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Gene Review

Nucb1  -  nucleobindin 1

Mus musculus

Synonyms: B230337F23Rik, C77483, CALNUC, Calnuc, MTEST82, ...
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Disease relevance of Nucb1

  • Taken together, Nuc is a new kind of growth and differentiation factor associated with lupus syndrome [1].
  • By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in Escherichia coli [2].

High impact information on Nucb1

  • When overexpressed in COS-1 cells, Nuc was found to be extracellularly released [3].
  • Calnuc, an EF-hand Ca(2+)-binding protein, is stored and processed in the Golgi and secreted by the constitutive-like pathway in AtT20 cells [4].
  • Calnuc is an ubiquitous, EF-hand Ca(2+) binding protein found in the cytoplasm where it binds to Galphai3, in the Golgi lumen where it constitutes a Ca(2+) storage pool, and secreted outside the cell [4].
  • We found by pulse-chase experiments that calnuc is synthesized in the endoplasmic reticulum, transported to the Golgi where it remains greater than 12 h and undergoes posttranslational modification (O-glycosylation and sulfation) followed by secretion into the culture medium [4].
  • By immunofluorescence and immunogold labeling, endogenous calnuc is found in immature secretion granules (ISG) but not mature regulated secretory granules (RSG), whereas overexpressed calnuc-green fluorescent protein (GFP) is found in both ISG and RSG, where it colocalizes with ACTH [4].

Biological context of Nucb1

  • These results suggest that Nuc is able to activate autoreactive peripheral T cells through an MHC-class II pathway leading to acceleration or induction of anti-DNA antibody production when it is excessively produced in lupus-prone mice or experimentally administered into normal mice [5].
  • These results suggest that upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is related to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc in the induction or enhancement of autoimmunity in lupus models of mice [6].

Anatomical context of Nucb1

  • The resident Golgi protein nucleobindin and fructose-bisphosphate aldolase were preferentially associated with membranes of polarized cells, whereas alphaB crystallin was detected exclusively and in high amounts in unpolarized cells [7].
  • Furthermore, antibodies against existing cytokines have so far not been shown to block Nuc activity on these B cells [1].
  • Activation of autoreactive T cells that help nucleobindin-injected mice produce anti-DNA antibodies [5].
  • In MRL/lpr mice, both expression of Nuc mRNA in enlarged lymph nodes and serum concentration of Nuc protein are shown to increase as disease progresses [5].

Associations of Nucb1 with chemical compounds

  • Assays involving proteinase K digestion, sodium carbonate extraction and Triton X-114 extraction revealed that the insect CALNUC-like protein was a soluble protein tightly associated with the luminal surface of Golgi membranes as reported for mammalian CALNUC [8].

Other interactions of Nucb1


  1. Purification of a novel B cell growth and differentiation factor associated with lupus syndrome. Kanai, Y., Tanuma, S. Immunol. Lett. (1992) [Pubmed]
  2. Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a study on MRL/n mice. Kanai, Y., Takeda, O., Kanai, Y., Miura, K., Kurosawa, Y. Immunol. Lett. (1993) [Pubmed]
  3. Interaction of cyclooxygenases with an apoptosis- and autoimmunity-associated protein. Ballif, B.A., Mincek, N.V., Barratt, J.T., Wilson, M.L., Simmons, D.L. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. Calnuc, an EF-hand Ca(2+)-binding protein, is stored and processed in the Golgi and secreted by the constitutive-like pathway in AtT20 cells. Lavoie, C., Meerloo, T., Lin, P., Farquhar, M.G. Mol. Endocrinol. (2002) [Pubmed]
  5. Activation of autoreactive T cells that help nucleobindin-injected mice produce anti-DNA antibodies. Kubota, T., Watanabe, N., Kaneko, T., Satake, F., Miura, K., Kurosawa, Y., Miyasaka, N., Kanai, Y. Immunol. Lett. (2001) [Pubmed]
  6. Enhanced expression of nucleobindin in lymphatic organs of lupus-prone mice. Iizuka, H., Kubota, T., Satake, F., Hirokawa, G., Miura, K., Kurosawa, Y., Miyasaka, N., Kanai, Y. Lupus (1997) [Pubmed]
  7. Loss of epithelial polarity is accompanied by differential association of proteins with intracellular membranes. Fialka, I., Pasquali, C., Kurzbauer, R., Lottspeich, F., Huber, L.A. Electrophoresis (1999) [Pubmed]
  8. CALNUC (nucleobindin) is localized in the Golgi apparatus in insect cells. Kawano, J., Kotani, T., Ogata, Y., Ohtaki, S., Takechi, S., Nakayama, T., Sawaguchi, A., Nagaike, R., Oinuma, T., Suganuma, T. Eur. J. Cell Biol. (2000) [Pubmed]
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