Retinoid X receptor/HNF4 (IPR000003)

Short name: Retinoid-X_rcpt/HNF4

Overlapping homologous superfamilies

Family relationships


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.

The retinoic acid (retinoid X) 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 differs between retinoic acid isoforms; the small highly-conserved DNA-binding domain (~65 residues) occupies the central portion of the protein; and the ligand binding domain lies at the receptor C terminus.

This entry represents retinoid X receptors. It also represents hepatocyte nuclear factor 4 (HNF4), which is a nuclear receptor protein expressed in the liver and kidney, and functions as a key regulator of many metabolic pathways. HNF4 was originally classified as an orphan receptor. Linoleic acid has now been identified as the endogenous ligand for HNF4 in mammalian cells [PMID: 19440305].

GO terms

Biological Process

GO:0006355 regulation of transcription, DNA-templated

Molecular Function

GO:0003677 DNA binding
GO:0003707 steroid hormone receptor activity
GO:0008270 zinc ion binding

Cellular Component

GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.