Small heterodimer partner

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Nuclear receptor subfamily 0, group B, member 2
Protein NR0B2 PDB 1YUC.png
Rendering based on PDB 1YUC​.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NR0B2 ; SHP; SHP1
External IDs OMIM604630 MGI1346344 HomoloGene8030 IUPHAR: 636 ChEMBL: 5603 GeneCards: NR0B2 Gene
RNA expression pattern
PBB GE NR0B2 206410 at tn.png
More reference expression data
Species Human Mouse
Entrez 8431 23957
Ensembl ENSG00000131910 ENSMUSG00000037583
UniProt Q15466 Q62227
RefSeq (mRNA) NM_021969 NM_011850
RefSeq (protein) NP_068804 NP_035980
Location (UCSC) Chr 1:
26.91 – 26.91 Mb
Chr 4:
133.55 – 133.56 Mb
PubMed search [1] [2]

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 technically it is 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.


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 been shown to interact 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]


Small heterodimer partner has been shown to interact with:


  1. ^ a b "Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2". 
  2. ^ Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS (Jun 1998). "Structure and expression of the orphan nuclear receptor SHP gene". The Journal of Biological Chemistry 273 (23): 14398–402. doi:10.1074/jbc.273.23.14398. PMID 9603951. 
  3. ^ Båvner A, Sanyal S, Gustafsson JA, Treuter E (Dec 2005). "Transcriptional corepression by SHP: molecular mechanisms and physiological consequences". Trends in Endocrinology and Metabolism 16 (10): 478–88. doi:10.1016/j.tem.2005.10.005. PMID 16275121. 
  4. ^ Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (Dec 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry 40 (50): 15369–77. doi:10.1021/bi011384o. PMID 11735420. 
  5. ^ Klinge CM, Jernigan SC, Risinger KE (Mar 2002). "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. doi:10.1210/en.143.3.853. PMID 11861507. 
  6. ^ a b Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD (Jan 2000). "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. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021. 
  7. ^ a b c Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (Sep 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243. 
  8. ^ Lee YK, Moore DD (Jan 2002). "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. doi:10.1074/jbc.M105161200. PMID 11668176. 
  9. ^ Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y (Jan 2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". The Journal of Biological Chemistry 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534. 
  10. ^ Seol W, Choi HS, Moore DD (May 1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science 272 (5266): 1336–9. doi:10.1126/science.272.5266.1336. PMID 8650544. 
  11. ^ Seol W, Hanstein B, Brown M, Moore DD (Oct 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Molecular Endocrinology 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978. 

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