Orphan nuclear receptor (IPR003070)

Short name: Nuc_orph_rcpt

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.

Novel members of the steroid receptor superfamily designated NOR-1 (neuron derived orphan receptor) [PMID: 7811288], Nurr1 (Nur-related factor 1) [PMID: 1491694], and NGFI-B [PMID: 1314418] have been identified from forebrain neuronal cells undergoing apoptosis, from brain cortex, and from lung, superior cervical ganglia and adrenal tissue respectively. The NOR-1 protein binds to the B1a response-element, which has been identified as the target sequence of the Nur77 family, suggesting that three members of the Nur77 family may transactivate common target gene(s) at different situations [PMID: 1491694, PMID: 1314418]. Ewing's sarcoma is characterised by chromosomal translocations that involve the NOR protein [PMID: 8570200].

GO terms

Biological Process

GO:0006355 regulation of transcription, DNA-templated

Molecular Function

GO:0003677 DNA binding
GO:0004879 nuclear receptor activity

Cellular Component

GO:0005634 nucleus

Contributing signatures

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