constitutive androstane receptor

アンドロスタン受容体、アンドロスタンレセプター

関

CAR

WordNet

1. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

1. =sense organ / 受信装置
2. =constituent1

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/15 19:49:21」(JST)

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[Wiki en表示]

Nuclear receptor subfamily 1, group I, member 3
PDB rendering based on 1xv9.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1XV9, 1XVP
Identifiers
Symbols	NR1I3; CAR; CAR1; MB67
External IDs	OMIM: 603881 MGI: 1346307 HomoloGene: 3759 IUPHAR: NR1I3 ChEMBL: 5503 GeneCards: NR1I3 Gene
Gene Ontology Molecular function • DNA binding • sequence-specific DNA binding transcription factor activity • transcription coactivator activity • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity • androgen receptor activity • thyroid hormone receptor activity • zinc ion binding • sequence-specific DNA binding • metal ion binding Cellular component • nucleus • nucleoplasm • cytoplasm • cytoskeleton Biological process • transcription initiation from RNA polymerase II promoter • signal transduction • gene expression • androgen receptor signaling pathway • intracellular receptor mediated signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9970	12355
Ensembl	ENSG00000143257	ENSMUSG00000005677
UniProt	Q14994	O35627
RefSeq (mRNA)	NM_001077469.2	NM_001243062.1
RefSeq (protein)	NP_001070937.1	NP_001229991.1
Location (UCSC)	Chr 1: 161.2 – 161.21 Mb	Chr 1: 171.21 – 171.22 Mb
PubMed search	[1]	[2]

The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with PXR functions as a sensor of endobiotic and xenobiotic substances and in response upregulates the expression of proteins responsible for the metabolism and excretion of these substances. Hence CAR (and PXR) are important in the detoxification of foreign substances such as drugs.

Function

CAR is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs.

References

Further reading

• Masuno M, Shimozawa N, Suzuki Y, et al. (1994). "Assignment of the human peroxisome assembly factor-1 gene (PXMP3) responsible for Zellweger syndrome to chromosome 8q21.1 by fluorescence in situ hybridization". Genomics 20 (1): 141–2. doi:10.1006/geno.1994.1144. PMID 8020947.
• Choi HS, Seol W, Moore DD (1996). "A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily". J. Steroid Biochem. Mol. Biol. 56 (1–6 Spec No): 23–30. doi:10.1016/0960-0760(95)00220-0. PMID 8603043.
• Seol W, Choi HS, Moore DD (1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science 272 (5266): 1336–9. doi:10.1126/science.272.5266.1336. PMID 8650544.
• Choi HS, Chung M, Tzameli I, et al. (1997). "Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR". J. Biol. Chem. 272 (38): 23565–71. doi:10.1074/jbc.272.38.23565. PMID 9295294.
• Seol W, Hanstein B, Brown M, Moore DD (1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978.
• Forman BM, Tzameli I, Choi HS, et al. (1998). "Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta". Nature 395 (6702): 612–5. doi:10.1038/26996. PMID 9783588.
• Gonzalez MM, Carlberg C (2002). "Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors". J. Biol. Chem. 277 (21): 18501–9. doi:10.1074/jbc.M200205200. PMID 11891224.
• Min G, Kim H, Bae Y, et al. (2002). "Inhibitory cross-talk between estrogen receptor (ER) and constitutively activated androstane receptor (CAR). CAR inhibits ER-mediated signaling pathway by squelching p160 coactivators". J. Biol. Chem. 277 (37): 34626–33. doi:10.1074/jbc.M205239200. PMID 12114525.
• Goodwin B, Hodgson E, D'Costa DJ, et al. (2002). "Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor". Mol. Pharmacol. 62 (2): 359–65. doi:10.1124/mol.62.2.359. PMID 12130689.
• Ferguson SS, LeCluyse EL, Negishi M, Goldstein JA (2002). "Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site". Mol. Pharmacol. 62 (3): 737–46. doi:10.1124/mol.62.3.737. PMID 12181452.
• Zhang J, Huang W, Chua SS, et al. (2002). "Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR". Science 298 (5592): 422–4. doi:10.1126/science.1073502. PMID 12376703.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/.
• Chang TK, Bandiera SM, Chen J (2003). "Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels". Drug Metab. Dispos. 31 (1): 7–10. doi:10.1124/dmd.31.1.7. PMID 12485946.
• Pascussi JM, Busson-Le Coniat M, Maurel P, Vilarem MJ (2003). "Transcriptional analysis of the orphan nuclear receptor constitutive androstane receptor (NR1I3) gene promoter: identification of a distal glucocorticoid response element". Mol. Endocrinol. 17 (1): 42–55. doi:10.1210/me.2002-0244. PMID 12511605.
• Shiraki T, Sakai N, Kanaya E, Jingami H (2003). "Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha. A possible link between xenobiotic response and nutritional state". J. Biol. Chem. 278 (13): 11344–50. doi:10.1074/jbc.M212859200. PMID 12551939.
• Maglich JM, Parks DJ, Moore LB, et al. (2003). "Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes". J. Biol. Chem. 278 (19): 17277–83. doi:10.1074/jbc.M300138200. PMID 12611900.
• Xie W, Yeuh MF, Radominska-Pandya A, et al. (2003). "Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 4150–5. doi:10.1073/pnas.0438010100. PMC 153063. PMID 12644700. //www.ncbi.nlm.nih.gov/pmc/articles/PMC153063/.
• Huang W, Zhang J, Chua SS, et al. (2003). "Induction of bilirubin clearance by the constitutive androstane receptor (CAR)". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 4156–61. doi:10.1073/pnas.0630614100. PMC 153064. PMID 12644704. //www.ncbi.nlm.nih.gov/pmc/articles/PMC153064/.
• Auerbach SS, Ramsden R, Stoner MA, et al. (2003). "Alternatively spliced isoforms of the human constitutive androstane receptor". Nucleic Acids Res. 31 (12): 3194–207. doi:10.1093/nar/gkg419. PMC 162252. PMID 12799447. //www.ncbi.nlm.nih.gov/pmc/articles/PMC162252/.

External links

• constitutive+androstane+receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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English Journal

• Coordinated roles of pregnane x receptor and constitutive androstane receptor in autoinduction of voriconazole metabolism in mice.

• Ohbuchi M, Yoshinari K, Kaneko H, Matsumoto S, Inoue A, Kawamura A, Usui T, Yamazoe Y.SourceDivision of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Science, Tohoku University, Miyagi, Japan.
• Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Mar;57(3):1332-8. doi: 10.1128/AAC.01900-12. Epub 2012 Dec 28.
• The antifungal efficacy of voriconazole (VRC) differs among host species, with potent efficacy in humans but less in rodents. We investigated the possible involvement of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in the species-specific efficacy of VRC through pharmacokinet
• PMID 23274663

• Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond.

• Chai X, Zeng S, Xie W.SourceZhejiang University, College of Pharmaceutical Sciences, Department of Pharmaceutical Analysis and Drug Metabolism , Hangzhou 310058 , China.
• Expert opinion on drug metabolism & toxicology.Expert Opin Drug Metab Toxicol.2013 Mar;9(3):253-66. doi: 10.1517/17425255.2013.754010. Epub 2013 Jan 17.
• Introduction: 'Orphan' nuclear receptors belong to the nuclear receptor (NR) superfamily of transcriptional factors. Binding of ligands to these receptors results in the recruitment of the co-activators, thereby regulating the expression of cognate target genes. Areas covered: This review disc
• PMID 23327618

• Expression of Human CAR Splicing Variants in BAC-Transgenic Mice.

• Zhang YK, Lu H, Klaassen CD.SourceDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160.
• Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2013 Mar;132(1):142-50. doi: 10.1093/toxsci/kfs321. Epub 2012 Nov 14.
• The nuclear receptor constitutive androstane receptor (CAR) is a key regulator for drug metabolism in liver. Human CAR (hCAR) transcripts are subjected to alternative splicing. Some hCAR splicing variants (SVs) have been shown to encode functional proteins by reporter assays. However, in vivo resear
• PMID 23152187

Japanese Journal

• Dehydroepiandrosterone sulfate and cytochrome P450 inducers alleviate fatty liver in male rats fed an orotic acid-supplemented diet

• Takeuchi Kenji,Goto Hirohiko,Ito Yuko [他],Sato Makoto,Matsumoto Satoshi,Senba Tadashi,Yamada Hideyuki,Umehara Ken
• The Journal of Toxicological Sciences 40(2), 181-191, 2015
• The effects of the peroxisome proliferator, dehydroepiandrosterone sulfate (DHEAS), and the typical cytochrome P450 (CYP) inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on fatty liver wer …
• NAID 130004904035

• P1-15-1 卵巣癌に対するConstitutive androstane receptorを介した抗癌剤効果増強,耐性克服に向けての新たな治療戦略(Group 15 卵巣腫瘍・基礎2,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

• 増山 寿,Wan Yang,延本 悦子,平松 祐司
• 日本産科婦人科學會雜誌 66(2), 509, 2014-02-01
• NAID 110009811748

• Roles of Xenobiotic Receptors in Vascular Pathophysiology

• Xiao Lei,Zhang Zihui,Luo Xiaoqin
• Circulation Journal 78(7), 1520-1530, 2014
• … The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. …
• NAID 130004926969

Related Links

• 核内レセプターconstitutive androstane receptor (CAR)の発現 ...

6 緒言 Constitutive androstane receptor (CAR; NR1I3)は核内レセプタースーパー ファミリーに属する転写因子であり、肝に多く発現している[1]。CARは細胞内 において主に細胞質に存在し、シャペロンタンパクであるheat shock protein 90 ...

• Constitutive Androstane Receptor

Academia.edu is a place to share and follow research. ... The constitutive androstane receptor (CAR; NR1I3) has emerged as one of the main drug- and xenobiotic-sensitive transcriptional regulators. It has a major effect on the ...

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リンク元	「アンドロスタン受容体」「アンドロスタンレセプター」
関連記事	「constitutive」

「アンドロスタン受容体」

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英

constitutive androstane receptor、CAR

関

コクサッキーウイルス・アデノウイルス受容体、アンドロスタンレセプター

「アンドロスタンレセプター」

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英

constitutive androstane receptor

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アンドロスタン受容体

「constitutive」

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構成的な、恒常的な、常時の、構成型の、常在型の、常時存在の、常時発現の

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constitutively