NR1I2 nuclear receptor subfamily 1, group I, member 2 [Homo sapiens] - Gene

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Summary

Official Symbol: NR1I2provided by HGNC
Official Full Name: nuclear receptor subfamily 1, group I, member 2provided by HGNC
Primary source: HGNC:7968
See related: Ensembl:ENSG00000144852; HPRD:04346; MIM:603065; Vega:OTTHUMG00000159400
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BXR; PAR; PRR; PXR; SAR; SXR; ONR1; PAR1; PAR2; PARq
Summary: This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 3q12-q13.3

Sequence :: Chromosome: 3; NC_000003.11 (119499331..119537332)

See NR1I2 in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

There is no association between PXR and ABCB1 polymorphisms and their haplotypes, and interaction between them, with response to monotherapy treatment of epilepsy in Chinese, Indian, and Malay subgroups.
Title: Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy.
Combined data of present and previous studies showed that high immunoreactivity scores for both the SXR and CYP3A4 correlated with significantly better cancer-specific survival rates in multivariate regression analyses.
Title: Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer.
Our results suggest that variants in the PXR gene should be considered in pharmacogenetic studies involving Brazilians from the southeast region, since the miscegenation varies from region to region.
Title: Frequency of genetic polymorphisms of PXR gene in the Brazilian population.
CAR transactivates ABCG2 through the DR5 motif located in its distal promoter in hepatocytes and the motif prefers CAR to pregnane X receptor.
Title: Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes.
The mechanism of ligand-dependent activation in pregnane X receptor differs significantly from that seen in many other nuclear receptors.
Title: Rifampicin-independent interactions between the pregnane X receptor ligand binding domain and peptide fragments of coactivator and corepressor proteins.
These results suggest that PROX1 could negatively regulate SXR signals in some tumor cells, such as HCC cells, where both SXR and PROX1 are expressed.
Title: PROX1 suppresses vitamin K-induced transcriptional activity of Steroid and Xenobiotic Receptor.
This study aimed to investigate the expression and genetic variation of PXR in reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma.
Title: Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma.
These results suggest that acetyl tributyl citrate specifically induces CYP3A in the intestine by activating SXR.
Title: Acetyl tributyl citrate, the most widely used phthalate substitute plasticizer, induces cytochrome p450 3a through steroid and xenobiotic receptor.
Presented is the 2.8 A resolution crystal structure of the human PXR ligand-binding domain in complex with PNU-142721.
Title: Activation of the human nuclear xenobiotic receptor PXR by the reverse transcriptase-targeted anti-HIV drug PNU-142721.
Data show that frog TFF2 activates protease-activated receptor (PAR) 1 to induce human platelet aggregation, and suggest that human TFF2 promotes cell migration via PAR4.
Title: Activation of protease-activated receptor (PAR) 1 by frog trefoil factor (TFF) 2 and PAR4 by human TFF2.

Submit: New GeneRIF Correction See all (147)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
O75469	P35609	ACTN2	HPRD	PubMed
O75469	Q15788	NCOA1	HPRD	PubMed
O75469	Q9Y6Q9	NCOA3	HPRD	PubMed
O75469	Q9Y618	NCOR2	HPRD	PubMed
O75469	O75469	NR1I2	HPRD	PubMed
O75469	P80303	NUCB2	HPRD	PubMed
O75469	P28069	POU1F1	HPRD	PubMed
O75469	Q9UBK2	PPARGC1A	HPRD	PubMed
O75469	P62195	PSMC5	HPRD	PubMed
O75469	P19793	RXRA	HPRD	PubMed
O75469	P28702	RXRB	HPRD	PubMed
O75469	P48443	RXRG	HPRD	PubMed
O75469	P12931	SRC	HPRD	PubMed
BioGRID:114380	BioGRID:106603	ACTN2	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:111148	CHMP1A	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:114217	EIF3I	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:114200	NCOA1	BioGRID	PubMed	Co-crystal Structure
BioGRID:114380	BioGRID:116691	NCOA6	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:114380	BioGRID:114973	NCOR1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:114380	BioGRID:114974	NCOR2	BioGRID	PubMed	Reconstituted Complex
BioGRID:114380	BioGRID:110979	NUCB2	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:201707	Ncoa1	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:111445	POU1F1	BioGRID	PubMed	Reconstituted Complex
BioGRID:114380	BioGRID:116097	PPARGC1A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:114380	BioGRID:109512	PRMT1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114380	BioGRID:202321	Ppargc1a	BioGRID	PubMed	Reconstituted Complex
BioGRID:114380	BioGRID:112168	RXRA	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:112169	RXRB	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:112170	RXRG	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:112592	SRC	BioGRID	PubMed	Two-hybrid
BioGRID:114380	BioGRID:115737	TADA3	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
drug binding	IDA Inferred from Direct Assay more info	PubMed
ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info
receptor activity	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
steroid hormone receptor activity	IEA Inferred from Electronic Annotation more info
transcription coactivator activity	TAS Traceable Author Statement more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
drug export	IDA Inferred from Direct Assay more info	PubMed
exogenous drug catabolic process	IDA Inferred from Direct Assay more info	PubMed
gene expression	TAS Traceable Author Statement more info
intracellular receptor mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
signal transduction	TAS Traceable Author Statement more info	PubMed
steroid metabolic process	TAS Traceable Author Statement more info	PubMed
xenobiotic metabolic process	IDA Inferred from Direct Assay more info	PubMed
xenobiotic transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: nuclear receptor subfamily 1 group I member 2

Names: nuclear receptor subfamily 1 group I member 2; pregnane X receptor; orphan nuclear receptor PXR; orphan nuclear receptor PAR1; steroid and xenobiotic receptor; pregnane X nuclear receptor variant 2

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011856.1 RefSeqGene

Range

5001..43002

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003889.3 → NP_003880.3 nuclear receptor subfamily 1 group I member 2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains an alternate 5' terminal exon compared to transcript variant 2, and initiates translation from an in-frame, downstream non-AUG (CUG) codon, resulting in a shorter isoform (1) with a different N-terminus compared to isoform 2.

Source sequence(s)

AC069444, AJ009936, AY091855, BC017304

Consensus CDS

CCDS43136.1

UniProtKB/Swiss-Prot

O75469

Related

ENSP00000377319, OTTHUMP00000215174, ENST00000393716, OTTHUMT00000355127

Conserved Domains (3) summary

cd06934
Location:236 – 428
Blast Score: 940

NR_LBD_PXR_like; The ligand binding domain of xenobiotic receptors:pregnane X receptor and constitutive androstane receptor

cl02596
Location:40 – 127
Blast Score: 434

NR_DBD_like; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers

cl11397
Location:143 – 175
Blast Score: 147

NR_LBD; The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators
NM_022002.2 → NP_071285.1 nuclear receptor subfamily 1 group I member 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longest isoform (2) and initiates translation from the standard AUG codon present in its 5' terminal exon.

Source sequence(s)

AF084644, AJ009936, BC017304

Consensus CDS

CCDS2995.1

UniProtKB/TrEMBL

F1D8P9

UniProtKB/Swiss-Prot

O75469

Related

ENSP00000336528, OTTHUMP00000215173, ENST00000337940, OTTHUMT00000355126

Conserved Domains (3) summary

cd06934
Location:275 – 467
Blast Score: 942

NR_LBD_PXR_like; The ligand binding domain of xenobiotic receptors:pregnane X receptor and constitutive androstane receptor

cd07162
Location:79 – 166
Blast Score: 439

NR_DBD_PXR; DNA-binding domain of pregnane X receptor (PXRs) is composed of two C4-type zinc fingers

cl11397
Location:182 – 214
Blast Score: 148

NR_LBD; The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators
NM_033013.2 → NP_148934.1 nuclear receptor subfamily 1 group I member 2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' terminal exon, and uses a different acceptor splice site at one of the internal coding exons, compared to transcript variant 2. It initiates translation from an in-frame, downstream non-AUG (CUG) codon, resulting in a shorter isoform (3) with a different N-terminus and missing an internal segment, compared to isoform 2.

Source sequence(s)

AC069444, AJ009937, AY091855, BC017304

Consensus CDS

CCDS54627.1

UniProtKB/Swiss-Prot

O75469

Related

ENSP00000420297, OTTHUMP00000215175, ENST00000466380, OTTHUMT00000355128

Conserved Domains (2) summary

cd06934
Location:143 – 391
Blast Score: 1037

NR_LBD_PXR_like; The ligand binding domain of xenobiotic receptors:pregnane X receptor and constitutive androstane receptor

cl02596
Location:40 – 127
Blast Score: 434

NR_DBD_like; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p5 Primary Assembly

Range

119499331..119537332

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

116874950..116913074

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC069444.17 (71551..109552)	None
genomic	AF364606.1	AAK38720.1
		AAK38721.1
		AAK38722.1
genomic	AY007189.1	AAG23345.1
genomic	CH471052.2	EAW79537.1
		EAW79538.1
		EAW79539.1
genomic	DQ911122.1	ABJ52965.1
genomic	DQ923326.1	ABJ52966.1
genomic	EF614253.1	ABR09276.1
mRNA	AB307701.1	BAH02292.1
mRNA	AF061056.1	AAD05436.1
mRNA	AF084644.1	AAC64557.1
mRNA	AF084645.1	AAC64558.1
mRNA	AJ009936.1	CAB55489.1
		CAB55490.1
		CAB55491.1
mRNA	AJ009937.1	CAB55492.1
		CAB55493.1
		CAB55494.1
mRNA	AK122990.1	BAG53837.1
mRNA	AK223456.1	None
mRNA	AK310789.1	None
mRNA	AY091855.1	AAM26736.1
mRNA	BC017304.2	AAH17304.2
mRNA	HQ692837.1	ADZ17348.1
mRNA	HQ709177.1	ADZ17384.1