Misplaced Pages

NR5A2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4RWV, 1YOK, 1YUC, 1ZDU, 2A66, 3PLZ, 3TX7, 4DOR, 4DOS, 4IS8, 4ONI, 4PLD, 4PLE
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
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.1 Start 200,027,614 bp End 200,177,420 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 59.98 cM|1 E4 Start 136,770,309 bp End 136,888,186 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas islet of Langerhans jejunal mucosa liver right lobe of liver duodenum rectum pancreatic ductal cell mucosa of colon mucosa of sigmoid colon Top expressed in cumulus cell ovarian follicle primordial pancreas left lobe of liver ovarian follicle cell primary follicle of ovary zygote left colon exocrine pancreas secondary oocyte More reference expression data BioGPS n/a
Gene ontology Molecular function RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA binding sequence-specific DNA binding DNA-binding transcription factor activity zinc ion binding DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding transcription cis-regulatory region binding metal ion binding steroid hormone receptor activity nuclear receptor activity protein binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding double-stranded DNA binding phospholipid binding lipid binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm nucleoplasm RNA polymerase II transcription regulator complex nucleus Biological process regulation of transcription, DNA-templated epithelial cell differentiation pancreas morphogenesis bile acid metabolic process transcription, DNA-templated positive regulation of transcription, DNA-templated intracellular receptor signaling pathway regulation of cell population proliferation tissue development hormone-mediated signaling pathway cholesterol homeostasis positive regulation of viral genome replication transcription initiation from RNA polymerase II promoter steroid hormone mediated signaling pathway positive regulation of transcription by RNA polymerase II homeostatic process calcineurin-mediated signaling cellular response to leukemia inhibitory factor embryo development ending in birth or egg hatching Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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
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. 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.

LRH-1 is important for maintaining pluripotence of stem cells during embryonic development.

Nr5a2 was recently identified at a totipotent pioneer factor. The orphan nuclear receptor Nr5a2 has been shown to be important in fertility, ovarian function, and zygotic genome activation (ZGA). 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. 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.

Interactions

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

References

1. ^ GRCh38: Ensembl release 89: ENSG00000116833 – Ensembl, May 2017
2. ^ 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. ^ 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. ^ 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.

Further reading

• Wong M, Ramayya MS, Chrousos GP, Driggers PH, Parker KL (October 1996). "Cloning and sequence analysis of the human gene encoding steroidogenic factor 1". Journal of Molecular Endocrinology. 17 (2): 139–147. doi:10.1677/jme.0.0170139. PMID 8938589.
• Li M, Xie YH, Kong YY, Wu X, Zhu L, Wang Y (October 1998). "Cloning and characterization of a novel human hepatocyte transcription factor, hB1F, which binds and activates enhancer II of hepatitis B virus". The Journal of Biological Chemistry. 273 (44): 29022–29031. doi:10.1074/jbc.273.44.29022. PMID 9786908.
• Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al. (September 2000). "A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis". Molecular Cell. 6 (3): 517–526. doi:10.1016/S1097-2765(00)00051-4. PMID 11030332.
• Wang ZN, Bassett M, Rainey WE (October 2001). "Liver receptor homologue-1 is expressed in the adrenal and can regulate transcription of 11 beta-hydroxylase". Journal of Molecular Endocrinology. 27 (2): 255–258. doi:10.1677/jme.0.0270255. PMID 11564608.
• Zhang CK, Lin W, Cai YN, Xu PL, Dong H, Li M, et al. (August 2001). "Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene". Gene. 273 (2): 239–249. doi:10.1016/S0378-1119(01)00586-8. PMID 11595170.
• Clyne CD, Speed CJ, Zhou J, Simpson ER (June 2002). "Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes". The Journal of Biological Chemistry. 277 (23): 20591–20597. doi:10.1074/jbc.M201117200. PMID 11927588.
• Brendel C, Gelman L, Auwerx J (June 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology. 16 (6): 1367–1377. doi:10.1210/mend.16.6.0843. PMID 12040021.
• Sirianni R, Seely JB, Attia G, Stocco DM, Carr BR, Pezzi V, et al. (September 2002). "Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes". The Journal of Endocrinology. 174 (3): R13 – R17. doi:10.1677/joe.0.174R013. PMID 12208674.
• Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA (June 2003). "Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1". Molecular Cell. 11 (6): 1575–1585. doi:10.1016/S1097-2765(03)00236-3. PMID 12820970.
• Privalsky ML (July 2003). "Activation incarnate". Developmental Cell. 5 (1): 1–2. doi:10.1016/S1534-5807(03)00196-5. PMID 12852843.
• Fayard E, Schoonjans K, Annicotte JS, Auwerx J (September 2003). "Liver receptor homolog 1 controls the expression of carboxyl ester lipase". The Journal of Biological Chemistry. 278 (37): 35725–35731. doi:10.1074/jbc.M302370200. PMID 12853459.
• Annicotte JS, Fayard E, Swift GH, Selander L, Edlund H, Tanaka T, et al. (October 2003). "Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development". Molecular and Cellular Biology. 23 (19): 6713–6724. doi:10.1128/MCB.23.19.6713-6724.2003. PMC 193920. PMID 12972592.
• Peng N, Kim JW, Rainey WE, Carr BR, Attia GR (December 2003). "The role of the orphan nuclear receptor, liver receptor homologue-1, in the regulation of human corpus luteum 3beta-hydroxysteroid dehydrogenase type II". The Journal of Clinical Endocrinology and Metabolism. 88 (12): 6020–6028. doi:10.1210/jc.2003-030880. PMID 14671206.
• Cai YN, Zhou Q, Kong YY, Li M, Viollet B, Xie YH, et al. (December 2003). "LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication". Cell Research. 13 (6): 451–458. doi:10.1038/sj.cr.7290187. PMID 14728801.
• Saxena D, Safi R, Little-Ihrig L, Zeleznik AJ (August 2004). "Liver receptor homolog-1 stimulates the progesterone biosynthetic pathway during follicle-stimulating hormone-induced granulosa cell differentiation". Endocrinology. 145 (8): 3821–3829. doi:10.1210/en.2004-0423. PMID 15117876.

External links

• NR5A2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on human chromosome 1 is a stub. You can help Misplaced Pages by expanding it.

• v
• t
• e

• Genes on human chromosome 1
• Nuclear receptors
• Human chromosome 1 gene stubs