Free for academic non-profit institutions. Other users need a Commercial license

Aliases for OTULIN Gene

Aliases for OTULIN Gene

  • OTU Deubiquitinase With Linear Linkage Specificity 2 3 5
  • OTU Domain-Containing Deubiquitinase With Linear Linkage Specificity 3 4
  • Family With Sequence Similarity 105, Member B 2 3
  • Deubiquitinating Enzyme Otulin 3 4
  • Ubiquitin Thioesterase Gumby 3 4
  • FAM105B 3 4
  • Ubiquitin Thioesterase Otulin 3
  • EC 3.4.19.12 4
  • Gumby 2
  • AIPDS 3
  • GUM 3

External Ids for OTULIN Gene

Previous HGNC Symbols for OTULIN Gene

  • FAM105B

Summaries for OTULIN Gene

Entrez Gene Summary for OTULIN Gene

  • This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]

GeneCards Summary for OTULIN Gene

OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) is a Protein Coding gene. Diseases associated with OTULIN include Otulipenia and Panniculitis. Among its related pathways are TNF signaling (REACTOME) and Metabolism of proteins. GO annotations related to this gene include cysteine-type peptidase activity and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is FAM105A.

UniProtKB/Swiss-Prot for OTULIN Gene

  • Deubiquitinase that specifically removes linear (Met-1-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327). Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). Required for homeostasis of the LUBAC complex by restricting autoubiquination of the LUBAC complex subunit RNF31 (PubMed:24726323). Some results have suggested that OTULIN function is restricted to homeostasis of the LUBAC complex, because it is not stably associated with TNF or NOD2 receptor signaling complexes (RSCs) (PubMed:26670046). However, further report have shown that it plays active roles in receptor signaling (PubMed:26997266, PubMed:27523608). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a key role in innate immune response by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (PubMed:23806334).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for OTULIN Gene

Genomics for OTULIN Gene

Regulatory Elements for OTULIN Gene

Enhancers for OTULIN Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH05F014663 0.9 FANTOM5 ENCODE 31.5 +1.4 1389 5.8 HDGF PKNOX1 CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 OTULIN EEF1A1P13 RBBP4P1 FAM105A GC05P014689
GH05F014669 1.4 FANTOM5 Ensembl ENCODE 19.8 +6.6 6581 3.9 SOX13 TBP WRNIP1 FEZF1 ZNF2 ZNF324 ZNF335 ZNF121 ZNF316 ZBTB48 OTULIN FAM105A GC05P014689
GH05F014674 1.4 FANTOM5 Ensembl ENCODE 16.6 +11.3 11303 2.7 HDGF CBX3 TBL1XR1 WRNIP1 SIN3A ZBTB40 CBX5 CREM SMARCA5 ZBTB2 OTULIN FAM105A GC05P014689
GH05F014163 1.2 FANTOM5 Ensembl ENCODE 11.8 -485.4 -485407 30.9 HDGF PKNOX1 WRNIP1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 CBX5 RBBP4P1 TRIO OTULIN ENSG00000281325
GH05F014152 1.3 FANTOM5 Ensembl ENCODE 11.8 -508.1 -508064 8.0 HDGF PKNOX1 WRNIP1 SIN3A FEZF1 ZNF2 FOS DEK ZNF263 SP3 RBBP4P1 OTULIN TRIO ENSG00000281325
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around OTULIN on UCSC Golden Path with GeneCards custom track

Promoters for OTULIN Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001407671 236 2601 HDGF PKNOX1 MLX CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A DMAP1 ZNF2

Genomic Location for OTULIN Gene

Chromosome:
5
Start:
14,664,664 bp from pter
End:
14,712,867 bp from pter
Size:
48,204 bases
Orientation:
Plus strand

Genomic View for OTULIN Gene

Genes around OTULIN on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for OTULIN Gene

Proteins for OTULIN Gene

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

    Protein Symbol:
    Q96BN8-OTUL_HUMAN
    Recommended name:
    Ubiquitin thioesterase otulin
    Protein Accession:
    Q96BN8
    Secondary Accessions:
    • D3DTD3
    • Q8NAS0
    • Q96IA3

    Protein attributes for OTULIN Gene

    Size:
    352 amino acids
    Molecular mass:
    40263 Da
    Quaternary structure:
    • Interacts (via the PUB domain) with RNF31 (via the PIM motif); the interaction is direct (PubMed:27523608, PubMed:23708998, PubMed:23746843, PubMed:24726323, PubMed:24726327). Interacts with DVL2 (By similarity).
    SequenceCaution:
    • Sequence=AAH07706.3; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAH15392.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAC03828.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for OTULIN Gene

neXtProt entry for OTULIN Gene

Post-translational modifications for OTULIN Gene

  • Acetylated.
  • Phosphorylated (PubMed:23746843, PubMed:24726323, PubMed:24726327). Phosphorylation at Tyr-56 prevents interaction with RNF31; dephosphorylation promotes interaction with RNF31 and the LUBAC complex (PubMed:24726323, PubMed:24726327).
  • Ubiquitinated.
  • Ubiquitination at Lys 34 and Lys 66
  • Modification sites at PhosphoSitePlus

Other Protein References for OTULIN Gene

No data available for DME Specific Peptides for OTULIN Gene

Domains & Families for OTULIN Gene

Gene Families for OTULIN Gene

Protein Domains for OTULIN Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for OTULIN Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96BN8

UniProtKB/Swiss-Prot:

OTUL_HUMAN :
  • The specificity for linear polyubiquitin is given by the Glu-16 residue in ubiquitin chain.
  • Belongs to the peptidase C65 family. Otulin subfamily.
Domain:
  • The specificity for linear polyubiquitin is given by the Glu-16 residue in ubiquitin chain.
  • The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31.
  • Contains 1 OTU domain.
Family:
  • Belongs to the peptidase C65 family. Otulin subfamily.
genes like me logo Genes that share domains with OTULIN: view

Function for OTULIN Gene

Molecular function for OTULIN Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=7.98 uM for linear diubiquitin {ECO:0000269 PubMed:23746843}; Note=Kcat is 6.3 sec(-1) with linear diubiquitin as substrate. {ECO:0000269 PubMed:23746843};
UniProtKB/Swiss-Prot CatalyticActivity:
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).
UniProtKB/Swiss-Prot Function:
Deubiquitinase that specifically removes linear (Met-1-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327). Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). Required for homeostasis of the LUBAC complex by restricting autoubiquination of the LUBAC complex subunit RNF31 (PubMed:24726323). Some results have suggested that OTULIN function is restricted to homeostasis of the LUBAC complex, because it is not stably associated with TNF or NOD2 receptor signaling complexes (RSCs) (PubMed:26670046). However, further report have shown that it plays active roles in receptor signaling (PubMed:26997266, PubMed:27523608). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a key role in innate immune response by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (PubMed:23806334).

Enzyme Numbers (IUBMB) for OTULIN Gene

Gene Ontology (GO) - Molecular Function for OTULIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA 23746843
GO:0005515 protein binding IPI 23708998
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IMP 23746843
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with OTULIN: view
genes like me logo Genes that share phenotypes with OTULIN: view

Animal Model Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for OTULIN Gene

Localization for OTULIN Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTULIN Gene

Cytoplasm.

Gene Ontology (GO) - Cellular Components for OTULIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 23746843
GO:0005829 cytosol TAS --
GO:0071797 LUBAC complex IEA --
genes like me logo Genes that share ontologies with OTULIN: view

No data available for Subcellular locations from COMPARTMENTS for OTULIN Gene

Pathways & Interactions for OTULIN Gene

genes like me logo Genes that share pathways with OTULIN: view

Pathways by source for OTULIN Gene

1 R&D Systems pathway for OTULIN Gene

Gene Ontology (GO) - Biological Process for OTULIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002040 sprouting angiogenesis IEA,ISS --
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS --
GO:0016055 Wnt signaling pathway IEA --
genes like me logo Genes that share ontologies with OTULIN: view

No data available for SIGNOR curated interactions for OTULIN Gene

Transcripts for OTULIN Gene

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

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

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7
SP1: - -
SP2: - - -
SP3:
SP4:

Relevant External Links for OTULIN Gene

GeneLoc Exon Structure for
OTULIN
ECgene alternative splicing isoforms for
OTULIN

Expression for OTULIN Gene

mRNA expression in normal human tissues for OTULIN Gene

Protein differential expression in normal tissues from HIPED for OTULIN Gene

This gene is overexpressed in Bone (36.4) and Peripheral blood mononuclear cells (7.6).

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



Protein tissue co-expression partners for OTULIN Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of OTULIN Gene:

OTULIN
genes like me logo Genes that share expression patterns with OTULIN: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for OTULIN Gene

Orthologs for OTULIN Gene

This gene was present in the common ancestor of chordates.

Orthologs for OTULIN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FAM105B 34 35
  • 99.9 (n)
dog
(Canis familiaris)
Mammalia FAM105B 34 35
  • 89.2 (n)
mouse
(Mus musculus)
Mammalia Fam105b 34 35
  • 87.69 (n)
Otulin 16
rat
(Rattus norvegicus)
Mammalia Fam105b 34
  • 86.84 (n)
cow
(Bos Taurus)
Mammalia FAM105B 34 35
  • 86.55 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia FAM105B 35
  • 80 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FAM105B 35
  • 78 (a)
OneToOne
chicken
(Gallus gallus)
Aves FAM105B 34 35
  • 66.45 (n)
lizard
(Anolis carolinensis)
Reptilia FAM105B 35
  • 59 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia fam105b 34
  • 60.9 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100001665 34
  • 56.39 (n)
fam105bb 35
  • 33 (a)
OneToMany
fam105ba 35
  • 15 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 41 (a)
OneToMany
Species where no ortholog for OTULIN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • fruit fly (Drosophila melanogaster)
  • 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 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 OTULIN Gene

ENSEMBL:
Gene Tree for OTULIN (if available)
TreeFam:
Gene Tree for OTULIN (if available)

Paralogs for OTULIN Gene

Paralogs for OTULIN Gene

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

Variants for OTULIN Gene

Sequence variations from dbSNP and Humsavar for OTULIN Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type
VAR_076865 Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) [MIM:617099]
VAR_076866 Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) [MIM:617099]
rs121908405 Pathogenic 14,716,716(-) CCTTC(-/TTC)CCAGT downstream-variant-500B, cds-indel
rs121908406 Pathogenic 14,716,722(-) TCTTC(-/TCC)TTCTT downstream-variant-500B, cds-indel
rs121908408 Pathogenic 14,711,206(-) GAGAG(-/GAG)AATGA intron-variant, upstream-variant-2KB, cds-indel

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

Variant ID Type Subtype PubMed ID
esv1000304 CNV insertion 20482838
esv28342 CNV loss 19812545
nsv1018187 CNV gain 25217958
nsv1026914 CNV gain 25217958
nsv4728 CNV insertion 18451855
nsv597254 CNV loss 21841781
nsv597255 CNV gain 21841781
nsv597256 CNV gain 21841781
nsv830211 CNV loss 17160897

Variation tolerance for OTULIN Gene

Residual Variation Intolerance Score: 54% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.64; 65.68% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for OTULIN Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
OTULIN

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

Disorders for OTULIN Gene

MalaCards: The human disease database

(2) MalaCards diseases for OTULIN Gene - From: ClinVar, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
otulipenia
  • autoinflammation, panniculitis and dermatosis syndrome
panniculitis
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

OTUL_HUMAN
  • Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) [MIM:617099]: An autosomal recessive autoinflammatory disorder characterized by neonatal-onset of fever, neutrophilic dermatitis, panniculitis, painful joints, failure to thrive. Patients do not exhibit overt primary immunodeficiency. {ECO:0000269 PubMed:27523608, ECO:0000269 PubMed:27559085}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for OTULIN

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
OTULIN
genes like me logo Genes that share disorders with OTULIN: view

No data available for Genatlas for OTULIN Gene

Publications for OTULIN Gene

  1. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. (PMID: 23708998) Rivkin E. … Cordes S.P. (Nature 2013) 2 3 4 64
  2. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1- linked polyubiquitin. (PMID: 23746843) Keusekotten K. … Komander D. (Cell 2013) 2 3 4 64
  3. CYLD limits Lys63- and Met1-linked ubiquitin at receptor complexes to regulate innate immune signaling. (PMID: 26997266) Hrdinka M. … Gyrd-Hansen M. (Cell Rep. 2016) 3 4 64
  4. The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. (PMID: 27523608) Damgaard R.B. … Komander D. (Cell 2016) 3 4 64
  5. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. (PMID: 27559085) Zhou Q. … Aksentijevich I. (Proc. Natl. Acad. Sci. U.S.A. 2016) 3 4 64

Products for OTULIN Gene

Sources for OTULIN Gene

Content
Loading form....