V-erbA-related gene

NR2F6
Identifiers
Aliases	NR2F6, EAR-2, EAR2, ERBAL2, nuclear receptor subfamily 2 group F member 6
External IDs	OMIM: 132880 MGI: 1352453 HomoloGene: 7706 GeneCards: NR2F6
Gene location (Human)
Chr.	Chromosome 19 (human)[1]
End	17,245,919 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	71,834,604 bp[2]
RNA expression pattern
	Top expressed in
	parotid gland; ; jejunal mucosa; ; palpebral conjunctiva; ; right lobe of liver; ; corpus epididymis; ; triceps brachii muscle; ; pylorus; ; epithelium of esophagus; ; placenta; ; duodenum;
	Top expressed in
	Paneth cell; ; proximal tubule; ; left lobe of liver; ; internal carotid artery; ; external carotid artery; ; cumulus cell; ; somite; ; ascending aorta; ; duodenum; ; renal corpuscle;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	metal ion binding; DNA-binding transcription repressor activity, RNA polymerase II-specific; sequence-specific DNA binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; zinc ion binding; nuclear receptor activity; DNA-binding transcription factor activity; DNA binding; protein binding; steroid hormone receptor activity; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	nucleoplasm; nucleus;
Biological process	transcription, DNA-templated; signal transduction; detection of temperature stimulus involved in sensory perception of pain; entrainment of circadian clock by photoperiod; negative regulation of transcription by RNA polymerase II; steroid hormone mediated signaling pathway; transcription initiation from RNA polymerase II promoter; neuron development; regulation of transcription, DNA-templated; intracellular receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	2063
	13864
	ENSG00000160113
	ENSMUSG00000002393
	P10588
	P43136
	NM_005234
	NM_010150
	NP_005225; NP_005225.2
	NP_034280
	Wikidata
View/Edit Human	View/Edit Mouse

V-erbA-related protein 2 (EAR-2) also known as NR2F6 (nuclear receptor subfamily 2 group F member 6) is a protein that in humans is encoded by the NR2F6 gene.[5] 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 (P03373), a helper of an oncoprotein called v-erbB in avian erythroblastosis virus.[6]

Function

Comparatively little is known about ear-2, but it has been shown to function as a coregulator of other nuclear receptors.[7][8]

Nr2f6 knockout mice show defects in development of the locus ceruleus.[9]

It was found that antigen receptor stimulation-induced NF-AT/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.[10]

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.[11]

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.[12]

Interactions

V-erbA-related gene has been shown to interact with:

References

GRCh38: Ensembl release 89: ENSG00000160113 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000002393 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Miyajima N, Kadowaki Y, Fukushige S, Shimizu S, Semba K, Yamanashi Y, Matsubara K, Toyoshima K, Yamamoto T (December 1988). "Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other". Nucleic Acids Research. 16 (23): 11057–74. doi:10.1093/nar/16.23.11057. PMC 338996. PMID 2905047.
Thormeyer, D; Baniahmad, A (October 1999). "The v-erbA oncogene (review)". International Journal of Molecular Medicine. 4 (4): 351–8. PMID 10493974.
Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY (April 2000). "The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function". Molecular and Cellular Biology. 20 (7): 2604–18. doi:10.1128/MCB.20.7.2604-2618.2000. PMC 85476. PMID 10713182.
Liu X, Huang X, Sigmund CD (May 2003). "Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription". Circulation Research. 92 (9): 1033–40. doi:10.1161/01.RES.0000071355.82009.43. PMID 12690040.
Warnecke M, Oster H, Revelli JP, Alvarez-Bolado G, Eichele G (March 2005). "Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception". Genes & Development. 19 (5): 614–25. doi:10.1101/gad.317905. PMC 551581. PMID 15741322.
Baier, G. and Hermann-Kleiter, N., Medizinische Universitat Innsbruck, (2011). Antagonists of NR2F6 For Augmenting The Immune Response. U.S. Patent Application 13/004,781.
Ichim, C.V. and Ichim, T., (2015). Modulation of Hematopoietic Stem Cell Differentiation. U.S. Patent 20,150,299,712.
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.
Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M (May 1999). "Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2". The Journal of Biological Chemistry. 274 (20): 14331–6. doi:10.1074/jbc.274.20.14331. PMC 2823254. PMID 10318855.

External links

NR2F6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160113 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002393 - 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.

[pmid2905047-5] Miyajima N, Kadowaki Y, Fukushige S, Shimizu S, Semba K, Yamanashi Y, Matsubara K, Toyoshima K, Yamamoto T (December 1988). "Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other". Nucleic Acids Research. 16 (23): 11057–74. doi:10.1093/nar/16.23.11057. PMC 338996. PMID 2905047.

[6] Thormeyer, D; Baniahmad, A (October 1999). "The v-erbA oncogene (review)". International Journal of Molecular Medicine. 4 (4): 351–8. PMID 10493974.

[pmid10713182-7] Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY (April 2000). "The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function". Molecular and Cellular Biology. 20 (7): 2604–18. doi:10.1128/MCB.20.7.2604-2618.2000. PMC 85476. PMID 10713182.

[pmid12690040-8] Liu X, Huang X, Sigmund CD (May 2003). "Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription". Circulation Research. 92 (9): 1033–40. doi:10.1161/01.RES.0000071355.82009.43. PMID 12690040.

[pmid15741322-9] Warnecke M, Oster H, Revelli JP, Alvarez-Bolado G, Eichele G (March 2005). "Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception". Genes & Development. 19 (5): 614–25. doi:10.1101/gad.317905. PMC 551581. PMID 15741322.

[10] Baier, G. and Hermann-Kleiter, N., Medizinische Universitat Innsbruck, (2011). Antagonists of NR2F6 For Augmenting The Immune Response. U.S. Patent Application 13/004,781.

[11] Ichim, C.V. and Ichim, T., (2015). Modulation of Hematopoietic Stem Cell Differentiation. U.S. Patent 20,150,299,712.

[12] 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.

[pmid10318855-13] Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M (May 1999). "Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2". The Journal of Biological Chemistry. 274 (20): 14331–6. doi:10.1074/jbc.274.20.14331. PMC 2823254. PMID 10318855.