OTUD4
372Annotation score:
D6RA27D6RA27_HUMAN
OTU domain-containing protein 4
OTUD4
139Annotation score:

Sequence cautioni

The sequence AAH57242 differs from that shown. Sequence of unknown origin in the N-terminal part.Curated
The sequence BAA82998 differs from that shown. Intron retention.Curated
The sequence BAB71229 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti809S → P in BAB71229 (PubMed:14702039).Curated1
Sequence conflicti915A → S in CAB70748 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029377194A → G1 PublicationCorresponds to variant dbSNP:rs36225458Ensembl.1
Natural variantiVAR_038848216A → T1 PublicationCorresponds to variant dbSNP:rs36225838Ensembl.1
Natural variantiVAR_070050398G → V Could be associated with cerebellar ataxia and hypogonadotropic hypogonadism. 1 PublicationCorresponds to variant dbSNP:rs148857745Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0388301 – 65Missing in isoform 2, isoform 3 and isoform 4. 3 PublicationsAdd BLAST65
Alternative sequenceiVSP_021671211 – 1114Missing in isoform 4. 1 PublicationAdd BLAST904
Alternative sequenceiVSP_053825231Missing in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056597 mRNA Translation: BAB71229.1 Different initiation.
AK302581 mRNA Translation: BAG63836.1
AC096757 Genomic DNA No translation available.
CH471056 Genomic DNA Translation: EAX05045.1
CH471056 Genomic DNA Translation: EAX05046.1
X68242 mRNA Translation: CAA48313.1
DQ427109 Genomic DNA Translation: ABD72605.1
BC057242 mRNA Translation: AAH57242.2 Sequence problems.
BC118572 mRNA Translation: AAI18573.1
BC118653 mRNA Translation: AAI18654.1
AB028969 mRNA Translation: BAA82998.2 Sequence problems.
AL137460 mRNA Translation: CAB70748.1
CCDSiCCDS3764.1 [Q01804-4]
CCDS47139.1 [Q01804-3]
PIRiS30247
T46403
RefSeqiNP_001096123.1, NM_001102653.1 [Q01804-3]
NP_059963.1, NM_017493.6 [Q01804-4]
XP_005263136.1, XM_005263079.4 [Q01804-1]
UniGeneiHs.270851

Genome annotation databases

EnsembliENST00000447906; ENSP00000395487; ENSG00000164164 [Q01804-1]
ENST00000454497; ENSP00000409279; ENSG00000164164 [Q01804-3]
ENST00000509620; ENSP00000424192; ENSG00000164164 [Q01804-4]
GeneIDi54726
KEGGihsa:54726
UCSCiuc003ika.5 human [Q01804-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056597 mRNA Translation: BAB71229.1 Different initiation.
AK302581 mRNA Translation: BAG63836.1
AC096757 Genomic DNA No translation available.
CH471056 Genomic DNA Translation: EAX05045.1
CH471056 Genomic DNA Translation: EAX05046.1
X68242 mRNA Translation: CAA48313.1
DQ427109 Genomic DNA Translation: ABD72605.1
BC057242 mRNA Translation: AAH57242.2 Sequence problems.
BC118572 mRNA Translation: AAI18573.1
BC118653 mRNA Translation: AAI18654.1
AB028969 mRNA Translation: BAA82998.2 Sequence problems.
AL137460 mRNA Translation: CAB70748.1
CCDSiCCDS3764.1 [Q01804-4]
CCDS47139.1 [Q01804-3]
PIRiS30247
T46403
RefSeqiNP_001096123.1, NM_001102653.1 [Q01804-3]
NP_059963.1, NM_017493.6 [Q01804-4]
XP_005263136.1, XM_005263079.4 [Q01804-1]
UniGeneiHs.270851

3D structure databases

ProteinModelPortaliQ01804
SMRiQ01804
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120112, 62 interactors
IntActiQ01804, 38 interactors
MINTiQ01804
STRINGi9606.ENSP00000409279

PTM databases

iPTMnetiQ01804
PhosphoSitePlusiQ01804

Polymorphism and mutation databases

DMDMi302393819

Proteomic databases

EPDiQ01804
MaxQBiQ01804
PaxDbiQ01804
PeptideAtlasiQ01804
PRIDEiQ01804
ProteomicsDBi57988
57990 [Q01804-3]
57991 [Q01804-4]

Protocols and materials databases

DNASUi54726
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000447906; ENSP00000395487; ENSG00000164164 [Q01804-1]
ENST00000454497; ENSP00000409279; ENSG00000164164 [Q01804-3]
ENST00000509620; ENSP00000424192; ENSG00000164164 [Q01804-4]
GeneIDi54726
KEGGihsa:54726
UCSCiuc003ika.5 human [Q01804-1]

Organism-specific databases

CTDi54726
DisGeNETi54726
EuPathDBiHostDB:ENSG00000164164.15
GeneCardsiOTUD4
HGNCiHGNC:24949 OTUD4
HPAiHPA036623
MIMi611744 gene
neXtProtiNX_Q01804
OpenTargetsiENSG00000164164
PharmGKBiPA142671216
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2605 Eukaryota
ENOG410XNYW LUCA
GeneTreeiENSGT00530000063508
HOVERGENiHBG082091
InParanoidiQ01804
KOiK13718
OMAiTEASVNG
OrthoDBiEOG091G00ZF
PhylomeDBiQ01804
TreeFamiTF326812

Miscellaneous databases

ChiTaRSiOTUD4 human
GeneWikiiOTUD4
GenomeRNAii54726
PROiPR:Q01804
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164164 Expressed in 241 organ(s), highest expression level in sigmoid colon
CleanExiHS_OTUD4
ExpressionAtlasiQ01804 baseline and differential
GenevisibleiQ01804 HS

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR038765 Papain_like_cys_pep_sf
PfamiView protein in Pfam
PF02338 OTU, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiOTUD4_HUMAN
AccessioniPrimary (citable) accession number: Q01804
Secondary accession number(s): B4DYS4
, Q147U2, Q1ZYK1, Q6PG39, Q96MQ5, Q9NT94, Q9UPV6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: March 19, 2014
Last modified: November 7, 2018
This is version 148 of the entry and version 4 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again