V-erbA-related protein 2 (EAR-2) also known as NR2F6 (nuclear receptor subfamily 2 group F member 6) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''NR2F6''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
V-erbA-related protein 2 is a member of the
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
family of
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s. It is named after its similarity to ''v-erbA'' (), a helper of an oncoprotein called ''v-erbB'' in
avian erythroblastosis virus
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*Avian (given name) (russian: Авиа́н, link=no), a male forename
Aviation
*Avro Avian, a series of light aircraft made by Avro in the 1920s and 1930s
*Avian Limited, a hang glider manufacture ...
.
Function
Comparatively little is known about ear-2, but it has been shown to function as a
coregulator of other nuclear receptors.
Nr2f6
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
show defects in development of the
locus ceruleus
The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.
The locus coeru ...
.
It was found that antigen receptor stimulation-induced
NF-AT
Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ...
/
AP-1 activity is regulated through the nuclear receptor NR2F6 (NR2F6 acts as a direct repressor of NF-AT/AP-1 transactivation) and that by preventing NR2F6 function, transcriptional activation of NF-AT/AP-1 is enhanced in immune cells which leads to an augmented immune response.
NR2F6 impairs the formation of mature red blood cells in animals that over-express NR2F6 in their bone marrow. Mice that over expression of NR2F6 in their bone marrow cells have a block at the pro-erythroblast stage of blood cell development both in the bone marrow and in the spleen of animals that have excessive expression of NR2F6. So, when inhibition of differentiation of stem cell is desired, inhibition of differentiation is achieved through induction of increased NR2F6 activity. In situations where differentiation of stem cells into a cell of increased maturity is desired, inhibition of NR2F6 activity must be performed.
Clinical significance
It was found that expression of NR2F6 was consistently upregulated in neoplastic tissues in leukemic, ovarian cancer and endometrial cancer as compared to non-malignant tissues, while the silencing of NR2F6 induces a reduction of cancer cell proliferation, inhibiting clonogenicity and self-renewal of proliferating cancer cells, and induces differentiation.
[Ichim, C. V. (2015)]
Methods and Compositions for treatment of cancer by inhibition of NR2F6
U.S. Patent No. 20,150,291,964. Washington, DC: U.S. Patent and Trademark Office.
Interactions
V-erbA-related gene has been shown to
interact
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with:
*
COUP-TFII
COUP-TFII (COUP transcription factor 2), also known as NR2F2 (nuclear receptor subfamily 2, group F, member 2) is a protein that in humans is encoded by the ''NR2F2'' gene. The COUP acronym stands for chicken ovalbumin upstream promoter.
Functio ...
*
Thyroid hormone receptor beta
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.
Function
The protein encoded by this gene is a nuclear ...
References
Further reading
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External links
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Intracellular receptors
Transcription factors
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