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
NUCLEIC ACIDS RES. 22(7) 1161-1166 (1994).
4. DANIELIAN, P.S., WHITE, R., LEES, J.A. AND PARKER, M.G.
Identification of a conserved region required for hormone dependent
transcriptional activation by steroid hormone receptors.
EMBO J. 11 1025-1033 (1992).
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 [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. . 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 oestrogen 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, termed ligand-responsive
elements; and a hormone binding domain. The N-terminal domain is unique to
the oestrogen receptors and spans approximately the first 180 residues; the
highly-conserved DNA-binding domain is smaller (around 65 residues) and
occupies the central portion of the protein; and the hormone binding
domain lies at the receptor C-terminus.
The oestrogen receptor  stimulates transcription via 2 distinct
transcriptional activation domains: TAF-1 in the N-terminal domain, and
TAF-2 in the hormone-binding domain. TAF-2 activity requires a region in
the C-terminus of the hormone-binding domain (between residues 538-552 in
the mouse oestrogen receptor) that is conserved in many nuclear hormone
receptors. It is therefore suggested that this region may be essential
for ligand-dependent transcriptional activation by other members of the
nuclear receptor family .
OESTROGENR is an 8-element fingerprint that provides a signature for the
oestrogen receptors. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs span the N-terminal modulatory domain preceding
the highly-conserved zinc-binding region shared by the steroid hormone
receptor family. Two iterations on OWL28.0 were required to reach
convergence, at which point a true set comprising 8 sequences was
identified. A single partial match was also found (ORZMER), an oestrogen
receptor from the killifish that matches motifs 5 and 6.
An update on SPTR57.15_40.15f identified a true set of 46 sequences,
together with numerous partial matches, all of which are family members
that fail to match one or more motifs.