Acts as a signaling pathway regulator involved in innate immune system response (PubMed:23956435). In response to interleukin 2/IL2 and interferon IFN-gamma/IFNG, interacts with signal transducer and activator of transcription/STAT which activate the transcription of downstream genes involved in a multitude of signals for development and homeostasis (By similarity). Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription (By similarity). In response to interferon IFN-alpha, associates in a complex with transcriptional regulator IFI35 to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 (By similarity). In complex with IFI35, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (By similarity). Negatively regulates virus-triggered type I interferon/IFN production by inducing proteosome-dependent degradation of IRF7, a transcriptional regulator of type I IFN, thereby interfering with cellular antiviral responses (PubMed:23956435). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation, when actively released by macrophage to the extracellular space during cell injury or pathogen invasion (By similarity). Macrophage-secreted NMI activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 binding and activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (By similarity). Interacts with MYCN and MYC, as well as with other transcription factors with a Zip, HLH or a HLH-Zip motif. Interacts with all STAT proteins except STAT2 (By similarity). Interacts with IRF7, the interaction is direct and leads to the inhibition of IRF7-mediated type I IFN production (PubMed:23956435). Interacts (via coiled-coil domain) with TRIM21 (via the SPRY domain); the interaction leads to 'Lys-63'-linked ubiquitination of NMI. Interacts with IFI35; the interaction is direct and is facilitated by TRIM21. Interacts with TLR4; the interaction is direct and leads to NF-kappa-B activation (By similarity). Cytoplasmic NMI localizes in punctate granular structures. Nuclear localization increased following IFN-alpha treatment. Extracelullar following secretion by macrophage. Expressed in macrophages. Induced by Sendai virus. The coiled-coil domain may be necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI. The NID domains are necessary for the interaction with IFI35 (By similarity). The NID domain 1 is necessary and IRF7 (PubMed:23956435). May be ubiquitinated. Knockout mice show decreased inflammatory response when exposed to infection of injury, which can lead to lower inflammation-induced mortality. Display normal development of the immune system. Belongs to the NMI family. The TRIM21-mediated ubiquitinated residue is not conserved in mice, therefore it remains unclear whether the physiological role of NMI ubiquitination is preserved throughout mammals.