Small heterodimer partner

Nuclear receptor subfamily 0, group B, member 2
Rendering based on PDB 1YUC.
Available structures PDB 1YUC, 2Q3Y, 2Z4J
Identifiers
Symbols	NR0B2; FLJ17090; SHP; SHP1
External IDs	OMIM: 604630 MGI: 1346344 HomoloGene: 8030 IUPHAR: NR0B2 GeneCards: NR0B2 Gene
Gene Ontology Molecular function • 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 • cholesterol metabolic process • response to glucose stimulus • gene expression • androgen receptor signaling pathway • organ regeneration • positive regulation of insulin secretion • regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor • 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_021969.2	NM_011850.2
RefSeq (protein)	NP_068804.1	NP_035980.1
Location (UCSC)	Chr 1: 27.24 – 27.24 Mb	Chr 4: 133.11 – 133.11 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.

Function

The principle 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. ^ ^{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. 
2. ^ 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. 
3. ^ Båvner 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. ^ Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 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 (March 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 (January 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. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85074. 
7. ^ ^{a b c} Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (September 2002). "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. 
8. ^ 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. 
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 (January 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. 
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 (October 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. 

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. 
• 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. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85074. 
• Johansson L, Båvner 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. PMC 85230. PMID 10648597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85230. 
• 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. PMC 14629. PMID 11136233. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14629. 
• 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. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• 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

• MeSH small+heterodimer+partner+protein