OTUD4

Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells.

Full Name

OTU domain containing 4

Function

Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066).
May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066).
Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111).

Biological Process

Innate immune responseIEA:UniProtKB-KW
Negative regulation of interleukin-1-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of toll-like receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of DNA demethylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein deubiquitinationManual Assertion Based On ExperimentIBA:GO_Central
Protein K48-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K63-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of protein K48-linked deubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm
Nucleus
Primarily cytoplasmic.

PTM

Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity.