NMI
Domain
The coiled-coil domain is necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI.
The NID domains are necessary for the interaction with IFI35 (PubMed:26342464). The NID domain 1 is necessary and IRF7 (By similarity).
Function
Acts as a signaling pathway regulator involved in innate immune system response (PubMed:26342464, PubMed:29038465, PubMed:29350881, PubMed:9989503). 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 (PubMed:29377960, PubMed:9989503). Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription (PubMed:9989503). In response to interferon IFN-alpha, associates in a complex with signaling pathway regulator IFI35 to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 (PubMed:10779520, PubMed:10950963). In complex with IFI35, inhibits virus-triggered type I IFN-beta production when ubiquitinated by ubiquitin-protein ligase TRIM21 (PubMed:26342464). 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 (PubMed:29350881). 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 (By similarity). 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 (PubMed:29038465). 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 (PubMed:29038465).
Post-translational modifications
Ubiquitinated. 'Lys-63'-linked ubiquitination by TRIM21 promotes interaction with IFI35 and inhibits virus-triggered type I IFN-beta production.
Sequence Similarities
Belongs to the NMI family.
Tissue Specificity
Expressed in adult spleen, liver, and kidney (PubMed:9781816). Expressed in fetal thymus, liver, placenta, spleen, lung, and kidney but not brain (PubMed:9781816). Expressed in macrophages (PubMed:29038465).
Cellular localization
- Cytoplasm
- Nucleus
- Secreted
- Cytoplasmic NMI localizes in punctate granular structures (PubMed:10950963, PubMed:9781816). Nuclear localization increased following IFN-alpha treatment (PubMed:10950963, PubMed:9781816). Extracelullar following secretion by macrophage (PubMed:29038465).
Alternative names
N-myc-interactor, Nmi, N-myc and STAT interactor, NMI