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Protein

Bile acid receptor

Gene

NR1H4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 innate immune response (PubMed:10334992, PubMed:10334993, 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 (By similarity). 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) (By similarity). 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:12754200, PubMed:15471871, PubMed:17895379). 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:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). 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 (PubMed:12806625, PubMed:16946559). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly (PubMed:12660231, PubMed:12554753, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). 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) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (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 (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). Mediates trans-repression 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 (PubMed:19864602). Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).By similarity2 Publications28 Publications
Isoform 1: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.1 Publication
Isoform 2: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA.1 Publication
Isoform 3: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.1 Publication
Isoform 4: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.2 Publications

Miscellaneous

Ursodeoxycholic (UDCA), a natural agonist of FXR, is approved to treat primary biliary cirrhosis. However, effects are discussed controversial. UDCA is also used to dissolve (cholesterol) gallstones as alternative to surgery.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei375AgonistBy similarity1
Binding sitei383AgonistBy similarity1
Binding sitei461AgonistBy similarity1
Binding sitei483AgonistBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi134 – 209Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri137 – 157NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri173 – 197NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-159418 Recycling of bile acids and salts
R-HSA-192105 Synthesis of bile acids and bile salts
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781 PPARA activates gene expression
R-HSA-211976 Endogenous sterols
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-4090294 SUMOylation of intracellular receptors
SignaLinkiQ96RI1
SIGNORiQ96RI1

Chemistry databases

SwissLipidsiSLP:000001581

Names & Taxonomyi

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
Gene namesi
Name:NR1H4
Synonyms:BAR, FXR, HRR1, RIP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000012504.13
HGNCiHGNC:7967 NR1H4
MIMi603826 gene
neXtProtiNX_Q96RI1

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

May be involved in intrahepatic cholestasis of pregnancy.1 Publication
May be involved in cholesterol cholelithiasis.1 Publication
Cholestasis, progressive familial intrahepatic, 5 (PFIC5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period.
See also OMIM:617049
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077017149Y → YK in PFIC5; loss of isoform 4 transcription regulatory region sequence-specific DNA binding activity; loss of isoform 4 function in regulation of transcription DNA-templated. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132K → R: Abrogates SUMO1-medieated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-289 and A-291. 1 Publication1
Mutagenesisi132K → R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and SETD7. 1 Publication1
Mutagenesisi145S → A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-164. 1 Publication1
Mutagenesisi164S → A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-145. 1 Publication1
Mutagenesisi167K → R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, no effect on interaction with RXRA and SETD7. 1 Publication1
Mutagenesisi220K → R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, impairs interaction with RXRA and SETD7. 1 Publication1
Mutagenesisi227K → R: Decreases transcriptional activation SC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, impairs interaction with RXRA and enhances interaction with SETD7, decreases association with ABCB11/BSEP promoter. 1 Publication1
Mutagenesisi289K → R: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and A-291. 1 Publication1
Mutagenesisi291E → A: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and R-289. 1 Publication1
Mutagenesisi353K → R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and SETD7, decreases association with ABCB11/BSEP promoter. 1 Publication1
Mutagenesisi456T → A: Impairs transcriptional activation of ABCB11/BSEP. 1 Publication1
Mutagenesisi474K → R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and impairs interaction with SETD7. 1 Publication1

Keywords - Diseasei

Disease mutation, Intrahepatic cholestasis

Organism-specific databases

DisGeNETi9971
MalaCardsiNR1H4
MIMi617049 phenotype
OpenTargetsiENSG00000012504
Orphaneti69665 Intrahepatic cholestasis of pregnancy
480476 Progressive familial intrahepatic cholestasis type 5
PharmGKBiPA31752

Chemistry databases

ChEMBLiCHEMBL2047
DrugBankiDB06777 Chenodeoxycholic acid
DB02545 Fexaramine
DB05990 Obeticholic acid
GuidetoPHARMACOLOGYi603

Polymorphism and mutation databases

BioMutaiNR1H4
DMDMi46577705

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535381 – 486Bile acid receptorAdd BLAST486

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki132Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Modified residuei145Phosphoserine; by PKC/PRKCA1 Publication1
Modified residuei164Phosphoserine; by PKC/PRKCA1 Publication1
Modified residuei167N6-acetyllysine; by EP3001
Modified residuei220N6-methyllysine; by SETD71 Publication1
Modified residuei227N6-acetyllysine; by EP3001
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Modified residuei456Phosphothreonine; by PKC/PRKCZ1 Publication1

Post-translational modificationi

Acetylated by EP300. Lys-227 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1.1 Publication
Methylation may increase transactivation of target genes.1 Publication
Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.1 Publication
Sumoylated upon ligand binding.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ96RI1
PeptideAtlasiQ96RI1
PRIDEiQ96RI1
ProteomicsDBi77963
77964 [Q96RI1-1]
77965 [Q96RI1-2]
77966 [Q96RI1-4]

PTM databases

iPTMnetiQ96RI1
PhosphoSitePlusiQ96RI1

Expressioni

Tissue specificityi

Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximately equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximately equal proportions. Expressed in pancreatic beta cells and macrophages.4 Publications

Gene expression databases

BgeeiENSG00000012504 Expressed in 90 organ(s), highest expression level in right lobe of liver
CleanExiHS_NR1H4
ExpressionAtlasiQ96RI1 baseline and differential
GenevisibleiQ96RI1 HS

Organism-specific databases

HPAiHPA047699

Interactioni

Subunit structurei

Binds DNA predominantly as a heterodimer with RXRA. After activation by agonist binding interacts with coactivators. Interacts with NCOA1, NCOA2, PPARGC1A, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1 (PubMed:15202934, PubMed:14684751, PubMed:15187081, PubMed:15471871, PubMed:15911693, PubMed:17895379, PubMed:18755856, PubMed:19805516, PubMed:23462506, PubMed:12718892, PubMed:12718893, PubMed:18621523, PubMed:18391212, PubMed:19410460, PubMed:19586769). Interacts with EP300 and SMARCD1 (By similarity). Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP (PubMed:19833092). Interacts with PAGR1 AND NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM) (PubMed:19556342).By similarity17 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115296, 25 interactors
DIPiDIP-39370N
IntActiQ96RI1, 14 interactors
STRINGi9606.ENSP00000447149

Chemistry databases

BindingDBiQ96RI1

Structurei

Secondary structure

1486
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96RI1
SMRiQ96RI1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96RI1

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini262 – 486NR LBDPROSITE-ProRule annotationAdd BLAST225

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni342 – 350Agonist bindingBy similarity9

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri137 – 157NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri173 – 197NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00870000136372
HOVERGENiHBG108655
InParanoidiQ96RI1
KOiK08537
OMAiYNNVQFP
OrthoDBiEOG091G0I4P
PhylomeDBiQ96RI1
TreeFamiTF316304

Family and domain databases

Gene3Di3.30.50.10, 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

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96RI1-3) [UniParc]FASTAAdd to basket
Also known as: FXRalpha2(+), FXRalpha1, FXRbeta1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN
60 70 80 90 100
LEVEPYSQYS NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR
110 120 130 140 150
MPAETLYQGE TEVAEMPVTK KPRMGASAGR IKGDELCVVC GDRASGYHYN
160 170 180 190 200
ALTCEGCKGF FRRSITKNAV YKCKNGGNCV MDMYMRRKCQ ECRLRKCKEM
210 220 230 240 250
GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG RDLRQVTSTT
260 270 280 290 300
KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI
310 320 330 340 350
LTEMATNHVQ VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF
360 370 380 390 400
NKKLPSGHSD LLEERIRNSG ISDEYITPMF SFYKSIGELK MTQEEYALLT
410 420 430 440 450
AIVILSPDRQ YIKDREAVEK LQEPLLDVLQ KLCKIHQPEN PQHFACLLGR
460 470 480
LTELRTFNHH HAEMLMSWRV NDHKFTPLLC EIWDVQ
Note: Produced by alternative promoter usage.
Length:486
Mass (Da):55,914
Last modified:April 26, 2004 - v2
Checksum:iC23283576A8CF76B
GO
Isoform 2 (identifier: Q96RI1-4) [UniParc]FASTAAdd to basket
Also known as: FXRalpha2(-), FXRalpha4, FXRbeta2

The sequence of this isoform differs from the canonical sequence as follows:
     207-210: Missing.

Note: Produced by alternative splicing of isoform 1.
Show »
Length:482
Mass (Da):55,462
Checksum:i2B9B563B0999C91D
GO
Isoform 3 (identifier: Q96RI1-1) [UniParc]FASTAAdd to basket
Also known as: FXRalpha1(+), FXRalpha1

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

Note: Produced by alternative promoter usage.
Show »
Length:476
Mass (Da):54,862
Checksum:i37FB0351FB447544
GO
Isoform 4 (identifier: Q96RI1-2) [UniParc]FASTAAdd to basket
Also known as: FXRalpha1(-), FXRalpha2

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     207-210: Missing.

Note: Produced by alternative splicing of isoform 3.
Show »
Length:472
Mass (Da):54,409
Checksum:i0A53D414B9049C4C
GO
Isoform 5 (identifier: Q96RI1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     159-209: Missing.

Note: Produced by alternative splicing of isoform 3. No experimental confirmation available.
Show »
Length:425
Mass (Da):48,795
Checksum:iF29FB6B5C5FA2257
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G8JLB0G8JLB0_HUMAN
Bile acid receptor
NR1H4
270Annotation score:
H0YHD5H0YHD5_HUMAN
Bile acid receptor
NR1H4
34Annotation score:
F8W1M1F8W1M1_HUMAN
Bile acid receptor
NR1H4
45Annotation score:
F8W656F8W656_HUMAN
Bile acid receptor
NR1H4
57Annotation score:

Sequence cautioni

The sequence BC144183 differs from that shown. Reason: Frameshift at position 156.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti198K → R in AAI44185 (PubMed:15489334).Curated1
Sequence conflicti217C → V in BC144183 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077017149Y → YK in PFIC5; loss of isoform 4 transcription regulatory region sequence-specific DNA binding activity; loss of isoform 4 function in regulation of transcription DNA-templated. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0101351 – 36MVMQF…MKPAK → MGSKMNLIEHSHLPTTDEFS FSENLF in isoform 3, isoform 4 and isoform 5. 3 PublicationsAdd BLAST36
Alternative sequenceiVSP_044547159 – 209Missing in isoform 5. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_003665207 – 210Missing in isoform 2 and isoform 4. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68233 mRNA Translation: AAB08107.1
AF384555 mRNA Translation: AAK60271.1
AF478445 mRNA Translation: AAM53550.1
AF478446 mRNA Translation: AAM53551.1
AK296612 mRNA Translation: BAH12398.1
AC010200 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97639.1
BC144183 mRNA No translation available.
BC144184 mRNA Translation: AAI44185.1
BC130573 mRNA Translation: AAI30574.1
CCDSiCCDS55873.1 [Q96RI1-1]
CCDS55874.1 [Q96RI1-5]
CCDS55875.1 [Q96RI1-4]
CCDS55876.1 [Q96RI1-3]
CCDS9078.1 [Q96RI1-2]
RefSeqiNP_001193906.1, NM_001206977.1 [Q96RI1-1]
NP_001193907.1, NM_001206978.1 [Q96RI1-5]
NP_001193908.1, NM_001206979.1 [Q96RI1-1]
NP_001193921.1, NM_001206992.1 [Q96RI1-4]
NP_001193922.1, NM_001206993.1 [Q96RI1-3]
NP_005114.1, NM_005123.3 [Q96RI1-2]
XP_011537342.1, XM_011539040.2 [Q96RI1-1]
UniGeneiHs.282735
Hs.732506

Genome annotation databases

EnsembliENST00000188403; ENSP00000188403; ENSG00000012504 [Q96RI1-4]
ENST00000392986; ENSP00000376712; ENSG00000012504 [Q96RI1-1]
ENST00000548884; ENSP00000448506; ENSG00000012504 [Q96RI1-2]
ENST00000549996; ENSP00000448978; ENSG00000012504 [Q96RI1-5]
ENST00000551379; ENSP00000447149; ENSG00000012504 [Q96RI1-3]
GeneIDi9971
KEGGihsa:9971
UCSCiuc001thp.3 human [Q96RI1-3]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Farnesoid X receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68233 mRNA Translation: AAB08107.1
AF384555 mRNA Translation: AAK60271.1
AF478445 mRNA Translation: AAM53550.1
AF478446 mRNA Translation: AAM53551.1
AK296612 mRNA Translation: BAH12398.1
AC010200 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97639.1
BC144183 mRNA No translation available.
BC144184 mRNA Translation: AAI44185.1
BC130573 mRNA Translation: AAI30574.1
CCDSiCCDS55873.1 [Q96RI1-1]
CCDS55874.1 [Q96RI1-5]
CCDS55875.1 [Q96RI1-4]
CCDS55876.1 [Q96RI1-3]
CCDS9078.1 [Q96RI1-2]
RefSeqiNP_001193906.1, NM_001206977.1 [Q96RI1-1]
NP_001193907.1, NM_001206978.1 [Q96RI1-5]
NP_001193908.1, NM_001206979.1 [Q96RI1-1]
NP_001193921.1, NM_001206992.1 [Q96RI1-4]
NP_001193922.1, NM_001206993.1 [Q96RI1-3]
NP_005114.1, NM_005123.3 [Q96RI1-2]
XP_011537342.1, XM_011539040.2 [Q96RI1-1]
UniGeneiHs.282735
Hs.732506

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OSHX-ray1.80A258-486[»]
1OSKmodel-A258-486[»]
3BEJX-ray1.90A/B249-486[»]
3DCTX-ray2.50A252-486[»]
3DCUX-ray2.95A252-486[»]
3FLIX-ray2.00A258-486[»]
3FXVX-ray2.26A258-486[»]
3GD2X-ray3.20A260-486[»]
3HC5X-ray2.60A257-486[»]
3HC6X-ray3.20A257-486[»]
3L1BX-ray1.90A258-486[»]
3OKHX-ray2.50A258-486[»]
3OKIX-ray2.00A/C258-486[»]
3OLFX-ray1.90A/C258-486[»]
3OMKX-ray1.90A/C258-486[»]
3OMMX-ray2.10A/C258-486[»]
3OOFX-ray2.29A/C258-486[»]
3OOKX-ray2.29A/C258-486[»]
3P88X-ray2.95A258-486[»]
3P89X-ray2.30A258-486[»]
3RUTX-ray3.00A258-486[»]
3RUUX-ray2.50A258-486[»]
3RVFX-ray3.10A257-486[»]
4OIVX-ray1.70A/B258-483[»]
4QE6X-ray1.65A258-486[»]
4QE8X-ray2.62A/B258-486[»]
4WVDX-ray2.90A/B258-468[»]
5IAWX-ray2.58A/B259-486[»]
5ICKX-ray2.47A/B258-486[»]
5Q0IX-ray1.70A258-486[»]
5Q0JX-ray2.00A/C258-486[»]
5Q0KX-ray1.80A258-486[»]
5Q0LX-ray2.50A/C258-486[»]
5Q0MX-ray2.20A258-486[»]
5Q0NX-ray2.40A/C258-486[»]
5Q0OX-ray1.90A/C258-486[»]
5Q0PX-ray1.80A/C258-486[»]
5Q0QX-ray2.60A/C258-486[»]
5Q0RX-ray1.91A258-486[»]
5Q0SX-ray2.50A/C258-486[»]
5Q0TX-ray2.14A258-486[»]
5Q0UX-ray1.90A/C258-486[»]
5Q0VX-ray1.87A/C258-486[»]
5Q0WX-ray1.90A258-486[»]
5Q0XX-ray2.26A258-486[»]
5Q0YX-ray2.20A/C258-486[»]
5Q0ZX-ray2.26A/C258-486[»]
5Q10X-ray2.20A258-486[»]
5Q11X-ray2.20A258-486[»]
5Q12X-ray2.00A258-486[»]
5Q13X-ray1.90A/C258-486[»]
5Q14X-ray1.85A/C258-486[»]
5Q15X-ray1.90A/C258-486[»]
5Q16X-ray2.00A/C258-486[»]
5Q17X-ray2.10A258-486[»]
5Q18X-ray1.90A/C258-486[»]
5Q19X-ray1.98A/C258-486[»]
5Q1AX-ray2.00A/C258-486[»]
5Q1BX-ray2.30A/C258-486[»]
5Q1CX-ray2.30A/C258-486[»]
5Q1DX-ray1.89A/C258-486[»]
5Q1EX-ray1.85A258-486[»]
5Q1FX-ray2.30A/C258-486[»]
5Q1GX-ray2.00A258-486[»]
5Q1HX-ray2.20A/C/E/G258-486[»]
5Q1IX-ray1.95A258-486[»]
5WZXX-ray2.95A/B258-485[»]
5Z12X-ray2.75A/D259-486[»]
ProteinModelPortaliQ96RI1
SMRiQ96RI1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115296, 25 interactors
DIPiDIP-39370N
IntActiQ96RI1, 14 interactors
STRINGi9606.ENSP00000447149

Chemistry databases

BindingDBiQ96RI1
ChEMBLiCHEMBL2047
DrugBankiDB06777 Chenodeoxycholic acid
DB02545 Fexaramine
DB05990 Obeticholic acid
GuidetoPHARMACOLOGYi603
SwissLipidsiSLP:000001581

PTM databases

iPTMnetiQ96RI1
PhosphoSitePlusiQ96RI1

Polymorphism and mutation databases

BioMutaiNR1H4
DMDMi46577705

Proteomic databases

PaxDbiQ96RI1
PeptideAtlasiQ96RI1
PRIDEiQ96RI1
ProteomicsDBi77963
77964 [Q96RI1-1]
77965 [Q96RI1-2]
77966 [Q96RI1-4]

Protocols and materials databases

DNASUi9971
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000188403; ENSP00000188403; ENSG00000012504 [Q96RI1-4]
ENST00000392986; ENSP00000376712; ENSG00000012504 [Q96RI1-1]
ENST00000548884; ENSP00000448506; ENSG00000012504 [Q96RI1-2]
ENST00000549996; ENSP00000448978; ENSG00000012504 [Q96RI1-5]
ENST00000551379; ENSP00000447149; ENSG00000012504 [Q96RI1-3]
GeneIDi9971
KEGGihsa:9971
UCSCiuc001thp.3 human [Q96RI1-3]

Organism-specific databases

CTDi9971
DisGeNETi9971
EuPathDBiHostDB:ENSG00000012504.13
GeneCardsiNR1H4
HGNCiHGNC:7967 NR1H4
HPAiHPA047699
MalaCardsiNR1H4
MIMi603826 gene
617049 phenotype
neXtProtiNX_Q96RI1
OpenTargetsiENSG00000012504
Orphaneti69665 Intrahepatic cholestasis of pregnancy
480476 Progressive familial intrahepatic cholestasis type 5
PharmGKBiPA31752
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00870000136372
HOVERGENiHBG108655
InParanoidiQ96RI1
KOiK08537
OMAiYNNVQFP
OrthoDBiEOG091G0I4P
PhylomeDBiQ96RI1
TreeFamiTF316304

Enzyme and pathway databases

ReactomeiR-HSA-159418 Recycling of bile acids and salts
R-HSA-192105 Synthesis of bile acids and bile salts
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781 PPARA activates gene expression
R-HSA-211976 Endogenous sterols
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-4090294 SUMOylation of intracellular receptors
SignaLinkiQ96RI1
SIGNORiQ96RI1

Miscellaneous databases

ChiTaRSiNR1H4 human
EvolutionaryTraceiQ96RI1
GeneWikiiFarnesoid_X_receptor
GenomeRNAii9971
PROiPR:Q96RI1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000012504 Expressed in 90 organ(s), highest expression level in right lobe of liver
CleanExiHS_NR1H4
ExpressionAtlasiQ96RI1 baseline and differential
GenevisibleiQ96RI1 HS

Family and domain databases

Gene3Di3.30.50.10, 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
ProtoNetiSearch...

Entry informationi

Entry nameiNR1H4_HUMAN
AccessioniPrimary (citable) accession number: Q96RI1
Secondary accession number(s): A1L4K5
, B7Z412, B7ZM06, F8VYG8, Q8NFP5, Q8NFP6, Q92943
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: April 26, 2004
Last modified: November 7, 2018
This is version 187 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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