Affinage

NR1I3

Nuclear receptor subfamily 1 group I member 3 · UniProt Q14994

Length
352 aa
Mass
39.9 kDa
Annotated
2026-06-10
35 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR1I3 (CAR) is a xenobiotic- and metabolite-sensing nuclear receptor that controls hepatic drug metabolism, lipid handling, and hepatocyte proliferation through ligand- and phosphorylation-gated transcriptional activity (PMID:19858220, PMID:38519460). In the basal state CAR is held inactive in the cytoplasm by protein kinase C phosphorylation of Thr38, which destabilizes the first zinc-finger helix and blocks DNA binding; dephosphorylation of this residue (triggered by activators such as phenobarbital) is required for nuclear translocation (PMID:19858220), and activated ERK1/2 binds phospho-CAR to repress Thr38 dephosphorylation, sustaining the inactive cytoplasmic pool (PMID:21873423). Once nuclear, CAR heterodimerizes with RXRα, binds enhancers genome-wide, and deposits H4K5 acetylation at activated genes, while repressing metabolic targets by competing for shared enhancers occupied by HNF4α, PPARα, or FXR (PMID:30396153); coactivator (SRC-1) recruitment drives transactivation and is opposed by the corepressor DAX-1, which directly binds CAR and blocks the CAR–SRC1 interaction (PMID:16099843, PMID:22896671). Beyond canonical xenobiotic targets, CAR directly transactivates the lipogenic gene THRSP through a DR-4 element (PMID:20185760) and the ribonucleotide reductase subunit RRM2 to drive de novo dNTP synthesis and hepatocyte ploidy [PMID:bio_10.1101_2025.04.29.651109], suppresses PPARα-driven fatty acid oxidation to control triglyceride levels (PMID:18941143), and is required for hepatic injury/regeneration responses including oval cell proliferation (PMID:21826054) and STAT3-dependent liver growth (PMID:35305226). CAR expression is itself transcriptionally induced by the glucocorticoid receptor via a promoter GRE (PMID:12511605) and by PPARα via a DR1 element (PMID:18023279), and is post-transcriptionally repressed by miR-214-3p targeting its 3'-UTR (PMID:39263307). Endogenous agonists include gut-microbiota-derived diindoles and tryptophan metabolites that activate both rodent and human CAR (PMID:38519460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established that CAR is not a fixed-expression receptor but a transcriptional target itself, placing it downstream of glucocorticoid signaling.

    Evidence Promoter deletion, EMSA, and ChIP showing GR binding to a distal GRE in hepatocytes

    PMID:12511605

    Open questions at the time
    • Does not address how GR-driven CAR induction integrates with ligand activation
    • Functional consequence for drug metabolism in vivo not tested
  2. 2005 Medium

    Resolved how the CAR3 splice variant and RXRα cooperate, showing RXR's AF-2 facilitates coactivator recruitment to CAR.

    Evidence Transient transfection reporter and mammalian two-hybrid assays with domain mutants

    PMID:16099843

    Open questions at the time
    • No structural or in vitro reconstitution of the heterodimer
    • Single lab, transfection-based
  3. 2007 Medium

    Identified a second transcriptional input (PPARα) controlling CAR levels and linked CAR induction to nutritional/fasting state.

    Evidence DR1 promoter reporter analysis plus PPARα-deficient mice

    PMID:18023279

    Open questions at the time
    • Direct PPARα binding to the DR1 not shown by ChIP
    • Free fatty acid mediation inferred, not proven
  4. 2008 Medium

    Revealed CAR's reciprocal control of PPARα, defining a metabolic role in triglyceride regulation beyond detoxification.

    Evidence CAR knockout mice, TCPOBOP activation, ob/ob and high-fat diet models with gene expression

    PMID:18941143

    Open questions at the time
    • Mechanism of PPARα suppression not molecularly defined here
    • Single lab
  5. 2009 High

    Defined the molecular switch controlling CAR activity: Thr38 phosphorylation by PKC destabilizes the DNA-binding helix and enforces cytoplasmic retention.

    Evidence In vitro kinase assay, molecular dynamics, helix-stabilizing mutagenesis, phospho-specific immunohistochemistry in human and mouse

    PMID:19858220

    Open questions at the time
    • Phosphatase responsible for activator-triggered dephosphorylation not identified
    • How phenobarbital triggers dephosphorylation unresolved
  6. 2010 Medium

    Showed CAR directly drives a lipogenic gene, demonstrating CAR/RXR binding to a DR-4 element in the THRSP promoter.

    Evidence Promoter reporter with mutations, EMSA with CAR/RXR, CAR-null mice

    PMID:20185760

    Open questions at the time
    • In vivo lipogenic phenotype consequences not fully traced
    • Single lab
  7. 2011 High

    Explained how the inactive cytoplasmic state is actively maintained: phospho-ERK1/2 binds phospho-CAR to block Thr38 dephosphorylation.

    Evidence Reciprocal Co-IP with phospho-mimetic/dead mutants, shRNA knockdown, MEK inhibition

    PMID:21873423

    Open questions at the time
    • Structural basis of the ERK–CAR interaction not solved
    • How activators displace ERK not defined
  8. 2011 Medium

    Placed CAR upstream of hepatic injury and progenitor (oval cell) responses, extending its role to liver regeneration.

    Evidence DDC-fed CAR knockout mice with nuclear fractionation, marker qPCR, and immunostaining

    PMID:21826054

    Open questions at the time
    • Direct CAR target genes driving oval cell proliferation not identified
    • Single lab
  9. 2012 High

    Identified DAX-1 as a direct CAR corepressor acting by disrupting the CAR–SRC1 coactivator interaction.

    Evidence Alpha-screen and Co-IP binding, domain mutagenesis, primary human hepatocyte CYP2B6 assays

    PMID:22896671

    Open questions at the time
    • Physiological contexts where DAX-1 represses CAR in vivo not defined
    • Single lab
  10. 2014 Medium

    Connected CAR to fibrosis, showing TGFβ/Smad induces CAR which then amplifies collagen synthesis in fibroblasts.

    Evidence siRNA, overexpression, COL1A2 reporter mutagenesis, bleomycin and TβRI-CA mouse fibrosis models

    PMID:25155144

    Open questions at the time
    • Direct CAR binding to fibrotic gene promoters not mapped
    • Single lab
  11. 2018 Medium

    Defined the genome-wide mechanism of CAR-mediated repression: enhancer competition with other nuclear receptors on shared sites.

    Evidence ChIP-seq for CAR, RXRα, and H4K5Ac in TCPOBOP-treated mouse liver

    PMID:30396153

    Open questions at the time
    • No mutagenesis validation of specific competed enhancers
    • Single lab
  12. 2022 Medium

    Linked CAR activation to a STAT3-cMyc-Cyclin D1 axis driving hepatocyte proliferation and liver growth.

    Evidence Western blot, immunofluorescence, qPCR in TCPOBOP-treated mouse liver

    PMID:35305226

    Open questions at the time
    • No epistasis or rescue establishing pathway order
    • Direct vs indirect STAT3 activation unresolved
  13. 2024 High

    Identified endogenous gut-microbiota-derived diindoles as high-affinity CAR agonists active on both rodent and human receptors.

    Evidence Biophysical binding, luciferase reporters, primary human hepatocyte and mouse liver gene expression

    PMID:38519460

    Open questions at the time
    • In vivo physiological role of microbial diindoles in CAR signaling not established
    • Single lab
  14. 2024 Medium

    Established post-transcriptional control of CAR by miR-214-3p, with functional consequences for warfarin metabolism.

    Evidence Dual luciferase 3'-UTR binding, qRT-PCR, siRNA rescue, rat pharmacokinetics

    PMID:39263307

    Open questions at the time
    • Endogenous regulators of miR-214-3p in liver not defined
    • Single lab
  15. 2024 Low

    Linked CAR to intestinal barrier integrity via regulation of CDH1/E-cadherin transcription.

    Evidence DSS colitis model, transcriptional analysis, in vivo E-cadherin knockdown

    PMID:39250508

    Open questions at the time
    • Mechanism of CAR regulation of CDH1 not characterized (no ChIP or promoter mutagenesis)
    • Single lab
    • Direct vs indirect transcriptional effect unknown
  16. 2025 Medium

    Showed CAR directly transactivates RRM2 to control de novo dNTP synthesis and hepatocyte ploidy.

    Evidence CAR knockout mice, RRM2 overexpression rescue, ploidy flow cytometry, transactivation assays, dNTP mass spectrometry (preprint)

    PMID:bio_10.1101_2025.04.29.651109

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Functional importance of CAR-driven ploidy for liver function unresolved
  17. 2025 Low

    Expanded the endogenous ligand repertoire and revealed mechanistically distinct modes of CAR inhibition among indole metabolites.

    Evidence Luciferase reporters and nuclear translocation assays in HepG2 cells

    PMID:40947077

    Open questions at the time
    • No binding affinity measurements or in vivo validation
    • Structural basis of skatole's translocation-inducing inhibition unknown
  18. 2025 Low

    Implicated CAR in colorectal cancer suppression through interaction with PCK1, shifting metabolism toward gluconeogenesis and arresting the cell cycle.

    Evidence Functional assays, gluconeogenesis measurements, xenograft model, CAR–PCK1 co-interaction assay

    PMID:40930396

    Open questions at the time
    • CAR–PCK1 interaction method not fully specified
    • Whether interaction is direct and stoichiometric unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The phosphatase that dephosphorylates Thr38 upon activator binding and the structural basis for ligand-gated nuclear translocation remain unidentified.
  • No phosphatase identified for activator-triggered Thr38 dephosphorylation
  • No structural model linking ligand binding to release of cytoplasmic retention

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
GO:0140110 transcription regulator activity 2 R-HSA-1430728 Metabolism 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9748784 Drug ADME 1
Partners
MAPK1MAPK3NCOA1NR0B1PCK1RXRA
Complex memberships
CAR/RXRα heterodimer

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Protein kinase C phosphorylates threonine 38 of human CAR (NR1I3), which destabilizes the alpha-helix spanning residues 29-42 (part of the first zinc finger), thereby inactivating CAR binding to DNA and sequestering it in the cytoplasm. Dephosphorylation of Thr38 is required for nuclear translocation and activation. Phenobarbital dephosphorylates the corresponding Thr48 of mouse CAR in the cytoplasm, enabling nuclear translocation. In vitro kinase assay, molecular dynamics simulation, helix-stabilizing mutagenesis, immunohistochemistry with anti-phospho-Thr38 antibody, co-immunoprecipitation The Journal of biological chemistry High 19858220
2011 Activated (phosphorylated) ERK1/2 interacts with phosphorylated CAR (NR1I3) at Thr-38 via the xenochemical response signal peptide near the C-terminus of CAR, repressing dephosphorylation of Thr-38 and thereby maintaining CAR in its inactive cytoplasmic state. EGF treatment increased this interaction, while MEK inhibitor U0126 or MEK1/2 knockdown decreased Thr-38 phosphorylation. Co-immunoprecipitation of FLAG-tagged CAR mutants (T38A, T38D) with endogenous phospho-ERK1/2; shRNA knockdown; pharmacological inhibition (U0126) The Journal of biological chemistry High 21873423
2003 The human CAR (NR1I3) gene promoter contains a functional glucocorticoid response element (GRE) at position -4447/-4432 that is recognized and transactivated by the glucocorticoid receptor (GR) in the presence of dexamethasone. Chromatin immunoprecipitation confirmed GR binding to this distal promoter region in cultured hepatocytes, establishing CAR as a primary GR-response gene. Deletion analysis and transient transfection, site-directed mutagenesis, gel shift assay (EMSA), chromatin immunoprecipitation (ChIP), cotransfection experiments, 5'-RACE, primer extension Molecular endocrinology (Baltimore, Md.) High 12511605
2005 The human CAR splice variant CAR3 (with a 5 amino acid insertion in the ligand-binding domain) is ligand-activated (by CITCO), in contrast to the constitutively active reference form CAR1. CAR3 transactivation requires its DNA-binding domain and AF-2 motif. RXRα co-transfection markedly enhances CAR3 activity via RXR's AF-2 function (but independently of RXR A/B and C domains/heterodimerization region), by facilitating coactivator (SRC-1) recruitment. Clotrimazole acts as a ligand activator of CAR3, whereas it is an inverse agonist of CAR1. Transient transfection reporter assays, domain deletion/mutation analysis, mammalian two-hybrid assay Molecular pharmacology Medium 16099843
2007 PPARα directly induces CAR (NR1I3) transcription in rat hepatocytes via a DR1 motif in the CAR promoter. This PPARα-dependent induction of CAR potentiates phenobarbital-induced transcription of the CAR target gene CYP2B1. Fasting-induced CAR expression was abrogated in PPARα-deficient mice, suggesting free fatty acids (PPARα ligands) mediate fasting-induced CAR upregulation. Promoter reporter assays with DR1 motif deletion, PPARα agonist treatment (WY14643) in rat hepatocytes, PPARα-deficient mouse model FEBS letters Medium 18023279
2008 CAR (NR1I3) regulates serum triglyceride levels under metabolic stress. CAR activity inversely regulates PPARα target gene expression; CAR activation (by TCPOBOP) decreases PPARα mRNA and suppresses hepatic fatty acid oxidation genes (Cyp4a14, CPT1α, CTE), whereas CAR-deficient mice show increased hepatic fatty acid oxidation and are protected from hypertriglyceridemia in ob/ob and high-fat diet models. CAR knockout mouse model, pharmacological activation (TCPOBOP), ob/ob × Car(-/-) cross, high-fat diet feeding, gene expression analysis Journal of lipid research Medium 18941143
2010 CAR (NR1I3) directly transactivates the lipogenic gene THRSP (Spot14/S14) promoter through a DR-4 thyroid hormone/PXR response element. Gel-shift analysis showed that the CAR/RXR heterodimer complex binds this element. Deletion or point mutation of this element abolished CAR-mediated transactivation. CAR-null mice did not show mCAR-activator-induced THRSP upregulation. Promoter reporter assay with deletion/point mutations, gel shift (EMSA) with CAR/RXR complex, CAR null mice with pharmacological activators, human hepatocyte treatment Endocrinology Medium 20185760
2011 CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation. DDC activates CAR (shown by nuclear CAR accumulation and CYP2B10 induction), and Car(-/-) mice fail to develop DDC-induced liver injury, ductular reaction, or oval cell proliferation, placing CAR upstream of these hepatic injury/regeneration responses. CAR knockout mouse model fed DDC diet, nuclear fractionation (CAR accumulation), real-time PCR (CYP2B10, oval cell markers), laser capture microdissection, immunostaining (A6 antibody) Laboratory investigation Medium 21826054
2012 DAX-1 (an orphan nuclear receptor) functions as a potent corepressor of human CAR (NR1I3). DAX-1's downstream LXXLL and PCFQVLP motifs are critical for corepression; DAX-1's C-terminal transcription silencing domain mediates the repression by inhibiting the CAR–SRC1 coactivator interaction (~50% inhibition). Direct CAR–DAX-1 interaction was demonstrated by alpha-screen and co-immunoprecipitation, enhanced by the CAR activator CITCO. DAX-1 inhibits CAR-mediated CITCO induction of CYP2B6 in primary human hepatocytes. Transactivation assays, domain deletion/mutagenesis, mammalian two-hybrid assay, alpha-screen, co-immunoprecipitation, primary human hepatocyte experiments Molecular pharmacology High 22896671
2018 Drug-activated CAR (NR1I3) binds genome-wide with its partner RXRα and induces H4K5 acetylation at stimulated genes. Transcriptional inhibition by CAR occurs when CAR binds the same enhancers occupied by HNF4α, PPARα, or FXR, suggesting functional competition among nuclear receptors on shared enhancers as the mechanism of CAR-mediated metabolic gene repression. Genome-wide ChIP-seq for CAR, RXRα, and H4K5Ac in mouse liver after TCPOBOP treatment iScience Medium 30396153
2014 TGFβ induces CAR (NR1I3) expression in dermal fibroblasts via a Smad-dependent mechanism. CAR activation amplifies TGFβ-stimulated collagen synthesis, myofibroblast differentiation, and COL1A2 transcription activity. Pharmacologic CAR agonist exacerbated bleomycin-induced and TβRI-CA-induced dermal fibrosis in vivo. siRNA knockdown, forced overexpression, site-directed mutagenesis, reporter assay (COL1A2 promoter), bleomycin and TβRI-CA mouse models, Western blot, qPCR, immunohistochemistry Arthritis & rheumatology (Hoboken, N.J.) Medium 25155144
2022 NR1I3 (CAR) activation by TCPOBOP induces STAT3 phosphorylation and nuclear translocation in mouse liver, and this NR1I3-STAT3 signaling pathway promotes hepatocyte proliferation and liver growth, at least in part through upregulation of cMyc and Cyclin D1. Western blot, immunofluorescence, real-time PCR in TCPOBOP-treated mouse liver Molecular biology reports Medium 35305226
2024 Diindole molecules (including diindolylmethane/DIM and diindolylethane/DIE) produced from commensal gut bacteria tryptophan metabolites are endogenous CAR (NR1I3) agonists with nanomolar binding affinities comparable to synthetic agonists. Unlike established synthetic agonists, they activate both rodent and human CAR orthologues. They selectively upregulate bona fide CAR target genes in primary human hepatocytes and mouse liver. Biophysical binding assays, luciferase reporter assays, primary human hepatocyte gene expression, mouse liver gene expression Nature communications High 38519460
2024 miR-214-3p directly binds the 3'-UTR of NR1I3 mRNA and downregulates NR1I3 expression. Panax notoginseng saponins (PNS) reduce miR-214-3p levels, thereby increasing NR1I3 and CYP2C9 expression and accelerating warfarin metabolism. NR1I3 knockdown rescued the PNS-induced acceleration of warfarin metabolism. Dual luciferase reporter assay (miR-214-3p binding to NR1I3 3'-UTR), qRT-PCR, immunoblotting, cellular immunofluorescence (NR1I3 localization), siRNA knockdown, rat pharmacokinetic studies Journal of ginseng research Medium 39263307
2024 NR1I3 (CAR) regulates CDH1 (E-cadherin) transcription in intestinal epithelial cells; L. gasseri ATCC33323 affects NR1I3 expression to promote E-cadherin expression, maintaining intestinal barrier integrity in DSS-induced colitis. Intestinal E-cadherin knockdown attenuated the protective effect of L. gasseri, confirming the functional relevance of the NR1I3–CDH1 axis. DSS-induced colitis mouse model, transcriptional analysis, in vitro experiments, E-cadherin knockdown in vivo PLoS pathogens Low 39250508
2025 NR1I3 (CAR) directly transactivates the Ribonucleotide Reductase-M2 (RRM2) gene (encoding the rate-limiting catalytic subunit of ribonucleotide reductase), thereby controlling de novo dNTP synthesis in hepatocytes. CAR deletion increases diploid (2c) hepatocytes with reduction of tetraploid (4c) hepatocytes; overexpression of RRM2 in CAR knockouts rescues DNA synthesis and restores tetraploidy. CAR ligand activation induces multiple de novo dNTP synthesis genes and raises hepatic dATP/dTTP levels. CAR knockout mouse model, RRM2 overexpression rescue experiment, DNA content flow cytometry (ploidy analysis), transactivation assays, dNTP level measurements (mass spectrometry) bioRxivpreprint Medium bio_10.1101_2025.04.29.651109
2025 Indole-containing intestinal bacterial metabolites of tryptophan differentially modulate CAR (NR1I3): tryptamine, indole-3-pyruvic acid, and indole-3-ethanol are agonists activating both mouse and human CAR in reporter assays; skatole (3-methylindole) inhibits mouse CAR activity but increases nuclear translocation (in contrast to androstanol inverse agonist which does not induce nuclear translocation), indicating mechanistically distinct modes of CAR inhibition. Luciferase reporter assay in HepG2 cells, nuclear translocation assay for mouse CAR Toxicology letters Low 40947077
2025 NR1I3 inhibits colorectal cancer cell growth by interacting with PCK1 (phosphoenolpyruvate carboxykinase 1), the rate-limiting enzyme of gluconeogenesis, thereby promoting gluconeogenesis, reducing glycolysis, depleting ATP, and arresting the cell cycle in G2/M phase. Pharmacological NR1I3 activation with CITCO reduced CRC cell growth and induced apoptosis in vitro and in vivo. Western blot, flow cytometry (cell cycle, apoptosis), colony formation assay, qRT-PCR, gluconeogenesis assays, animal xenograft model, co-immunoprecipitation or co-interaction assay with PCK1 Chemico-biological interactions Low 40930396

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3). The Journal of biological chemistry 109 19858220
2005 Genetic variants of PXR (NR1I2) and CAR (NR1I3) and their implications in drug metabolism and pharmacogenetics. Current drug metabolism 98 16101575
2003 Transcriptional analysis of the orphan nuclear receptor constitutive androstane receptor (NR1I3) gene promoter: identification of a distal glucocorticoid response element. Molecular endocrinology (Baltimore, Md.) 94 12511605
2008 The nuclear receptor CAR (NR1I3) regulates serum triglyceride levels under conditions of metabolic stress. Journal of lipid research 93 18941143
2005 Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3). Molecular pharmacology 72 16099843
2011 Active ERK1/2 protein interacts with the phosphorylated nuclear constitutive active/androstane receptor (CAR; NR1I3), repressing dephosphorylation and sequestering CAR in the cytoplasm. The Journal of biological chemistry 47 21873423
2007 PPARalpha-dependent induction of the energy homeostasis-regulating nuclear receptor NR1i3 (CAR) in rat hepatocytes: potential role in starvation adaptation. FEBS letters 36 18023279
2019 Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. Journal of cellular and molecular medicine 34 31880390
2010 Hepatic expression of thyroid hormone-responsive spot 14 protein is regulated by constitutive androstane receptor (NR1I3). Endocrinology 33 20185760
2011 Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver. Laboratory investigation; a journal of technical methods and pathology 28 21826054
2013 Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with tacrolimus pharmacokinetics in liver transplant patients. Drug metabolism and pharmacokinetics 24 24351870
2018 Binding of Drug-Activated CAR/Nr1i3 Alters Metabolic Regulation in the Liver. iScience 22 30396153
2014 Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital. Toxicology 20 25489928
2016 Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients. Clinical pharmacokinetics 19 27116457
2024 Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands. Nature communications 17 38519460
2024 Lactobacillus gasseri ATCC33323 affects the intestinal mucosal barrier to ameliorate DSS-induced colitis through the NR1I3-mediated regulation of E-cadherin. PLoS pathogens 17 39250508
2012 PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms and lipid and lipoprotein levels in a Southern Brazilian population. Molecular biology reports 17 23079705
2014 The nuclear receptor constitutive androstane receptor/NR1I3 enhances the profibrotic effects of transforming growth factor β and contributes to the development of experimental dermal fibrosis. Arthritis & rheumatology (Hoboken, N.J.) 13 25155144
2013 Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid-lowering efficacy and safety of statin therapy. Arquivos brasileiros de endocrinologia e metabologia 13 24232815
2022 Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor PNLIPRP1 and the xenobiotic receptor NR1I3. Journal of evolutionary biology 11 34882899
2014 Bovine NR1I3 gene polymorphisms and its association with feed efficiency traits in Nellore cattle. Meta gene 11 25606404
2012 The orphan nuclear receptor DAX-1 functions as a potent corepressor of the constitutive androstane receptor (NR1I3). Molecular pharmacology 11 22896671
2012 Cytogenetic evaluation and the association with polymorphisms of the CPY1A1 and NR1I3 genes in individuals exposed to BTEX. Environmental monitoring and assessment 8 23138419
2006 ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Xenobiotica; the fate of foreign compounds in biological systems 8 17118917
2021 Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals. The pharmacogenomics journal 6 34504302
2017 Transactivation Assays that Identify Indirect and Direct Activators of Human Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR, NR1I3). Drug metabolism letters 6 29219065
2015 Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 6 25714878
2015 High resolution melting analysis of the NR1I3 genetic variants: Is there an association with neonatal hyperbilirubinemia? Gene 3 26188155
2022 Promotion of NR1I3-mediated liver growth is accompanied by STAT3 activation. Molecular biology reports 2 35305226
2024 Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples. Drug metabolism and disposition: the biological fate of chemicals 1 39884819
2025 NR1I3 modulates Wnt signaling to promote anterior-posterior axis patterning. BMC biology 0 40739628
2025 NR1I3 inhibits colorectal cancer growth by enhancing PCK1-mediated gluconeogenesis. Chemico-biological interactions 0 40930396
2025 Distinct responses of the constitutive androstane receptor NR1I3 to indole-containing metabolites of bacterial origin. Toxicology letters 0 40947077
2024 Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin. Journal of ginseng research 0 39263307
2024 Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study. Frontiers in genetics 0 39512799

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