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 NR0B2gene.[1] SHP is a member of the nuclear receptor family of intracellulartranscription 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.
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]
Interactions
Small heterodimer partner has been shown to interact with:
↑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. PMID9603951.
↑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. PMID16275121.
↑Wu N, Kang HK, Zhou Y, Lee JM, Kettner NM, Mamrosh JL, Choi S, Fu L, Moore DD (Jul 2016). "Small heterodimer partner (NR0B2) coordinates nutrient signaling and the circadian clock in mice". Molecular Endocrinology. 30 (9): 988–95. doi:10.1210/me.2015-1295.
↑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. PMID11735420.
↑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. PMID11861507.
↑ 8.08.18.2Brendel 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. PMID12198243.
↑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. PMID11668176.
↑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. PMID11696534.
↑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. PMID8650544.
↑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. PMID9773978.
Further reading
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. PMID8650544.
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. PMID9773978.
Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ (Sep 2000). "Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors". Molecular Cell. 6 (3): 507–15. doi:10.1016/S1097-2765(00)00050-2. PMID11030331.
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. PMID11668176.
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. PMID11696534.
Sanyal S, Kim JY, Kim HJ, Takeda J, Lee YK, Moore DD, Choi HS (Jan 2002). "Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms". The Journal of Biological Chemistry. 277 (3): 1739–48. doi:10.1074/jbc.M106140200. PMID11705994.
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. PMID11735420.
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. PMID11861507.
Ogata M, Awaji T, Iwasaki N, Miyazaki S, Bell GI, Iwamoto Y (Mar 2002). "Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells". Biochemical and Biophysical Research Communications. 292 (1): 8–12. doi:10.1006/bbrc.2002.6593. PMID11890664.
Cao H, Hegele RA (2002). "Identification of polymorphisms in the human SHP1 gene". Journal of Human Genetics. 47 (8): 445–7. doi:10.1007/s100380200062. PMID12181644.
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. PMID12198243.
Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E (Dec 2002). "Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP". The Journal of Biological Chemistry. 277 (51): 49761–6. doi:10.1074/jbc.M205641200. PMID12324453.
Hung CC, Farooqi IS, Ong K, Luan J, Keogh JM, Pembrey M, Yeo GS, Dunger D, Wareham NJ, O' Rahilly S (May 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. PMID12716767.
Lai K, Harnish DC, Evans MJ (Sep 2003). "Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner". The Journal of Biological Chemistry. 278 (38): 36418–29. doi:10.1074/jbc.M303913200. PMID12842887.
Kovacic A, Speed CJ, Simpson ER, Clyne CD (Jan 2004). "Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes". Molecular Endocrinology. 18 (1): 252–9. doi:10.1210/me.2003-0211. PMID14593077.