country

Change Language

EN - English
FR - Français
DE - Deutsch
ES - Español
JA - 日本語
KO - 한국어

Country or Region:

United States

Product Name	Size / Unit Price	Qty

Total: USD 0.00 Checkout

Nuclear receptor ROR-alpha

Definition:

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development. Regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC1 and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.

References:

[1]. G B Atkins, et al. Coactivators for the orphan nuclear receptor RORalpha. Mol Endocrinol. 1999 Sep;13(9):1550-7. [Content Brief]

[2]. Y Zhu, et al. RORA, a large common fragile site gene, is involved in cellular stress response. Oncogene. 2006 May 11;25(20):2901-8. [Content Brief]

[3]. Laura A Solt, et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature. 2011 Apr 28;472(7344):491-4. [Content Brief]

[4]. P Delerive, et al. The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response. EMBO Rep. 2001 Jan;2(1):42-8. [Content Brief]

[5]. Ulrika Lind, et al. Identification of the human ApoAV gene as a novel RORalpha target gene. Biochem Biophys Res Commun. 2005 Apr 29;330(1):233-41. [Content Brief]

[6]. Jianguang Du, et al. Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3. J Immunol. 2008 Apr 1;180(7):4785-92. [Content Brief]

[7]. Adriane Lechtken, et al. Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro. Biochem Biophys Res Commun. 2007 Jul 6;358(3):890-6. [Content Brief]

[8]. Eun-Jin Kim, et al. Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling. Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1796-802. [Content Brief]

[9]. E Raspé, et al. Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha. J Biol Chem. 2001 Jan 26;276(4):2865-71. [Content Brief]

[10]. Anna N Moraitis, et al. The co-repressor hairless protects RORalpha orphan nuclear receptor from proteasome-mediated degradation. J Biol Chem. 2003 Dec 26;278(52):52511-8. [Content Brief]

[11]. Annelise Genoux, et al. Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalpha. Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1186-92. [Content Brief]

[12]. Eric Duplus, et al. Phosphorylation and transcriptional activity regulation of retinoid-related orphan receptor alpha 1 by protein kinases C. J Neurochem. 2008 Mar;104(5):1321-32. [Content Brief]

[13]. H P Harding, et al. Transcriptional activation and repression by RORalpha, an orphan nuclear receptor required for cerebellar development. Mol Endocrinol. 1997 Oct;11(11):1737-46. [Content Brief]

[14]. Yongjun Wang, et al. Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands. J Biol Chem. 2010 Feb 12;285(7):5013-25. [Content Brief]

[15]. V Giguère, et al. Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev. 1994 Mar 1;8(5):538-53. [Content Brief]

[16]. P Lau, et al. Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD. Nucleic Acids Res. 1999 Jan 15;27(2):411-20. [Content Brief]

[17]. Claire Guissart, et al. Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia. Am J Hum Genet. 2018 May 3;102(5):744-759. [Content Brief]

[18]. Joerg A Kallen, et al. X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Structure. 2002 Dec;10(12):1697-707. [Content Brief]

[19]. H Sundvold, et al. Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor RORalpha1. Biochem Biophys Res Commun. 2001 Sep 21;287(2):383-90. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #