Liver X receptor beta

Protein-coding gene in the species Homo sapiens
NR1H2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1P8D, 1PQ6, 1PQ9, 1PQC, 1UPV, 1UPW, 3KFC, 3L0E, 4DK7, 4DK8, 4RAK, 5HJP, 4NQA, 5I4V,%%s4NQA

Identifiers
AliasesNR1H2, LXR-b, LXRB, NER, NER-I, RIP15, UNR, Liver X receptor beta, nuclear receptor subfamily 1 group H member 2
External IDsOMIM: 600380 MGI: 1352463 HomoloGene: 21397 GeneCards: NR1H2
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for NR1H2
Genomic location for NR1H2
Band19q13.33Start50,329,653 bp[1]
End50,383,388 bp[1]
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)[2]
Chromosome 7 (mouse)
Genomic location for NR1H2
Genomic location for NR1H2
Band7|7 B3Start44,199,040 bp[2]
End44,203,375 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • popliteal artery

  • right coronary artery

  • thoracic aorta

  • left coronary artery

  • ascending aorta

  • gastric mucosa

  • gastrocnemius muscle

  • right lung

  • left uterine tube

  • right uterine tube
Top expressed in
  • lip

  • superior frontal gyrus

  • duodenum

  • thymus

  • esophagus

  • cerebellar cortex

  • molar

  • yolk sac

  • saccule

  • right lung
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • DNA binding
  • sequence-specific DNA binding
  • DNA-binding transcription factor activity
  • ATPase binding
  • zinc ion binding
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • metal ion binding
  • retinoid X receptor binding
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • steroid hormone receptor activity
  • apolipoprotein A-I receptor binding
  • nuclear receptor activity
  • protein binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • transcription cis-regulatory region binding
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • transcription factor binding
  • nuclear receptor coactivator activity
  • signaling receptor activity
Cellular component
  • cytoplasm
  • nucleoplasm
  • nucleus
  • RNA polymerase II transcription regulator complex
Biological process
  • positive regulation of high-density lipoprotein particle assembly
  • negative regulation of proteolysis
  • positive regulation of triglyceride biosynthetic process
  • positive regulation of protein metabolic process
  • negative regulation of interferon-gamma-mediated signaling pathway
  • positive regulation of cholesterol transport
  • regulation of transcription, DNA-templated
  • cellular lipid metabolic process
  • regulation of transcription by RNA polymerase II
  • positive regulation of secretion of lysosomal enzymes
  • positive regulation of lipid storage
  • positive regulation of lipoprotein lipase activity
  • negative regulation of transcription by RNA polymerase II
  • positive regulation of fatty acid biosynthetic process
  • negative regulation of gene expression
  • transcription, DNA-templated
  • positive regulation of transcription, DNA-templated
  • negative regulation of cholesterol storage
  • negative regulation of pinocytosis
  • positive regulation of gene expression
  • retinoic acid receptor signaling pathway
  • positive regulation of cholesterol efflux
  • positive regulation of pancreatic juice secretion
  • lipid homeostasis
  • negative regulation of lipid transport
  • transcription initiation from RNA polymerase II promoter
  • negative regulation of transcription, DNA-templated
  • negative regulation of macrophage derived foam cell differentiation
  • positive regulation of transcription by RNA polymerase II
  • steroid hormone mediated signaling pathway
  • cholesterol homeostasis
  • lipid metabolism
  • multicellular organism development
  • cell differentiation
  • cellular response to lipopolysaccharide
  • negative regulation of cold-induced thermogenesis
  • intracellular receptor signaling pathway
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

7376

22260

Ensembl

ENSG00000131408

ENSMUSG00000060601

UniProt

P55055

Q60644

RefSeq (mRNA)

NM_007121
NM_001256647

NM_001285517
NM_001285518
NM_001285519
NM_009473

RefSeq (protein)

NP_001243576
NP_009052
NP_009052.3

NP_001272446
NP_001272447
NP_001272448
NP_033499

Location (UCSC)Chr 19: 50.33 – 50.38 MbChr 7: 44.2 – 44.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the NR1H2 gene (nuclear receptor subfamily 1, group H, member 2).[5]

Function

The liver X receptors (LXRs) were originally identified as orphan members of the nuclear receptor superfamily because their ligands were unknown. Like other receptors in the family, LXRs heterodimerize with retinoid X receptor and bind to specific response elements (LXREs) characterized by direct repeats separated by 4 nucleotides. Two genes, alpha (LXRA) and beta, are known to encode LXR proteins.[5][6]

Structure

Crystal structure of human liver X receptor β(LXRβ) forming heterodimer with its partner retinoid X receptor α(RXRα) on its cognate element, an AGGTCA direct repeat spaced by 4 nt shows an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element.[7]

Interactions

Liver X receptor beta has been shown to interact with NCOA6[8] and Retinoid X receptor alpha.[9]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131408 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060601 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: NR1H2 nuclear receptor subfamily 1, group H, member 2".
  6. ^ Song C, Hiipakka RA, Kokontis JM, Liao S (Jun 1995). "Ubiquitous receptor: structures, immunocytochemical localization, and modulation of gene activation by receptors for retinoic acids and thyroid hormones". Annals of the New York Academy of Sciences. 761 (2): 38–49. Bibcode:1995NYASA.761...38S. doi:10.1111/j.1749-6632.1995.tb31367.x. PMID 7625741. S2CID 27208069.
  7. ^ Lou X, Toresson G, Benod C, Suh JH, Philips KJ, Webb P, Gustafsson JA (Mar 2014). "Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA". Nature Structural & Molecular Biology. 21 (3): 277–81. doi:10.1038/nsmb.2778. PMID 24561505. S2CID 23226682.
  8. ^ Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (Feb 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Molecular Endocrinology. 15 (2): 241–54. doi:10.1210/mend.15.2.0595. PMID 11158331.
  9. ^ Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.

Further reading

  • Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.
  • Le Beau MM, Song C, Davis EM, Hiipakka RA, Kokontis JM, Liao S (Mar 1995). "Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization". Genomics. 26 (1): 166–8. doi:10.1016/0888-7543(95)80100-Z. PMID 7782080.
  • Shinar DM, Endo N, Rutledge SJ, Vogel R, Rodan GA, Schmidt A (Sep 1994). "NER, a new member of the gene family encoding the human steroid hormone nuclear receptor". Gene. 147 (2): 273–6. doi:10.1016/0378-1119(94)90080-9. PMID 7926814.
  • Song C, Kokontis JM, Hiipakka RA, Liao S (Nov 1994). "Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors". Proceedings of the National Academy of Sciences of the United States of America. 91 (23): 10809–13. Bibcode:1994PNAS...9110809S. doi:10.1073/pnas.91.23.10809. PMC 45115. PMID 7971966.
  • Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ (Jan 1999). "Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta". Proceedings of the National Academy of Sciences of the United States of America. 96 (1): 266–71. Bibcode:1999PNAS...96..266J. doi:10.1073/pnas.96.1.266. PMC 15128. PMID 9874807.
  • Feltkamp D, Wiebel FF, Alberti S, Gustafsson JA (Apr 1999). "Identification of a novel DNA binding site for nuclear orphan receptor OR1". The Journal of Biological Chemistry. 274 (15): 10421–9. doi:10.1074/jbc.274.15.10421. PMID 10187832.
  • Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (Feb 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Molecular Endocrinology. 15 (2): 241–54. doi:10.1210/mend.15.2.0595. PMID 11158331.
  • Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, Wilson JG, Willson TM, Collins JL, Kliewer SA (Nov 2001). "Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages". The Journal of Biological Chemistry. 276 (47): 43509–15. doi:10.1074/jbc.M106155200. PMID 11546778.
  • Whitney KD, Watson MA, Collins JL, Benson WG, Stone TM, Numerick MJ, Tippin TK, Wilson JG, Winegar DA, Kliewer SA (Jun 2002). "Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system". Molecular Endocrinology. 16 (6): 1378–85. doi:10.1210/mend.16.6.0835. PMID 12040022.
  • Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (Sep 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
  • Mo J, Fang SJ, Chen W, Blobe GC (Dec 2002). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". The Journal of Biological Chemistry. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874.
  • Williams S, Bledsoe RK, Collins JL, Boggs S, Lambert MH, Miller AB, Moore J, McKee DD, Moore L, Nichols J, Parks D, Watson M, Wisely B, Willson TM (Jul 2003). "X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch". The Journal of Biological Chemistry. 278 (29): 27138–43. doi:10.1074/jbc.M302260200. PMID 12736258.
  • Färnegårdh M, Bonn T, Sun S, Ljunggren J, Ahola H, Wilhelmsson A, Gustafsson JA, Carlquist M (Oct 2003). "The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands". The Journal of Biological Chemistry. 278 (40): 38821–8. doi:10.1074/jbc.M304842200. PMID 12819202.
  • Fukuchi J, Song C, Ko AL, Liao S (Sep 2003). "Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors". Steroids. 68 (7–8): 685–91. doi:10.1016/S0039-128X(03)00100-4. PMID 12957674. S2CID 6023862.
  • Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H (Dec 2003). "Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist". Journal of Molecular Biology. 334 (5): 853–61. doi:10.1016/j.jmb.2003.10.033. PMID 14643652.
  • Walczak R, Joseph SB, Laffitte BA, Castrillo A, Pei L, Tontonoz P (Mar 2004). "Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors". The Journal of Biological Chemistry. 279 (11): 9905–11. doi:10.1074/jbc.M310587200. PMID 14699103.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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  • 1p8d: X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol
    1p8d: X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol
  • 1pq6: HUMAN LXR BETA HORMONE RECEPTOR / GW3965 COMPLEX
    1pq6: HUMAN LXR BETA HORMONE RECEPTOR / GW3965 COMPLEX
  • 1pq9: HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317 COMPLEX
    1pq9: HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317 COMPLEX
  • 1pqc: HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317
    1pqc: HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317
  • 1upv: CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST
    1upv: CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST
  • 1upw: CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST
    1upw: CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies
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FXRTooltip Farnesoid X receptor and LXRTooltip liver X receptor modulators
FXRTooltip Farnesoid X receptor
LXRTooltip Liver X receptor
See also
Receptor/signaling modulators
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