OTUD5
Function
Deubiquitinating enzyme that functions as a negative regulator of the innate immune system (PubMed:17991829, PubMed:22245969, PubMed:23827681, PubMed:33523931). Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:22245969). Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro) (PubMed:22245969). Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production (PubMed:17991829). Controls neuroectodermal differentiation through cleaving 'Lys-48'-linked ubiquitin chains to counteract degradation of select chromatin regulators such as ARID1A, HDAC2 and HCF1 (PubMed:33523931). Acts as a positive regulator of mTORC1 and mTORC2 signaling following phosphorylation by MTOR: acts by mediating deubiquitination of BTRC, leading to its stability (PubMed:33110214).
Involvement in disease
Multiple congenital anomalies-neurodevelopmental syndrome, X-linked
MCAND
An X-linked recessive, congenital disorder characterized by central nervous system, craniofacial, cardiac, skeletal, and genitourinary anomalies. Clinical features include poor growth, short stature, global developmental delay, impaired intellectual development, microcephaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and other variable abnormalities. Brain imaging typically shows ventriculomegaly and thin corpus callosum. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-177 is required for deubiquitinating activity (PubMed:22245969, PubMed:33523931). Phosphorylation at Ser-328, Ser-337 and Ser-508 by MTOR promotes its activity (PubMed:33110214).
Sequence Similarities
Belongs to the peptidase C85 family.
Tissue Specificity
Expressed in various tissues, including the liver and placenta, as well as in peripheral blood leukocytes.
Cellular localization
- Nucleus
Alternative names
OTU domain-containing protein 5, Deubiquitinating enzyme A, DUBA, OTUD5