Rev-Erb

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Diagram showing how REV-ERB regulates circadian gene expression through the secondary loop of the circadian transcription/translation feedback loop (TTFL) Model of REV-ERB-mediated Circadian Gene Expression.png
Diagram showing how REV-ERB regulates circadian gene expression through the secondary loop of the circadian transcription/translation feedback loop (TTFL)
nuclear receptor subfamily 1, group D, member 1
Identifiers
Symbol NR1D1
Alt. symbolsear-1, hRev, Rev-ErbAalpha, THRA1
NCBI gene 9572
HGNC 7962
OMIM 602408
RefSeq NM_021724
UniProt P20393
Other data
Locus Chr. 17 q11.2
nuclear receptor subfamily 1, group D, member 2
Identifiers
Symbol NR1D2
Alt. symbolsBD73, RVR, EAR-1r, HZF2, Hs.37288
NCBI gene 9975
HGNC 7963
OMIM 602304
RefSeq XM_001130839
UniProt Q14995
Other data
Locus Chr. 3 p24.1

The Rev-Erb proteins are members of the nuclear receptor (NR) superfamily of intracellular transcription factors and key regulatory components of the circadian clock. There are two forms of the receptor, Rev-Erb alpha and Rev-Erb beta, which are each encoded by a separate gene (NR1D1 and NR1D2, respectively). [1] [2]  

Contents

These proteins act as key regulators of clock gene expression through transcriptional repression of Bmal1. Through their regulation of clock-controlled genes, the Rev-Erb proteins affect several physiological processes throughout the body, including metabolic, endocrine, and immune pathways. [3] [4] [5]

In the NRNC classification scheme, Rev-Erb is nuclear receptor subfamily 1 group D (NR1D). The name "Rev-Erb" derived by truncation from "Rev-ERBA" (Rev-Erbα), which in turn was named because it was on the opposite strand of ERBA (THRA) oncogene. The paralogous Rev-Erbβ does not seem to have anything special on its reverse strand. Older sources may use "Rev-ERBA" as the family name. [6]

See also

Related Research Articles

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A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response.

Nuclear receptor Protein

In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, cholesterol, and vitamins. 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 co-repressor 1

The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.

Nuclear receptor co-repressor 2

The nuclear receptor co-repressor 2 (NCOR2) is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T3 receptor-associating cofactor 1 (TRAC-1).

Nuclear receptor 4A1 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.

Small heterodimer partner 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.

V-erbA-related gene Protein-coding gene in the species Homo sapiens

V-erbA-related protein 2 (EAR-2) also known as NR2F6 is a protein that in humans is encoded by the NR2F6 gene. V-erbA-related protein 2 is a member of the nuclear receptor family of intracellular transcription factors. It is named after its similarity to v-erbA, a helper of an oncoprotein called v-erbB in avian erythroblastosis virus.

Rev-ErbA alpha 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.

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.

Rev-ErbA beta 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.

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.

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.

COUP-TFI Protein-coding gene in the species Homo sapiens

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.

Thyroid hormone receptor alpha Protein-coding gene in the species Homo sapiens

Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.

Thyroid hormone receptor beta Protein-coding gene in the species Homo sapiens

Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the THRB gene.

RAR-related orphan receptor gamma 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.

Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes.

ARNTL Protein-coding gene in the species Homo sapiens

Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the ARNTL gene, also known as BMAL1, MOP3, and, less commonly, bHLHe5, BMAL, BMAL1C, JAP3, PASD3, and TIC.

References

  1. ↑ Lazar MA, Jones KE, Chin WW (March 1990). "Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone". DNA and Cell Biology. 9 (2): 77–83. doi:10.1089/dna.1990.9.77. PMID   1971514.
  2. ↑ Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD (August 1994). "A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb". Molecular Endocrinology. 8 (8): 996–1005. doi: 10.1210/mend.8.8.7997240 . PMID   7997240.
  3. ↑ Scheiermann C, Kunisaki Y, Frenette PS (March 2013). "Circadian control of the immune system". Nature Reviews. Immunology. 13 (3): 190–8. doi:10.1038/nri3386. PMC   4090048 . PMID   23391992.
  4. ↑ Duez H, Staels B (December 2009). "Rev-erb-alpha: an integrator of circadian rhythms and metabolism". Journal of Applied Physiology. 107 (6): 1972–80. doi:10.1152/japplphysiol.00570.2009. PMC   2966474 . PMID   19696364.
  5. ↑ Wang S, Li F, Lin Y, Wu B (2020). "Targeting REV-ERBα for therapeutic purposes: promises and challenges". Theranostics. 10 (9): 4168–4182. doi:10.7150/thno.43834. PMC   7086371 . PMID   32226546.
  6. ↑ PMID 25066191
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