レチノイン酸受容体αとは？わかりやすく解説

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遺伝子はヒトでは17番染色体（英語版）の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（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。

BAG1（英語版）^[11]
CLOCK（英語版）^[12]
CCND3^[13]
NCOA6（英語版）^[14]^[15]^[16]
NCOR1（英語版）^[17]^[18]
NCOR2（英語版）^[19]^[20]
NPAS2（英語版）^[12]
NRIP1（英語版）^[21]^[22]^[23]
NR0B2^[24]^[25]
NR4A2（英語版）^[26]
PML^[27]
RXRA（英語版）^[28]^[29]
Src^[30]^[31]
TADA3（英語版）^[32]
ZBTB16（英語版）^[33]

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:
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^ “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.
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^ ^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.
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^ “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.
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レチノイン酸受容体αとは？わかりやすく解説