Affinage

Showing NR1H2 — LXRB is a alias.

NR1H2

Oxysterols receptor LXR-beta · UniProt P55055

Length
460 aa
Mass
51.0 kDa
Annotated
2026-06-10
100 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR1H2 (LXRβ, originally NER) is a ubiquitously expressed member of the steroid hormone nuclear receptor gene family, encoding a 461-amino-acid protein with conserved DNA-binding and ligand-binding domains most homologous to retinoic acid receptors (PMID:7926814). Its own gene is transcriptionally controlled through two conserved ETS/Elk1 and SRF binding sites in its promoter, which are required for basal transcription and mediate glucose-induced transcriptional activation (PMID:17626048). Beyond its cloning, expression pattern, and this promoter-level regulation, no ligand, target gene, or downstream mechanistic role for the NR1H2 protein has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1994 Medium

    Established NR1H2 as a distinct nuclear receptor by cloning it and defining its domain architecture, placing it within the steroid hormone receptor family and adjacent to retinoic acid receptors.

    Evidence cDNA library cloning from human osteosarcoma cells with sequence analysis and Northern blotting

    PMID:7926814

    Open questions at the time
    • No ligand identified for the receptor
    • No target genes or DNA response elements defined
    • Functional role of the protein not addressed
  2. 2007 High

    Resolved how the NR1H2 gene itself is regulated, showing its promoter is driven by Elk1/SRF and is responsive to glucose, linking receptor expression to metabolic state.

    Evidence Promoter-reporter assays, EMSA, site-directed mutagenesis, and siRNA knockdown of SRF and Elk1 in human cells

    PMID:17626048

    Open questions at the time
    • Does not define the receptor's own ligand or downstream targets
    • Does not establish the physiological consequence of glucose-induced LXRB expression
    • Mechanism connecting glucose signaling to Elk1/SRF activation not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous ligand, target gene network, and physiological function of the NR1H2 protein remain uncharacterized in the available corpus.
  • No ligand identified
  • No direct target genes mapped
  • No tissue-specific functional role established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 1 GO:0140110 transcription regulator activity 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 NR1H2 (NER) was identified as a new member of the steroid hormone nuclear receptor gene family, encoding a 461 amino acid polypeptide containing conserved DNA-binding and ligand-binding domains. It shows highest homology to retinoic acid receptors (55% at the DNA-binding domain, 38-40% at the ligand-binding domain). A single 2.3 kb transcript was detected in all cells and tissues tested, suggesting ubiquitous expression. cDNA library cloning from human osteosarcoma SAOS/B10 cells, sequence analysis, Northern blotting Gene Medium 7926814
2007 The human LXRB (NR1H2) gene promoter contains two highly conserved and functional ETS/Elk1 and SRF binding sites that are required for basal transcription and mediate glucose-induced transcriptional activation. Mutation of either site abolished factor binding and significantly reduced promoter activity; siRNA knockdown of SRF and Elk1 impaired both basal promoter activity and the glucose response. Transcription start site mapping, promoter-reporter assays, electrophoretic mobility shift assays (EMSA), site-directed mutagenesis, siRNA knockdown Nucleic acids research High 17626048

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Molecular cell 313 20227374
2010 NER factors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack. Molecular cell 181 20385089
2007 Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step. The EMBO journal 134 18079701
1994 NER, a new member of the gene family encoding the human steroid hormone nuclear receptor. Gene 125 7926814
2013 DNA damage triggers a chronic autoinflammatory response, leading to fat depletion in NER progeria. Cell metabolism 118 24011075
2010 Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation. Molecular cell 102 20932474
2000 DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes. Mutation research 92 11056291
2004 A model for initial DNA lesion recognition by NER and MMR based on local conformational flexibility. DNA repair 80 15162792
2017 MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway. Scientific reports 72 28074905
2008 Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer causes & control : CCC 68 18478337
2011 Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation. Proceedings of the National Academy of Sciences of the United States of America 66 21808022
2013 Blinded by the UV light: how the focus on transcription-coupled NER has distracted from understanding the mechanisms of Cockayne syndrome neurologic disease. DNA repair 64 23683874
2013 NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites. DNA repair 59 23422745
2019 Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B. Nucleic acids research 55 31372632
2003 p210 BCR/ABL kinase regulates nucleotide excision repair (NER) and resistance to UV radiation. Blood 54 12829601
2007 CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER-deficient human cells. DNA repair 51 18096446
2007 Tissue specific mutagenic and carcinogenic responses in NER defective mouse models. Mutation research 50 16769089
1984 Regulation of Mu transposition. I. Localization of the presumed recognition sites for HimD and Ner functions controlling bacteriophage Mu transcription. Gene 49 6096223
2008 Cetuximab potentiates oxaliplatin cytotoxic effect through a defect in NER and DNA replication initiation. British journal of cancer 48 18182978
2004 The potential roles of p53 tumor suppressor in nucleotide excision repair (NER) and base excision repair (BER). Experimental & molecular medicine 47 15665582
2015 Histone modification and chromatin remodeling during NER. DNA repair 46 26422133
2018 Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk. Molecular therapy. Nucleic acids 45 30161024
2020 A key interaction with RPA orients XPA in NER complexes. Nucleic acids research 42 31925419
2012 Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria. Proceedings of the National Academy of Sciences of the United States of America 42 22323595
2011 Dynamics of mammalian NER proteins. DNA repair 40 21550320
2010 NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans. Cell death and differentiation 40 21151025
1999 New lines of host defense: inhibition of Ty1 retrotransposition by Fus3p and NER/TFIIH. Trends in genetics : TIG 40 10098404
2006 Epidermal stem and progenitor cells in murine epidermis accumulate UV damage despite NER proficiency. Carcinogenesis 39 17127714
2015 Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly. Computational and structural biotechnology journal 38 26865925
2011 Replication protein A safeguards genome integrity by controlling NER incision events. The Journal of cell biology 38 21282463
2005 Development of new EBV-based vectors for stable expression of small interfering RNA to mimick human syndromes: application to NER gene silencing. Molecular cancer research : MCR 38 16179499
2019 FACT subunit Spt16 controls UVSSA recruitment to lesion-stalled RNA Pol II and stimulates TC-NER. Nucleic acids research 37 30715484
2016 Triplex structures induce DNA double strand breaks via replication fork collapse in NER deficient cells. Nucleic acids research 37 27298253
2012 Nucleotide excision repair (NER) machinery recruitment by the transcription-repair coupling factor involves unmasking of a conserved intramolecular interface. Proceedings of the National Academy of Sciences of the United States of America 37 22331906
2011 DNA polymerases and repair synthesis in NER in human cells. DNA repair 35 21601536
2014 Synergistic exposure of rice seeds to different doses of γ-ray and salinity stress resulted in increased antioxidant enzyme activities and gene-specific modulation of TC-NER pathway. BioMed research international 34 24551849
2011 Structure and stability of DNA containing an aristolactam II-dA lesion: implications for the NER recognition of bulky adducts. Nucleic acids research 34 22121223
1998 NER rat strain: a new type of genetic model in epilepsy research. Epilepsia 34 9578020
1988 Purification and characterization of the DNA-binding protein Ner of bacteriophage Mu. Gene 33 2970420
2007 NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans. Prostate cancer and prostatic diseases 32 18026184
1988 Long-range 15N-1H correlation as an aid to sequential proton resonance assignment of proteins. Application to the DNA-binding protein ner from phage Mu. FEBS letters 32 3049156
2014 The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system: is there a correlation? DNA repair 31 24784728
2016 New design of nucleotide excision repair (NER) inhibitors for combination cancer therapy. Journal of molecular graphics & modelling 30 26939044
2012 Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2. Nucleic acids research 30 22373916
2008 Characterization of the mycobacterial NER system reveals novel functions of the uvrD1 helicase. Journal of bacteriology 30 19011038
2013 Expressional analysis of inwardly rectifying Kir4.1 channels in Noda epileptic rat (NER). Brain research 29 23603404
2007 Moving toward individualized therapy based on NER polymorphisms that predict platinum sensitivity in ovarian cancer patients. Gynecologic oncology 29 17825393
2005 Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease. Neurobiology of aging 29 16207502
1986 Role of ner protein in bacteriophage Mu transposition. Journal of bacteriology 29 3015876
2020 Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells. Proceedings of the National Academy of Sciences of the United States of America 28 32513688
2015 Triptolide potentiates lung cancer cells to cisplatin-induced apoptosis by selectively inhibiting the NER activity. Biomarker research 28 26161259
2015 APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER. Mutation research 28 26164266
2015 The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients. Journal of gynecologic oncology 28 26463438
2012 NER and DDR: classical music with new instruments. Cell cycle (Georgetown, Tex.) 28 22373527
2001 DMBA-induced toxic and mutagenic responses vary dramatically between NER-deficient Xpa, Xpc and Csb mice. Carcinogenesis 28 11408355
1989 Determination of the secondary structure of the DNA binding protein Ner from phage Mu using 1H homonuclear and 15N-1H heteronuclear NMR spectroscopy. Biochemistry 28 2527559
1985 The cloning and characterization of the bacteriophage D108 regulatory DNA-binding protein ner. The EMBO journal 26 2998774
2019 MicroRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway. Oncology letters 25 31289483
2012 Structure and stability of duplex DNA containing (5'S)-5',8-cyclo-2'-deoxyadenosine: an oxidatively generated lesion repaired by NER. Chemical research in toxicology 25 22928555
2010 Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes. Journal of molecular medicine (Berlin, Germany) 25 21042792
2007 Crosslinking of the NER damage recognition proteins XPC-HR23B, XPA and RPA to photoreactive probes that mimic DNA damages. Biochimica et biophysica acta 25 17320292
1986 The overproduction and characterization of the bacteriophage Mu regulatory DNA-binding protein ner. Virology 25 2934891
2014 Ubiquitin at work: the ubiquitous regulation of the damage recognition step of NER. Experimental cell research 23 25062985
2011 A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia. BMC medical genetics 23 22029530
2014 Structural and energetic characterization of the major DNA adduct formed from the food mutagen ochratoxin A in the NarI hotspot sequence: influence of adduct ionization on the conformational preferences and implications for the NER propensity. Nucleic acids research 22 25217592
2012 Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways. Ecotoxicology (London, England) 22 22543959
2008 The NER protein Rad33 shows functional homology to human Centrin2 and is involved in modification of Rad4. DNA repair 22 18387345
2005 Repair characteristics and differentiation propensity of long-term cultures of epidermal keratinocytes derived from normal and NER-deficient mice. DNA repair 22 16182615
1994 Secondary structure and interaction of phage D108 Ner repressor with a 61-base-pair operator: evidence for altered protein and DNA structures in the complex. Biochemistry 22 8075070
2018 Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 29719287
2007 Dynamics of cell cycle phase perturbations by trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach. Cell proliferation 21 18021177
2021 Circadian Rhythm of NER and ATR Pathways. Biomolecules 20 34064641
2015 Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis. Toxicology and applied pharmacology 20 25818601
2015 Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer. International journal of clinical and experimental pathology 20 26191265
2014 Insight in the multilevel regulation of NER. Experimental cell research 20 25128816
2009 Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER). Epilepsy research 20 19713079
2007 Dual role of NER in mutagenesis in Pseudomonas putida. DNA repair 20 17720631
2013 Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors. Asian Pacific journal of cancer prevention : APJCP 19 23679317
2008 How to make the most of NE dictionaries in statistical NER. BMC bioinformatics 19 19025691
2007 Elk1 and SRF transcription factors convey basal transcription and mediate glucose response via their binding sites in the human LXRB gene promoter. Nucleic acids research 19 17626048
2007 Bacterial DNA repair genes and their eukaryotic homologues: 4. The role of nucleotide excision DNA repair (NER) system in mammalian cells. Acta biochimica Polonica 19 17893751
2022 The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma. Cancers 18 35954493
2021 Significant association of LXRβ (NR1H2) polymorphisms (rs28514894, rs2303044) with type 2 diabetes mellitus and laboratory characteristics. Journal of diabetes and metabolic disorders 18 34178836
2012 The nucleotide excision repair (NER) system of Helicobacter pylori: role in mutation prevention and chromosomal import patterns after natural transformation. BMC microbiology 18 22559785
2006 Identification of MMS19 domains with distinct functions in NER and transcription. DNA repair 18 16797255
2000 Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures. Epilepsia 18 10961618
2023 Triptolide enhances carboplatin-induced apoptosis by inhibiting nucleotide excision repair (NER) activity in melanoma. Frontiers in pharmacology 17 37324464
2015 Association of single nucleotide polymorphisms of DNA repair genes in NER pathway and susceptibility to pancreatic cancer. International journal of clinical and experimental pathology 17 26617894
2015 Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population. International journal of clinical and experimental pathology 17 26617899
1989 Cloning and sequencing of an Escherichia coli gene, nlp, highly homologous to the ner genes of bacteriophages Mu and D108. Journal of bacteriology 17 2670911
2019 Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage. Mutation research. Genetic toxicology and environmental mutagenesis 16 30744808
2019 Microbial Turnover of Glyphosate to Biomass: Utilization as Nutrient Source and Formation of AMPA and Biogenic NER in an OECD 308 Test. Environmental science & technology 16 30994338
2016 The Bacterial Mfd Protein Prevents DNA Damage Induced by the Host Nitrogen Immune Response in a NER-Independent but RecBC-Dependent Pathway. PloS one 16 27711223
2013 DNA Helicases in NER, BER, and MMR. Advances in experimental medicine and biology 16 23161013
2010 Effect of gliclazide on nucleotide excision repair (NER) and non-homologous DNA end joining (NHEJ) in normal and cancer cells. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 16 20610866
2007 Impaired expression of NER gene network in sporadic solid tumors. Nucleic acids research 16 17332015
2004 Participation of BER and NER pathways in the repair of DNA lesions induced at low N-nitrosodiethylamine concentrations. Toxicology letters 16 15475187
2019 Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large-scale analysis of 14 published GWAS datasets in the DRIVE study. International journal of cancer 15 31026346
2019 NER-factor DDB2 regulates HIF1α and hypoxia-response genes in HNSCC. Oncogene 15 31740787
1989 DNA-directed oligomerization of the monomeric Ner repressor from the Mu-like bacteriophage D108. The EMBO journal 15 2531076

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