RAR-related orphan receptor beta

Last updated
RORB
Protein RORB PDB 1k4w.png
Identifiers
Aliases RORB , NR1F2, ROR-BETA, RZR-BETA, RZRB, bA133M9.1, RAR-related orphan receptor beta, RAR related orphan receptor B, EIG15
External IDs OMIM: 601972 MGI: 1343464 HomoloGene: 38250 GeneCards: RORB
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006914
NM_001365023

NM_001043354
NM_001289921
NM_146095

RefSeq (protein)

NP_008845
NP_001351952

NP_001036819
NP_001276850
NP_666207

Location (UCSC) Chr 9: 74.5 – 74.69 Mb Chr 19: 18.91 – 19.09 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

RAR-related orphan receptor beta (ROR-beta), also known as NR1F2 (nuclear receptor subfamily 1, group F, member 2) is a nuclear receptor that in humans is encoded by the RORB gene. [5]

Contents

Function

The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The specific functions of this protein are not known, but it has been shown to interact with NM23-2, a nucleoside-diphosphate kinase involved in organogenesis and differentiation. [6]

In the brain, ROR-beta is concentrated in layer 4 of the cerebral cortex, where it plays a role in the development of structures such as barrel columns. [7]

A mutation in this gene also results in the loss of spinal cord interneurons and of saltatorial locomotion, [8] a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents.

Interactions

RAR-related orphan receptor beta has been shown to interact with NME1. [9]

See also

Related Research Articles

The retinoic acid receptor (RAR) is a type of nuclear receptor which can also act as a ligand-activated transcription factor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, retinoid active derivatives of Vitamin A. They are typically found within the nucleus. There are three retinoic acid receptors (RAR), RAR-alpha, RAR-beta, and RAR-gamma, encoded by the RARA, RARB, RARG genes, respectively. Within each RAR subtype there are various isoforms differing in their N-terminal region A. Multiple splice variants have been identified in human RARs: four for RARA, five for RARB, and two for RARG. As with other type II nuclear receptors, RAR heterodimerizes with RXR and in the absence of ligand, the RAR/RXR dimer binds to hormone response elements known as retinoic acid response elements (RAREs) complexed with corepressor protein. Binding of agonist ligands to RAR results in dissociation of corepressor and recruitment of coactivator protein that, in turn, promotes transcription of the downstream target gene into mRNA and eventually protein. In addition, the expression of RAR genes is under epigenetic regulation by promoter methylation. Both the length and magnitude of the retinoid response is dependent of the degradation of RARs and RXRs through the ubiquitin-proteasome. This degradation can lead to elongation of the DNA transcription through disruption of the initiation complex or to end the response to facilitate further transcriptional programs. Due to RAR/RXR heterodimers acting as subtrates to the non steroid hormone ligand retinoid they are extensively involved in cell differentiation, proliferation, and apoptosis.

The retinoid X receptor (RXR) is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance, and 9-cis-13,14-dihydroretinoic acid, which is likely to be the major endogenous mammalian RXR-selective agonist.

Retinoid receptors are nuclear receptors that bind to retinoids. When bound to a retinoid, they act as transcription factors, altering the expression of genes with corresponding response elements. Significant age-related declines in the levels of retinoid receptors in the forebrains of rats have been reversed by supplementation with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which can restore neurogenesis.

The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors. There are three forms of ROR, ROR-α, -β, and -γ and each is encoded by a separate gene, RORA, RORB, and RORC respectively. The RORs are somewhat unusual in that they appear to bind as monomers to hormone response elements as opposed to the majority of other nuclear receptors which bind as dimers. They bind to DNA elements called ROR response elements (RORE).

<span class="mw-page-title-main">Nuclear receptor 4A1</span> Mammalian protein found in Homo sapiens

The nuclear receptor 4A1 also known as Nur77, TR3, and NGFI-B is a protein that in humans is encoded by the NR4A1 gene.

<span class="mw-page-title-main">Germ cell nuclear factor</span> Protein-coding gene in the species Homo sapiens

The germ cell nuclear factor (GCNF), also known as RTR or NR6A1, is a protein that in humans is encoded by the NR6A1 gene. GCNF is a member of the nuclear receptor family of intracellular transcription factors.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein-coding gene in the species Homo sapiens

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. 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.

<span class="mw-page-title-main">Rev-ErbA alpha</span> Protein-coding gene in the species Homo sapiens

Rev-Erb alpha (Rev-Erbɑ), also known as nuclear receptor subfamily 1 group D member 1 (NR1D1), is one of two Rev-Erb proteins in the nuclear receptor (NR) family of intracellular transcription factors. In humans, REV-ERBɑ is encoded by the NR1D1 gene, which is highly conserved across animal species.

<span class="mw-page-title-main">RAR-related orphan receptor alpha</span> 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.

<span class="mw-page-title-main">Rev-ErbA beta</span> Protein-coding gene in the species Homo sapiens

Rev-Erb beta (Rev-Erbβ), also known as nuclear receptor subfamily 1 group D member 2 (NR1D2), is a member of the Rev-Erb protein family. Rev-Erbβ, like Rev-Erbα, belongs to the nuclear receptor superfamily of transcription factors and can modulate gene expression through binding to gene promoters. Together with Rev-Erbα, Rev-Erbβ functions as a major regulator of the circadian clock. These two proteins are partially redundant. Current research suggests that Rev-Erbβ is less important in maintaining the circadian clock than Rev-Erbα; knock-out studies of Rev-Erbα result in significant circadian disruption but the same has not been found with Rev-Erbβ. Rev-Erbβ compensation for Rev-Erbα varies across tissues, and further research is needed to elucidate the separate role of Rev-Erbβ.

<span class="mw-page-title-main">Retinoid X receptor alpha</span> 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.

<span class="mw-page-title-main">Retinoic acid receptor alpha</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">NME1</span> Protein-coding gene in the species Homo sapiens

Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene. It is thought to be a metastasis suppressor.

<span class="mw-page-title-main">Retinoid X receptor gamma</span> Protein-coding gene in the species Homo sapiens

Retinoid X receptor gamma (RXR-gamma), also known as NR2B3 is a nuclear receptor that in humans is encoded by the RXRG gene.

<span class="mw-page-title-main">Retinoid X receptor beta</span> Protein-coding gene in the species Homo sapiens

Retinoid X receptor beta (RXR-beta), also known as NR2B2 is a nuclear receptor that in humans is encoded by the RXRB gene.

<span class="mw-page-title-main">Retinoic acid receptor gamma</span> Protein-coding gene in the species Homo sapiens

Retinoic acid receptor gamma (RAR-γ), also known as NR1B3 is a nuclear receptor encoded by the RARG gene. Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma and its agonism of the gamma subtype is largely responsible for adapalene's observed effects.

<span class="mw-page-title-main">Liver X receptor beta</span> 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.

<span class="mw-page-title-main">RAR-related orphan receptor gamma</span> Cellular receptor

RAR-related orphan receptor gamma (RORγ) is a protein that in humans is encoded by the RORC gene. RORγ is a member of the nuclear receptor family of transcription factors. It is mainly expressed in immune cells and it also regulates circadian rhythms. It may be involved in the progression of certain types of cancer.

<span class="mw-page-title-main">NME2</span> Protein-coding gene in the species Homo sapiens

Nucleoside diphosphate kinase B is an enzyme that in humans is encoded by the NME2 gene.

<span class="mw-page-title-main">CGP 52608</span> Chemical compound

CGP 52608 is a selective ligand of the RAR-related orphan receptor alpha. It has been used as a biochemical tool to investigate nuclear and membrane signaling of melatonin. CGP 52608 has also been reported to possess antiarthritic activity. The pharmaceutical company Novartis brought it to clinical trials for rheumatoid arthritis, but development was discontinued in 2006.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000198963 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036192 - 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. Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G (March 1994). "Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors". Genes Dev. 8 (5): 538–53. doi: 10.1101/gad.8.5.538 . PMID   7926749.
  6. "Entrez Gene: RORB RAR-related orphan receptor B".
  7. Jabaudon D, Shnider SJ, Tischfield DJ, Galazo MJ, Macklis JD (May 2012). "RORβ induces barrel-like neuronal clusters in the developing neocortex". Cereb. Cortex. 22 (5): 996–1006. doi:10.1093/cercor/bhr182. PMC   3328343 . PMID   21799210.
  8. Carneiro, Miguel; Vieillard, Jennifer; Andrade, Pedro; Boucher, Samuel; Afonso, Sandra; Blanco-Aguiar, José A.; Santos, Nuno; Branco, João; Esteves, Pedro J.; Ferrand, Nuno; Kullander, Klas; Andersson, Leif (2021). "A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits". PLOS Genetics. 17 (3): e1009429. doi: 10.1371/journal.pgen.1009429 . PMC   7993613 . PMID   33764968.
  9. Paravicini G, Steinmayr M, André E, Becker-André M (October 1996). "The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily". Biochem. Biophys. Res. Commun. 227 (1): 82–7. doi:10.1006/bbrc.1996.1471. PMID   8858107.

Further reading