Nuclear receptor ROR (IPR003079)
Short name: ROR_rcpt
Overlapping homologous superfamilies
- Nuclear hormone receptor (IPR001723)
- Nuclear receptor ROR (IPR003079)
Steroid or nuclear hormone receptors (4A nuclear receptor, 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 [PMID: 14747695]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [PMID: 7899080, PMID: 8165128]. 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.
Three isoforms of a novel member of the steroid hormone nuclear receptor superfamily related to retinoic acid receptors have been identified. The isoforms (designated ROR alpha 1, ROR alpha 2 and ROR alpha 3) share common DNA- and putative ligand-binding domains but are characterised by distinct N-terminal domains generated by alternative RNA processing. These differences in the N-terminal domains result in differential DNA- binding activity for the different isoforms: ROR alpha 1 binds to and constitutively activates transcription from a large subset of ROR elements, while ROR alpha 2 recognises ROR elements with strict specificity and displays weaker transcriptional activity. The N-terminal domain and zinc finger region work in concert to confer high affinity and specific DNA-binding properties to the ROR isoforms and suggest a novel strategy to control DNA-binding activity of nuclear receptors [PMID: 7926749].
Synonym(s): 1F nuclear receptor
- PR01293 (RORNUCRECPTR)