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Gene Review

NMI  -  N-myc (and STAT) interactor

Homo sapiens

Synonyms: N-myc and STAT interactor, N-myc-interactor, Nmi
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Disease relevance of NMI

  • We observed a novel endogenous association of BRCA1 with Nmi (N-Myc-interacting protein) in breast cancer cells [1].
  • Among several cancer cell lines, high expression of Nmi was found in myeloid leukemias, which also express high levels of C-myc [2].
  • Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN [3].
  • NMI did not actively inhibit DC maturation as NMI-infected DC subsequently matured if treated with Escherichia coli LPS or Nine Mile phase II [4].
  • Muscle sympathetic nerve activity (MSNA) assessed from multiunit discharges and from single units (s-MSNA) was obtained in matched patients with UA ( n =9), AMI ( n =14) and stable CAD (coronary artery disease, n =11), patients with chest pain in which AMI was excluded (NMI, n =9) and normal controls (NCs, n =14) [5].

Psychiatry related information on NMI

  • An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects [6].
  • The longitudinal course of mental health in a combined group of NMI and MMD subjects was predicted by sex of the subject (chi2(1) = 4.04; P < 0.05), but not by age or family history of mental illness [7].

High impact information on NMI

  • We evaluated two cytokine systems, IL-2 and IFNgamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines [8].
  • We further show that Nmi interacts with all STATs except Stat2 [8].
  • The association with Pol I requires phosphorylation of TIF-IA at Ser 649 by RSK kinase, indicating a role for NMI in the growth-dependent regulation of rRNA synthesis [9].
  • We have investigated the role of actin and nuclear myosin I (NMI) in the transcription of ribosomal RNA genes (rDNA) [9].
  • Homodimerization of Nmi enhanced its association with BRCA1 [1].

Chemical compound and disease context of NMI


Biological context of NMI


Anatomical context of NMI

  • The association of Nmi and IFP 35 into a complex can be demonstrated in multiple cell lines and is not dependent on treatment with IFN [14].
  • We demonstrate that NMI is present in cell nuclei of all mouse tissues examined except for cells in terminal stages of spermiogenesis [15].
  • In the nucleoplasm of resting lymphocytes, both actin and NMI were localized mostly in condensed chromatin [16].
  • We show for the first time the spatial association of nuclear myosin I (NMI) and actin with the SSU already at the nucleolar periphery to the nuclear pore [17].

Associations of NMI with chemical compounds


Physical interactions of NMI

  • The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi [11].
  • Nmi was found to interact specifically with BRCA1, both in vitro and in vivo, by binding to two major domains in BRCA1, amino acid residues 298-683 and 1301-1863 [1].
  • A deletion analysis revealed that Nmi must interact with IFP 35 to prevent its degradation and that the amino terminus of Nmi is required, but not sufficient, for this function [14].
  • Nmi interacts with c-Myc, N-Myc, Max, and fos, as demonstrated by yeast two-hybrid and coimmunoprecipitation assays [12].

Regulatory relationships of NMI

  • The carboxyl terminus of Nmi shows homology to an interferon-induced leucine zipper protein, IFP 35, whereas its amino terminus is homologous to a coiled-coil heptad repeat in the C. elegans protein, CEF59 [2].

Other interactions of NMI

  • Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors [8].
  • Nmi functioned as an adaptor molecule to recruit c-Myc to a complex containing Nmi.c-Myc.BRCA1 [1].
  • The stabilization of IFP 35 by Nmi may serve to amplify the physiologic effects of IFNs [14].
  • Co-precipitation studies of Nmi with N-myc and C-myc confirmed the interaction in mammalian cells [2].
  • The ratio of Nmi to CKIP-1 determines the stability of IFP35 and control cytokine signaling in a novel mechanism [22].

Analytical, diagnostic and therapeutic context of NMI

  • Nmi and IFP 35 proteins associate into a high molecular mass complex of 300-400 kDa as determined by native gel electrophoresis and gel filtration [14].
  • NID may mediate cytoplasmic localization of the full-length Nmi protein through NID-NID protein interactions as demonstrated by yeast two-hybrid assay, immunoprecipitation, and the presence of Nmi in a high molecular weight protein complex [23].
  • Immunofluorescence demonstrates that both in 293 embryonic kidney cells and in Kelly neuroblastoma cells all detectable ectopically expressed Nmi is localized in the cytoplasm, in part in a punctate, granular pattern [3].
  • RT-PCR and Western blotting confirmed the increase in the levels of STAT1 and Nmi mRNA and protein [13].
  • Microinjection of antibodies against actin or NMI, as well as short interfering RNA-mediated depletion of NMI, decreased Pol I transcription in vivo, whereas overexpression of NMI augmented pre-rRNA synthesis [9].


  1. A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer. Li, H., Lee, T.H., Avraham, H. J. Biol. Chem. (2002) [Pubmed]
  2. Isolation and characterization of Nmi, a novel partner of Myc proteins. Bao, J., Zervos, A.S. Oncogene (1996) [Pubmed]
  3. Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN. Bannasch, D., Weis, I., Schwab, M. Oncogene (1999) [Pubmed]
  4. Virulent Coxiella burnetii does not activate human dendritic cells: role of lipopolysaccharide as a shielding molecule. Shannon, J.G., Howe, D., Heinzen, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Sympathetic neural hyperactivity and its normalization following unstable angina and acute myocardial infarction. Graham, L.N., Smith, P.A., Stoker, J.B., Mackintosh, A.F., Mary, D.A. Clin. Sci. (2004) [Pubmed]
  6. An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects. Kernohan, A.F., McIntyre, M., Hughes, D.M., Tam, S.W., Worcel, M., Reid, J.L. British journal of clinical pharmacology. (2005) [Pubmed]
  7. Selection of 'normal' control subjects for psychiatric research: update on a model for centralized recruitment. Schechter, D., Singer, T.M., Kuperman, J., Endicott, J. Psychiatry research. (1998) [Pubmed]
  8. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Zhu, M., John, S., Berg, M., Leonard, W.J. Cell (1999) [Pubmed]
  9. Nuclear actin and myosin I are required for RNA polymerase I transcription. Philimonenko, V.V., Zhao, J., Iben, S., Dingová, H., Kyselá, K., Kahle, M., Zentgraf, H., Hofmann, W.A., de Lanerolle, P., Hozák, P., Grummt, I. Nat. Cell Biol. (2004) [Pubmed]
  10. Platelet function in patients admitted with a diagnosis of myocardial infarction. Mikhailidis, D.P., Barradas, M.A., Mier, A., Boag, F., Jeremy, J.Y., Havard, C.W., Dandona, P. Angiology. (1987) [Pubmed]
  11. The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi. Schlierf, B., Lang, S., Kosian, T., Werner, T., Wegner, M. J. Mol. Biol. (2005) [Pubmed]
  12. Interferon-induced upregulation and cytoplasmic localization of Myc-interacting protein Nmi. Lebrun, S.J., Shpall, R.L., Naumovski, L. J. Interferon Cytokine Res. (1998) [Pubmed]
  13. STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell. Jung, H.H., Lee, J., Kim, J.H., Ryu, K.J., Kang, S.A., Park, C., Sung, K., Nam, D.H., Kang, W.K., Park, K., Im, Y.H. FEBS Lett. (2005) [Pubmed]
  14. 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. Chen, J., Shpall, R.L., Meyerdierks, A., Hagemeier, M., Böttger, E.C., Naumovski, L. J. Biol. Chem. (2000) [Pubmed]
  15. Nuclear myosin is ubiquitously expressed and evolutionary conserved in vertebrates. Kahle, M., Pridalová, J., Spacek, M., Dzijak, R., Hozák, P. Histochem. Cell Biol. (2007) [Pubmed]
  16. Nuclear distribution of actin and myosin I depends on transcriptional activity of the cell. Kyselá, K., Philimonenko, A.A., Philimonenko, V.V., Janácek, J., Kahle, M., Hozák, P. Histochem. Cell Biol. (2005) [Pubmed]
  17. Small ribosomal subunits associate with nuclear myosin and actin in transit to the nuclear pores. Cisterna, B., Necchi, D., Prosperi, E., Biggiogera, M. FASEB J. (2006) [Pubmed]
  18. Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35. Zhou, X., Liao, J., Meyerdierks, A., Feng, L., Naumovski, L., Bottger, E.C., Omary, M.B. J. Biol. Chem. (2000) [Pubmed]
  19. Guanine modification during chemical DNA synthesis. Eadie, J.S., Davidson, D.S. Nucleic Acids Res. (1987) [Pubmed]
  20. Genetic diversity of the Q fever agent, Coxiella burnetii, assessed by microarray-based whole-genome comparisons. Beare, P.A., Samuel, J.E., Howe, D., Virtaneva, K., Porcella, S.F., Heinzen, R.A. J. Bacteriol. (2006) [Pubmed]
  21. Rapid esterification of nucleosides to solid-phase supports for oligonucleotide synthesis using uronium and phosphonium coupling reagents. Pon, R.T., Yu, S., Sanghvi, Y.S. Bioconjug. Chem. (1999) [Pubmed]
  22. The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling. Zhang, L., Tang, Y., Tie, Y., Tian, C., Wang, J., Dong, Y., Sun, Z., He, F. Cell. Signal. (2007) [Pubmed]
  23. Subcellular localization of interferon-inducible Myc/stat-interacting protein Nmi is regulated by a novel IFP 35 homologous domain. Lee, N.D., Chen, J., Shpall, R.L., Naumovski, L. J. Interferon Cytokine Res. (1999) [Pubmed]
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