Small heterodimer partner

Last updated
NR0B2
Protein NR0B2 PDB 1YUC.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NR0B2 , SHP, SHP1, nuclear receptor subfamily 0 group B member 2
External IDs OMIM: 604630 MGI: 1346344 HomoloGene: 8030 GeneCards: NR0B2
Orthologs
SpeciesHumanMouse
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: 133.28 – 133.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] SHP is a member of the nuclear receptor family of intracellular transcription factors. [6] 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.

Contents

Function

The principal role of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer. [7] The protein has also been identified as a mediating factor in the metabolic circadian clock [8] 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. [5]

Structure and ligands

A crystal structure of the LBD-only SHP, generated by co-crystallisation with EID1, has been obtained. Instead binding to the usual AF-2 site, EID1 fills in the place of what is usually helix α1 of an LBD and makes SHP more soluble. The overall structure resembles the apo (ligandless) form of other LBDs. Some synthetic retinoid ligands can bind to SHP's LBD and promote its interaction with LXXLL-containing corepressors using the AF-2 site. [9]

Interactions

Large and medium scale Y2H experiments as well as text mining of the NR literature have highlighted the important role of SHP in the Nuclear Receptor dimerization network and its relatively highly connected status, compared to other NRs. [10]

Small heterodimer partner has been shown to interact with:

Related Research Articles

Estrogen receptor Proteins activated by the hormone estrogen

Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).

Androgen receptor Mammalian protein found in Homo sapiens

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

Estrogen receptor alpha Protein-coding gene in the species Homo sapiens

Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.

Farnesoid X receptor Protein-coding gene in the species Homo sapiens

The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4, is a nuclear receptor that is encoded by the NR1H4 gene in humans.

Constitutive androstane receptor Protein-coding gene in humans

The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of endobiotic and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs.

Nuclear receptor Protein

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.

Nuclear receptor coactivator 1

The nuclear receptor coactivator 1 (NCOA1) is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression.

Nuclear receptor coactivator 2 Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

Liver receptor homolog-1 Protein-coding gene in the species Homo sapiens

The liver receptor homolog-1 (LRH-1) also known as NR5A2 is a protein that in humans is encoded by the NR5A2 gene. LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.

RAR-related orphan receptor alpha Protein-coding gene in the species Homo sapiens

RAR-related orphan receptor alpha (RORα), also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene. RORα participates in the transcriptional regulation of some genes involved in circadian rhythm. In mice, RORα is essential for development of cerebellum through direct regulation of genes expressed in Purkinje cells. It also plays an essential role in the development of type 2 innate lymphoid cells (ILC2) and mutant animals are ILC2 deficient. In addition, although present in normal numbers, the ILC3 and Th17 cells from RORα deficient mice are defective for cytokine production.

Retinoid X receptor alpha Protein-coding gene in the species Homo sapiens

Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.

Hepatocyte nuclear factor 4 alpha Protein-coding gene in the species Homo sapiens

Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 is a nuclear receptor that in humans is encoded by the HNF4A gene.

Retinoic acid receptor alpha

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.

Liver X receptor alpha Protein-coding gene in the species Homo sapiens

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.

NRIP1 Protein-coding gene in the species Homo sapiens

Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.

COUP-TFI

COUP-TF1 also known as NR2F1 is a protein that in humans is encoded by the NR2F1 gene. This protein is a member of nuclear hormone receptor family of steroid hormone receptors.

Testicular receptor 2

The testicular receptor 2 (TR2) also known as NR2C1 is protein that in humans is encoded by the NR2C1 gene. TR2 is a member of the nuclear receptor family of transcription factors.

Testicular receptor 4 Protein-coding gene in the species Homo sapiens

Testicular receptor 4 also known as NR2C2 is a protein that in humans is encoded by the NR2C2 gene.

Liver X receptor beta Protein-coding gene in the species Homo sapiens

Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the NR1H2 gene.

NCOA6

Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000131910 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037583 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2".
  6. ↑ Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, et al. (June 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.
  7. ↑ Båvner A, Sanyal S, Gustafsson JA, Treuter E (December 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. S2CID   7884363.
  8. ↑ Wu N, Kim KH, Zhou Y, Lee JM, Kettner NM, Mamrosh JL, et al. (September 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. PMC   5004116 . PMID   27427832.
  9. 1 2 Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, et al. (January 2014). "Structural insights into gene repression by the orphan nuclear receptor SHP". Proceedings of the National Academy of Sciences of the United States of America. 111 (2): 839–44. Bibcode:2014PNAS..111..839Z. doi: 10.1073/pnas.1322827111 . PMC   3896210 . PMID   24379397.
  10. ↑ Amoutzias GD, Pichler EE, Mian N, De Graaf D, Imsiridou A, Robinson-Rechavi M, et al. (July 2007). "A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network". BMC Systems Biology. 1: 34. doi:10.1186/1752-0509-1-34. PMC   1971058 . PMID   17672894.
  11. ↑ 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.
  12. ↑ 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/endo.143.3.8676 . PMID   11861507.
  13. 1 2 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". Molecular and Cellular Biology. 20 (1): 187–95. doi:10.1128/MCB.20.1.187-195.2000. PMC   85074 . PMID   10594021.
  14. 1 2 3 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". Molecular Endocrinology. 16 (9): 2065–76. doi: 10.1210/me.2001-0194 . PMID   12198243.
  15. ↑ Lee YK, Moore DD (January 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.
  16. ↑ Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, et al. (January 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.
  17. ↑ 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. Bibcode:1996Sci...272.1336S. doi:10.1126/science.272.5266.1336. PMID   8650544. S2CID   32853062.
  18. ↑ Seol W, Hanstein B, Brown M, Moore DD (October 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.

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