Human RARB

retinoic acid receptor, beta

By David Laperriere, Marieke Rozendaal, and Sylvie Mader

Classification	Homo sapiens » Zinc-coordinating Group » Hormone-nuclear Receptor Family » Subfamily 1 (TR, RAR, PPAR, REV-ERB, E78, RZR/ROR, CNR14, ECR, VDR, DHR96, NHR1, and 27 individual genes)
Related TF(s)	(none defined here)
Homologs	• Rarb
Links	ENSG00000077092 (Ensembl) 5915 (Entrez Gene) Homologene 180220 (OMIM)
Synonyms	RRB2, NR1B2, HAP

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Summary Structure TFBS Targets Protein Interactions Genetics Expression Ontologies Papers

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Overview

The DNA binding domain of nuclear receptors is highly conserved throughout the superfamily (more than 40% amino acid identity over a 67-residue region) and is composed of two zinc fingers that fold to form a single structural unit. Each zinc finger contains a group of four Cys residues that co-ordinates a single zinc atom. An alpha helix at the end of the first zinc finger is inserted into the major groove of DNA and several residues engage in specific interactions with base pairs of the PuGGTCA motifs.^[1] RAR-RXR heterodimers bind DNA with the RXR monomer bound 5' to the RAR monomer in DR2 and DR5 repeats, but in the reverse polarity on DR1 repeats, switching the activity of the heterodimer from activator to repressor of transcription.The dimeric interface on a DR5 element involves a region (D box) in the second zinc finger of the DNA binding domain of RXR and the tip of the RAR first zinc finger, while on a DR1 element association is mediated via the second zinc finger of RAR and the T box within the C-terminal extension of the RXR DNA binding domain.^[2]^[3]^[4]^[5]^[6]

References

Khorasanizadeh S and Rastinejad F. Nuclear-receptor interactions on DNA-response elements. Trends Biochem. Sci., 26(6):384-90. (PMID 11406412)
Mader S et al. The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains. EMBO J., 12(13):5029-41. (PMID 8262045)
Predki PF et al. Ordered binding of retinoic acid and retinoid-X receptors to asymmetric response elements involves determinants adjacent to the DNA-binding domain. Mol. Endocrinol., 8(1):31-9. (PMID 8152429)

Zechel C et al. The dimerization interfaces formed between the DNA binding domains of RXR, RAR and TR determine the binding specificity and polarity of the full-length receptors to direct repeats. EMBO J., 13(6):1425-33. (PMID 8137826)
Zechel C et al. Dimerization interfaces formed between the DNA binding domains determine the cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements. EMBO J., 13(6):1414-24. (PMID 8137825)
Rastinejad F et al. Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1. EMBO J., 19(5):1045-54. (PMID 10698945)

Structures

About this section

This section contains 3D PDB models of structural predictions for this transcription factor. METHODS: The template selection protocol follows that of Morozov and Siggia, in which templates are selected to optimize similarity of DNA-binding residues (Morozov AV, Siggia ED. PNAS 104(17):7068-73). This has been shown to increase modeling accuracy at the DNA-binding interface. For all solved structures containing DNA, amino acids within 4A of DNA (DNA-binding residues) are stored. Pfam domain hits of each DNA-bound chain are detected by hmmer, and each hit is added to a list mapping domain family name to chain hits. Pfam domain hits of each unsolved structure are detected by HMMER. For each identified Pfam family, the unsolved sequence is aligned to all solved family members (putative templates). Alignments are scored based on similarity of the DNA-binding residues in the template to the aligned residues of the unsolved sequence. For each subsequence of the unsolved protein identified as a DNA-binding domain, the top scoring template is selected. For sequences known to form homodimers, a homodimeric template is selected. The model is constructed from the template using Modeller 9v2. DNA bound to the template is added to the model by superimposition of the solved and modeled structures.

RARB 5915 2hanB

Image 3D Model .PDB File