| 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. WILSON, T.E., PAULSEN, R.E., PADGETT, K.A. AND MILBRANDT, J.
Participation of non-zinc finger residues in DNA binding by two nuclear
orphan receptors.
SCIENCE 256 107-110 (1992).
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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].
NGFI-B is an early response protein and orphan member of the steroid
hormone receptor superfamily [4]. It is expressed in the lung, brain and
superior cervical ganglia, and high levels are also seen in adrenal
tissue. While members of this superfamily typically bind DNA as dimers,
NGFI-B binds as a monomer. A domain separate from the NGFI-B zinc fingers
(the so-called A box) has been identified and is required for recognition
of two adenine-thymidine base pairs at the 5' end of the NGFI-B DNA binding
element [4].
HMRNUCRECPTR is a 9-element fingerprint that provides a signature for the
HMR orphan nuclear receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise the HMR nuclear receptors but distinguish them from the
rest of the nuclear receptor family - motifs 1-7 lie N-terminal to the
zinc finger domain; motif 8 falls after the zinc finger domain; and motif 9
resides at the C-terminus. A single iteration on SPTR37_10f was required to
reach convergence, no further sequences being identified beyond the starting
set. A single partial match was found, Q15627, a human TR3beta fragment that
matches the N-terminal motifs.
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