| 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. OHKURA, N., HIJIKURO, M., YAMAMOTO, A. AND MIKI, K.
Molecular cloning of a novel thyroid/steroid receptor superfamily gene from
cultured rat neuronal cells.
BIOCHEM.BIOPHYS.RES.COMMUN. 205 1959-1965 (1994).
5. LAW, S.W., CONNEELY, O.M., DEMAYO, F.J. AND O'MALLEY, B.W.
Identification of a new brain-specific transcription factor, NURR1.
MOL.ENDOCRINOL. 2129-2135 (1992).
6. 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).
7. CLARK, J., BENJAMIN, H., GILL, S., SIDHAR, S., GOODWIN, G., CREW, J.,
GUSTERSON, B.A., SHIPLEY, J. AND COOPER, C.S.
Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor
gene superfamily, in a human myxoid chondrosarcoma.
ONCOGENE 12 229-235 (1996).
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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].
Novel members of the steroid receptor superfamily designated NOR-1 (neuron
derived orphan receptor) [4], Nurr1 (Nur-related factor 1) [5], and NGFI-B
[6] have been identified from forebrain neuronal cells undergoing apoptosis,
from brain cortex, and from lung, superior cervical ganglia and adrenal
tissue respectively. The NOR-1 protein binds to the B1a response-element,
which has been identified as the target sequence of the Nur77 family,
suggesting that three members of the Nur77 family may transactivate common
target gene(s) at different situations [4]. Ewing's sarcoma is characterised
by chromosomal translocations that involve the NOR protein [7].
NUCLEARECPTR is an 11-element fingerprint that provides a signature for the
orphan nuclear receptor family. The fingerprint was derived from an initial
alignment of 11 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise members of the nuclear receptor family but distinguish
them from the rest of the steroid hormone receptor superfamily - motifs 1-3
lie N-terminal to the zinc finger domain; motifs 4 and 5 lie between the
zinc fingers and putative ligand-binding domain; motifs 6 and 7 encode the
N- and C-terminal extremities of the ligand-binding domain; and motifs 8-11
reside at the C-terminus. A single iteration on SPTR37_10f was required to
reach convergence, no further sequences being identified beyond the starting
set. Several partial matches were found, all of which appear to be N- or
C-terminally truncated homologues.
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