| 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. GIGUERE, V., TINI, M., FLOCK, G., ONG, E., EVANS, R.M. AND OTULAKOWSKI, G.
Isoform-specific amino-terminal domains dictate DNA-binding properties of
ROR alpha, a novel family of orphan hormone nuclear receptors.
GENES DEV. 8 538-553 (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].
Three isoforms of a novel member of the steroid hormone nuclear receptor
superfamily related to retinoic acid receptors have been identified [4].
The isoforms (designated ROR alpha 1, ROR alpha 2 and ROR alpha 3) share
common DNA- and putative ligand-binding domains but are characterised by
distinct N-terminal domains generated by alternative RNA processing [4].
These differences in the N-terminal domains result in differential DNA-
binding activity for the different isoforms: ROR alpha 1 binds to and
constitutively activates transcription from a large subset of ROR elements,
while ROR alpha 2 recognises ROR elements with strict specificity and
displays weaker transcriptional activity [4]. The N-terminal domain and
zinc finger region work in concert to confer high affinity and specific
DNA-binding properties to the ROR isoforms and suggest a novel strategy
to control DNA-binding activity of nuclear receptors [4].
RORNUCRECPTR is a 5-element fingerprint that provides a signature for the
nuclear receptor ROR family. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved regions
spanning the C-terminal half of the alignment, focusing on those sections
that characterise the ROR receptors but distinguish them from the rest of
the steroid hormone receptor superfamily - motif 1 lies at the C-terminal
extremity of the hinge region, and motifs 2-5 reside in the ligand-binding
domain. Two iterations on SPTR37_10f were required to reach convergence,
at which point a true set comprising 13 sequences was identified. Five
partial matches were also found, all of which are related steroid hormone
receptors.
An update on SPTR57.15_40.15f identified a true set of 24 sequences, and
twelve partial matches, all of which are translated genomic sequences that
fail to match one or more motifs.
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