NR1H4 nuclear receptor subfamily 1 group H member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NR1H4provided by HGNC
Official Full Name: nuclear receptor subfamily 1 group H member 4provided by HGNC
Primary source: HGNC:HGNC:7967
See related: Ensembl:ENSG00000012504 MIM:603826; AllianceGenome:HGNC:7967
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: BAR; FXR; HRR1; HRR-1; PFIC5; RIP14
Summary: This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]
Expression: Biased expression in liver (RPKM 14.7), small intestine (RPKM 8.3) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q23.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (100473866..100564414)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (100435311..100525835)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (100867644..100958192)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes.
Title: Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes.
NR1H4 disease: rapidly progressing neonatal intrahepatic cholestasis and early death.
Title: NR1H4 disease: rapidly progressing neonatal intrahepatic cholestasis and early death.
Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation.
Title: Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation.
FXR overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in alcoholic liver disease.
Title: FXR overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in alcoholic liver disease.
Farnesoid X receptor overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in nonalcoholic fatty liver disease.
Title: Farnesoid X receptor overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in nonalcoholic fatty liver disease.
Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease.
Title: Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease.
NR1H4-mediated circRHOBTB3 modulates the proliferation, metastasis, and Warburg effects of cervical cancer through interacting with IGF2BP3.
Title: NR1H4-mediated circRHOBTB3 modulates the proliferation, metastasis, and Warburg effects of cervical cancer through interacting with IGF2BP3.
Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis.
Title: Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis.
Farnesoid X receptor represses human sulfotransferase 1A3 expression through direct binding to the promoter.
Title: Farnesoid X receptor represses human sulfotransferase 1A3 expression through direct binding to the promoter.
Farnesoid X receptor enhances epithelial ACE2 expression and inhibits virally induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2.
Title: Farnesoid X receptor enhances epithelial ACE2 expression and inhibits virally induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2.

Submit: New GeneRIF Correction See all GeneRIFs (252)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cholestasis, progressive familial intrahepatic, 5 MedGen: C4310747 OMIM: 617049 GeneReviews: Pediatric Genetic Cholestatic Liver Disease Overview	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
matrix	gag	Treatment of human PBMCs with HIV-1 MA upregulates the expression of MCP-1, ICAM-1, CD40, CD86 and CD36 and downregulates the expression of nuclear receptors FXR and PPARgamma	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G64580 (e-PCR)
- UniSTS:163844

RH79063 (e-PCR)
- UniSTS:73504

NR1I2_2318 (e-PCR)
- UniSTS:280873

D12S332 (e-PCR), detects polymorphism
- UniSTS:75347

NoName (e-PCR)
- UniSTS:495214

SHGC-81175 (e-PCR)
- UniSTS:102001

RH15652 (e-PCR)
- UniSTS:63145

D12S871 (e-PCR)
- UniSTS:62137

G64833 (e-PCR)
- UniSTS:164798

PMC219489P1 (e-PCR)
- UniSTS:272083

PMC219489P2 (e-PCR)
- UniSTS:272084

PMC219489P3 (e-PCR)
- UniSTS:272085

AFM326tf5 (e-PCR)
- UniSTS:43736

SGC33913 (e-PCR)
- UniSTS:18145

PMC137182P6 (e-PCR)
- UniSTS:270827

D12S332 (e-PCR), detects polymorphism
- UniSTS:41461

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables bile acid binding	IBA Inferred from Biological aspect of Ancestor more info
enables bile acid binding	IDA Inferred from Direct Assay more info	PubMed
enables bile acid nuclear receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables chenodeoxycholic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables nuclear receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor binding	TAS Traceable Author Statement more info	PubMed
enables nuclear retinoid X receptor binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables transcription coregulator binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in bile acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in bile acid signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell junction assembly	IEA Inferred from Electronic Annotation more info
involved_in cellular response to bile acid	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to bile acid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to fatty acid	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cholesterol homeostasis	IEA Inferred from Electronic Annotation more info
involved_in defense response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in fatty acid homeostasis	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intracellular glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular triglyceride homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of interleukin-1 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of monocyte chemotactic protein-1 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type II interferon production	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of very-low-density lipoprotein particle remodeling	IDA Inferred from Direct Assay more info	PubMed
involved_in nuclear receptor-mediated bile acid signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in nuclear receptor-mediated bile acid signaling pathway	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of adipose tissue development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ammonia assimilation cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glutamate metabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidic acid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of bile acid biosynthetic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cholesterol metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of insulin secretion involved in cellular response to glucose stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of low-density lipoprotein particle clearance	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of urea metabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in toll-like receptor 9 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of RNA polymerase II transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info
located_in chromatin	IC Inferred by Curator more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in euchromatin	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bile acid receptor

Names: RXR-interacting protein 14; farnesoid X nuclear receptor; farnesoid X-activated receptor; farnesol receptor HRR-1; retinoid X receptor-interacting protein 14

NCBI Reference Sequences (RefSeq)

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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_029843.1 RefSeqGene

Range

5094..95642

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001206977.2 → NP_001193906.1 bile acid receptor isoform 1

See identical proteins and their annotated locations for NP_001193906.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) contains an alternate exon in the 5' UTR compared to variant 1. Variants 1 and 6 encode the same isoform (1, also known as FXRalpha+).

Source sequence(s)

AC010200, AF384555, BC035654, DA011411

Consensus CDS

CCDS55873.1

UniProtKB/TrEMBL

B2R7F1, F1DAL1

Related

ENSP00000496908.1, ENST00000648861.1

Conserved Domains (2) summary

cd06936
Location:251 → 471

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:124 → 211

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers
NM_001206978.2 → NP_001193907.1 bile acid receptor isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an in-frame exon compared to variant 1. This results in a shorter isoform (5) than isoform 1.

Source sequence(s)

AC010200, BC035654, BC130573, BC144183, DA011411

Consensus CDS

CCDS55874.1

UniProtKB/TrEMBL

B2R7F1

Related

ENSP00000448978.1, ENST00000549996.5

Conserved Domains (2) summary

cd06936
Location:200 → 420

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cl02596
Location:127 → 149

NR_DBD_like; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers
NM_001206979.2 → NP_001193908.1 bile acid receptor isoform 1

See identical proteins and their annotated locations for NP_001193908.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1 (also known as FXRalpha+). Variants 1 and 6 encode the same isoform (1).

Source sequence(s)

AC010200, BC035654, BC130573, DA011411

Consensus CDS

CCDS55873.1

UniProtKB/TrEMBL

B2R7F1, F1DAL1

Related

ENSP00000376712.3, ENST00000392986.8

Conserved Domains (2) summary

cd06936
Location:251 → 471

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:124 → 211

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers
NM_001206992.2 → NP_001193921.1 bile acid receptor isoform 4

See identical proteins and their annotated locations for NP_001193921.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs 5' UTR, lacks a portion of the 5' coding region, and uses an alternate in-frame splice site, compared to variant 1. It represents use of an alternate promoter and initiates translation at an alternate start codon. The encoded isoform (4, also known as FXRbeta-) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

AC010200, AF478445, BC035654

Consensus CDS

CCDS55875.1

UniProtKB/TrEMBL

Q7Z2W0

Related

ENSP00000188403.7, ENST00000188403.7

Conserved Domains (2) summary

cd06936
Location:257 → 477

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:134 → 217

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers
NM_001206993.2 → NP_001193922.1 bile acid receptor isoform 3

See identical proteins and their annotated locations for NP_001193922.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs 5' UTR and lacks a portion of the 5' coding region compared to variant 1. It represents use of an alternate promoter and initiates translation at an alternate start codon. The encoded isoform (3, also known as FXRbeta+) has a distinct, longer N-terminus, compared to isoform 1.

Source sequence(s)

AC010200, AF478446, BC035654

Consensus CDS

CCDS55876.1

UniProtKB/Swiss-Prot

A1L4K5, B7Z412, B7ZM06, F8VYG8, Q8NFP5, Q8NFP6, Q92943, Q96RI1

UniProtKB/TrEMBL

Q7Z2W0

Related

ENSP00000447149.1, ENST00000551379.5

Conserved Domains (2) summary

cd06936
Location:261 → 481

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:134 → 221

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers
NM_005123.4 → NP_005114.1 bile acid receptor isoform 2

See identical proteins and their annotated locations for NP_005114.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1. This results in a shorter isoform (2, also known as FXRalpha-) compared to isoform 1.

Source sequence(s)

AC010200, BC035654, DA011411, U68233

Consensus CDS

CCDS9078.1

UniProtKB/TrEMBL

B2R7F1, B6ZGS9

Related

ENSP00000448506.1, ENST00000548884.5

Conserved Domains (2) summary

cd06936
Location:247 → 467

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:124 → 207

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers

RNA

NR_135146.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate internal splice site compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC010200, AK312959, BC035654, BC144187

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

100473866..100564414

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047429943.1 → XP_047285899.1 bile acid receptor isoform X2

UniProtKB/TrEMBL

B2R7F1, B6ZGS9
XM_047429944.1 → XP_047285900.1 bile acid receptor isoform X5

UniProtKB/TrEMBL

G8JLB0

Related

ENSP00000315442.5, ENST00000321046.9
XM_011539040.3 → XP_011537342.1 bile acid receptor isoform X1

See identical proteins and their annotated locations for XP_011537342.1

UniProtKB/TrEMBL

B2R7F1, F1DAL1

Conserved Domains (2) summary

cd06936
Location:251 → 471

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cd06962
Location:124 → 211

NR_DBD_FXR; DNA-binding domain of Farnesoid X receptor (FXR) family is composed of two C4-type zinc fingers
XM_011539041.3 → XP_011537343.1 bile acid receptor isoform X3

UniProtKB/TrEMBL

Q7Z2W0

Conserved Domains (2) summary

cd06936
Location:210 → 430

NR_LBD_Fxr; The ligand binding domain of Farnesoid X receptor:a member of the nuclear receptor superfamily of ligand-activated transcription factors

cl02596
Location:137 → 159

NR_DBD_like; DNA-binding domain of nuclear receptors is composed of two C4-type zinc fingers
XM_006719719.3 → XP_006719782.1 bile acid receptor isoform X4

UniProtKB/TrEMBL

G8JLB0

Conserved Domains (1) summary

cl02596
Location:134 → 221

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

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

100435311..100525835

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054373954.1 → XP_054229929.1 bile acid receptor isoform X2

UniProtKB/TrEMBL

B2R7F1, B6ZGS9
XM_054373957.1 → XP_054229932.1 bile acid receptor isoform X5

UniProtKB/TrEMBL

G8JLB0
XM_054373953.1 → XP_054229928.1 bile acid receptor isoform X1

UniProtKB/TrEMBL

B2R7F1, F1DAL1
XM_054373955.1 → XP_054229930.1 bile acid receptor isoform X3

UniProtKB/TrEMBL

Q7Z2W0
XM_054373956.1 → XP_054229931.1 bile acid receptor isoform X4

UniProtKB/TrEMBL

G8JLB0