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

Summary

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: mouse all
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Genomic context

Location:: 5p15.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (14664718..14716525)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (14604209..14656024)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (14664827..14699959)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
Title: OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
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.
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.
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.
Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin.
Title: Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.
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.
OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
Title: OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
Title: Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
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.
Authors define an additional, non-catalytic function of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.
Title: Regulation of the endosomal SNX27-retromer by OTULIN.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC33915 (e-PCR)
- UniSTS:60198

D8S2279 (e-PCR)
- UniSTS:473907

RH18318 (e-PCR)
- UniSTS:16971

D5S1623E (e-PCR)
- UniSTS:26050

WI-16043 (e-PCR)
- UniSTS:77531

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	IBA Inferred from Biological aspect of Ancestor more info
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	IBA Inferred from Biological aspect of Ancestor more info
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

EC 3.4.19.12

XP_011512453.1

EC 3.4.19.12

XP_011512456.1

EC 3.4.19.12

XP_016865504.1

EC 3.4.19.12

XP_047273820.1

EC 3.4.19.12

XP_054209727.1

EC 3.4.19.12

XP_054209728.1

EC 3.4.19.12

XP_054209729.1

EC 3.4.19.12

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

NG_051625.1 RefSeqGene

Range

8925..44057

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

14664718..14716525

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Conserved Domains (1) summary

pfam16218
Location:81 → 344

Peptidase_C101; Peptidase family C101
XM_011514154.3 → XP_011512456.1 ubiquitin thioesterase otulin isoform X4

Conserved Domains (1) summary

pfam16218
Location:81 → 254

Peptidase_C101; Peptidase family C101
XM_017010015.2 → XP_016865504.1 ubiquitin thioesterase otulin isoform X3
XM_047417864.1 → XP_047273820.1 ubiquitin thioesterase otulin isoform X2

RNA

XR_007058658.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

14604209..14656024

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

D3DTD3, Q8NAS0, Q96BN8, Q96IA3
XM_054353754.1 → XP_054209729.1 ubiquitin thioesterase otulin isoform X4
XM_054353753.1 → XP_054209728.1 ubiquitin thioesterase otulin isoform X3