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OTULIN OTU deubiquitinase with linear linkage specificity [ Homo sapiens (human) ]

Gene ID: 90268, updated on 27-Nov-2024

Summary

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Official Symbol
OTULINprovided by HGNC
Official Full Name
OTU deubiquitinase with linear linkage specificityprovided by HGNC
Primary source
HGNC:HGNC:25118
See related
Ensembl:ENSG00000154124 MIM:615712; AllianceGenome:HGNC:25118
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GUM; AIPDS; IMD107; FAM105B
Summary
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]
Expression
Ubiquitous expression in bone marrow (RPKM 5.9), skin (RPKM 4.5) and 25 other tissues See more
Orthologs
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Genomic context

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See OTULIN in Genome Data Viewer
Location:
5p15.2
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (14664718..14716525)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (14604209..14656024)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (14664827..14699959)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 13 Neighboring gene small nucleolar RNA, C/D box 141B Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:14663902-14664704 Neighboring gene Sharpr-MPRA regulatory region 4048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22409 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22411 Neighboring gene OTULIN divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22412 Neighboring gene uncharacterized LOC100130744 Neighboring gene uncharacterized LOC124900944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22413 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:14727488-14727682 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14727811-14728770 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14728771-14729729 Neighboring gene ANKH inorganic pyrophosphate transport regulator Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22414 Neighboring gene RBBP4 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers. Batlle-Masó L, et al. J Clin Immunol, 2024 Apr 5. PMID 38578307
  2. Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker. Huang Z, et al. Front Biosci (Landmark Ed), 2023 Nov 27. PMID 38062820
  3. Downregulation of otulin induces inflammasome activation in neutrophilic asthma. Quoc QL, et al. J Allergy Clin Immunol, 2024 Sep. PMID 38599290
  4. Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death. Douglas T, et al. Cell Rep, 2019 Dec 10. PMID 31825842
  5. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin. Spaan AN, et al. Science, 2022 Jun 17. PMID 35587511, Free PMC Article

See all (83) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Downregulation of otulin induces inflammasome activation in neutrophilic asthma.
    Title: Downregulation of otulin induces inflammasome activation in neutrophilic asthma.
  2. OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
    Title: OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
  3. Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker.
    Title: Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker.
  4. An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.
    Title: An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.
  5. Reciprocal interplay between OTULIN-LUBAC determines genotoxic and inflammatory NF-kappaB signal responses.
    Title: Reciprocal interplay between OTULIN-LUBAC determines genotoxic and inflammatory NF-κB signal responses.
  6. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin.
    Title: Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.
  7. LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.
    Title: LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.
  8. OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
    Title: OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
  9. Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
    Title: Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
  10. ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/beta-catenin activation to enhance drug resistance in breast cancers.
    Title: ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection
MedGen: C5774192 OMIM: 619986 GeneReviews: Not available
not available
Infantile-onset periodic fever-panniculitis-dermatosis syndrome
MedGen: C4310614 OMIM: 617099 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ34884

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cysteine-type deubiquitinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables cysteine-type deubiquitinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type deubiquitinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type deubiquitinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables cysteine-type peptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in innate immune response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in innate immune response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of inflammatory response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein linear deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein ubiquitination TAS
Traceable Author Statement
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of canonical Wnt signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of tumor necrosis factor-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of tumor necrosis factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in sprouting angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
part_of LUBAC complex IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
ubiquitin thioesterase otulin
Names
OTU domain-containing deubiquitinase with linear linkage specificity
deubiquitinating enzyme otulin
family with sequence similarity 105, member B
ubiquitin thioesterase Gumby
NP_612357.4
XP_011512453.1
XP_011512456.1
XP_016865504.1
XP_047273820.1
XP_054209727.1
XP_054209728.1
XP_054209729.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_051625.1 RefSeqGene

    Range
    8925..44057
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_138348.6 → NP_612357.4  ubiquitin thioesterase otulin

    See identical proteins and their annotated locations for NP_612357.4

    Status: REVIEWED

    Source sequence(s)
    AC010491, BC007706, BC015392, CK817982, DB238080
    Consensus CDS
    CCDS43302.1
    UniProtKB/Swiss-Prot
    D3DTD3, Q8NAS0, Q96BN8, Q96IA3
    Related
    ENSP00000284274.4, ENST00000284274.5
    Conserved Domains (1) summary
    pfam16218
    Location:81 → 344
    Peptidase_C101; Peptidase family C101

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    14664718..14716525
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011514151.3 → XP_011512453.1  ubiquitin thioesterase otulin isoform X1

    See identical proteins and their annotated locations for XP_011512453.1

    UniProtKB/Swiss-Prot
    D3DTD3, Q8NAS0, Q96BN8, Q96IA3
    Related
    ENSP00000520900.1, ENST00000850613.1
    Conserved Domains (1) summary
    pfam16218
    Location:81 → 344
    Peptidase_C101; Peptidase family C101

  2. XM_011514154.3 → XP_011512456.1  ubiquitin thioesterase otulin isoform X4

    Conserved Domains (1) summary
    pfam16218
    Location:81 → 254
    Peptidase_C101; Peptidase family C101

  3. XM_017010015.2 → XP_016865504.1  ubiquitin thioesterase otulin isoform X3

  4. XM_047417864.1 → XP_047273820.1  ubiquitin thioesterase otulin isoform X2

RNA

  1. XR_007058658.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    14604209..14656024
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054353752.1 → XP_054209727.1  ubiquitin thioesterase otulin isoform X1

    UniProtKB/Swiss-Prot
    D3DTD3, Q8NAS0, Q96BN8, Q96IA3

  2. XM_054353754.1 → XP_054209729.1  ubiquitin thioesterase otulin isoform X4

  3. XM_054353753.1 → XP_054209728.1  ubiquitin thioesterase otulin isoform X3

RNA

  1. XR_008487194.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96BN8.3 GenPept UniProtKB/Swiss-Prot:Q96BN8

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