Liver X receptor alpha

Last updated
NR1H3
Protein NR1H3 PDB 1uhl.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NR1H3 , LXR-a, LXRA, RLD-1, Liver X receptor alpha, nuclear receptor subfamily 1 group H member 3
External IDs OMIM: 602423 MGI: 1352462 HomoloGene: 21165 GeneCards: NR1H3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001130101
NM_001130102
NM_001251934
NM_001251935
NM_005693

Contents

NM_001177730
NM_013839
NM_001355279

RefSeq (protein)

NP_001171201
NP_038867
NP_001342208

Location (UCSC) Chr 11: 47.25 – 47.27 Mb Chr 2: 91.01 – 91.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor subfamily 1, group H, member 3). [5] [6]

Expression

miRNA hsa-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613. [7]

Function

The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases. [8] The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs) and regulate expression of target genes containing LXR response elements. [9] [10] Restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin. [11]

Interactions

Liver X receptor alpha has been shown to interact with EDF1 [12] and Small heterodimer partner. [13] LXRα activates the transcription factor SREBP-1c, resulting in lipogenesis. [14]

In 2016, a study found 70% of individuals in two families with a rare form of rapidly progressing multiple sclerosis had a mutation in NR1H3. [15] However, an analysis from The International Multiple Sclerosis Genetics Consortium using a 13-fold larger sample size could not find any evidence that the mutation in question (p.Arg415Gln) associated with multiple sclerosis, refuting these findings. [16]

Related Research Articles

<span class="mw-page-title-main">Peroxisome proliferator-activated receptor</span> Group of nuclear receptor proteins

In the field of molecular biology, the peroxisome proliferator–activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism, and tumorigenesis of higher organisms.

<span class="mw-page-title-main">Sterol regulatory element-binding protein</span> Protein family

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.

<span class="mw-page-title-main">Estrogen receptor alpha</span> Protein-coding gene in the species Homo sapiens

Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.

<span class="mw-page-title-main">Farnesoid X receptor</span> Protein-coding gene in the species Homo sapiens

The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4, is a nuclear receptor that is encoded by the NR1H4 gene in humans.

<span class="mw-page-title-main">Liver X receptor</span> Nuclear receptor

The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized.

The ERRs are orphan nuclear receptors, meaning the identity of their endogenous ligand has yet to be unambiguously determined. They are named because of sequence homology with estrogen receptors, but do not appear to bind estrogens or other tested steroid hormones.

<span class="mw-page-title-main">Nuclear receptor coactivator 1</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 1 (NCOA1), also called steroid receptor coactivator-1 (SRC-1), is a transcriptional coregulatory protein that contains several nuclear receptor–interacting domains and possesses intrinsic histone acetyltransferase activity. It is encoded by the gene NCOA1.

<span class="mw-page-title-main">Liver receptor homolog-1</span> Protein-coding gene in the species Homo sapiens

The liver receptor homolog-1 (LRH-1) also known as totipotency pioneer factor NR5A2 is a protein that in humans is encoded by the NR5A2 gene. LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein-coding gene in the species Homo sapiens

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

<span class="mw-page-title-main">Peroxisome proliferator-activated receptor gamma</span> Nuclear receptor protein found in humans

Peroxisome proliferator-activated receptor gamma, also known as the glitazone reverse insulin resistance receptor, or NR1C3 is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the PPARG gene.

<span class="mw-page-title-main">Rev-ErbA alpha</span> Protein-coding gene in the species Homo sapiens

Rev-Erb alpha (Rev-Erbɑ), also known as nuclear receptor subfamily 1 group D member 1 (NR1D1), is one of two Rev-Erb proteins in the nuclear receptor (NR) family of intracellular transcription factors. In humans, REV-ERBɑ is encoded by the NR1D1 gene, which is highly conserved across animal species.

<span class="mw-page-title-main">Retinoid X receptor alpha</span> Protein-coding gene in the species Homo sapiens

Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.

<span class="mw-page-title-main">PPARGC1A</span> Protein

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a protein that in humans is encoded by the PPARGC1A gene. PPARGC1A is also known as human accelerated region 20 (HAR20). It may, therefore, have played a key role in differentiating humans from apes.

<span class="mw-page-title-main">Peroxisome proliferator-activated receptor alpha</span> Nuclear receptor protein found in humans

Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1, is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the PPARA gene. Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.

<span class="mw-page-title-main">Retinoic acid receptor alpha</span> Protein-coding gene in the species Homo sapiens

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.

<span class="mw-page-title-main">NRIP1</span> Protein-coding gene in the species Homo sapiens

Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.

<span class="mw-page-title-main">Peroxisome proliferator-activated receptor delta</span> Nuclear receptor protein found in humans

Peroxisome proliferator-activated receptor delta(PPAR-delta), or (PPAR-beta), also known as Nuclear hormone receptor 1(NUC1) is a nuclear receptor that in humans is encoded by the PPARD gene.

<span class="mw-page-title-main">Estrogen-related receptor alpha</span> Protein-coding gene in the species Homo sapiens

Estrogen-related receptor alpha (ERRα), also known as NR3B1, is a nuclear receptor that in humans is encoded by the ESRRA gene. ERRα was originally cloned by DNA sequence homology to the estrogen receptor alpha, but subsequent ligand binding and reporter-gene transfection experiments demonstrated that estrogens did not regulate ERRα. Currently, ERRα is considered an orphan nuclear receptor.

<span class="mw-page-title-main">Liver X receptor beta</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">PRIC285</span> Human gene

Peroxisomal proliferator-activated receptor A interacting complex 285, also known as PRIC285, is a human gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000025434 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000002108 - 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. Miyata KS, McCaw SE, Patel HV, Rachubinski RA, Capone JP (Apr 1996). "The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling". The Journal of Biological Chemistry. 271 (16): 9189–92. doi: 10.1074/jbc.271.16.9189 . PMID   8621574.
  6. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ (May 1995). "LXR, a nuclear receptor that defines a distinct retinoid response pathway". Genes & Development. 9 (9): 1033–45. doi: 10.1101/gad.9.9.1033 . PMID   7744246.
  7. http://mend.endojournals.org/content/25/4/584.abstract [ dead link ]
  8. Christoffolete MA, Doleschall M, Egri P, Liposits Z, Zavacki AM, Bianco AC, et al. (2010). "Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway". The Journal of Endocrinology. 205 (2): 179–86. doi:10.1677/JOE-09-0448. PMC   3133926 . PMID   20176747.
  9. Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B, Gustafsson JA, et al. (Jun 2009). "Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice". The Journal of Clinical Investigation. 119 (6): 1626–37. doi:10.1172/JCI35288. PMC   2689129 . PMID   19436111.
  10. "Entrez Gene: nuclear receptor subfamily 1".
  11. Gupta DS, Kaul D, Kanwar AJ, Parsad D (Jan 2010). "Psoriasis: crucial role of LXR-alpha RNomics". Genes and Immunity. 11 (1): 37–44. doi: 10.1038/gene.2009.63 . PMID   19798078.
  12. Brendel C, Gelman L, Auwerx J (Jun 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology. 16 (6): 1367–77. doi: 10.1210/mend.16.6.0843 . PMID   12040021.
  13. 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.
  14. Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, et al. (2010). "Leptin therapy in insulin-deficient type I diabetes". Proceedings of the National Academy of Sciences of the United States of America . 107 (11): 4813–9. Bibcode:2010PNAS..107.4813W. doi: 10.1073/pnas.0909422107 . PMC   2841945 . PMID   20194735.
  15. Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, et al. (2016). "Nuclear Receptor NR1H3 in Familial Multiple Sclerosis". Neuron. 90 (5): 948–54. doi:10.1016/j.neuron.2016.04.039. PMC   5092154 . PMID   27253448.
  16. Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, et al. (International Multiple Sclerosis Genetics Consortium) (October 2016). "NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk". Neuron. 92 (2): 333–335. doi:10.1016/j.neuron.2016.09.052. PMC   5641967 . PMID   27764667.

Further reading

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