Skip to main content

Nr0b2

  • Reference work entry
  • First Online:
  • 63 Accesses

Synonyms

Nuclear receptor subfamily 0 group B member 2; SHP; SHP1; Small heterodimer partner

Historical Background

The nuclear receptor small heterodimer partner (SHP, Nr0b2) was originally identified in 1996 as a transcriptional repressor based on its protein-protein interactions with several nuclear receptor superfamily members such as retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67 (Seol et al. 1996). The SHP gene consists of two exons and one intron located at human chromosome 1p36.11, mouse chromosome 4 D2.3, and rat chromosome 5q36. Since no endogenous ligand for SHP has been identified so for, SHP is classified as an orphan nuclear receptor. However, SHP is present in a variety of tissues. In mice, SHP is abundant in the gallbladder and liver while expressed at lower levels in the brainstem, cerebellum, adrenal, pancreas, stomach, duodenum, jejunum, ileum, colon, kidney, ovary, testis, and heart. In humans, SHP expression is detectable in the...

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Boulias K, Katrakili N, Bamberg K, Underhill P, Greenfield A, Talianidis I. Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP. EMBO J. 2005;24:2624–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6:517–26.

    Article  CAS  PubMed  Google Scholar 

  • He N, Park K, Zhang Y, Huang J, Lu S, Wang L. Epigenetic inhibition of nuclear receptor small heterodimer partner is associated with and regulates hepatocellular carcinoma growth. Gastroenterology. 2008;134:793–802.

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Iqbal J, Saha PK, Liu J, Chan L, Hussain MM, et al. Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver. Hepatology. 2007;46:147–57.

    Article  CAS  PubMed  Google Scholar 

  • Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217–25.

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Kwon S, Byun S, Xiao Z, Park S, Wu SY, et al. Critical role of RanBP2-mediated SUMOylation of small heterodimer partner in maintaining bile acid homeostasis. Nat Commun. 2016;7:12179.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li YT, Swales KE, Thomas GJ, Warner TD, Bishop-Bailey D. Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration. Arterioscler Thromb Vasc Biol. 2007;27:2606–11.

    Article  CAS  PubMed  Google Scholar 

  • Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell. 2000;6:507–15.

    Article  CAS  PubMed  Google Scholar 

  • Matsukuma KE, Wang L, Bennett MK, Osborne TF. A key role for orphan nuclear receptor liver receptor homologue-1 in activation of fatty acid synthase promoter by liver X receptor. J Biol Chem. 2007;282:20164–71.

    Article  CAS  PubMed  Google Scholar 

  • Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, et al. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci USA. 2001;98:575–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pan X, Zhang Y, Wang L, Hussain MM. Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. Cell Metab. 2010;12:174–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park MJ, Kong HJ, Kim HY, Kim HH, Kim JH, Cheong JH. Transcriptional repression of the gluconeogenic gene PEPCK by the orphan nuclear receptor SHP through inhibitory interaction with C/EBPalpha. Biochem J. 2007;402:567–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science. 1996;272:1336–9.

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Lee YK, Bundman D, Han Y, Thevananther S, Kim CS, et al. Redundant pathways for negative feedback regulation of bile acid production. Dev Cell. 2002;2:721–31.

    Article  CAS  PubMed  Google Scholar 

  • Yang CS, Kim JJ, Kim TS, Lee PY, Kim SY, Lee HM, et al. Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome. Nat Commun. 2015;6:6115.

    Article  PubMed  CAS  Google Scholar 

  • Yuk JM, Shin DM, Lee HM, Kim JJ, Kim SW, Jin HS, et al. The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors. Nat Immunol. 2011;12:742–51.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Andrews GK, Wang L. Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear receptor SHP. Nucleic Acids Res. 2012;40:4850–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Hagedorn CH, Wang L. Role of nuclear receptor SHP in metabolism and cancer. Biochim Biophys Acta. 2011;1812:893–908.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Xu P, Park K, Choi Y, Moore DD, Wang L. Orphan receptor small heterodimer partner suppresses tumorigenesis by modulating cyclin D1 expression and cellular proliferation. Hepatology. 2008;48:289–98.

    Article  PubMed  CAS  Google Scholar 

  • Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, et al. Structural insights into gene repression by the orphan nuclear receptor SHP. Proc Natl Acad Sci USA. 2014;111:839–44.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuxia Zhang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Zhang, Y. (2018). Nr0b2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101707

Download citation

Publish with us

Policies and ethics