The Human Transcription Factors

Conclusion

Assessment	Binding Mode	Motif Status	Notes	Comments
Known motif	1 Monomer or homomultimer	High-throughput in vitro

Description

Description:

nuclear receptor subfamily 1 group I member 3 [Source:HGNC Symbol;Acc:HGNC:7969]

Entrez Summary

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]

Ensembl ID:

ENSG00000143257

External Link:

CisBP

Interpro

IPR000536; IPR001628; IPR001723; IPR001728; IPR008946; ;

Protein Domain:

ENSP00000356958

Protein Domain:

ENSP00000356960

Protein Domain:

ENSP00000356961

Protein Domain:

ENSP00000356962

Protein Domain:

ENSP00000356963

Protein Domain:

ENSP00000356965

Protein Domain:

ENSP00000399361

Protein Domain:

ENSP00000412672

Protein Domain:

ENSP00000407446

Protein Domain:

ENSP00000406493

Protein Domain:

ENSP00000421374

Protein Domain:

ENSP00000424345

Protein Domain:

ENSP00000424934

Protein Domain:

ENSP00000422982

Protein Domain:

ENSP00000423666

Protein Domain:

ENSP00000427175

Protein Domain:

ENSP00000427600

Protein Domain:

ENSP00000426292

Protein Domain:

ENSP00000425417

Protein Domain:

ENSP00000421588

Protein Domain:

ENSP00000423089

Protein Domain:

ENSP00000427034

Domain:

Protein: ENSP00000356958	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000356960	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000356961	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000356962	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000356963	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000356965	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000399361	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000412672	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000407446	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000406493	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000421374	DBD: Nuclear Hormone Receptor	Other:
Protein: ENSP00000424345	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000424934	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000422982	DBD: Nuclear Hormone Receptor	Other:
Protein: ENSP00000423666	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000427175	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000427600	DBD: Nuclear Hormone Receptor	Other:
Protein: ENSP00000426292	DBD: Nuclear Hormone Receptor	Other:
Protein: ENSP00000425417	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000421588	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000423089	DBD: Nuclear Hormone Receptor	Other: Hormone_recep
Protein: ENSP00000427034	DBD: Nuclear Hormone Receptor	Other: Hormone_recep

Previous Annotations

Source	Annotation
TF-CAT classification	TF Gene_DNA-Binding sequence-specific_DNA Binding Transactivation_ PMIDS:8114692 12511605
Vaquerizas 2009 TF classification "a" Has direct evidence of TF function; "b" Has evidence for an orthologous TF; "c" contains likely DBDs, but has no functional evidence; "x" is an unlikely TF such as predicted gene, genes with likely non-specific DBDs or that have function outside transcription; "other" category contains proteins without clear DBDs they curated from external sources.	a
CisBP considers it as a TF?	Yes
TFclass considers it as a TF?	Yes
Has GO:0003700 "transcription factor activity, sequence-specific DNA binding"	Yes
GO-Info	GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor IDA - PMID:11114890 GO:0003700 sequence-specific DNA binding transcription factor activity TAS - PMID:8020947, PMID:8114692 GO:0004879 ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity TAS - PMID:8114692 GO:0004882 androgen receptor activity TAS - PMID:9783588 GO:0004887 thyroid hormone receptor activity IEA - GO_REF:0000002
Initial Assessment 1a1 Protein has a high confidence PWM (HT-SELEX, PBM or B1H model) or there is a crystal structure that supports sequence specific DNA binding; 1a2 There is high confidence data for a close ortholog (as defined in CisBP); 2a1 There is lower confidence direct evidence, such as a Jaspar, Hocomoco or Transfac model; 2a2 There is lower confidence evidence for an close ortholog; 3a There is decent circumstantial evidence for its role as a TF or not; 4a Two or more datasets predict it as a TF; 5a One of the source datasets predicts is as a TF	1a1, Direct HQ evidence
TF has conditional DNA-binding requirements

DNA-Binding

Published Motif Data

Source	Annotation	Motif	Evidence
HT-SELEX	Nitta2015		Direct
HT-SELEX	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
Misc	HocoMoco		Direct
Misc	HocoMoco		Direct

Structure

Structure	PDB	Not_Covered

Experimental History

Method	Constructs
Tried in PBM? (Whether the protein was tried in PBM or not)
Tried in HT-SELEX (Whether the protein was tried in HT-SELEX or not, and if so, then what kind of clones were tested)
Other Information? (Tried with another method and failed?)

External Contribution

Name
Email
Comment
Reference

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{"regions": [{"startStyle": "curved", "end": 78, "endStyle": "curved", "aliStart": 10, "text": "NHR", "colour": "#2cb42c", "aliEnd": 78, "start": 9, "href": "http://pfam.xfam.org/family/PF00105.16", "type": "pfama", "display": "true", "metadata": {"end": 78, "description": "In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.", "database": "PfamA", "aliStart": 10, "scoreName": "E-value", "accession": "PF00105.16", "start": 9, "score": 1.9e-28, "identifier": "Zinc finger, C4 type (two domains)", "type": "DBD", "aliEnd": 78}}, {"startStyle": "jagged", "end": 237, "endStyle": "jagged", "aliStart": 167, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 212, "start": 157, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 237, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 167, "scoreName": "E-value", "accession": "PF00104.28", "start": 157, "score": 3.4000000000000003e-09, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 212}}, {"startStyle": "jagged", "end": 299, "endStyle": "straight", "aliStart": 243, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 291, "start": 235, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 299, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 243, "scoreName": "E-value", "accession": "PF00104.28", "start": 235, "score": 3.4000000000000003e-09, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 291}}], "length": 315}

{"regions": [{"startStyle": "jagged", "end": 49, "endStyle": "curved", "aliStart": 7, "text": "NHR", "colour": "#2cb42c", "aliEnd": 49, "start": 5, "href": "http://pfam.xfam.org/family/PF00105.16", "type": "pfama", "display": "true", "metadata": {"end": 49, "description": "In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.", "database": "PfamA", "aliStart": 7, "scoreName": "E-value", "accession": "PF00105.16", "start": 5, "score": 3.7e-11, "identifier": "Zinc finger, C4 type (two domains)", "type": "DBD", "aliEnd": 49}}, {"startStyle": "jagged", "end": 204, "endStyle": "jagged", "aliStart": 138, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 181, "start": 128, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 204, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 138, "scoreName": "E-value", "accession": "PF00104.28", "start": 128, "score": 1.9e-09, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 181}}, {"startStyle": "jagged", "end": 266, "endStyle": "straight", "aliStart": 207, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 258, "start": 187, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 266, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 207, "scoreName": "E-value", "accession": "PF00104.28", "start": 187, "score": 1.9e-09, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 258}}], "length": 281}

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{"regions": [{"startStyle": "jagged", "end": 49, "endStyle": "curved", "aliStart": 7, "text": "NHR", "colour": "#2cb42c", "aliEnd": 49, "start": 5, "href": "http://pfam.xfam.org/family/PF00105.16", "type": "pfama", "display": "true", "metadata": {"end": 49, "description": "In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.", "database": "PfamA", "aliStart": 7, "scoreName": "E-value", "accession": "PF00105.16", "start": 5, "score": 3.5e-11, "identifier": "Zinc finger, C4 type (two domains)", "type": "DBD", "aliEnd": 49}}, {"startStyle": "jagged", "end": 218, "endStyle": "jagged", "aliStart": 138, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 197, "start": 128, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 218, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 138, "scoreName": "E-value", "accession": "PF00104.28", "start": 128, "score": 2e-06, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 197}}, {"startStyle": "jagged", "end": 240, "endStyle": "jagged", "aliStart": 208, "text": "Hormone_recep", "colour": "#9999ff", "aliEnd": 229, "start": 195, "href": "http://pfam.xfam.org/family/PF00104.28", "type": "pfama", "display": "true", "metadata": {"end": 240, "description": "This all helical domain is involved in binding the hormone in these receptors.", "database": "PfamA", "aliStart": 208, "scoreName": "E-value", "accession": "PF00104.28", "start": 195, "score": 2e-06, "identifier": "Ligand-binding domain of nuclear hormone receptor", "type": "DBD", "aliEnd": 229}}], "length": 268}

TF Info Page for NR1I3 (Nuclear receptor)

Conclusion

Description

Previous Annotations

DNA-Binding

Published Motif Data

Structure

Experimental History

External Contribution