OTULIN

Chr 5p15.2

OTU deubiquitinase with linear linkage specificity

Aliases:: FLJ34884
MANE:: ENST00000284274.5

OMIM: 615712 ↗NCBI: 90268 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

OTULIN · Q96BN8

v62025-08-01

Predicted Aligned Error matrix for OTULIN — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

83.8/ 100

Confident

352 residues

Confidence breakdown

Very high(≥ 90)72%
Confident(70–90)3%
Low(50–70)7%
Very low(< 50)18%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Autoinflammatory disorders
BIALLELIC, autosomal or pseudoautosomal
COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal epithelial barrier disorders
BIALLELIC, autosomal or pseudoautosomal
Infantile enterocolitis & monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Periodic fever syndromes
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe insulin resistance and lipodystrophy syndromes
BIALLELIC, autosomal or pseudoautosomal

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Disease associations (Open Targets)

autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive
0.80
immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection
0.68
autoinflammation, panniculitis, and dermatosis syndrome
0.56
craniometaphyseal dysplasia
0.51
allergic rhinitis
0.41
chondrocalcinosis 2
0.41
autoinflammatory syndrome
0.37
Eczematoid dermatitis
0.36
asthma
0.36
autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant
0.33

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Ubiquitin thioesterase otulin

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:24726323, PubMed:24726327, PubMed:26997266, PubMed:27523608, PubMed:27559085, PubMed:28919039, PubMed:30804083, PubMed:35170849, PubMed:35587511, PubMed:38630025, PubMed:38652464). 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 regulating the activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met-1'-linked autoubiquitination of the LUBAC complex, thereby preventing inactivation of the LUBAC complex (PubMed:26670046). 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 role in innate immune response by restricting linear polyubiquitin formation on LUBAC complex in response to NOD2 stimulation, probably to limit NOD2-dependent pro-inflammatory signaling (PubMed:23806334)