NKIRAS2 Human

NFKB Inhibitor Interacting Ras-Like 2 (NKIRAS2), also known as KBRAS2, is a protein encoded by the NKIRAS2 gene. It belongs to the Ras-like small GTPases family, which are involved in various cellular processes, including signal transduction .

NKIRAS2 is an atypical Ras-like protein that plays a crucial role in regulating NF-kappa-B (NF-κB) activity. NF-κB is a transcription factor involved in immune and inflammatory responses, cell growth, and survival. NKIRAS2 prevents the degradation of NF-κB inhibitor beta (NFKBIB) by blocking its phosphorylation and the nuclear localization of the p65/RELA NF-κB subunit .

NKIRAS2 interacts with the PEST domains of IκB alpha and IκB beta, decreasing their rate of degradation. This interaction stabilizes the NF-κB inhibitors, thereby inhibiting the activation of NF-κB signaling pathways . Both GTP- and GDP-bound forms of NKIRAS2 can block the phosphorylation of NFKBIB, making it a potent regulator of NF-κB activity .

The regulation of NKIRAS2 involves its interaction with other proteins and its localization within the cell. It is predominantly located in the cytoplasm and nucleoplasm, where it exerts its regulatory functions . The expression of NKIRAS2 is also influenced by various signaling pathways, including the Toll-Like Receptor 3 (TLR3) cascade and cytosolic sensors of pathogen-associated DNA .

NKIRAS2’s role in regulating NF-κB activity makes it a potential target for therapeutic interventions in diseases characterized by dysregulated NF-κB signaling, such as inflammatory disorders, autoimmune diseases, and certain cancers .