Ovarian tumor domain-containing protein 5 (OTUD5)

Ovarian tumor domain-containing protein 5 (OTUD5) is a member of the OTU family deubiquitinases, functioning as an enzyme that removes ubiquitin moieties from specific substrate proteins[1][2][3][4]. OTUD5 regulates multiple cellular pathways, notably acting as a positive regulator of the mTOR signaling pathway by stabilizing βTrCP1, leading to DEPTOR degradation and promoting cell growth and proliferation[1][3]. It also modulates innate and adaptive immunity through the deubiquitination of molecular mediators (such as MyD88, STING, and TRAF3), impacting both inflammation and antiviral defenses[2][3]. Additionally, OTUD5 participates in DNA damage response and chromatin remodeling, safeguarding specific chromatin regulators from proteasomal degradation[4]. Germline mutations in OTUD5 cause a developmental disorder referred to as LINKED syndrome, with neurodevelopmental, craniofacial, cardiac, and skeletal anomalies, and somatic roles have been described in cancer and inflammation[4][1][3][2]. OTUD5 is considered a promising, though still largely research-stage, therapeutic target across cancer, inflammatory, and certain rare genetic diseases.

Other names

OTUD5DUBADKFZp761A052deubiquitinating enzyme Adeubiquitinase AMCANDOTU domain-containing protein 5OTU domain-containing 5deubiquinating enzyme A

Inhibition of OTUD5 deubiquitinase activity (potential, not clinically established) Stabilization or destabilization of substrate proteins via deubiquitination