OTUD5

This gene encodes a member of the OTU (ovarian tumor) domain-containing cysteine protease superfamily. The OTU domain confers deubiquitinase activity and the encoded protein has been shown to suppress the type I interferon-dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein. Cleavage results in disassociation of the adaptor protein from a downstream signaling complex and disruption of the type I interferon signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2008]

Full Name

OTU Deubiquitinase 5

Function

Deubiquitinating enzyme that functions as negative regulator of the innate immune system. Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production. Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro). 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).

Biological Process

Negative regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIMP:FlyBase
Negative regulation of type I interferon productionTAS:Reactome
Neural crest cell differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of TORC1 signalingManual Assertion Based On ExperimentIMP:FlyBase
Positive regulation of TORC2 signalingManual Assertion Based On ExperimentIMP:FlyBase
Protein deubiquitinationManual Assertion Based On ExperimentIDA:MGI
Protein K48-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K63-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Response to lipopolysaccharideManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Nucleus

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.

PTM

Phosphorylation at Ser-177 is required for deubiquitinating activity.