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 (PubMed:24726323, PubMed:24726327, PubMed:27458237). Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31 (PubMed:24726323, PubMed:24726327).
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:35170849, PubMed:35587511). 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).
Autoinflammation, panniculitis, and dermatosis syndrome
AIPDS
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Immunodeficiency 107, susceptibility to invasive Staphylococcus aureus infection
IMD107
An autosomal dominant immunologic disorder characterized by increased susceptibility to invasive and severe Staphylococcus aureus infection, causing life-threatening skin or pulmonary necrosis. Clinically, penetrance is incomplete and expressivity is variable.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry. OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in non-leukocytic cells.
Ubiquitinated.
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).
Belongs to the peptidase C65 family. Otulin subfamily.
Proteins
Immuno-oncology
40263Da
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ab151117