Recombinant Mouse N-myc-interactor (Nmi)

Function

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)

Subcellular Location

Cytoplasm; Nucleus; Secreted

Tissue Specificity

Expressed in macrophages

Subunit

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)

• Mehtani S. et al. PubMed: CI-8DLA2L8SV0QME (AUG-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Wang J. et al. Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7. — J. Immunol. (2013)
• Xiahou Z. et al. NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury. — Nat. Commun. (2017)