Liver receptor homolog-1

Last updated

NR5A2
Protein NR5A2 PDB 1yok.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NR5A2 , B1F, B1F2, CPF, FTF, FTZ-F1, FTZ-F1beta, LRH-1, LRH1, hB1F-2, nuclear receptor subfamily 5 group A member 2
External IDs OMIM: 604453; MGI: 1346834; HomoloGene: 20827; GeneCards: NR5A2; OMA:NR5A2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2494

26424

Ensembl

ENSG00000116833

ENSMUSG00000026398

UniProt

O00482

P45448

RefSeq (mRNA)

NM_001276464
NM_003822
NM_205860

NM_001159769
NM_030676

RefSeq (protein)

NP_001263393
NP_003813
NP_995582

NP_001153241
NP_109601

Location (UCSC) Chr 1: 200.03 – 200.18 Mb Chr 1: 136.77 – 136.89 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The liver receptor homolog-1 (LRH-1) also known as totipotency pioneer factor NR5A2 (nuclear receptor subfamily 5, group A, member 2) is a protein that in humans is encoded by the NR5A2 gene. [5] [6] LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.

LRH-1 plays a critical role in the regulation of development, cholesterol transport, bile acid homeostasis and steroidogenesis. [7] [8] [9] [10]

LRH-1 is important for maintaining pluripotence of stem cells during embryonic development. [11] [10]

Nr5a2 was recently identified at a totipotent pioneer factor. [10] The orphan nuclear receptor Nr5a2 has been shown to be important in fertility, ovarian function, [12] and zygotic genome activation (ZGA). [10] Heterozygosity for Nr5a2 is associated with reduced ovarian function, specifically in the synthesis of progesterone. This impaired progesterone production was associated with infertility in female mice, as well as increased incidence of pregnancy loss. [12] The loss of embryos around implantation associated with Nr5a2+/- mice indicated a possible interaction with genome-wide gene expression in early embryo development. Upon further investigation, Nr5a2 was found to regulate ZGA in mice embryos similar to that of Zelda in Drosophila. Nr5a2 is maternally contributed and regulates transcription activity in the early embryo by binding to distal cis-regulatory sequences and promoting chromatin accessibility. The change in chromatin conformation allows for the activation of transcription of about 72% of genes involved in ZGA. [10]

Interactions

Liver receptor homolog-1 has been shown to interact with the small heterodimer partner. [13] [14]

Related Research Articles

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Glucocorticoid receptor</span> Receptor to which cortisol and other glucocorticoids bind

The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind.

<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">Pregnane X receptor</span> Mammalian protein found in Homo sapiens

In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 gene.

<span class="mw-page-title-main">Constitutive androstane receptor</span> Protein-coding gene in humans

The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of endobiotic and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs.

<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">Nuclear receptor 4A1</span> Mammalian protein found in Homo sapiens

The nuclear receptor 4A1 also known as Nur77, TR3, and NGFI-B is a protein that in humans is encoded by the NR4A1 gene.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein found in humans

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">RELA</span> Protein-coding gene in the species Homo sapiens

Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.

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

RAR-related orphan receptor alpha (RORα), also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene. RORα participates in the transcriptional regulation of some genes involved in circadian rhythm. In mice, RORα is essential for development of cerebellum through direct regulation of genes expressed in Purkinje cells. It also plays an essential role in the development of type 2 innate lymphoid cells (ILC2) and mutant animals are ILC2 deficient. In addition, although present in normal numbers, the ILC3 and Th17 cells from RORα deficient mice are defective for cytokine production.

<span class="mw-page-title-main">Liver X receptor alpha</span> Nuclear receptor protein found in humans

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.

<span class="mw-page-title-main">COUP-TFI</span> Protein found in humans

COUP-TF1 also known as NR2F1 is a protein that in humans is encoded by the NR2F1 gene. This protein is a member of nuclear hormone receptor family of steroid hormone receptors.

<span class="mw-page-title-main">COUP-TFII</span> Protein found in humans

COUP-TFII, also known as NR2F2 is a protein that in humans is encoded by the NR2F2 gene. The COUP acronym stands for chicken ovalbumin upstream promoter.

<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">Testicular receptor 4</span> Protein-coding gene in the species Homo sapiens

Testicular receptor 4 also known as NR2C2 is a protein that in humans is encoded by the NR2C2 gene.

<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">SIM1</span> Genetic protein

Single-minded homolog 1, also known as class E basic helix-loop-helix protein 14 (bHLHe14), is a protein that in humans is encoded by the SIM1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116833 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026398 – 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. ↑ Bernier D, Thomassin H, Allard D, Guertin M, Hamel D, Blaquière M, et al. (March 1993). "Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer". Molecular and Cellular Biology. 13 (3): 1619–1633. doi:10.1128/mcb.13.3.1619. PMC   359474 . PMID   7680097.
  6. ↑ Galarneau L, Drouin R, Bélanger L (1998). "Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization". Cytogenetics and Cell Genetics. 82 (3–4): 269–270. doi:10.1159/000015116. PMID   9858833. S2CID   46813832.
  7. ↑ Fayard E, Auwerx J, Schoonjans K (May 2004). "LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis". Trends in Cell Biology. 14 (5): 250–260. doi:10.1016/j.tcb.2004.03.008. PMID   15130581.
  8. ↑ Luo Y, Liang CP, Tall AR (July 2001). "The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor". The Journal of Biological Chemistry. 276 (27): 24767–24773. doi: 10.1074/jbc.M100912200 . PMID   11331284.
  9. ↑ Nitta M, Ku S, Brown C, Okamoto AY, Shan B (June 1999). "CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene". Proceedings of the National Academy of Sciences of the United States of America. 96 (12): 6660–6665. Bibcode:1999PNAS...96.6660N. doi: 10.1073/pnas.96.12.6660 . PMC   21971 . PMID   10359768.
  10. 1 2 3 4 5 Gassler J, Kobayashi W, Gáspár I, Ruangroengkulrith S, Mohanan A, Gómez Hernández L, et al. (December 2022). "Zygotic genome activation by the totipotency pioneer factor Nr5a2". Science. 378 (6626): 1305–1315. Bibcode:2022Sci...378.1305G. doi:10.1126/science.abn7478. PMID   36423263. S2CID   248923539.
  11. ↑ Gu P, Goodwin B, Chung AC, Xu X, Wheeler DA, Price RR, et al. (May 2005). "Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development". Molecular and Cellular Biology. 25 (9): 3492–3505. doi:10.1128/MCB.25.9.3492-3505.2005. PMC   1084298 . PMID   15831456.
  12. 1 2 Labelle-Dumais C, Paré JF, Bélanger L, Farookhi R, Dufort D (August 2007). "Impaired progesterone production in Nr5a2+/- mice leads to a reduction in female reproductive function". Biology of Reproduction. 77 (2): 217–225. doi:10.1095/biolreprod.106.059121. PMID   17409375.
  13. ↑ Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (September 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–2076. doi: 10.1210/me.2001-0194 . PMID   12198243.
  14. ↑ Lee YK, Moore DD (January 2002). "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner". The Journal of Biological Chemistry. 277 (4): 2463–2467. doi: 10.1074/jbc.M105161200 . PMID   11668176.

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