Biology:Small heterodimer partner

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

The small heterodimer partner (SHP) also known as NR0B2 (nuclear receptor subfamily 0, group B, member 2) is a protein that in humans is encoded by the NR0B2 gene.[1] SHP is a member of the nuclear receptor family of intracellular transcription factors.[2] SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

Function

The principal role of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer.[3] The protein has also been identified as a mediating factor in the metabolic circadian clock [4] Research shows that it interacts with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function.[1]

Structure and ligands

A crystal structure of the LBD-only SHP, generated by co-crystallisation with EID1, has been obtained. Instead binding to the usual AF-2 site, EID1 fills in the place of what is usually helix α1 of an LBD and makes SHP more soluble. The overall structure resembles the apo (ligandless) form of other LBDs. Some synthetic retinoid ligands can bind to SHP's LBD and promote its interaction with LXXLL-containing corepressors using the AF-2 site.[5]

Interactions

Large and medium scale Y2H experiments as well as text mining of the NR literature have highlighted the important role of SHP in the Nuclear Receptor dimerization network and its relatively highly connected status, compared to other NRs. [6]

Small heterodimer partner has been shown to interact with:


References

  1. ↑ 1.0 1.1 "Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8431. 
  2. ↑ "Structure and expression of the orphan nuclear receptor SHP gene". The Journal of Biological Chemistry 273 (23): 14398–402. June 1998. doi:10.1074/jbc.273.23.14398. PMID 9603951. 
  3. ↑ "Transcriptional corepression by SHP: molecular mechanisms and physiological consequences". Trends in Endocrinology and Metabolism 16 (10): 478–88. December 2005. doi:10.1016/j.tem.2005.10.005. PMID 16275121. 
  4. ↑ "Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice". Molecular Endocrinology 30 (9): 988–95. September 2016. doi:10.1210/me.2015-1295. PMID 27427832. 
  5. ↑ 5.0 5.1 "Structural insights into gene repression by the orphan nuclear receptor SHP". Proceedings of the National Academy of Sciences of the United States of America 111 (2): 839–44. January 2014. doi:10.1073/pnas.1322827111. PMID 24379397. Bibcode: 2014PNAS..111..839Z. 
  6. ↑ "A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network". BMC Systems Biology 1: 34. July 2007. doi:10.1186/1752-0509-1-34. PMID 17672894. 
  7. ↑ "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry 40 (50): 15369–77. December 2001. doi:10.1021/bi011384o. PMID 11735420. 
  8. ↑ "The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cells". Endocrinology 143 (3): 853–67. March 2002. doi:10.1210/endo.143.3.8676. PMID 11861507. 
  9. ↑ 9.0 9.1 "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression". Molecular and Cellular Biology 20 (1): 187–95. January 2000. doi:10.1128/MCB.20.1.187-195.2000. PMID 10594021. 
  10. ↑ 10.0 10.1 10.2 "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology 16 (9): 2065–76. September 2002. doi:10.1210/me.2001-0194. PMID 12198243. 
  11. ↑ "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner". The Journal of Biological Chemistry 277 (4): 2463–7. January 2002. doi:10.1074/jbc.M105161200. PMID 11668176. 
  12. ↑ "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". The Journal of Biological Chemistry 277 (2): 1586–92. January 2002. doi:10.1074/jbc.M104301200. PMID 11696534. 
  13. ↑ "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science 272 (5266): 1336–9. May 1996. doi:10.1126/science.272.5266.1336. PMID 8650544. Bibcode: 1996Sci...272.1336S. 
  14. ↑ "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Molecular Endocrinology 12 (10): 1551–7. October 1998. doi:10.1210/me.12.10.1551. PMID 9773978. 

Further reading

External links



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