| 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).
4. TALBOT, W.S., SWYRYD, E.A. AND HOGNESS, D.S.
Drosophila tissues with different metamorphic responses to ecdysone express
different ecdysone receptor isoforms.
CELL 73 1323-1337 (1993).
5. CHO, W.L., KAPITSKAYA, M.Z. AND RAIKHEL, A.S.
Mosquito ecdysteroid receptor: analysis of the cDNA and expression during
vitellogenesis.
INSECT BIOCHEM.MOL.BIOL. 25 19-27 (1995).
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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].
In Drosophila melanogaster, the steroid hormone ecdysone triggers larval-to-
adult metamorphosis, a process in which the hormone induces imaginal tissues
to generate adult structures, and larval tissues to degenerate [4]. The
ecdysone receptor (EcR) binds DNA with high specificity at ecdysone response
elements. EcR is nuclear and is found in larval wing discs, pupal wings and
in prothoracic glands.
In the mosquito Aedes aegypti, 20-hydroxyecdysone plays an important role
in the regulation of egg maturation [5]. There are three EcR transcripts
(of 4.2kb, 6kb and 11kb) in adult mosquitoes; 4.2kb mRNA is predominantly
expressed in female mosquitoes during vitellogenesis [5]. In both the fat
body and ovaries of the female mosquito, the level of EcR mRNA is high at
the previtellogenic period and after the onset of vitellogenesis [5].
ECDYSTEROIDR is an 8-element fingerprint that provides a signature for
ecdysone receptors. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length, focusing on those sections that
characterise the ecdysone receptors but distinguish them from the rest of
the steroid hormone receptor superfamily - motif 1 lies at the C-terminus
of the putative modulating domain; motif 2 lies immediately C-terminal to
the zinc fingers; and motifs 3-8 span the hormone binding domain. Two
iterations on SPTR37_10f were required to reach convergence, at which
point a true set comprising 14 sequences was identified.
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