Small ubiquitin-like modifier 4 (SUMO4)

Small ubiquitin-like modifier 4 is a post-translational modifier protein found mainly in the cytoplasm. It covalently attaches to target proteins, most notably IκBα, leading to repression of NF-κB-dependent transcription and attenuation of pro-inflammatory gene expression. SUMO4 also potentiates SENP1 catalytic activity and acts as a SUMO deconjugation component, thereby regulating DNA damage-induced SUMO signaling during repair processes. Genetic polymorphism, notably M55V, impairs SUMO4's ability to inhibit NF-κB, resulting in increased inflammatory signaling and susceptibility to autoimmune diseases such as type 1 diabetes. SUMO4 participates in a negative feedback loop with NF-κB and its expression is sensitive to cellular stress, playing a broader role in the fine-tuning of stress and immune pathways.

Other names

IDDM5SUMO-4SMT3H4dJ281H8.4Small ubiquitin-related modifier 4Small ubiquitin-like protein 4insulin-dependent diabetes mellitus 5small ubiquitin-related modifier 4 proteinSMT3 suppressor of mif two 3 homolog 4

Modulation of SUMOylation affects transcription factor activity and the immune response, but no direct drug mechanism targeting SUMO4 is established in clinical use