View source for Biology:V-erbA-related gene

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''V-erbA-related protein 2''' (EAR-2) also known as '''NR2F6''' (nuclear receptor subfamily 2 group F member 6) is a [[Biology:Protein|protein]] that in humans is encoded by the ''NR2F6'' [[Biology:Gene|gene]].<ref name="pmid2905047">{{cite journal | vauthors = Miyajima N, Kadowaki Y, Fukushige S, Shimizu S, Semba K, Yamanashi Y, Matsubara K, Toyoshima K, Yamamoto T | title = Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other | journal = Nucleic Acids Research | volume = 16 | issue = 23 | pages = 11057–74 | date = December 1988 | pmid = 2905047 | pmc = 338996 | doi = 10.1093/nar/16.23.11057 }}</ref> V-erbA-related protein 2 is a member of the [[Biology:Nuclear receptor|nuclear receptor]] family of [[Biology:Intracellular|intracellular]] [[Biology:Transcription factor|transcription factor]]s. It is named after its similarity to ''v-erbA'' ({{UniProt|P03373}}), a helper of an oncoprotein called ''v-erbB'' in avian erythroblastosis virus.<ref>{{cite journal |last1=Thormeyer |first1=D |last2=Baniahmad |first2=A |title=The v-erbA oncogene (review). |journal=International Journal of Molecular Medicine |date=October 1999 |volume=4 |issue=4 |pages=351–8 |pmid=10493974}}</ref>

== Function ==

Comparatively little is known about ear-2, but it has been shown to function as a [[Biology:Transcription coregulator|coregulator]] of other nuclear receptors.<ref name="pmid10713182">{{cite journal | vauthors = Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY | title = The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function | journal = Molecular and Cellular Biology | volume = 20 | issue = 7 | pages = 2604–18 | date = April 2000 | pmid = 10713182 | pmc = 85476 | doi = 10.1128/MCB.20.7.2604-2618.2000 }}</ref><ref name="pmid12690040">{{cite journal | vauthors = Liu X, Huang X, Sigmund CD | title = Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription | journal = Circulation Research | volume = 92 | issue = 9 | pages = 1033–40 | date = May 2003 | pmid = 12690040 | doi = 10.1161/01.RES.0000071355.82009.43 | doi-access = free }}</ref>

Nr2f6 knockout mice show defects in development of the locus ceruleus.<ref name="pmid15741322">{{cite journal | vauthors = Warnecke M, Oster H, Revelli JP, Alvarez-Bolado G, Eichele G | title = Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception | journal = Genes & Development | volume = 19 | issue = 5 | pages = 614–25 | date = March 2005 | pmid = 15741322 | pmc = 551581 | doi = 10.1101/gad.317905 }}</ref>

It was found that antigen receptor stimulation-induced [[Biology:NFAT|NF-AT]]/[[Biology:AP-1 transcription factor|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.<ref>Baier, G. and Hermann-Kleiter, N., Medizinische Universitat Innsbruck, (2011). [https://www.google.com/patents/US20110236427   Antagonists of NR2F6 For Augmenting The Immune Response]. U.S. Patent Application 13/004,781.</ref>

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.<ref>Ichim, C.V. and Ichim, T., (2015). [http://www.freepatentsonline.com/y2015/0299712.html  Modulation of Hematopoietic Stem Cell Differentiation]. U.S. Patent 20,150,299,712.</ref>

==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.<ref>Ichim, C. V. (2015). [http://www.freepatentsonline.com/y2015/0291964.html  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.</ref>

== Interactions ==

V-erbA-related gene has been shown to interact with:
*  [[Biology:COUP-TFII|COUP-TFII]]<ref name="pmid10318855">{{cite journal | vauthors = Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M | title = Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14331–6 | date = May 1999 | pmid = 10318855 | pmc = 2823254 | doi = 10.1074/jbc.274.20.14331 | doi-access = free }}</ref>
* [[Biology:Thyroid hormone receptor beta|Thyroid hormone receptor beta]]<ref name="pmid10713182" />

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

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Bähler M, Kehrer I, Gordon L, Stoffler HE, Olsen AS | title = Physical mapping of human myosin-IXB (MYO9B), the human orthologue of the rat myosin myr 5, to chromosome 19p13.1 | journal = Genomics | volume = 43 | issue = 1 | pages = 107–9 | date = July 1997 | pmid = 9226381 | doi = 10.1006/geno.1997.4776 }}
* {{cite journal | vauthors = Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M | title = Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14331–6 | date = May 1999 | pmid = 10318855 | pmc = 2823254 | doi = 10.1074/jbc.274.20.14331 | doi-access = free }}
* {{cite journal | vauthors = Zhang Y, Dufau ML | title = Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor | journal = The Journal of Biological Chemistry | volume = 275 | issue = 4 | pages = 2763–70 | date = January 2000 | pmid = 10644740 | doi = 10.1074/jbc.275.4.2763 | doi-access = free }}
* {{cite journal | vauthors = Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY | title = The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function | journal = Molecular and Cellular Biology | volume = 20 | issue = 7 | pages = 2604–18 | date = April 2000 | pmid = 10713182 | pmc = 85476 | doi = 10.1128/MCB.20.7.2604-2618.2000 }}
* {{cite journal | vauthors = Liu X, Huang X, Sigmund CD | title = Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription | journal = Circulation Research | volume = 92 | issue = 9 | pages = 1033–40 | date = May 2003 | pmid = 12690040 | doi = 10.1161/01.RES.0000071355.82009.43 | doi-access = free }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B | doi-access = free }}
{{refend}}

== External links ==
* {{MeshName|NR2F6+protein,+human}}

{{Transcription factors|g2}}

[[Category:Transcription factors]]


{{Sourceattribution|V-erbA-related gene}}