| Structural highlights
Function
NMI_HUMAN 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).[UniProtKB:O35309][1] [2] [3] [4] [5] [6]
References
- ↑ Zhou X, Liao J, Meyerdierks A, Feng L, Naumovski L, Bottger EC, Omary MB. Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35. J Biol Chem. 2000 Jul 14;275(28):21364-71. doi: 10.1074/jbc.M003177200. PMID:10779520 doi:https://dx.doi.org/10.1074/jbc.M003177200
- ↑ Chen J, Shpall RL, Meyerdierks A, Hagemeier M, Bottger EC, Naumovski L. Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP 35 into a high molecular mass complex and inhibits proteasome-mediated degradation of IFP 35. J Biol Chem. 2000 Nov 17;275(46):36278-84. doi: 10.1074/jbc.M006975200. PMID:10950963 doi:https://dx.doi.org/10.1074/jbc.M006975200
- ↑ Das A, Dinh PX, Pattnaik AK. Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response. Virology. 2015 Nov;485:383-92. PMID:26342464 doi:10.1016/j.virol.2015.08.013
- ↑ Xiahou Z, Wang X, Shen J, Zhu X, Xu F, Hu R, Guo D, Li H, Tian Y, Liu Y, Liang H. NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury. Nat Commun. 2017 Oct 16;8(1):950. PMID:29038465 doi:10.1038/s41467-017-00930-9
- ↑ Jian D, Wang W, Zhou X, Jia Z, Wang J, Yang M, Zhao W, Jiang Z, Hu X, Zhu J. Interferon-induced protein 35 inhibits endothelial cell proliferation, migration and re-endothelialization of injured arteries by inhibiting the nuclear factor-kappa B pathway. Acta Physiol (Oxf). 2018 Jul;223(3):e13037. PMID:29350881 doi:10.1111/apha.13037
- ↑ Zhu M, John S, Berg M, Leonard WJ. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell. 1999 Jan 8;96(1):121-30. doi: 10.1016/s0092-8674(00)80965-4. PMID:9989503 doi:https://dx.doi.org/10.1016/s0092-8674(00)80965-4
|
