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Entry version 189 (22 Apr 2020)
Sequence version 3 (27 Jul 2011)
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Protein

Bile acid receptor

Gene

Nr1h4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved in innate immune response (PubMed:11030617, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (PubMed:20091679, PubMed:20483916). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (PubMed:21383957, PubMed:25651182, PubMed:25545350). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:21383957). In ileal enterocytes activates FABP6/IBABP (involved in cytosolic transport), SLC51A/OSTA and SLC51B/OSTB (involved in secretion of conjugated BAs to the portal blood), and repressor NR0B2/SHP thereby indirectly inhibiting SLC10A2/ASBT (involved in BA uptake) (By similarity). In the intestine activates FGF15 expression and secretion leading to hepatic CYP7A1 repression; the function also involves the coordinated induction of hepatic KLB/beta-klotho expression (PubMed:16213224, PubMed:26505219). Transcriptional activation of FABP6/IBAP and SCD1 but not of ABCB11 is isoform-specific (PubMed:12393883). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (By similarity). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 isoform SREBP-1C (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly) (PubMed:12421815, PubMed:15146238). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 probably involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557, PubMed:15146238). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:15564327, PubMed:16446356, PubMed:16557297, PubMed:16410358, PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (PubMed:16473946, PubMed:21242261). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:19864602). Mediates transrepression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (By similarity). Involved in the TLR9-mediated protective mechanism in intestinal inflammation (PubMed:23372731). Plays a anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling (PubMed:18972444).By similarity2 Publications27 Publications
Activates transcription of IBAP and SDC1.1 Publication
Activates transcription of IBAP and SDC1.1 Publication

Miscellaneous

Mouse Nr1h4/FXR is less responsive to CDCA and more responsive to cholic acid (CA) than human FXR.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei377AgonistBy similarity1
Binding sitei385AgonistBy similarity1
Binding sitei463AgonistBy similarity1
Binding sitei485AgonistBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position and type of each DNA-binding domain present within the protein.<p><a href='/help/dna_bind' target='_top'>More...</a></p>DNA bindingi135 – 210Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri138 – 158NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri174 – 198NR C4-typePROSITE-ProRule annotationAdd BLAST25

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, DNA-binding, Receptor, Repressor
Biological processImmunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-159418 Recycling of bile acids and salts
R-MMU-192105 Synthesis of bile acids and bile salts
R-MMU-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-MMU-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-MMU-211976 Endogenous sterols
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Bile acid receptor
Alternative name(s):
Farnesoid X-activated receptor
Farnesol receptor HRR-1
Nuclear receptor subfamily 1 group H member 4
Retinoid X receptor-interacting protein 14
Short name:
RXR-interacting protein 14
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Nr1h4
Synonyms:Bar, Fxr, Rip14
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 10

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:1352464 Nr1h4

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Activation protects mice against cholestasis, development of chronical intestinal inflammation and fibrosis. May suppress intestinal tumorigenesis.3 Publications

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. Reduced bile acid pools and reduced fecal bile acid excretion.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi370K → N: Increases affinity to CDCA and transcriptional activity in response to CDCA; when associated with I-388. 1 Publication1
Mutagenesisi388V → I: Increases affinity to CDCA and transcriptional activity in response to CDCA; when associated with N-370. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL5343

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000535391 – 488Bile acid receptorAdd BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki133Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei146Phosphoserine; by PKC/PRKCABy similarity1
Modified residuei165Phosphoserine; by PKC/PRKCABy similarity1
Modified residuei168N6-acetyllysine; by EP300By similarity1
Modified residuei221N6-methyllysine; by SETD7By similarity1
Modified residuei228N6-acetyllysine; by EP300By similarity1
Cross-linki291Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei458Phosphothreonine; by PKC/PRKCZBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Acetylated by EP300 (PubMed:18842595). Lys-228 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1 (By similarity). Elevated acetylation levels are found in metabolic disease states (mouse models of obesity and type II diabetes) (PubMed:19883617).By similarity2 Publications
Methylation may increase transactivation of target genes.By similarity
Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.By similarity
Sumoylated upon ligand binding.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q60641

PRoteomics IDEntifications database

More...
PRIDEi
Q60641

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q60641

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q60641

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in liver and kidney. Expressed in pancreatic beta cells and macrophages. Expressed in the villus epithelium in adult ileum, with highest expression in the intervillus regions. Expression in colon is reduced by inflammation.4 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000047638 Expressed in epithelium of small intestine and 109 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q60641 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q60641 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterodimer with RXRA; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity). Binds DNA predominantly as a heterodimer with RXRA (PubMed:7760852). After activation by agonist binding interacts with coactivators.

Interacts with PPARGC1A, SMARCA4 and EP300 (PubMed:14729567, PubMed:18842595, PubMed:19805516).

Interacts with NCOA1, NCOA2, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1.

Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP.

Interacts with PAGR1 AND NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM) (By similarity).

Interacts with NR5A2 (PubMed:20483916).

By similarity5 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
203043, 7 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q60641

Database of interacting proteins

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DIPi
DIP-443N

Protein interaction database and analysis system

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IntActi
Q60641, 1 interactor

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000053092

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q60641

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
Q60641 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q60641

Database of comparative protein structure models

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ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini264 – 488NR LBDPROSITE-ProRule annotationAdd BLAST225

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni344 – 352Agonist bindingBy similarity9

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 158NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri174 – 198NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3575 Eukaryota
ENOG410XRZC LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158037

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_007368_12_3_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q60641

KEGG Orthology (KO)

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KOi
K08537

Identification of Orthologs from Complete Genome Data

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OMAi
HPDNPQH

Database of Orthologous Groups

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OrthoDBi
1137281at2759

TreeFam database of animal gene trees

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TreeFami
TF316304

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.565.10, 1 hit
3.30.50.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR035500 NHR-like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA

Pfam protein domain database

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Pfami
View protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48508 SSF48508, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q60641-1) [UniParc]FASTAAdd to basket
Also known as: FXRbeta1, FXRalpha3, FXRalpha2(+)

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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MVMQFQGLEN PIQISLHHSH RLSGFVPEGM SVKPAKGMLT EHAAGPLGQN
60 70 80 90 100
LDLESYSPYN NVPFPQVQPQ ISSSSYYSNL GFYPQQPEDW YSPGIYELRR
110 120 130 140 150
MPAETGYQGE TEVSEMPVTK KPRMAAASAG RIKGDELCVV CGDRASGYHY
160 170 180 190 200
NALTCEGCKG FFRRSITKNA VYKCKNGGNC VMDMYMRRKC QECRLRKCKE
210 220 230 240 250
MGMLAECMYT GLLTEIQCKS KRLRKNVKQH ADQTANEDDS EGRDLRQVTS
260 270 280 290 300
TTKFCREKTE LTADQQTLLD YIMDSYNKQR MPQEITNKIL KEEFSAEENF
310 320 330 340 350
LILTEMATSH VQILVEFTKK LPGFQTLDHE DQIALLKGSA VEAMFLRSAE
360 370 380 390 400
IFNKKLPAGH ADLLEERIRK SGISDEYITP MFSFYKSVGE LKMTQEEYAL
410 420 430 440 450
LTAIVILSPD RQYIKDREAV EKLQEPLLDV LQKLCKMYQP ENPQHFACLL
460 470 480
GRLTELRTFN HHHAEMLMSW RVNDHKFTPL LCEIWDVQ
Note: Produced by alternative promoter usage.
Length:488
Mass (Da):55,994
Last modified:July 27, 2011 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3E59B7146F8ECC86
GO
Isoform 2 (identifier: Q60641-2) [UniParc]FASTAAdd to basket
Also known as: FXRbeta2, FXFRalpha4, FXRalpha2(-)

The sequence of this isoform differs from the canonical sequence as follows:
     208-211: Missing.

Note: Produced by alternative splicing of isoform 1.Curated
Show »
Length:484
Mass (Da):55,542
Checksum:i06B56494305A438A
GO
Isoform 3 (identifier: Q60641-3) [UniParc]FASTAAdd to basket
Also known as: FXRalpha1, FXRalpha1(+)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISLHHSHRLSGFVPEGMSVKPAK → MNLIGHSHLQATDEFSLSESLF

Note: Produced by alternative promoter usage.Curated
Show »
Length:474
Mass (Da):54,439
Checksum:i8629C4BAD8DC75B0
GO
Isoform 4 (identifier: Q60641-4) [UniParc]FASTAAdd to basket
Also known as: FXRalpha2, FXRalpha1(-)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISLHHSHRLSGFVPEGMSVKPAK → MNLIGHSHLQATDEFSLSESLF
     208-211: Missing.

Note: Produced by alternative splicing of isoform 3.Curated
Show »
Length:470
Mass (Da):53,987
Checksum:i01E7DDA2F92BD35B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti28E → D in AAC53066 (PubMed:7760852).Curated1
Sequence conflicti28E → D in AAH15261 (PubMed:15489334).Curated1
Sequence conflicti199K → R in AAC53065 (PubMed:7760852).Curated1
Sequence conflicti199K → R in AAC53066 (PubMed:7760852).Curated1
Sequence conflicti199K → R in AAC52978 (PubMed:7760852).Curated1
Sequence conflicti199K → R in AAH15261 (PubMed:15489334).Curated1
Sequence conflicti235A → V in AAC53065 (PubMed:7760852).Curated1
Sequence conflicti235A → V in AAC53066 (PubMed:7760852).Curated1
Sequence conflicti235A → V in AAC52978 (PubMed:7760852).Curated1
Sequence conflicti235A → V in AAH15261 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0581571 – 36MVMQF…VKPAK → MNLIGHSHLQATDEFSLSES LF in isoform 3 and isoform 4. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_003666208 – 211Missing in isoform 2 and isoform 4. 3 Publications4

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U09416 mRNA Translation: AAC53066.1
U09417 mRNA Translation: AAC53065.1
U09418 mRNA Translation: AAC52978.1
AC152417 Genomic DNA No translation available.
BC015261 mRNA Translation: AAH15261.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS24116.1 [Q60641-2]
CCDS48668.1 [Q60641-1]
CCDS48669.1 [Q60641-3]

Protein sequence database of the Protein Information Resource

More...
PIRi
I49018
I49019
I49020

NCBI Reference Sequences

More...
RefSeqi
NP_001156976.1, NM_001163504.1 [Q60641-3]
NP_001157172.1, NM_001163700.1 [Q60641-1]
XP_006513454.1, XM_006513391.3 [Q60641-3]
XP_006513456.1, XM_006513393.3 [Q60641-4]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000058126; ENSMUSP00000053092; ENSMUSG00000047638 [Q60641-2]
ENSMUST00000105296; ENSMUSP00000100933; ENSMUSG00000047638 [Q60641-1]
ENSMUST00000105297; ENSMUSP00000100934; ENSMUSG00000047638 [Q60641-3]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
20186

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:20186

UCSC genome browser

More...
UCSCi
uc007gsg.2 mouse [Q60641-1]
uc007gsh.2 mouse

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09416 mRNA Translation: AAC53066.1
U09417 mRNA Translation: AAC53065.1
U09418 mRNA Translation: AAC52978.1
AC152417 Genomic DNA No translation available.
BC015261 mRNA Translation: AAH15261.1
CCDSiCCDS24116.1 [Q60641-2]
CCDS48668.1 [Q60641-1]
CCDS48669.1 [Q60641-3]
PIRiI49018
I49019
I49020
RefSeqiNP_001156976.1, NM_001163504.1 [Q60641-3]
NP_001157172.1, NM_001163700.1 [Q60641-1]
XP_006513454.1, XM_006513391.3 [Q60641-3]
XP_006513456.1, XM_006513393.3 [Q60641-4]

3D structure databases

SMRiQ60641
ModBaseiSearch...

Protein-protein interaction databases

BioGridi203043, 7 interactors
CORUMiQ60641
DIPiDIP-443N
IntActiQ60641, 1 interactor
STRINGi10090.ENSMUSP00000053092

Chemistry databases

BindingDBiQ60641
ChEMBLiCHEMBL5343

PTM databases

iPTMnetiQ60641
PhosphoSitePlusiQ60641

Proteomic databases

PaxDbiQ60641
PRIDEiQ60641

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
17868 424 antibodies

Genome annotation databases

EnsembliENSMUST00000058126; ENSMUSP00000053092; ENSMUSG00000047638 [Q60641-2]
ENSMUST00000105296; ENSMUSP00000100933; ENSMUSG00000047638 [Q60641-1]
ENSMUST00000105297; ENSMUSP00000100934; ENSMUSG00000047638 [Q60641-3]
GeneIDi20186
KEGGimmu:20186
UCSCiuc007gsg.2 mouse [Q60641-1]
uc007gsh.2 mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
9971
MGIiMGI:1352464 Nr1h4

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00940000158037
HOGENOMiCLU_007368_12_3_1
InParanoidiQ60641
KOiK08537
OMAiHPDNPQH
OrthoDBi1137281at2759
TreeFamiTF316304

Enzyme and pathway databases

ReactomeiR-MMU-159418 Recycling of bile acids and salts
R-MMU-192105 Synthesis of bile acids and bile salts
R-MMU-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-MMU-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-MMU-211976 Endogenous sterols
R-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-4090294 SUMOylation of intracellular receptors

Miscellaneous databases

Protein Ontology

More...
PROi
PR:Q60641
RNActiQ60641 protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000047638 Expressed in epithelium of small intestine and 109 other tissues
ExpressionAtlasiQ60641 baseline and differential
GenevisibleiQ60641 MM

Family and domain databases

Gene3Di1.10.565.10, 1 hit
3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR-like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNR1H4_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q60641
Secondary accession number(s): D3YTT2
, E9QJW2, Q60642, Q60643
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: July 27, 2011
Last modified: April 22, 2020
This is version 189 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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