Glucocorticoid receptor (IPR001409)
Short name: Glcrtcd_rcpt
- Nuclear hormone receptor (IPR001723)
- Glucocorticoid receptor (IPR001409)
Steroid or nuclear hormone receptors (NRs) constitute an important super- family 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 [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.
The glucocorticoid receptor consists of 3 functional and structural domains: an N-terminal (modulatory) domain; a DNA binding domain that mediates specific binding to target DNA sequences (ligand-responsive elements); and a hormone binding domain. The N-terminal domain is unique to the glucocorticoid receptors; it spans the first 440 residues, and is primarily responsible for transcriptional activation. The smaller (around 65 residues), highly-conserved central portion of the protein is the DNA binding domain, which plays a role in DNA binding specificity, homo- dimerisation and in interactions with other proteins. The hormone binding domain comprises approximately 250 residues at the C terminus of the receptor. This domain mediates receptor activity via interaction with heat shock proteins and cyclophilins, or with hormone.