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{{short description|Type of protein}}
{{short description|Type of protein}}
{{cs1 config|name-list-style=vanc}}
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{{infobox protein | Name = [[Rev-ErbA alpha|nuclear receptor subfamily 1, group D, member 1]] | caption = | image = | width = | HGNCid = 7962 | Symbol = [[NR1D1]] | AltSymbols = ear-1, hRev, Rev-ErbAalpha, THRA1 | EntrezGene = 9572 | OMIM = 602408 | RefSeq = NM_021724 | UniProt = P20393 | PDB = | ECnumber = | Chromosome = 17 | Arm = q | Band = 11.2 | LocusSupplementaryData = }}
[[File:Model_of_REV-ERB-mediated_Circadian_Gene_Expression.png|thumb|400x400px|Diagram showing how REV-ERB regulates circadian gene expression through the secondary loop of the circadian transcription/translation feedback loop (TTFL)]]
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{{infobox protein|Name = [[Rev-ErbA alpha|nuclear receptor subfamily 1, group D, member 1]]|caption =|image =|width =|HGNCid = 7962|Symbol = [[NR1D1]]|AltSymbols = ear-1, hRev, Rev-ErbAalpha, THRA1|EntrezGene = 9572|OMIM = 602408|RefSeq = NM_021724|UniProt = P20393|PDB =|ECnumber =|Chromosome = 17|Arm = q|Band = 11.2|LocusSupplementaryData = }}


{{infobox protein | Name = [[Rev-ErbA beta|nuclear receptor subfamily 1, group D, member 2]] | caption = | image = | width = | HGNCid = 7963 | Symbol = [[NR1D2]] | AltSymbols = BD73, RVR, EAR-1r, HZF2, Hs.37288 | EntrezGene = 9975 | OMIM = 602304 | RefSeq = XM_001130839 | UniProt = Q14995 | PDB = | ECnumber = | Chromosome = 3 | Arm = p | Band = 24.1 | LocusSupplementaryData = }}
{{infobox protein|Name = [[Rev-ErbA beta|nuclear receptor subfamily 1, group D, member 2]]|caption =|image =|width =|HGNCid = 7963|Symbol = [[NR1D2]]|AltSymbols = BD73, RVR, EAR-1r, HZF2, Hs.37288|EntrezGene = 9975|OMIM = 602304|RefSeq = XM_001130839|UniProt = Q14995|PDB =|ECnumber =|Chromosome = 3|Arm = p|Band = 24.1|LocusSupplementaryData = }}


The '''Rev-ErbA''' proteins are members of the [[nuclear receptor]] family of [[intracellular]] [[transcription factor]]s. There are two forms of the receptor, '''[[Rev-ErbA alpha|alpha]]''' and '''[[Rev-ErbA beta|beta]]''', each encoded by a separate gene ({{gene|NR1D1}} and {{gene|NR1D2}} respectively).<ref name="pmid1971514"/><ref name="pmid7997240">{{cite journal | vauthors = Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD | title = A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb | journal = Mol. Endocrinol. | volume = 8 | issue = 8 | pages = 996–1005 | year = 1994 | pmid = 7997240 | doi = 10.1210/me.8.8.996 }}</ref>
The '''Rev-Erb proteins''' are members of the [[Nuclear receptor|nuclear receptor (NR)]] superfamily of [[Transcription factor|intracellular transcription factors]] and key regulatory components of the [[circadian clock]]. There are two forms of the receptor, [[Rev-ErbA alpha|Rev-Erb alpha]] and [[Rev-ErbA beta|Rev-Erb beta]], which are each encoded by a separate gene (''NR1D1'' and ''NR1D2'', respectively).<ref>{{cite journal | vauthors = Lazar MA, Jones KE, Chin WW | title = 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 | journal = DNA and Cell Biology | volume = 9 | issue = 2 | pages = 77–83 | date = March 1990 | pmid = 1971514 | doi = 10.1089/dna.1990.9.77 }}</ref><ref>{{cite journal | vauthors = Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, Moore DD | title = A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb | journal = Molecular Endocrinology | volume = 8 | issue = 8 | pages = 996–1005 | date = August 1994 | pmid = 7997240 | doi = 10.1210/mend.8.8.7997240 | doi-access = free }}</ref>  


These proteins act as key regulators of [[Circadian clock|clock gene]] expression through [[Transcription (biology)|transcriptional]] repression of [[BMAL1|Bmal1]]. Through their regulation of clock-controlled genes, the Rev-Erb proteins affect several physiological processes throughout the body, including [[Metabolism|metabolic]], [[Endocrine system|endocrine]], and [[Immune system|immune]] pathways.<ref>{{cite journal | vauthors = Scheiermann C, Kunisaki Y, Frenette PS | title = Circadian control of the immune system | journal = Nature Reviews. Immunology | volume = 13 | issue = 3 | pages = 190–8 | date = March 2013 | pmid = 23391992 | pmc = 4090048 | doi = 10.1038/nri3386 }}</ref><ref>{{cite journal | vauthors = Duez H, Staels B | title = Rev-erb-alpha: an integrator of circadian rhythms and metabolism | journal = Journal of Applied Physiology | volume = 107 | issue = 6 | pages = 1972–80 | date = December 2009 | pmid = 19696364 | pmc = 2966474 | doi = 10.1152/japplphysiol.00570.2009 }}</ref><ref>{{cite journal | vauthors = Wang S, Li F, Lin Y, Wu B | title = Targeting REV-ERBα for therapeutic purposes: promises and challenges | journal = Theranostics | volume = 10 | issue = 9 | pages = 4168–4182 | date = 2020 | pmid = 32226546 | pmc = 7086371 | doi = 10.7150/thno.43834 }}</ref>
The rev-Erb-α gene is highly unusual in that it is encoded on the opposite strand of the alpha-[[thyroid hormone receptor]] (TR) gene.<ref name="pmid1971514">{{cite journal | vauthors = Lazar MA, Jones KE, Chin WW | title = 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 | journal = DNA Cell Biol. | volume = 9 | issue = 2 | pages = 77–83 | year = 1990 | pmid = 1971514 | doi = 10.1089/dna.1990.9.77 }}</ref>


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.<ref>PMID 25066191</ref>
The rev-Erb-α protein is a key regulatory component of the circadian clock.<ref name="pmid16484495">{{cite journal | vauthors = Yin L, Wang J, Klein PS, Lazar MA | title = Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock | journal = Science | volume = 311 | issue = 5763 | pages = 1002–5 | year = 2006 | pmid = 16484495 | doi = 10.1126/science.1121613 | s2cid = 11240826 }}</ref><ref name="pmid16968709">{{cite journal | vauthors = Wang J, Yin L, Lazar MA | title = The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1 | journal = J. Biol. Chem. | volume = 281 | issue = 45 | pages = 33842–8 | year = 2006 | pmid = 16968709 | doi = 10.1074/jbc.M607873200 | doi-access = free }}</ref> In addition, rev-Erb-α appears also to regulate the breakdown of [[cartilage]].<ref name="pmid17075855">{{cite journal | vauthors = Chaturvedi P, Pratta M, Steplewski K, Connor J, Kumar S | title = Functional characterization of an orphan nuclear receptor, Rev-ErbAalpha, in chondrocytes and its potential role in osteoarthritis | journal = Arthritis Rheum. | volume = 54 | issue = 11 | pages = 3513–22 | year = 2006 | pmid = 17075855 | doi = 10.1002/art.22170 | doi-access = free }}</ref>
==Ligands==
*[[SR9009]] (aka [[Stenabolic]]) is listed as an agonist


The receptors are potential drug targets for [[non-alcoholic steatohepatitis]].<ref>{{cite journal |last1=Griffett |first1=Kristine |last2=Hayes |first2=Matthew E. |last3=Boeckman |first3=Michael P. |last4=Burris |first4=Thomas P. |title=The role of REV-ERB in NASH |journal=Acta Pharmacologica Sinica |date=May 2022 |volume=43 |issue=5 |pages=1133–1140 |doi=10.1038/s41401-022-00883-w |pmid=35217816 |pmc=9061770 |language=en |issn=1745-7254|doi-access=free }}</ref>
*[[SR9011]] is listed as an agonist

== See also ==

* [[Rev-ErbA alpha|Rev-Erbɑ]]
* [[Rev-ErbA beta|Rev-Erbβ]]
* [[Nuclear receptor|Nuclear Receptors]]
* [[Transcription factor|Transcription Factors]]
* [[Circadian clock|Circadian Clock]]


== References ==
== References ==
{{Reflist|2}}
{{Reflist|2}}


==External links==
== External links ==
* {{MeshName|HZF-2alpha}}
* {{MeshName|HZF-2alpha}}
* {{MeshName|HZF-2beta}}
* {{MeshName|HZF-2beta}}
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[[Category:Nuclear receptors|1]]
[[Category:Nuclear receptors|1]]



{{gene-17-stub}}
{{gene-17-stub}}

Latest revision as of 09:06, 4 January 2024

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
SymbolNR1D1
Alt. symbolsear-1, hRev, Rev-ErbAalpha, THRA1
NCBI gene9572
HGNC7962
OMIM602408
RefSeqNM_021724
UniProtP20393
Other data
LocusChr. 17 q11.2
Search for
StructuresSwiss-model
DomainsInterPro
nuclear receptor subfamily 1, group D, member 2
Identifiers
SymbolNR1D2
Alt. symbolsBD73, RVR, EAR-1r, HZF2, Hs.37288
NCBI gene9975
HGNC7963
OMIM602304
RefSeqXM_001130839
UniProtQ14995
Other data
LocusChr. 3 p24.1
Search for
StructuresSwiss-model
DomainsInterPro

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]  

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]

The receptors are potential drug targets for non-alcoholic steatohepatitis.[7]

See also

[edit]

References

[edit]
  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
  7. ^ Griffett K, Hayes ME, Boeckman MP, Burris TP (May 2022). "The role of REV-ERB in NASH". Acta Pharmacologica Sinica. 43 (5): 1133–1140. doi:10.1038/s41401-022-00883-w. ISSN 1745-7254. PMC 9061770. PMID 35217816.
[edit]
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