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Normal Function
The OTULIN gene provides instructions for making a protein that helps regulate inflammation, which is part of the body's early immune response to foreign invaders. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight the invaders and facilitate tissue repair. Inflammation can be turned on by a cellular process called ubiquitination, in which molecules called ubiquitin are attached to certain proteins. When foreign invaders are recognized, chains of ubiquitin molecules linked end-to-end, called linear ubiquitin chains, are attached to particular proteins. The addition of these chains stimulates signaling pathways that result in inflammation. Once the infection is under control, the body stops the inflammatory response to prevent damage to its own cells and tissues. The OTULIN protein helps control inflammation by removing linear ubiquitin chains.
In addition to inflammation, the OTULIN protein is thought to be involved in regulating development before birth and controlling cell death. Researchers are working to understand the protein's role in these processes.
Health Conditions Related to Genetic Changes
Otulipenia
At least three mutations in the OTULIN gene have been found to cause otulipenia, a condition that causes abnormal inflammation in the body, beginning in infancy. Affected babies have recurrent episodes of fever, diarrhea, painful joints, and skin rashes. The gene mutations involved in otulipenia reduce the function of the OTULIN protein. As a result, removal of linear ubiquitin chains is impaired, and signaling pathways that cause inflammation are abnormally active. The excessive inflammation that results causes the signs and symptoms of otulipenia and damages organs in the body; it can be life-threatening if not treated.
More About This Health ConditionOther Names for This Gene
- AIPDS
- deubiquitinating enzyme otulin
- FAM105B
- family with sequence similarity 105, member B
- FLJ34884
- GUM
- OTU domain-containing deubiquitinase with linear linkage specificity
- ubiquitin thioesterase Gumby
- ubiquitin thioesterase otulin
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Damgaard RB, Walker JA, Marco-Casanova P, Morgan NV, Titheradge HL, Elliott PR, McHale D, Maher ER, McKenzie ANJ, Komander D. The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity. Cell. 2016 Aug 25;166(5):1215-1230.e20. doi: 10.1016/j.cell.2016.07.019. Epub 2016 Aug 11. Citation on PubMed or Free article on PubMed Central
- Elliott PR, Komander D. Regulation of Met1-linked polyubiquitin signalling by the deubiquitinase OTULIN. FEBS J. 2016 Jan;283(1):39-53. doi: 10.1111/febs.13547. Epub 2015 Nov 2. Citation on PubMed or Free article on PubMed Central
- Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell. 2013 Jun 6;153(6):1312-26. doi: 10.1016/j.cell.2013.05.014. Citation on PubMed or Free article on PubMed Central
- Kupka S, Reichert M, Draber P, Walczak H. Formation and removal of poly-ubiquitin chains in the regulation of tumor necrosis factor-induced gene activation and cell death. FEBS J. 2016 Jul;283(14):2626-39. doi: 10.1111/febs.13644. Epub 2016 Jan 24. Citation on PubMed
- Schaeffer V, Akutsu M, Olma MH, Gomes LC, Kawasaki M, Dikic I. Binding of OTULIN to the PUB domain of HOIP controls NF-kappaB signaling. Mol Cell. 2014 May 8;54(3):349-61. doi: 10.1016/j.molcel.2014.03.016. Epub 2014 Apr 10. Citation on PubMed
- Zhou Q, Yu X, Demirkaya E, Deuitch N, Stone D, Tsai WL, Kuehn HS, Wang H, Yang D, Park YH, Ombrello AK, Blake M, Romeo T, Remmers EF, Chae JJ, Mullikin JC, Guzel F, Milner JD, Boehm M, Rosenzweig SD, Gadina M, Welch SB, Ozen S, Topaloglu R, Abinun M, Kastner DL, Aksentijevich I. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10127-32. doi: 10.1073/pnas.1612594113. Epub 2016 Aug 24. Citation on PubMed or Free article on PubMed Central
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