NMI
NMI (N-myc and STAT interactor) is a signalling pathway regulator involved in the innate immune response. It acts inside the cell on STAT, NF-kappa-B and interferon signalling, and can also act outside the cell as a damage-associated molecular pattern. Browse Assay Genie's current range of NMI research reagents below, or read on for the biology behind the target.
NMI is an intracellular regulator of cytokine signalling. In response to interleukin 2 (IL-2) and interferon gamma (IFN-gamma), it interacts with signal transducer and activator of transcription (STAT) proteins. It enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, which increases STAT1- and STAT5-dependent transcription. In response to interferon alpha, NMI forms a complex with IFI35. This complex formation prevents proteasome-mediated degradation of IFI35.
NMI also acts as a negative regulator of antiviral and inflammatory signalling. With IFI35, it inhibits nuclear translocation, activation and transcription of the NF-kappa-B subunit p65/RELA. This inhibits endothelial cell proliferation, migration and re-endothelialization of injured arteries. When ubiquitinated by TRIM21, the NMI-IFI35 complex inhibits virus-triggered type I IFN-beta production. NMI also induces proteasome-dependent degradation of IRF7, a transcriptional regulator of type I interferon, and so interferes with cellular antiviral responses.
Beyond these intracellular roles, NMI functions extracellularly as a damage-associated molecular pattern (DAMP). Macrophages actively release it during cell injury or pathogen invasion. Secreted NMI binds and activates Toll-like receptor 4 (TLR4) on adjacent macrophages. This drives NF-kappa-B translocation into the nucleus and the release of pro-inflammatory cytokines.
The NMI gene was named for its interaction with NMYC and CMYC, members of the Myc oncogene family, and with other transcription factors containing a Zip, HLH or HLH-Zip motif. The NMI protein interacts with all STATs except STAT2. NMI mRNA expression is low in human foetal and adult tissues tested, except brain, and high in myeloid leukaemia cancer cell lines. The NMI protein belongs to the NMI family.
NMI augments STAT-mediated transcription in response to IL-2 and IFN-gamma, making it a useful node for studying cytokine signal output.
Secreted NMI acts as a DAMP that engages TLR4 on macrophages and activates NF-kappa-B, linking injury and infection to inflammatory cytokine release.
NMI promotes IRF7 degradation and, with IFI35, limits virus-triggered type I interferon production, which makes it relevant to antiviral regulation.
NMI-IFI35 limits endothelial proliferation and arterial repair, and NMI interacts with Myc proteins and is highly expressed in myeloid leukaemia cell lines.
NMI regulates signalling in the innate immune response. It enhances STAT1- and STAT5-dependent transcription, and with IFI35 it restrains NF-kappa-B signalling. It also promotes IRF7 degradation. Outside the cell, macrophage-secreted NMI acts as a DAMP through TLR4 to promote inflammation.
NMI stands for N-myc and STAT interactor. The previous name was N-myc (and STAT) interactor. UniProt lists the protein as N-myc-interactor. The name reflects its interactions with NMYC, CMYC and STAT transcription factors. No other aliases are recorded in the sources.
The mouse has an ortholog, Nmi. In humans, NMI mRNA is low in all foetal and adult tissues tested except brain, and high in myeloid leukaemia cancer cell lines. Check the datasheet of any product for its validated reactivity.
Interferon, STAT and NF-kappa-B pathway partners and innate immune targets related to NMI.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13287; product specifications from Assay Genie datasheets.