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Nuclear receptor subfamily 0, group B, member 2
Identifiers
Symbols NR0B2; SHP1; SHP
External IDs OMIM604630 MGI1346344 HomoloGene8030 GeneCards: NR0B2 Gene
RNA expression pattern
PBB GE NR0B2 206410 at tn.png
More reference expression data
Orthologs
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:
27.11 - 27.11 Mb
Chr 4:
132.83 - 132.83 Mb
PubMed search [1] [2]

The small heterodimer partner (SHP) protein is a member of the nuclear receptor family of intracellular transcription factors[1] and is encoded by the NR0B2 (nuclear receptor subfamily 0, group B, member 2) gene.[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 main function 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.[2]

Contents

Interactions

Small heterodimer partner has been shown to interact with Retinoic acid receptor alpha,[4][5] Peroxisome proliferator-activated receptor gamma,[6] Liver X receptor alpha,[7] Androgen receptor,[8] Estrogen receptor alpha,[5][9] Hepatocyte nuclear factor 4 alpha,[10] Retinoid X receptor alpha[10][7] and Liver receptor homolog-1.[7][11]

References

  1. ^ Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS (1998). "Structure and expression of the orphan nuclear receptor SHP gene". J. Biol. Chem. 273 (23): 14398?402. doi:10.1074/jbc.273.23.14398. PMID 9603951.  
  2. ^ a b "Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8431.  
  3. ^ B�vner A, Sanyal S, Gustafsson JA, Treuter E (2005). "Transcriptional corepression by SHP: molecular mechanisms and physiological consequences". Trends Endocrinol. Metab. 16 (10): 478?88. doi:10.1016/j.tem.2005.10.005. PMID 16275121.  
  4. ^ Seol, W; Choi H S, Moore D D (May. 1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science (UNITED STATES) 272 (5266): 1336–9. ISSN 0036-8075. PMID 8650544.  
  5. ^ a b Seol, W; Hanstein B, Brown M, Moore D D (Oct. 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. (UNITED STATES) 12 (10): 1551–7. ISSN 0888-8809. PMID 9773978.  
  6. ^ Nishizawa, Hitoshi; Yamagata Kazuya, Shimomura Iichiro, Takahashi Masahiko, Kuriyama Hiroshi, Kishida Ken, Hotta Kikuko, Nagaretani Hiroyuki, Maeda Norikazu, Matsuda Morihiro, Kihara Shinji, Nakamura Tadashi, Nishigori Hidekazu, Tomura Hideaki, Moore David D, Takeda Jun, Funahashi Tohru, Matsuzawa Yuji (Jan. 2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". J. Biol. Chem. (United States) 277 (2): 1586–92. doi:10.1074/jbc.M104301200. ISSN 0021-9258. PMID 11696534.  
  7. ^ a b c Brendel, Carole; Schoonjans Kristina, Botrugno Oronza A, Treuter Eckardt, Auwerx Johan (Sep. 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Mol. Endocrinol. (United States) 16 (9): 2065–76. ISSN 0888-8809. PMID 12198243.  
  8. ^ Gobinet, J; Auzou G, Nicolas J C, Sultan C, Jalaguier S (Dec. 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry (United States) 40 (50): 15369–77. ISSN 0006-2960. PMID 11735420.  
  9. ^ Klinge, Carolyn M; Jernigan Sarah C, Risinger Kelly E (Mar. 2002). "The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cells". Endocrinology (United States) 143 (3): 853–67. ISSN 0013-7227. PMID 11861507.  
  10. ^ a b Lee, Y K; Dell H, Dowhan D H, Hadzopoulou-Cladaras M, Moore D D (Jan. 2000). "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression". Mol. Cell. Biol. (UNITED STATES) 20 (1): 187–95. ISSN 0270-7306. PMID 10594021.  
  11. ^ Lee, Yoon-Kwang; Moore David D (Jan. 2002). "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner". J. Biol. Chem. (United States) 277 (4): 2463–7. doi:10.1074/jbc.M105161200. ISSN 0021-9258. PMID 11668176.  

Further reading

  • Seol W, Choi HS, Moore DD (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.  
  • Lee HK, Lee YK, Park SH, et al. (1998). "Structure and expression of the orphan nuclear receptor SHP gene.". J. Biol. Chem. 273 (23): 14398?402. doi:10.1074/jbc.273.23.14398. PMID 9603951.  
  • Seol W, Hanstein B, Brown M, Moore DD (1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner).". Mol. Endocrinol. 12 (10): 1551?7. doi:10.1210/me.12.10.1551. PMID 9773978.  
  • Lee YK, Dell H, Dowhan DH, et al. (2000). "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression.". Mol. Cell. Biol. 20 (1): 187?95. PMID 10594021.  
  • Johansson L, B�vner A, Thomsen JS, et al. (2000). "The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors.". Mol. Cell. Biol. 20 (4): 1124?33. doi:10.1128/MCB.20.4.1124-1133.2000. PMID 10648597.  
  • Lu TT, Makishima M, Repa JJ, et al. (2000). "Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors.". Mol. Cell 6 (3): 507?15. doi:10.1016/S1097-2765(00)00050-2. PMID 11030331.  
  • Nishigori H, Tomura H, Tonooka N, et al. (2001). "Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 575?80. doi:10.1073/pnas.021544398. PMID 11136233.  
  • Lee YK, Moore DD (2002). "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner.". J. Biol. Chem. 277 (4): 2463?7. doi:10.1074/jbc.M105161200. PMID 11668176.  
  • Nishizawa H, Yamagata K, Shimomura I, et al. (2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation.". J. Biol. Chem. 277 (2): 1586?92. doi:10.1074/jbc.M104301200. PMID 11696534.  
  • Sanyal S, Kim JY, Kim HJ, et al. (2002). "Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms.". J. Biol. Chem. 277 (3): 1739?48. doi:10.1074/jbc.M106140200. PMID 11705994.  
  • Gobinet J, Auzou G, Nicolas JC, et al. (2002). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP.". Biochemistry 40 (50): 15369?77. doi:10.1021/bi011384o. PMID 11735420.  
  • Klinge CM, Jernigan SC, Risinger KE (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.  
  • Ogata M, Awaji T, Iwasaki N, et al. (2002). "Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells.". Biochem. Biophys. Res. Commun. 292 (1): 8?12. doi:10.1006/bbrc.2002.6593. PMID 11890664.  
  • Cao H, Hegele RA (2002). "Identification of polymorphisms in the human SHP1 gene.". J. Hum. Genet. 47 (8): 445?7. doi:10.1007/s100380200062. PMID 12181644.  
  • Brendel C, Schoonjans K, Botrugno OA, et al. (2003). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity.". Mol. Endocrinol. 16 (9): 2065?76. doi:10.1210/me.2001-0194. PMID 12198243.  
  • Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E (2003). "Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP.". J. Biol. Chem. 277 (51): 49761?6. doi:10.1074/jbc.M205641200. PMID 12324453.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899?903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Hung CC, Farooqi IS, Ong K, et al. (2003). "Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations.". Diabetes 52 (5): 1288?91. doi:10.2337/diabetes.52.5.1288. PMID 12716767.  
  • Lai K, Harnish DC, Evans MJ (2003). "Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner.". J. Biol. Chem. 278 (38): 36418?29. doi:10.1074/jbc.M303913200. PMID 12842887.  
  • Kovacic A, Speed CJ, Simpson ER, Clyne CD (2004). "Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes.". Mol. Endocrinol. 18 (1): 252?9. doi:10.1210/me.2003-0211. PMID 14593077.  

External links

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