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Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA binding domains (2DBD-NRs).

ABSTRACT: Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Typical NRs possess a conserved DNA binding domain (DBD) and a ligand binding domain (LBD). Since we discovered a type of novel NRs each of them has two DBDs and single LBD (2DBD-NRs) more than decade ago, there has been very few studies about 2DBD-NRs. Recently, 2DBD-NRs have been only reported in Platyhelminths and Mollusca and are thought to be specific NRs to lophotrochozoan. In this study, we searched different databases and identified 2DBD-NRs in different animals from both protostomes and deuterostomes. Phylogenetic analysis shows that at least two ancient 2DBD-NR genes were present in the urbilaterian, a common ancestor of protostomes and deuterostomes. 2DBD-NRs underwent gene duplication and loss after the split of different animal phyla, most of them in a certain animal phylum are paralogues, rather than orthologues, like in other animal phyla. Amino acid sequence analysis shows that the conserved motifs in typical NRs are also present in 2DBD-NRs and they are gene specific. From our phylogenetic analysis of 2DBD-NRs and following the rule of Nomenclature System for the Nuclear Receptors, a nomenclature for 2DBD-NRs is proposed.

SUBMITTER: Wu W

PROVIDER: S-EPMC10497141 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA binding domains (2DBD-NRs).

Wu Wenjie W LoVerde Philip T PT

PloS one 20230912 9

Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Typical NRs possess a conserved DNA binding domain (DBD) and a ligand binding domain (LBD). Since we discovered a type of novel NRs each of them has two DBDs and single LBD (2DBD-NRs) more than decade ago, there has been very few studies about 2DBD-NRs. Recently, 2DBD-NRs have been only reported in Platyhelminths and Mollusca and are thought to be specific NRs to lophotrochozoan. In this study, we searched different d ...[more]

PMID: 37699039

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Project description:Nuclear receptors (NRs) are important transcriptional modulators in metazoans which regulate transcription through binding to the promoter region of their target gene by the DNA binding domain (DBD) and activation or repression of mRNA synthesis through co-regulators bound to the ligand binding domain (LBD). NRs typically have a single DBD with a LBD.Three nuclear receptors named 2DBD-NRs, were identified from the flatworm Schistosoma mansoni that each possess a novel set of two DBDs in tandem with a LBD. They represent a novel NR modular structure: A/B-DBD-DBD-hinge-LBD. The 2DBD-NRs form a new subfamily of NRs, VII. By database mining, 2DBD-NR genes from other flatworm species (Schmidtea mediterranea and Dugesia japonica), from Mollusks (Lottia gigantean) and from arthropods (Daphnia pulex) were also identified. All 2DBD-NRs possess a P-box sequence of CEACKK in the first DBD, which is unique to 2DBD-NRs, and a P-box sequence of CEGCKG in the second DBD. Phylogenetic analyses of both DBD and ligand binding domain sequences showed that 2DBD-NR genes originate from a common two DBD-containing ancestor gene. A single 2DBD-NR orthologue was found in Arthropoda, Platyhelminths and Mollusca. Subsequent 2DBD-NR gene evolution in Mollusks and Platyhelminths involved gene duplication. Chromosome localization of S. mansoni 2DBD-NR genes by Fluorescent in situ hybridization (FISH) suggests that 2DBD-NR genes duplicated on different chromosomes in the Platyhelminths. Dimerization of Sm2DBDalpha indicates that 2DBD-NRs may act as homodimers, suggesting either that two repeats of a half-site are necessary for each DBD of 2DBD-NRs to bind to its target gene, or that each 2DBD-NR can recognize multiple sites.2DBD-NRs share a common ancestor gene which possessed an extra DBD that likely resulted from a recombination event. After the split of the Arthropods, Mollusks and Platyhelminths, 2DBD-NR underwent a recent duplication in a common ancestor of Mollusks, while two rounds of duplication occurred in a common ancestor of the Platyhelminths. This demonstrates that certain NR gene underwent recent duplication in Prostostome lineages after the split of the Prostostomia and Deuterostomia.

Dataset Information

Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA binding domains (2DBD-NRs).

Publications

Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA binding domains (2DBD-NRs).

Similar Datasets

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