1. NUCLEAR RECEPTORS NOMENCLATURE COMMITTEE
A unified nomenclature system for the nuclear receptor superfamily.
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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. QIU, Y., COONEY, A.J., KURATANI, S., DEMAYO, F.J., TSAI, S.Y.
AND TSAI, M.J.
Spatiotemporal expression patterns of chicken ovalbumin upstream
promoter-transcription factors in the developing mouse central nervous
system: evidence for a role in segmental patterning of the diencephalon.
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Cloning and expression during development of three murine members of the
COUP family of nuclear orphan receptors.
MECH.DEV. 47 81-97 (1994).
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 .
Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes
encode transcription factors that belong to the orphan group of the
steroid/thyroid hormone receptor superfamily . COUP-TF binds to the
ovalbumin promoter and, in conjunction with the S300-II protein, stimulates
initiation of transcription. The protein binds to both direct repeats and
palindromes of the 5'-AGGTCA-3' motif.
Murine homologues of members of the COUP-TF family, COUP-TF1, ARP-1 and
EAR2, have been isolated and shown to be highly similar to their human
counterparts . Although these three genes appear to be expressed in
tissues derived from all three germ layers, COUP-TF1 and ARP-1 have been
found to be expressed predominantly in the developing central nervous
system in mutually exclusive domains . Strong ARP-1 expression has
also been detected in lung and kidney . Results from such studies
suggest an important role for the members of the COUP-TF family in the
hormonal control of gene expression regulating embryogenesis, and in the
development and differentiation of the CNS, including the specification
of diencephalic neuromeres .
COUPTNFACTOR is a 9-element fingerprint that provides a signature for
the COUP-related transcription factor family. The fingeprint was derived
from an initial alignment of 7 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the COUP-related nuclear receptors but
distinguish them from the rest of the steroid hormone receptor superfamily
- motifs 1-8 span the putative ligand-binding domain; and motifs 7-9 reside
within the putative dimerisation domain. Two iterations on SPTR37_10f were
required to reach convergence, at which point a true set comprising 15
sequences was identified. Several partial matches were also found:
7UP2_DROME is a Drosophila seven-up type 2 steroid receptor that fails to
match the C-terminal motifs; O96680 and Q9YGL3 are related sequences that
match only 2 motifs.