レチノイン酸受容体α

RARA
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1DKF, 1DSZ, 3A9E, 3KMR, 3KMZ, 4DQM, 5K13
識別子
記号	RARA, NR1B1, RAR, retinoic acid receptor alpha, RARalpha
外部ID	OMIM: 180240 MGI: 97856 HomoloGene: 20262 GeneCards: RARA
遺伝子の位置 (ヒト)
染色体	17番染色体 (ヒト)
終点	40,357,643 bp
遺伝子の位置 (マウス)
染色体	11番染色体 (マウス)
終点	98,865,768 bp
RNA発現パターン
	; ; ; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• retinoic acid binding; • transcription corepressor activity; • protein domain specific binding; • DNA-binding transcription factor activity; • nuclear receptor activity; • mRNA 5'-UTR binding; • 受容体結合; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • retinoic acid-responsive element binding; • 転写因子結合; • 金属イオン結合; • steroid hormone receptor activity; • 酵素結合; • zinc ion binding; • 血漿タンパク結合; • DNA結合; • sequence-specific DNA binding; • transcription coactivator activity; • protein kinase A binding; • protein kinase B binding; • translation repressor activity, mRNA regulatory element binding; • alpha-actinin binding; • protein heterodimerization activity; • chromatin DNA binding; • DNA-binding transcription factor activity, RNA polymerase II-specific; • ヒストンデアセチラーゼ結合; • transcription cis-regulatory region binding; • nuclear receptor coactivator activity; • シグナル伝達受容体活性;
細胞の構成要素	• 細胞質; • actin cytoskeleton; • perinuclear region of cytoplasm; • neuron projection; • 細胞核; • cell surface; • 核質; • soma; • 樹状突起; • 細胞質基質; • RNA polymerase II transcription regulator complex;
生物学的プロセス	• growth plate cartilage development; • germ cell development; • cellular response to retinoic acid; • ureteric bud development; • positive regulation of interleukin-5 production; • 前立腺発生; • 四肢の発生; • apoptotic cell clearance; • chondroblast differentiation; • regulation of granulocyte differentiation; • タンパク質リン酸化; • response to vitamin A; • face development; • 精子形成; • response to ethanol; • negative regulation of cell population proliferation; • steroid hormone mediated signaling pathway; • regulation of apoptotic process; • response to cytokine; • negative regulation of translation; • regulation of transcription, DNA-templated; • negative regulation of cell differentiation; • 遺伝子発現の負の調節; • transcription, DNA-templated; • cellular response to estrogen stimulus; • positive regulation of transcription, DNA-templated; • positive regulation of cell cycle; • regulation of myelination; • positive regulation of neuron differentiation; • negative regulation of tumor necrosis factor production; • transcription initiation from RNA polymerase II promoter; • 気管軟骨発生; • glandular epithelial cell development; • 男性生殖腺発生; • negative regulation of cartilage development; • response to retinoic acid; • negative regulation of granulocyte differentiation; • multicellular organism growth; • female pregnancy; • negative regulation of apoptotic process; • negative regulation of transcription by RNA polymerase II; • positive regulation of interleukin-4 production; • シナプス可塑性の制御; • outflow tract septum morphogenesis; • negative regulation of transcription, DNA-templated; • negative regulation of interferon-gamma production; • エストラジオールへの反応; • negative regulation of translational initiation; • embryonic camera-type eye development; • positive regulation of interleukin-13 production; • neural tube closure; • positive regulation of binding; • retinoic acid receptor signaling pathway; • positive regulation of gene expression; • Sertoli cell fate commitment; • positive regulation of cell population proliferation; • positive regulation of T-helper 2 cell differentiation; • ventricular cardiac muscle cell differentiation; • 肝臓発生; • cellular response to lipopolysaccharide; • 骨発生; • 海馬発生; • シグナル伝達; • positive regulation of transcription by RNA polymerase II; • 多細胞個体の発生; • hormone-mediated signaling pathway; • 細胞分化; • 脂質への反応; • 腺発生; • bone morphogenesis; • 上皮の発生;
	出典:Amigo / QuickGO
オルソログ
	5914
	19401
	ENSG00000131759
	ENSMUSG00000037992
	P10276,Q6I9R7,J3KSJ4
	P11416
	NM_000964; NM_001024809; NM_001033603; NM_001145301; NM_001145302
	NM_001176528; NM_001177302; NM_001177303; NM_009024; NM_001361954
NP_000955; NP_001019980; NP_001138773; NP_001138774; NP_000955.1;
	NP_001138773.1
	NP_001169999; NP_001170773; NP_001170774; NP_033050; NP_001348883
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

レチノイン酸受容体α（英: retinoic acid receptor alpha、略称: RARα）またはNR1B1（nuclear receptor subfamily 1, group B, member 1）は、ヒトではRARA遺伝子にコードされる核内受容体である^[5]^[6]。

RARA遺伝子は17番染色体（英語版）17q21.2に位置し、転写因子として機能する核内ホルモン受容体をコードする。レチノイン酸受容体（RAR）はRARαの他に、RARβ（英語版）、RARγ（英語版）の2種類が存在する^[7]^[8]。

機能

レチノイドシグナルは、レチノイン酸受容体（RAR）とレチノイドX受容体（英語版）（RXR）の2種類の核内受容体ファミリーからなるRXR/RARヘテロ二量体によって伝達される。リガンドが存在しない場合には、DNAに結合したRXR/RARαはコリプレッサーであるNCOR1（英語版）、NCOR2（英語版）（SMRT）、そしてヒストンデアセチラーゼをリクルートすることで転写を抑制する。リガンドが複合体に結合すると、コンフォメーション変化が生じてコアクチベーター、ヒストンアセチルトランスフェラーゼ、基本転写装置のリクルートが可能となる^[8]。RARαはビタミンA誘導体であるレチノイン酸と相互作用し、細胞成長、分化、胚発生時の器官形成に重要な役割を果たす^[8]^[9]。

臨床的意義

レチノイン酸シグナルは、初期胚発生時のいくつかのシグナル伝達経路と関係している。レチノイン酸は体軸の形成に関与しており、対称性を確立する。また、レチノイン酸はプロニューラル因子であるニューロゲニン2（英語版）（Neurog2）の発現を調節することで神経分化に影響を与える。レチノイン酸は心臓形成にも影響を与え、具体的には心房の形成に関与している。また、膵臓、腎臓、肺、四肢の発生にも関与している^[9]。

RARA遺伝子の再配置を伴う染色体転座は、急性前骨髄球性白血病（APL）の主要な特徴である。最も高頻度でみられる転座はt(15,17)(q21;q22)であり、RARA遺伝子がPML遺伝子と融合している^[10]。

相互作用

RARαは次に挙げる因子と相互作用することが示されている。

リガンド

アンタゴニスト

BMS-189453（非選択的）
YCT529（英語版） (RARα選択的)

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000131759 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037992 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Identification of a receptor for the morphogen retinoic acid”. Nature 330 (6149): 624–9. (1987). Bibcode: 1987Natur.330..624G. doi:10.1038/330624a0. PMID 2825036.
^ “High-density genetic map of the BRCA1 region of chromosome 17q12-q21”. Genomics 17 (3): 618–23. (September 1993). doi:10.1006/geno.1993.1381. PMID 8244378.
^ “Gene symbol report | HUGO Gene Nomenclature Committee”. www.genenames.org. 2021年4月27日閲覧。
^ ^a ^b ^c “OMIM Entry - * 180240 - RETINOIC ACID RECEPTOR, ALPHA; RARA”. www.omim.org. 2021年4月27日閲覧。
^ ^a ^b “Retinoic acid synthesis and functions in early embryonic development”. Cell & Bioscience 2 (1): 11. (March 2012). doi:10.1186/2045-3701-2-11. PMC 3325842. PMID 22439772.
^ “Acute promyelocytic leukemia: new issues on pathogenesis and treatment response”. The International Journal of Biochemistry & Cell Biology 39 (6): 1063–70. (2007). doi:10.1016/j.biocel.2007.01.028. PMID 17468032.
^ “Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells”. The Journal of Biological Chemistry 273 (27): 16985–92. (July 1998). doi:10.1074/jbc.273.27.16985. PMID 9642262.
^ ^a ^b “Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock”. Cell 105 (7): 877–89. (June 2001). doi:10.1016/S0092-8674(01)00401-9. PMID 11439184.
^ “Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II”. The Journal of Biological Chemistry 278 (8): 6355–62. (February 2003). doi:10.1074/jbc.M210697200. PMID 12482873.
^ “Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2”. Molecular Endocrinology 15 (2): 241–54. (February 2001). doi:10.1210/mend.15.2.0595. PMID 11158331.
^ “A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo”. The Journal of Biological Chemistry 274 (48): 34283–93. (November 1999). doi:10.1074/jbc.274.48.34283. PMID 10567404.
^ “Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator”. Proceedings of the National Academy of Sciences of the United States of America 97 (11): 6212–7. (May 2000). Bibcode: 2000PNAS...97.6212K. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961.
^ “Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein”. The Journal of Biological Chemistry 274 (22): 15901–7. (May 1999). doi:10.1074/jbc.274.22.15901. PMID 10336495.
^ “Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia”. Blood 91 (8): 2634–42. (April 1998). doi:10.1182/blood.V91.8.2634.2634_2634_2642. PMID 9531570.
^ “Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways”. Blood 99 (8): 2637–46. (April 2002). doi:10.1182/blood.V99.8.2637. PMID 11929748.
^ “SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia”. Proceedings of the National Academy of Sciences of the United States of America 94 (17): 9028–33. (August 1997). Bibcode: 1997PNAS...94.9028H. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429.
^ “Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation”. The Journal of Biological Chemistry 279 (1): 319–25. (January 2004). doi:10.1074/jbc.M307621200. PMID 14581481.
^ “Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity”. Biochemistry 42 (4): 971–9. (February 2003). doi:10.1021/bi020497k. PMID 12549917.
^ “RIP-140 interacts with multiple nuclear receptors by means of two distinct sites”. Molecular and Cellular Biology 16 (11): 6029–36. (November 1996). doi:10.1128/MCB.16.11.6029. PMC 231605. PMID 8887632.
^ “An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors”. Science 272 (5266): 1336–9. (May 1996). Bibcode: 1996Sci...272.1336S. doi:10.1126/science.272.5266.1336. PMID 8650544.
^ “Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)”. Molecular Endocrinology 12 (10): 1551–7. (October 1998). doi:10.1210/mend.12.10.0184. PMID 9773978.
^ “A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1”. Genes & Development 9 (7): 769–82. (April 1995). doi:10.1101/gad.9.7.769. PMID 7705655.
^ “A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins”. Nature Genetics 23 (3): 287–95. (November 1999). doi:10.1038/15463. PMID 10610177.
^ “Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter”. Molecular and Cellular Biology 22 (13): 4522–34. (July 2002). doi:10.1128/MCB.22.13.4522-4534.2002. PMC 133906. PMID 12052862.
^ “RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors”. The EMBO Journal 11 (4): 1409–18. (April 1992). doi:10.1002/j.1460-2075.1992.tb05186.x. PMC 556590. PMID 1314167.
^ “Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation”. Molecular and Cellular Biology 19 (9): 6323–32. (September 1999). doi:10.1128/mcb.19.9.6323. PMC 84603. PMID 10454579.
^ “Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs”. Molecular and Cellular Biology 23 (6): 2135–50. (March 2003). doi:10.1128/MCB.23.6.2135-2150.2003. PMC 149467. PMID 12612084.
^ “Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator”. The Journal of Biological Chemistry 277 (47): 45611–8. (November 2002). doi:10.1074/jbc.M208447200. PMID 12235159.
^ “PLZF is a negative regulator of retinoic acid receptor transcriptional activity”. Nuclear Receptor 1 (1): 6. (September 2003). doi:10.1186/1478-1336-1-6. PMC 212040. PMID 14521715.

レチノイン酸受容体α

目次

機能

臨床的意義

相互作用

リガンド

アンタゴニスト

出典

関連文献

関連項目