Protein: N-myc-interactor (Nmi) (N-myc and STAT interactor) (Q13287)
Organism: Homo sapiens (Human)
Function: Acts as a signaling pathway regulator involved in innate immune system response. 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. Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription. 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. In complex with IFI35, inhibits virus-triggered type I IFN-beta production when ubiquitinated by ubiquitin-protein ligase TRIM21. 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. 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. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:10779520, ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:29377960, ECO:0000269|PubMed:9781816}. Nucleus {ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:9781816}. Secreted {ECO:0000269|PubMed:29038465}. Note=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). {ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:29038465, ECO:0000269|PubMed:9781816}.
Interaction partners:
- N-myc proto-oncogene protein
- Interferon-induced 35 kDa protein
- Myc proto-oncogene protein
- Signal transducer and activator of transcription 2
- Transcription factor SOX-10
- Histone acetyltransferase KAT5
- Signal transducer and activator of transcription 1-alpha/beta
- Breast cancer metastasis-suppressor 1
- Ubiquitin/ISG15-conjugating enzyme E2 L6
- E3 ubiquitin-protein ligase TRIM21
Sequence:
MEADKDDTQQILKEHSPDEFIKDEQNKGLIDEITKKNIQLKKEIQKLETELQEATKEFQIKEDIPETKMKFLSVETPENDSQLSNISCSFQVSSKVPYEIQKGQALITFEKEEVAQNVVSMSKHHVQIKDVNLEVTAKPVPLNSGVRFQVYVEVSKMKINVTEIPDTLREDQMRDKLELSFSKSRNGGGEVDRVDYDRQSGSAVITFVEIGVADKILKKKEYPLYINQTCHRVTVSPYTEIHLKKYQIFSGTSKRTVLLTGMEGIQMDEEIVEDLINIHFQRAKNGGGEVDVVKCSLGQPHIAYFEE