| Literature References | 1. NUCLEAR RECEPTORS NOMENCLATURE COMMITTEE
A unified nomenclature system for the nuclear receptor superfamily.
CELL 97 161-163 (1999).
2. NISHIKAWA, J-I., KITAURA, M., IMAGAWA, M. AND NISHIHARA, T.
Vitamin D receptor contains multiple dimerisation interfaces that
are functionally different.
NUCLEIC ACIDS RES. 23(4) 606-611 (1995).
3. DE VOS, P., SCHMITT, J., VERHOEVEN, G. AND STUNNENBERG, G.
Human androgen receptor expressed in HeLa cells activates transcription
in vitro.
NUCLEIC ACIDS RES. 22(7) 1161-1166 (1994).
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| Documentation | 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 [1]. 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 [2,3]. 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. [1]. 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 [1].
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.
RETINOIDXR is an 4-element fingerprint that provides a signature for the
retinoid X receptors. The fingerprint was derived from an initial alignment
of 31 sequences: motif 1 lies in the hinge region; and motifs 2-4 reside in
the ligand-binding domain. Five iterations on SPTR57.15_40.15f were required
to reach convergence, at which point a true set comprising 125 sequences was
identified. Several partial matches were also found, all of which are family
members that fail to make significant matches with one or more motifs.
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