| 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. OHKURA, N., ITO, M., TSUKADA, T., SASAKI, K., YAMAGUCHI, K. AND MIKI, K.
Structure, mapping and expression of a human NOR-1 gene, the third member
of the Nur77/NGFI-B family.
BIOCHIM.BIOPHYS.ACTA 1308 205-214 (1996).
6. 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].
A novel member of the steroid receptor superfamily designated NOR-1 (neuron
derived orphan receptor) has been identified from forebrain neuronal cells
undergoing apoptosis [4]. The receptor, which contains 628 amino acids, is
highly similar to the Nur77 family in its DNA-binding domain and moderately
similar to its putative ligand-binding domain [4]. 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].
Human NOR-1 mRNA has been detected in adult heart and skeletal muscle, as
well as in foetal brain, indicating that its expression is not restricted
to events that occur during neural development [5]. It has been shown that
in a skeletal myxoid chondrosarcoma, the EWS gene becomes fused to NOR1 [6].
The chimaeric EWS-NOR gene encodes a EWS-NOR fusion protein in which the
C-terminal RNA-binding domain of EWS is replaced by the entire NOR protein,
comprising a long N-terminal domain, a central DNA binding domain and a
C-terminal ligand-binding/dimerisation domain [6].
NURRNUCRCPTR is a 10-element fingerprint that provides a signature for the
NOR orphan nuclear receptors. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise the NOR nuclear receptors but distinguish them from the
rest of the nuclear receptor family - motifs 1-7 lie N-terminal to the zinc
finger domain; motifs 8 and 9 precede the putative ligand-binding domain;
and motif 10 resides at the C-terminus. Two iterations on SPTR37_10f were
required to reach convergence, at which point a true set comprising 3
sequences was identified. Three partial matches were also found, all of
which appear to be NOR2 orphan nuclear receptors that lack the final two
C-terminal motifs.
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