Human Gene NR1I3 (ENST00000367984.8) from GENCODE V44
  Description: Homo sapiens nuclear receptor subfamily 1 group I member 3 (NR1I3), transcript variant 5, mRNA. (from RefSeq NM_001077471)
RefSeq Summary (NM_001077471): This gene encodes 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. In addition to drug metabolism, the CAR protein is also reported to regulate genes involved in glucose metabolism, lipid metabolism, cell proliferation, and circadian clock regulation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020].
Gencode Transcript: ENST00000367984.8
Gencode Gene: ENSG00000143257.12
Transcript (Including UTRs)
   Position: hg38 chr1:161,229,772-161,238,111 Size: 8,340 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg38 chr1:161,229,797-161,236,565 Size: 6,769 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:161,229,772-161,238,111)mRNA (may differ from genome)Protein (309 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NR1I3_HUMAN
DESCRIPTION: RecName: Full=Nuclear receptor subfamily 1 group I member 3; AltName: Full=Constitutive activator of retinoid response; Short=Constitutive active response; AltName: Full=Constitutive androstane receptor; Short=CAR; AltName: Full=Orphan nuclear receptor MB67;
FUNCTION: Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
SUBUNIT: Interacts with ECT2 (By similarity). Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Directly interacts with DNAJC7. The DNAJC7-NR1I3 complex may also include HSP90 (By similarity).
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Recruited to the cytoplasm by DNAJC7 (By similarity).
TISSUE SPECIFICITY: Predominantly expressed in liver.
INDUCTION: By dexamethasone.
DOMAIN: Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization domains.
PTM: Phosphorylated at Thr-38 by PKC, dephosphorylation of Thr-38 is required for nuclear translocation and activation.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: NR1I3
Diseases sorted by gene-association score: biliary tract disease (12), hyperparathyroidism, neonatal (10), intrahepatic cholestasis (8), neonatal jaundice (8), cholestasis (8), bilirubin metabolic disorder (7), idiopathic hypercalciuria (6), acute porphyria (5), hyperparathyroidism, familial primary (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 54.05 RPKM in Liver
Total median expression: 65.34 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -30.90104-0.297 Picture PostScript Text
3' UTR 0.00250.000 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008946 - Nucl_hormone_rcpt_ligand-bd
IPR000536 - Nucl_hrmn_rcpt_lig-bd_core
IPR001723 - Str_hrmn_rcpt
IPR001728 - ThyrH_rcpt
IPR001628 - Znf_hrmn_rcpt
IPR013088 - Znf_NHR/GATA

Pfam Domains:
PF00104 - Ligand-binding domain of nuclear hormone receptor
PF00105 - Zinc finger, C4 type (two domains)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1XV9 - X-ray MuPIT 1XVP - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q14994
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003707 steroid hormone receptor activity
GO:0003713 transcription coactivator activity
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
GO:0004882 androgen receptor activity
GO:0004887 thyroid hormone receptor activity
GO:0008270 zinc ion binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0030521 androgen receptor signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0043401 steroid hormone mediated signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton


-  Descriptions from all associated GenBank mRNAs
  HQ447449 - Synthetic construct Homo sapiens clone IMAGE:100070777; CCSB013990_01 nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene, encodes complete protein.
KJ898127 - Synthetic construct Homo sapiens clone ccsbBroadEn_07521 NR1I3 gene, encodes complete protein.
KR711359 - Synthetic construct Homo sapiens clone CCSBHm_00023120 NR1I3 (NR1I3) mRNA, encodes complete protein.
KR711360 - Synthetic construct Homo sapiens clone CCSBHm_00023121 NR1I3 (NR1I3) mRNA, encodes complete protein.
Z30425 - H.sapiens mRNA for orphan nuclear hormone receptor.
BC069626 - Homo sapiens nuclear receptor subfamily 1, group I, member 3, mRNA (cDNA clone MGC:97209 IMAGE:7262456), complete cds.
BC069651 - Homo sapiens nuclear receptor subfamily 1, group I, member 3, mRNA (cDNA clone MGC:97144 IMAGE:7262385), complete cds.
AY572806 - Homo sapiens constitutive androstane receptor SV1 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572807 - Homo sapiens constitutive androstane receptor SV2 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572808 - Homo sapiens constitutive androstane receptor SV3 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572809 - Homo sapiens constitutive androstane receptor SV4 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572810 - Homo sapiens constitutive androstane receptor SV5 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572811 - Homo sapiens constitutive androstane receptor SV6 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572812 - Homo sapiens constitutive androstane receptor SV7 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572813 - Homo sapiens constitutive androstane receptor SV8 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572814 - Homo sapiens constitutive androstane receptor SV9 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572815 - Homo sapiens constitutive androstane receptor SV10 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572816 - Homo sapiens constitutive androstane receptor SV11 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572817 - Homo sapiens constitutive androstane receptor SV12 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572818 - Homo sapiens constitutive androstane receptor SV13 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572819 - Homo sapiens constitutive androstane receptor SV14 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572820 - Homo sapiens constitutive androstane receptor SV15 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572821 - Homo sapiens constitutive androstane receptor SV16 (NR1I3) mRNA, partial cds, alternatively spliced.
AY572822 - Homo sapiens constitutive androstane receptor SV17 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572823 - Homo sapiens constitutive androstane receptor SV18 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572824 - Homo sapiens constitutive androstane receptor SV19 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572825 - Homo sapiens constitutive androstane receptor SV20 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572826 - Homo sapiens constitutive androstane receptor SV21 (NR1I3) mRNA, complete cds, alternatively spliced.
AY572827 - Homo sapiens constitutive androstane receptor SV22 (NR1I3) mRNA, complete cds, alternatively spliced.
BC121120 - Homo sapiens nuclear receptor subfamily 1, group I, member 3, mRNA (cDNA clone MGC:150433 IMAGE:40120664), complete cds.
BC121121 - Homo sapiens nuclear receptor subfamily 1, group I, member 3, mRNA (cDNA clone MGC:150434 IMAGE:40120665), complete cds.
JD205246 - Sequence 186270 from Patent EP1572962.
JD140847 - Sequence 121871 from Patent EP1572962.
AB307702 - Homo sapiens NR1I3 mRNA for constitutive androstane receptor, complete cds.
DQ022681 - Homo sapiens nuclear receptor subfamily 1, group I, member 3 mRNA, complete cds, alternatively spliced.
HQ692838 - Homo sapiens constitutive androstane nuclear receptor variant 2 (NR1i3) mRNA, complete cds.
HQ692839 - Homo sapiens constitutive androstane nuclear receptor variant 3 (NR1i3) mRNA, complete cds.
HQ692840 - Homo sapiens constitutive androstane nuclear receptor variant 4 (NR1i3) mRNA, complete cds.
HQ692841 - Homo sapiens constitutive androstane nuclear receptor variant 5 (NR1i3) mRNA, complete cds.
HQ709178 - Homo sapiens constitutive androstane nuclear receptor (NR1I3) mRNA, complete cds.
CU686946 - Synthetic construct Homo sapiens gateway clone IMAGE:100022636 5' read NR1I3 mRNA.
AK303757 - Homo sapiens cDNA FLJ50348 complete cds, highly similar to Orphan nuclear receptor NR1I3.
AK310773 - Homo sapiens cDNA, FLJ17815.
AK316208 - Homo sapiens cDNA, FLJ79107 complete cds, highly similar to Orphan nuclear receptor NR1I3.
AK303796 - Homo sapiens cDNA FLJ56764 complete cds, highly similar to Orphan nuclear receptor NR1I3.
BC030972 - Homo sapiens nuclear receptor subfamily 1, group I, member 3, mRNA (cDNA clone IMAGE:4556554), with apparent retained intron.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_nuclearRsPathway - Nuclear Receptors in Lipid Metabolism and Toxicity
h_AcetaminophenPathway - Mechanism of Acetaminophen Activity and Toxicity

Reactome (by CSHL, EBI, and GO)

Protein Q14994 (Reactome details) participates in the following event(s):

R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: CAR, ENST00000367984.1, ENST00000367984.2, ENST00000367984.3, ENST00000367984.4, ENST00000367984.5, ENST00000367984.6, ENST00000367984.7, F1D8Q0, F1D8Q1, NM_001077471, NR1I3_HUMAN, Q0VAC9, Q14994, Q5VTW5, Q5VTW6, Q6GZ68, Q6GZ84, Q6GZ85, Q6GZ87, uc001gab.1, uc001gab.2, uc001gab.3, uc001gab.4
UCSC ID: ENST00000367984.8
RefSeq Accession: NM_001077471
Protein: Q14994 (aka NR1I3_HUMAN or NRI3_HUMAN)
CCDS: CCDS41428.1, CCDS44262.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.