Nr0b1 11614

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Gene ID: 11614
Gene symbol: nr0b1
Gene Description: nuclear receptor subfamily 0, group b, member 1
Aliases: Ahc; Ahch; AHX; DAX-1; Dax1
Human Ortholog Gene ID: [190]
Reviewer Judgement: TF Gene
Functional Classification: DNA-Binding: non-sequence-specific;

Transcription Factor Binding: tf co-factor binding; DNA-Binding: sequence-specific

Homolog Cluster(s): 110784

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[9384387] DNA Binding Human Strong Paper: DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis
  • found that DAX-1 efficiently recognizes DNA hairpin structures in vitro and that binding is equally efficient to stems composed of 10 to 24 nucleotides, but is less efficient with shorter stems - binding shows no strong sequence specificity
  • DAX-1 represses StAR expression and consequently suppresses steroidogenesis by binding to a hairpin in the StAR promoter (transfection assay)
  • DAX-1 also exerts its repression function in a heterologous system. Fusion of the DAX-1 carboxy terminus to the GAL4 DNA-binding domain (DBD) results in a protein that efficiently represses a globin promoter containing GAL4-binding site
Debra Fulton
[12482977] Transactivation Human Strong Paper: LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1.

Although the carboxy-terminal region of DAX-1 is homologous to the ligand-binding domain of nuclear receptors, it lacks a characteristic zinc finger DNA binding region. DAX-1 consists of three and one-half repeats of a 65- to 67-amino-acid motif that has been proposed to serve as a DNA-binding domain.

Transient expression assays demonstrate that DAX1 inhibits SF-1 trancriptional activation. Protein-protein binding assay detect DAX1-interaction with SF-1 and EMSA assays demonstrate that DAX-1 does not alter SF-1 binding to DNA.

DAX-1 mutants on GAL4-SF-1 induced transactivation inhibition localizes to its carboxy teriminus.

Debra Fulton
[15155786] Transactivation Other Strong Paper: The Atypical Orphan Nuclear Receptor DAX-1 Interacts with Orphan Nuclear Receptor Nur77 and Represses Its Transactivation

____ Previous studies have demonstrated that DAX-1 physically interacts with SF-1, LRH-1, ERs, AR, and PR, and acts as a potent corepressor.

  • Demonstrate that DAX-1 represses the Nur77 transactivation by transient transfection assays and siRNAs.
  • Specific interaction between Nur77 and DAX-1 was detected by coimmunoprecipitation, yeast two-hybrid, and glutathione-S-transferase pull-down assays.
  • the ligand binding domain of DAX-1 and the activation function-2 domain of Nur77 were determined as the direct interaction domains
  • In vitro competition binding assay showed that DAX-1 repressed Nur77 transactivation through the competition with steroid receptor coactivator-1 for the binding of Nur77
Debra Fulton
[15464421] Co-activation Human Strong Paper: DAX-1 functions as an LXXLL-containing corepressor for activated estrogen receptors.
  • Interaction of DAX-1 with Liganded ERs via the N-terminal Repeat Domain (all 3 repeats) demonstrated with pull-down assays
  • mutation of the third LXXLL motif abolised binding of ERs to this repeat
  • Gel shift (indicating ternary complex formation) and coimmunoprecipitation assay - indicate that DAX-1 interaction with other nuclear receptors is not interfering with dimerization and DNA binding but instead resembles coactivator-type interactions with the AF-2 domain via LXXLL motifs
  • transient tranfections showed that Dax-1 repressed transcription ER-alpha and ER-beta
  • mammalian two-hybrid experiment showed that DAX-1 may serve as a bridging protein between liganded ER and the corepressor N-CoR
  • Model describing the interplay of DAX-1 with upstream and downstream targets

http://www.jbc.org/cgi/content/full/275/51/39855/F5

Debra Fulton
[16709599] TF PPI Other Medium In mammals: "DAX1 (NR0B1), and SHP (NR0B2) are atypical nuclear receptor superfamily members that function primarily as corepressors through heterodimeric interactions with other nuclear receptors." Jared Roach
[9032275] Co-activation Human Medium Inhibits SF-1-induced transcriptional activation in a luciferase reporter assay of SF-1 response element-containing reporter genes.

Dax1 interacts directly with SF-1 in an affinity pull-down assay.

Sarav Sundararajan
[9384387] DNA Binding Human Strong Binds to a DNA hairpin structure in it's own promoter region

Represses activation of a StAR reporter construct by cAMP

Sarav Sundararajan
[10848616] Other Mouse Strong Ligand binding domain binds to RNA homopolymers (specifically poly-A and poly-C) Sarav Sundararajan
[11053406] Co-activation Mouse Strong Binds to and acts as a corepressor of ER-alpha and ER-beta by co-immunoprecipitation and reporter assays. Sarav Sundararajan
[11427738] Co-activation Mouse Medium Represses transactivation of Cyp19 by SF-1 in a luciferase reporter assay Sarav Sundararajan
[9032275] Transactivation Human Strong The DAX-1 C-terminus contains a transcriptional repression domain. DAX-1 interacts directly with SF-1 and represses transcription in transient transfection assays. Rob Sladek
[9384387] DNA Binding Human Medium DAX-1 binds to DNA hairpins with stems containing 10-24bp in vitro. The putative DNA-binding domain is contained in the DAX-1 N-terminus: DAX-1 does not contain a consensus zinc-finger DNA-binding domain. DAX-1 directly represses hairpin-containing promoters in transient transfection assays. Rob Sladek
[9661652] Transactivation Human Strong Transient transfection assays perfromed with a chimeric gal4DBD-DAX1 fusion protein identify a transcriptional repression domain in the DAX-1 C-terminus. Rob Sladek
[10848616] Other Human Strong DAX-1 is associated with polyribosomes and polyadenylated RNA. DAX-1 directly binds to RNA through N- and C-terminus interaction domains. Rob Sladek
Additional Reviewer Comments:
Reviewer: Jared Roach

NR0B1 and NR0B2 when analyzed by NCBI's "Conserved Domain" tool show only the HOLI domain (Ligand binding domain of hormone receptors [smart00430]). HMMER hmmpfam analysis of human NR0B1 with the Pfam database shows PF00104.17 (Ligand-binding domain of nuclear hormone) as the top hit with a E-value of 4.3e-28, and PF02037.14 (SAP domain) as a distant second with and E-value of 0.00041. The SAP (after SAF-A/B, Acinus and PIAS) motif is a putative DNA binding domain found in diverse nuclear proteins. The NCBI GEnRIF for human NR0B1 states "This gene encodes a protein that contains a DNA-binding domain", while the entry for human NR0B2 states "The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain". Indeed, the canonical length of human NR0B1 is 470 AA, while the canonical length of human NR0B2 is 257 AA, consistent with the presence an extra domain (e.g., DNA binding) in NR0B1. HMMER hmmpfam analysis of human NR0B2 with the Pfam database shows PF00104.17 (Ligand-binding domain of nuclear hormone) as the top hit with a E-value of 6.9e-32, and PF03681.4 (Uncharacterised protein family) as a distant second with and E-value of 0.0022. Together, these considerations suggest that NR0B1 is a DNA-binding TF, and NR0B2 does not bind DNA, and is rather a co-factor.

Reviewer: Rob Sladek

DAX-1 is a member of the nuclear receptor superfamily that does not contain a consensus zinc-finger DNA-binding domain. Transient transfection assays perfromed with a chimeric gal4DBD-DAX1 fusion protein identify a transcriptional repression domain in the DAX-1 C-terminus. DAX-1 also interacts directly with SF-1 and represses transcription in transient transfection assays. DAX-1 binds to DNA hairpins with stems containing 10-24bp in vitro and directly represses hairpin-containing promoters in transient transfection assays. DAX-1 is associated with polyribosomes and polyadenylated RNA. DAX-1 directly binds to RNA through N- and C-terminus interaction domains.


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Facts about Nr0b1 11614RDF feed
Gene description nuclear receptor subfamily 0, group b, member 1  +
Gene id 11,614  +
Gene judgment TF Gene  +
Gene symbol nr0b1  +, Ahc  +, Ahch  +, AHX  +, DAX-1  +, and Dax1  +
Gene taxonomy DNA-Binding: non-sequence-specific  +, Transcription Factor Binding: tf co-factor binding  +, and DNA-Binding: sequence-specific  +
Homolog cluster 110,784  +
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