Small heterodimer partner

Nuclear receptor subfamily 0, group B, member 2
Rendering based on PDB 1YUC​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1YUC​, 2Q3Y​, 2Z4J​, 4DOR​, 4ONI​
Identifiers
Symbols	NR0B2 ; SHP; SHP1
External IDs	OMIM: 604630 MGI: 1346344 HomoloGene: 8030 IUPHAR: 636 ChEMBL: 5603 GeneCards: NR0B2 Gene
Gene ontology Molecular function • DNA binding • transcription factor activity, sequence-specific DNA binding • steroid hormone receptor activity • transcription corepressor activity • protein binding • protein domain specific binding • protein complex binding • protein homodimerization activity • peroxisome proliferator activated receptor binding • retinoid X receptor binding • thyroid hormone receptor binding Cellular component • nucleus • nucleoplasm • cytoplasm • protein complex Biological process • negative regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • cholesterol metabolic process • response to glucose • gene expression • positive regulation of gene expression • negative regulation of gene expression • organ regeneration • positive regulation of insulin secretion • steroid hormone mediated signaling pathway • negative regulation of sequence-specific DNA binding transcription factor activity Sources: Amigo / QuickGO
RNA expression pattern
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: 26.91 – 26.91 Mb	Chr 4: 133.55 – 133.56 Mb
PubMed search

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.

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 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]

Interactions

Small heterodimer partner has been shown to interact with:

• Androgen receptor,^[4]
• Estrogen receptor alpha,^[5]
• Hepatocyte nuclear factor 4 alpha,^[6]
• Liver receptor homolog-1,^[7][8]
• Liver X receptor alpha,^[7]
• Peroxisome proliferator-activated receptor gamma,^[9]
• Retinoic acid receptor alpha,^[10][11] and
• Retinoid X receptor alpha.^[6][7]

References

1. "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. 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. 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.

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. PMID 8650544.
• 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.
• 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.
• Johansson L, Båvner A, Thomsen JS, Färnegårdh M, Gustafsson JA, Treuter E (Feb 2000). "The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors". Molecular and Cellular Biology 20 (4): 1124–33. doi:10.1128/MCB.20.4.1124-1133.2000. PMC 85230. PMID 10648597.
• 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. PMID 11030331.
• Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J (Jan 2001). "Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects". Proceedings of the National Academy of Sciences of the United States of America 98 (2): 575–80. doi:10.1073/pnas.021544398. PMC 14629. PMID 11136233.
• 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.
• 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.
• 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. PMID 11705994.
• 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.
• 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.
• 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. PMID 11890664.
• 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. PMID 12181644.
• 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.
• 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. PMID 12324453.
• 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. PMID 12716767.
• 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. PMID 12842887.
• 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. PMID 14593077.

External links

• small heterodimer partner protein at the US National Library of Medicine Medical Subject Headings (MeSH)