NMI

NMYC interactor (NMI) encodes a protein that interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. The NMI protein also interacts with all STATs except STAT2 and augments STAT-mediated transcription in response to cytokines IL2 and IFN-gamma. The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias. [provided by RefSeq, Jul 2008]

Full Name

N-Myc And STAT Interactor

Function

Acts as a signaling pathway regulator involved in innate immune system response (PubMed:9989503, PubMed:26342464, PubMed:29038465, PubMed:29350881).
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:9989503, PubMed:29377960).
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).

Biological Process

Interferon-gamma-mediated signaling pathwayIEA:InterPro
Macrophage activation involved in immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of innate immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of interferon-alpha productionIEA:Ensembl
Negative regulation of interferon-beta productionIEA:Ensembl
Negative regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of inflammatory responseISS:UniProtKB
Positive regulation of innate immune responseISS:UniProtKB
Positive regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein K48-linked ubiquitinationIEA:Ensembl
Receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentTAS:UniProtKB
Response to virusISS:UniProtKB
Toll-like receptor 4 signaling pathwayISS:UniProtKB
Transcription by RNA polymerase IIIEA:InterPro

Cellular Location

Cytoplasm
Nucleus
Secreted
Cytoplasmic NMI localizes in punctate granular structures (PubMed:9781816, PubMed:10950963).
Nuclear localization increased following IFN-alpha treatment (PubMed:9781816, PubMed:10950963).
Extracelullar following secretion by macrophage (PubMed:29038465).

PTM

Ubiquitinated. 'Lys-63'-linked ubiquitination by TRIM21 promotes interaction with IFI35 and inhibits virus-triggered type I IFN-beta production.