Family

Peroxisome proliferator-activated receptor, gamma (IPR003077)

Short name: 1Cnucl_rcpt_G

Family relationships

Description

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.

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Three cDNAs encoding PPARs have been isolated from Xenopus laevis: xPPAR alpha, beta and gamma [PMID: 8274443]. All three xPPARs appear to be activated by both synthetic peroxisome proliferators and naturally occurring fatty acids, suggesting a common mode of action for all members of this subfamily of receptors [PMID: 8274443]. Furthermore, the multiplicity of the receptors suggests the existence of hitherto unknown cellular signalling pathways for xenobiotics and putative endogenous ligands [PMID: 1312391].

A human cognate of the mouse PPAR-gamma (hPPAR gamma) has been cloned from a placental cDNA library [PMID: 8706692]. Sequence analysis reveals a high degree of similarity to the mouse receptor (mPPAR) and, like other PPARs, hPPAR gamma forms heterodimers with RXR alpha. hPPAR gamma is expressed strongly in adipose tissue, but significant levels are also detectable in placenta, lung and ovary [PMID: 8706692]. In vitro trans-activation data suggest hPPAR gamma is only poorly activated by xenobiotic peroxisome proliferators, although certain fatty acids and eicosanoids are potent activators of this receptor. Both mPARR and hPPAR gamma may be activated by thiazolidinedione drugs, although the receptors appear to differ in their sensitivity to these compounds. These data suggest a high degree of structural and functional similarity between mPARR and hPPAR gamma, and provide evidence for variation in human receptor structure that may result in differential sensitivity to activators [PMID: 8706692].

GO terms

Biological Process

GO:0006355 regulation of transcription, DNA-templated

Molecular Function

GO:0003677 DNA binding
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding

Cellular Component

GO:0005634 nucleus

Contributing signatures

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