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OTULIN

OverviewProducts

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 (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).

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:26997266, PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327, PubMed:28919039). 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 proinflammatory signaling (PubMed:23806334).

Involvement in disease

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.

Post-translational modifications

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).

Sequence similarities

Belongs to the peptidase C65 family. Otulin subfamily.

Cellular localization

  • Cytoplasm

Alternative names

  • Ubiquitin thioesterase otulin
  • Deubiquitinating enzyme otulin
  • OTU domain-containing deubiquitinase with linear linkage specificity
  • Ubiquitin thioesterase Gumby
  • OTULIN
  • FAM105B

Database links

Target type

Proteins

Molecular weight

40263Da