DNA-binding domain of Retinoid-related orphan receptors (RORs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. ROR interacts with specific DNA sites upstream of the target gene and modulates the rate of transcriptional initiation. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence [].RORs are orphan NRs (steroid or nuclear hormone receptors) related to retinoic acid receptors and include ROR-alpha, ROR-beta and ROR-gamma, which are also referred to as RORA, RORB and RORC. ROR-alpha, ROR-beta and ROR-gamma regulate circadian rhythms with ROR-alpha playing the central role []. ROR-alpha has a key role in the development of the cerebellum. ROR-beta is necessary for the proliferation and differentiation of retinal cells. ROR-gamma is required for lymph-node organogenesis []. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, retinoid-related orphan receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain.
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands []. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [, ]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.Retinoic acid-related orphan receptors (RORs) are orphan NRs related to retinoic acid receptors and include ROR-alpha, ROR-beta and ROR-gamma, which are also referred to as RORA, RORB and RORC. ROR-alpha, ROR-beta and ROR-gamma regulate circadian rhythms with ROR-alpha playing the central role []. ROR-alpha has a key role in the development of the cerebellum. ROR-beta is necessary for the proliferation and differentiation of retinal cells. ROR-gamma is required for lymph-node organogenesis [].
