Neuralized E3 ubiquitin protein ligase 3 (NEURL3)

Neuralized E3 ubiquitin protein ligase 3 (NEURL3) is a 262-amino-acid enzyme containing a neuralized homology repeat (NHR) and a RING finger domain, and functions as a ubiquitin-protein ligase (E3 ligase)[1][3][5]. It is involved in the regulation of protein ubiquitination and degradation, influencing cellular processes such as metastasis through targeting substrates like Vimentin for K48-linked polyubiquitination and subsequent proteasomal degradation[1]. Downregulation of NEURL3, often due to promoter hypermethylation, is associated with poor prognosis and increased metastasis in nasopharyngeal carcinoma (NPC)[1][3]. NEURL3 also contributes to innate immune responses, especially as an antiviral effector, evidenced by its inhibition of hepatitis C virus (HCV) assembly via direct interaction with viral glycoproteins, a function requiring its NHR but not RING domain[2]. NEURL3 participates in various biological roles—including lung development, immune defense, and spermatogenesis—but direct pharmacological targeting is currently investigational with no known drug interactions as of this writing[1][2][5].

Other names

LINCRRNF132Lung-inducible neuralized-related C3HC4 RING domain proteinNeuralized-like protein 3Neuralized homolog 3 pseudogene

K48-linked polyubiquitination and proteasomal degradation of target proteins (e.g., Vimentin in NPC); K63-linked polyubiquitination of IRF7 in antiviral innate immune response; Inhibition of viral assembly by disrupting viral envelope protein interactions (e.g., HCV E1/E2)