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词条 Liver X receptor beta
释义

  1. Function

  2. Structure

  3. Interactions

  4. References

  5. Further reading

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

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.[1][2]

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.[3]

Interactions

Liver X receptor beta has been shown to interact with NCOA6[4] and Retinoid X receptor alpha.[5]

References

1. ^1 {{cite web | title = Entrez Gene: NR1H2 nuclear receptor subfamily 1, group H, member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7376| accessdate = }}
2. ^{{cite journal | vauthors = Song C, Hiipakka RA, Kokontis JM, Liao S | title = Ubiquitous receptor: structures, immunocytochemical localization, and modulation of gene activation by receptors for retinoic acids and thyroid hormones | journal = Annals of the New York Academy of Sciences | volume = 761 | issue = | pages = 38–49 | date = Jun 1995 | pmid = 7625741 | doi = 10.1111/j.1749-6632.1995.tb31367.x }}
3. ^{{cite journal | vauthors = Lou X, Toresson G, Benod C, Suh JH, Philips KJ, Webb P, Gustafsson JA | title = Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA | journal = Nature Structural & Molecular Biology | volume = 21 | issue = 3 | pages = 277–81 | date = Mar 2014 | pmid = 24561505 | doi = 10.1038/nsmb.2778 }}
4. ^{{cite journal | vauthors = Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW | title = Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2 | journal = Molecular Endocrinology | volume = 15 | issue = 2 | pages = 241–54 | date = Feb 2001 | pmid = 11158331 | doi = 10.1210/me.15.2.241 }}
5. ^{{cite journal | vauthors = Seol W, Choi HS, Moore DD | title = Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors | journal = Molecular Endocrinology | volume = 9 | issue = 1 | pages = 72–85 | date = Jan 1995 | pmid = 7760852 | doi = 10.1210/mend.9.1.7760852 }}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Seol W, Choi HS, Moore DD | title = Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors | journal = Molecular Endocrinology | volume = 9 | issue = 1 | pages = 72–85 | date = Jan 1995 | pmid = 7760852 | doi = 10.1210/mend.9.1.7760852 }}
  • {{cite journal | vauthors = Le Beau MM, Song C, Davis EM, Hiipakka RA, Kokontis JM, Liao S | title = Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization | journal = Genomics | volume = 26 | issue = 1 | pages = 166–8 | date = Mar 1995 | pmid = 7782080 | doi = 10.1016/0888-7543(95)80100-Z }}
  • {{cite journal | vauthors = Shinar DM, Endo N, Rutledge SJ, Vogel R, Rodan GA, Schmidt A | title = NER, a new member of the gene family encoding the human steroid hormone nuclear receptor | journal = Gene | volume = 147 | issue = 2 | pages = 273–6 | date = Sep 1994 | pmid = 7926814 | doi = 10.1016/0378-1119(94)90080-9 }}
  • {{cite journal | vauthors = Song C, Kokontis JM, Hiipakka RA, Liao S | title = Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 23 | pages = 10809–13 | date = Nov 1994 | pmid = 7971966 | pmc = 45115 | doi = 10.1073/pnas.91.23.10809 }}
  • {{cite journal | vauthors = Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ | title = Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 1 | pages = 266–71 | date = Jan 1999 | pmid = 9874807 | pmc = 15128 | doi = 10.1073/pnas.96.1.266 }}
  • {{cite journal | vauthors = Feltkamp D, Wiebel FF, Alberti S, Gustafsson JA | title = Identification of a novel DNA binding site for nuclear orphan receptor OR1 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10421–9 | date = Apr 1999 | pmid = 10187832 | doi = 10.1074/jbc.274.15.10421 }}
  • {{cite journal | vauthors = Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW | title = Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2 | journal = Molecular Endocrinology | volume = 15 | issue = 2 | pages = 241–54 | date = Feb 2001 | pmid = 11158331 | doi = 10.1210/me.15.2.241 }}
  • {{cite journal | vauthors = Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, Wilson JG, Willson TM, Collins JL, Kliewer SA | title = Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages | journal = The Journal of Biological Chemistry | volume = 276 | issue = 47 | pages = 43509–15 | date = Nov 2001 | pmid = 11546778 | doi = 10.1074/jbc.M106155200 }}
  • {{cite journal | vauthors = Whitney KD, Watson MA, Collins JL, Benson WG, Stone TM, Numerick MJ, Tippin TK, Wilson JG, Winegar DA, Kliewer SA | title = Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system | journal = Molecular Endocrinology | volume = 16 | issue = 6 | pages = 1378–85 | date = Jun 2002 | pmid = 12040022 | doi = 10.1210/me.16.6.1378 }}
  • {{cite journal | vauthors = Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J | title = The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2065–76 | date = Sep 2002 | pmid = 12198243 | doi = 10.1210/me.2001-0194 }}
  • {{cite journal | vauthors = Mo J, Fang SJ, Chen W, Blobe GC | title = Regulation of ALK-1 signaling by the nuclear receptor LXRbeta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 52 | pages = 50788–94 | date = Dec 2002 | pmid = 12393874 | doi = 10.1074/jbc.M210376200 }}
  • {{cite journal | vauthors = 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 | title = X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch | journal = The Journal of Biological Chemistry | volume = 278 | issue = 29 | pages = 27138–43 | date = Jul 2003 | pmid = 12736258 | doi = 10.1074/jbc.M302260200 }}
  • {{cite journal | vauthors = Färnegårdh M, Bonn T, Sun S, Ljunggren J, Ahola H, Wilhelmsson A, Gustafsson JA, Carlquist M | title = The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands | journal = The Journal of Biological Chemistry | volume = 278 | issue = 40 | pages = 38821–8 | date = Oct 2003 | pmid = 12819202 | doi = 10.1074/jbc.M304842200 }}
  • {{cite journal | vauthors = Fukuchi J, Song C, Ko AL, Liao S | title = Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors | journal = Steroids | volume = 68 | issue = 7-8 | pages = 685–91 | date = Sep 2003 | pmid = 12957674 | doi = 10.1016/S0039-128X(03)00100-4 }}
  • {{cite journal | vauthors = Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H | title = Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist | journal = Journal of Molecular Biology | volume = 334 | issue = 5 | pages = 853–61 | date = Dec 2003 | pmid = 14643652 | doi = 10.1016/j.jmb.2003.10.033 }}
  • {{cite journal | vauthors = Walczak R, Joseph SB, Laffitte BA, Castrillo A, Pei L, Tontonoz P | title = Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors | journal = The Journal of Biological Chemistry | volume = 279 | issue = 11 | pages = 9905–11 | date = Mar 2004 | pmid = 14699103 | doi = 10.1074/jbc.M310587200 }}
{{refend}}{{NLM content}}{{PDB Gallery|geneid=7376}}{{Transcription factors|g2}}{{Nuclear receptor ligands}}{{gene-19-stub}}

2 : Intracellular receptors|Transcription factors
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