Small heterodimer partner

NR0B2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YUC, 2Q3Y, 2Z4J, 4DOR, 4ONI
Identifiers
Aliases	NR0B2, SHP, SHP1, nuclear receptor subfamily 0 group B member 2
External IDs	OMIM: 604630 MGI: 1346344 HomoloGene: 8030 GeneCards: NR0B2
Gene ontology Molecular function • DNA binding • protein homodimerization activity • protein domain specific binding • protein complex binding • retinoid X receptor binding • thyroid hormone receptor binding • steroid hormone receptor activity • protein binding • peroxisome proliferator activated receptor binding • retinoic acid receptor binding • transcription factor binding • transcription corepressor activity Cellular component • nucleoplasm • protein complex • nucleus • cytoplasm Biological process • Notch signaling pathway • regulation of transcription, DNA-templated • cholesterol metabolic process • negative regulation of transcription from RNA polymerase II promoter • response to glucose • negative regulation of sequence-specific DNA binding transcription factor activity • negative regulation of gene expression • transcription, DNA-templated • positive regulation of gene expression • animal organ regeneration • transcription initiation from RNA polymerase II promoter • negative regulation of transcription, DNA-templated • positive regulation of insulin secretion • steroid hormone mediated signaling pathway 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_068804.1	NP_035980.1
Location (UCSC)	Chr 1: 26.91 – 26.91 Mb	Chr 4: 133.55 – 133.56 Mb
PubMed search	[1]	[2]
Wikidata

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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.^[3] SHP is a member of the nuclear receptor family of intracellular transcription factors.^[4] 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.^[5] 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.^[3]

Interactions

Small heterodimer partner has been shown to interact with:

• Androgen receptor,^[6]
• Estrogen receptor alpha,^[7]
• Hepatocyte nuclear factor 4 alpha,^[8]
• Liver receptor homolog-1,^[9][10]
• Liver X receptor alpha,^[9]
• Peroxisome proliferator-activated receptor gamma,^[11]
• Retinoic acid receptor alpha,^[12][13] and
• Retinoid X receptor alpha.^[8][9]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2".
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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)