Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010] See more...

Aliases for OTUD4 Gene

Aliases for OTUD4 Gene

  • OTU Deubiquitinase 4 2 3 5
  • OTU Domain-Containing Protein 4 3 4
  • KIAA1046 2 4
  • HSHIN1 2 3
  • DUBA6 2 3
  • HIV-1 Induced Protein HIN-1 3
  • HIV-1-Induced Protein HIN-1 4
  • OTU Domain Containing 4 2
  • EC 3.4.19.12 4
  • OTUD4 5
  • HIN-1 4
  • HIN1 3

External Ids for OTUD4 Gene

Previous GeneCards Identifiers for OTUD4 Gene

  • GC04M146413
  • GC04M146274
  • GC04M146054
  • GC04M141787

Summaries for OTUD4 Gene

Entrez Gene Summary for OTUD4 Gene

  • Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010]

GeneCards Summary for OTUD4 Gene

OTUD4 (OTU Deubiquitinase 4) is a Protein Coding gene. Diseases associated with OTUD4 include Boucher-Neuhauser Syndrome and Gordon Holmes Syndrome. Gene Ontology (GO) annotations related to this gene include thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is OTUD5.

UniProtKB/Swiss-Prot Summary for OTUD4 Gene

  • 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).

Gene Wiki entry for OTUD4 Gene

Additional gene information for OTUD4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for OTUD4 Gene

Genomics for OTUD4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for OTUD4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J145175 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 601.9 +1.2 1188 8 SP1 HNRNPL PRDM10 RFX1 SIX5 NFKBIZ POLR2A BACH1 LARP7 PRDM1 OTUD4 lnc-ANAPC10-4 ANAPC10 ABCE1 MMAA HE856056
GH04J145096 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11 +82.1 82095 4.2 HNRNPL CREB1 GATAD2A ATF7 PRDM10 REST ZNF629 TFE3 SIX5 NFKBIZ ANAPC10 ABCE1 ENSG00000285713 lnc-OTUD4-5 ENSG00000248356 OTUD4
GH04J145617 Promoter/Enhancer 1.9 Ensembl ENCODE CraniofacialAtlas 9.8 -438.9 -438866 3.6 SP1 CTCF HNRNPL ZNF629 REST TFE3 POLR2A ZNF692 RCOR2 BACH1 MMAA ENSG00000248356 SLC10A7 OTUD4 LSM6 NCOA4P3 LINC02491 C4orf51
GH04J145812 Enhancer 1.1 Ensembl ENCODE dbSUPER 11.9 -632.6 -632612 2 CREB1 PKNOX1 ATF7 BRCA1 CTBP1 CEBPB FOS JUN RCOR1 JUND OTUD4 lnc-C4orf51-5 lnc-SLC10A7-8 ZNF827 C4orf51
GH04J145130 Enhancer 0.9 Ensembl ENCODE 11.5 +48.6 48593 3.6 POLR2A STAT3 PRDM1 RELA IKZF2 EED ARID3A DPF2 RELB RUNX3 MN297119-002 OTUD4 ABCE1 ANAPC10
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around OTUD4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for OTUD4

Top Transcription factor binding sites by QIAGEN in the OTUD4 gene promoter:
  • E47
  • GATA-2
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1b
  • N-Myc
  • p300
  • Sox9
  • Tal-1beta

Genomic Locations for OTUD4 Gene

Genomic Locations for OTUD4 Gene
chr4:145,110,838-145,180,589
(GRCh38/hg38)
Size:
69,752 bases
Orientation:
Minus strand
chr4:146,031,990-146,101,313
(GRCh37/hg19)
Size:
69,324 bases
Orientation:
Minus strand

Genomic View for OTUD4 Gene

Genes around OTUD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
OTUD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for OTUD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for OTUD4 Gene

Proteins for OTUD4 Gene

  • Protein details for OTUD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q01804-OTUD4_HUMAN
    Recommended name:
    OTU domain-containing protein 4
    Protein Accession:
    Q01804
    Secondary Accessions:
    • B4DYS4
    • Q147U2
    • Q1ZYK1
    • Q6PG39
    • Q96MQ5
    • Q9NT94
    • Q9UPV6

    Protein attributes for OTUD4 Gene

    Size:
    1114 amino acids
    Molecular mass:
    124045 Da
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=AAH57242.2; Type=Miscellaneous discrepancy; Note=Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA82998.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAB71229.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 4]: Predicted from a chimeric transcript isolated from HIV-1-infected cells. The premature stop may be due to intron retention.

    Alternative splice isoforms for OTUD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for OTUD4 Gene

Post-translational modifications for OTUD4 Gene

  • Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Abcam antibodies for OTUD4
  • Boster Bio Antibodies for OTUD4

No data available for DME Specific Peptides for OTUD4 Gene

Domains & Families for OTUD4 Gene

Gene Families for OTUD4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for OTUD4 Gene

InterPro:
Blocks:
  • OTU-like cysteine protease
ProtoNet:

Suggested Antigen Peptide Sequences for OTUD4 Gene

GenScript: Design optimal peptide antigens:
  • OTUD4 protein (A0PJA7_HUMAN)
  • HIV-1-induced protein HIN-1 (OTUD4_HUMAN)
genes like me logo Genes that share domains with OTUD4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for OTUD4 Gene

Function for OTUD4 Gene

Molecular function for OTUD4 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=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).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066};.
UniProtKB/Swiss-Prot Induction:
By HIV-1 insertion.
UniProtKB/Swiss-Prot EnzymeRegulation:
Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity.

Enzyme Numbers (IUBMB) for OTUD4 Gene

Phenotypes From GWAS Catalog for OTUD4 Gene

Gene Ontology (GO) - Molecular Function for OTUD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22681889
GO:0004843 thiol-dependent ubiquitin-specific protease activity IBA,IDA 23827681
GO:0005515 protein binding IPI 25416956
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with OTUD4: view
genes like me logo Genes that share phenotypes with OTUD4: view

Animal Models for OTUD4 Gene

MGI Knock Outs for OTUD4:
  • Otud4 Otud4<tm1b(EUCOMM)Hmgu>

Animal Model Products

CRISPR Products

miRNA for OTUD4 Gene

miRTarBase miRNAs that target OTUD4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTUD4

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for OTUD4 Gene

Localization for OTUD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTUD4 Gene

Cytoplasm. Nucleus. Note=Primarily cytoplasmic. {ECO:0000269 PubMed:25944111}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for OTUD4 gene
Compartment Confidence
cytosol 5
nucleus 4
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for OTUD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with OTUD4: view

Pathways & Interactions for OTUD4 Gene

PathCards logo

SuperPathways for OTUD4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for OTUD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0016579 protein deubiquitination IBA 21873635
GO:0034122 negative regulation of toll-like receptor signaling pathway IBA,IDA 29395066
GO:0045087 innate immune response IEA --
genes like me logo Genes that share ontologies with OTUD4: view

No data available for Pathways by source and SIGNOR curated interactions for OTUD4 Gene

Drugs & Compounds for OTUD4 Gene

No Compound Related Data Available

Transcripts for OTUD4 Gene

mRNA/cDNA for OTUD4 Gene

5 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTUD4

Alternative Splicing Database (ASD) splice patterns (SP) for OTUD4 Gene

No ASD Table

Relevant External Links for OTUD4 Gene

GeneLoc Exon Structure for
OTUD4

Expression for OTUD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for OTUD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for OTUD4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (13.2), Fetal ovary (10.2), Tlymphocyte (7.8), and CD8 Tcells (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for OTUD4 Gene



Protein tissue co-expression partners for OTUD4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for OTUD4

SOURCE GeneReport for Unigene cluster for OTUD4 Gene:

Hs.270851

Evidence on tissue expression from TISSUES for OTUD4 Gene

  • Nervous system(4.5)
  • Liver(4.2)
  • Muscle(2.2)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with OTUD4: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for OTUD4 Gene

Orthologs for OTUD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for OTUD4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia OTUD4 30 31
  • 99.65 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia OTUD4 30 31
  • 91.37 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Otud4 30 17 31
  • 88.21 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Otud4 30
  • 86.97 (n)
Cow
(Bos Taurus)
Mammalia OTUD4 30 31
  • 85.92 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 68 (a)
OneToMany
-- 31
  • 63 (a)
OneToMany
-- 31
  • 58 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia OTUD4 31
  • 66 (a)
OneToOne
Chicken
(Gallus gallus)
Aves OTUD4 30 31
  • 68.67 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia OTUD4 31
  • 45 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia otud4 30
  • 59.72 (n)
Str.19581 30
Zebrafish
(Danio rerio)
Actinopterygii otud4 31
  • 15 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta CG3251 31
  • 20 (a)
ManyToMany
otu 31
  • 18 (a)
ManyToMany
Species where no ortholog for OTUD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for OTUD4 Gene

ENSEMBL:
Gene Tree for OTUD4 (if available)
TreeFam:
Gene Tree for OTUD4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for OTUD4: view image

Paralogs for OTUD4 Gene

Paralogs for OTUD4 Gene

(1) SIMAP similar genes for OTUD4 Gene using alignment to 6 proteins:

  • OTUD4_HUMAN
  • A0PJA7_HUMAN
  • D6RA27_HUMAN
  • D6RI06_HUMAN
  • G3V0I6_HUMAN
  • L8EAV3_HUMAN

Pseudogenes.org Pseudogenes for OTUD4 Gene

genes like me logo Genes that share paralogs with OTUD4: view

Variants for OTUD4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for OTUD4 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs147253069 Conflicting Interpretations: not specified; not provided 145,137,772(-) A/T SYNONYMOUS_VARIANT
rs148857745 Uncertain Significance: Variant of unknown significance. - 145,150,579(-) C/Ap.Gly398Val MISSENSE_VARIANT
rs36225458 Uncertain Significance: not specified. - 145,159,551(-) G/Cp.Ala194Gly MISSENSE_VARIANT
rs369308038 Uncertain Significance: not specified 145,155,463(-) C/T MISSENSE_VARIANT
rs36225838 - p.Ala216Thr

Additional dbSNP identifiers (rs#s) for OTUD4 Gene

Structural Variations from Database of Genomic Variants (DGV) for OTUD4 Gene

Variant ID Type Subtype PubMed ID
nsv1073805 CNV deletion 25765185
nsv966326 CNV duplication 23825009

Variation tolerance for OTUD4 Gene

Residual Variation Intolerance Score: 43.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.49; 43.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for OTUD4 Gene

Human Gene Mutation Database (HGMD)
OTUD4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
OTUD4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for OTUD4 Gene

Disorders for OTUD4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for OTUD4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
boucher-neuhauser syndrome
  • bnhs
gordon holmes syndrome
  • gdhs
kallmann syndrome
  • hypogonadotropic hypogonadism and anosmia
- elite association - COSMIC cancer census association via MalaCards
Search OTUD4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with OTUD4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for OTUD4 Gene

Publications for OTUD4 Gene

  1. HIV-1 promotor insertion revealed by selective detection of chimeric provirus-host gene transcripts. (PMID: 1475186) Raineri I … Senn HP (Nucleic acids research 1992) 2 3 4
  2. OTUD4 Is a Phospho-Activated K63 Deubiquitinase that Regulates MyD88-Dependent Signaling. (PMID: 29395066) Zhao Y … Mosammaparast N (Molecular cell 2018) 3 4
  3. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase. (PMID: 25944111) Zhao Y … Mosammaparast N (The EMBO journal 2015) 3 4
  4. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. (PMID: 23827681) Mevissen TE … Komander D (Cell 2013) 3 4
  5. Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination. (PMID: 23656588) Margolin DH … Seminara SB (The New England journal of medicine 2013) 3 4

Products for OTUD4 Gene

  • Signalway Proteins for OTUD4

Sources for OTUD4 Gene