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Gene Review

Nr0b2  -  nuclear receptor subfamily 0, group B,...

Mus musculus

Synonyms: Nuclear receptor subfamily 0 group B member 2, Orphan nuclear receptor SHP, SHP, SHP-1, Shp, ...
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Disease relevance of Nr0b2


Psychiatry related information on Nr0b2

  • The SHP complexes were the most reactive toward DNA and produced a greater reduction in the transforming activity of Bacillus subtilis DNA after 3-hr reaction times than did the DDP or DDCP complexes [7].

High impact information on Nr0b2

  • In mammalian cells, SHP specifically inhibited transactivation by the superfamily members with which it interacted [8].
  • SHP is an orphan member of the nuclear hormone receptor superfamily that contains the dimerization and ligand-binding domain found in other family members but lacks the conserved DNA binding domain [8].
  • In the yeast two-hybrid system, SHP interacted with several conventional and orphan members of the receptor superfamily, including retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67 [8].
  • Since specific tyrosine phosphorylation of proteins is important for biological activities induced by chemokines, we examined the role of SHP-1 in functions of chemokines using viable motheaten (me(v)/me(v)) mice that were deficient in SHP-1 [9].
  • Mice in which the Lyn, Cd22, or Shp-1 gene has been disrupted have hyperactive B cells and autoantibodies [10].

Chemical compound and disease context of Nr0b2

  • Significant increases in the number of lung adenomas in A/J mice were induced by multiple i.p. injections of cis-DDP and each of the DDCP and SHP complexes (total doses, 21 to 108 mumol/kg body weight) [7].

Biological context of Nr0b2

  • These results establish a structural model for understanding how SHP interacts with LRH-1 to regulate cholesterol homeostasis and provide new insights into how nuclear receptor/coregulator selectivity is achieved [11].
  • Chemotaxis, however, was severely diminished in the SHP-deficient neutrophils relative to control neutrophils, which was possibly attributable to a combination of defective deadhesion and altered actin assembly [12].
  • One of these elements contains an estrogen response element half-site that bound purified ERalpha, and ERalpha with a mutated DNA binding domain was unable to stimulate SHP promoter activity [13].
  • Finally, we show that the transcriptional repressor SHP (small heterodimer partner) suppressed APOAI gene expression by inhibiting LRH-1 transcriptional activity [14].
  • The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP [1].

Anatomical context of Nr0b2

  • It has been shown previously that hepatocyte nuclear factor-4alpha (HNF-4) and the alpha(1)-fetoprotein transcription factor (FTF) are activators of 7alpha-and 12alpha-hydroxylase transcription and that the small heterodimer partner (SHP) suppresses bile acid biosynthesis by heterodimerizing with FTF [15].
  • The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes [1].
  • In addition, T cell-APC conjugate assays provide direct evidence that a greater proportion of SHP-1-deficient T cells are capable of forming stable conjugates with APCs and this may explain, at least in part, their hyperproliferative response to TCR-triggered stimulation [16].
  • As expected from this expression pattern, the activity of the mouse SHP promoter measured by transient transfection was significantly higher in the adrenal-derived Y1 cells than HeLa cells [17].
  • Src homology 2 domain-containing protein tyrosine phosphatase (SHP) substrate-1 (SHPS-1) is a transmembrane protein that is expressed predominantly in macrophages [18].

Associations of Nr0b2 with chemical compounds


Regulatory relationships of Nr0b2

  • The expression of Cyp7a1 and Cyp8b1 is known to be repressed by dietary bile acids via both SHP-dependent and -independent regulations [22].
  • In contrast, SHP reporter or BSEP reporter genes were activated to similar degrees by each of the FXR isoforms [23].

Other interactions of Nr0b2

  • Here, we report structural and biochemical analyses of the LRH-1/SHP interaction [11].
  • Here, we describe the isolation of mouse E1A-like inhibitor of differentiation 1 (EID1) as a candidate coinhibitor for SHP [24].
  • Here, we report that bile acids inhibit the expression of gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase, and fructose 1,6-bis phosphatase in an SHP-dependent fashion [20].
  • We conclude that mice overexpressing Abcb11 display an increase in biliary bile salt secretion and taurodeoxycholate content, which is associated with FXR/SHP-mediated changes in hepatic and ileal gene expression [25].
  • Bile acid-induced, farnesoid X receptor (FXR)-mediated induction of the nuclear repressor short heterodimer partner (SHP) has been proposed as a key mechanism reducing Ntcp expression [26].

Analytical, diagnostic and therapeutic context of Nr0b2


  1. The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes. Wang, L., Liu, J., Saha, P., Huang, J., Chan, L., Spiegelman, B., Moore, D.D. Cell metabolism. (2005) [Pubmed]
  2. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. Watanabe, M., Houten, S.M., Wang, L., Moschetta, A., Mangelsdorf, D.J., Heyman, R.A., Moore, D.D., Auwerx, J. J. Clin. Invest. (2004) [Pubmed]
  3. A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development. Qu, C.K., Shi, Z.Q., Shen, R., Tsai, F.Y., Orkin, S.H., Feng, G.S. Mol. Cell. Biol. (1997) [Pubmed]
  4. Resistance of SHP-null mice to bile acid-induced liver damage. Wang, L., Han, Y., Kim, C.S., Lee, Y.K., Moore, D.D. J. Biol. Chem. (2003) [Pubmed]
  5. Deficiency of SHP-1 protein-tyrosine phosphatase in "viable motheaten" mice results in retinal degeneration. Lyons, B.L., Smith, R.S., Hurd, R.E., Hawes, N.L., Burzenski, L.M., Nusinowitz, S., Hasham, M.G., Chang, B., Shultz, L.D. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  6. Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver. Huang, J., Iqbal, J., Saha, P.K., Liu, J., Chan, L., Hussain, M.M., Moore, D.D., Wang, L. Hepatology (2007) [Pubmed]
  7. Mutagenicity, tumorigenicity, and electrophilic reactivity of the stereoisomeric platinum(II) complexes of 1,2-diaminocyclohexane. Leopold, W.R., Batzinger, R.P., Miller, E.C., Miller, J.A., Earhart, R.H. Cancer Res. (1981) [Pubmed]
  8. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Seol, W., Choi, H.S., Moore, D.D. Science (1996) [Pubmed]
  9. Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses. Kim, C.H., Qu, C.K., Hangoc, G., Cooper, S., Anzai, N., Feng, G.S., Broxmeyer, H.E. J. Exp. Med. (1999) [Pubmed]
  10. Inhibition of the B cell by CD22: a requirement for Lyn. Smith, K.G., Tarlinton, D.M., Doody, G.M., Hibbs, M.L., Fearon, D.T. J. Exp. Med. (1998) [Pubmed]
  11. Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner. Li, Y., Choi, M., Suino, K., Kovach, A., Daugherty, J., Kliewer, S.A., Xu, H.E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Deficiency of Src homology 2-containing phosphatase 1 results in abnormalities in murine neutrophil function: studies in motheaten mice. Kruger, J., Butler, J.R., Cherapanov, V., Dong, Q., Ginzberg, H., Govindarajan, A., Grinstein, S., Siminovitch, K.A., Downey, G.P. J. Immunol. (2000) [Pubmed]
  13. Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner. Lai, K., Harnish, D.C., Evans, M.J. J. Biol. Chem. (2003) [Pubmed]
  14. Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription. Delerive, P., Galardi, C.M., Bisi, J.E., Nicodeme, E., Goodwin, B. Mol. Endocrinol. (2004) [Pubmed]
  15. The role of alpha1-fetoprotein transcription factor/LRH-1 in bile acid biosynthesis: a known nuclear receptor activator that can act as a suppressor of bile acid biosynthesis. del Castillo-Olivares, A., Campos, J.A., Pandak, W.M., Gil, G. J. Biol. Chem. (2004) [Pubmed]
  16. Loss of Src Homology Region 2 Domain-Containing Protein Tyrosine Phosphatase-1 Increases CD8+ T Cell-APC Conjugate Formation and Is Associated with Enhanced In Vivo CTL Function. Sathish, J.G., Dolton, G., Leroy, F.G., Matthews, R.J. J. Immunol. (2007) [Pubmed]
  17. Structure and expression of the orphan nuclear receptor SHP gene. Lee, H.K., Lee, Y.K., Park, S.H., Kim, Y.S., Park, S.H., Lee, J.W., Kwon, H.B., Soh, J., Moore, D.D., Choi, H.S. J. Biol. Chem. (1998) [Pubmed]
  18. Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. Okazawa, H., Motegi, S., Ohyama, N., Ohnishi, H., Tomizawa, T., Kaneko, Y., Oldenborg, P.A., Ishikawa, O., Matozaki, T. J. Immunol. (2005) [Pubmed]
  19. Farnesoid X receptor is essential for normal glucose homeostasis. Ma, K., Saha, P.K., Chan, L., Moore, D.D. J. Clin. Invest. (2006) [Pubmed]
  20. Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1. Yamagata, K., Daitoku, H., Shimamoto, Y., Matsuzaki, H., Hirota, K., Ishida, J., Fukamizu, A. J. Biol. Chem. (2004) [Pubmed]
  21. Repression of farnesoid X receptor during the acute phase response. Kim, M.S., Shigenaga, J., Moser, A., Feingold, K., Grunfeld, C. J. Biol. Chem. (2003) [Pubmed]
  22. Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho. Ito, S., Fujimori, T., Furuya, A., Satoh, J., Nabeshima, Y., Nabeshima, Y. J. Clin. Invest. (2005) [Pubmed]
  23. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. Zhang, Y., Kast-Woelbern, H.R., Edwards, P.A. J. Biol. Chem. (2003) [Pubmed]
  24. A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP. Båvner, A., Johansson, L., Toresson, G., Gustafsson, J.A., Treuter, E. EMBO Rep. (2002) [Pubmed]
  25. Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. Figge, A., Lammert, F., Paigen, B., Henkel, A., Matern, S., Korstanje, R., Shneider, B.L., Chen, F., Stoltenberg, E., Spatz, K., Hoda, F., Cohen, D.E., Green, R.M. J. Biol. Chem. (2004) [Pubmed]
  26. Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver. Zollner, G., Wagner, M., Fickert, P., Geier, A., Fuchsbichler, A., Silbert, D., Gumhold, J., Zatloukal, K., Kaser, A., Tilg, H., Denk, H., Trauner, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  27. Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP. Boulias, K., Katrakili, N., Bamberg, K., Underhill, P., Greenfield, A., Talianidis, I. EMBO J. (2005) [Pubmed]
  28. Cytokine-independent repression of rodent Ntcp in obstructive cholestasis. Geier, A., Zollner, G., Dietrich, C.G., Wagner, M., Fickert, P., Denk, H., van Rooijen, N., Matern, S., Gartung, C., Trauner, M. Hepatology (2005) [Pubmed]
  29. Induction of short heterodimer partner 1 precedes downregulation of Ntcp in bile duct-ligated mice. Zollner, G., Fickert, P., Silbert, D., Fuchsbichler, A., Stumptner, C., Zatloukal, K., Denk, H., Trauner, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  30. Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes. Kovacic, A., Speed, C.J., Simpson, E.R., Clyne, C.D. Mol. Endocrinol. (2004) [Pubmed]
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