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PR01286

Identifier
NORNUCRECPTR  [View Relations]  [View Alignment]  
Accession
PR01286
No. of Motifs
10
Creation Date
16-FEB-2000
Title
Orphan nuclear receptor NOR1 signature
Database References
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). 

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. 
Summary Information
   3 codes involving 10 elements
0 codes involving 9 elements
3 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
103333333333
90000000000
83333333300
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
NR43_HUMAN    NR43_RAT      O97726        
True Positive Partials
Codes involving 8 elements
NOR2_RAT O97727 Q14979
Sequence Titles
NR43_HUMAN  NUCLEAR HORMONE RECEPTOR NOR-1 (NEURON-DERIVED ORPHAN RECEPTOR 1) (MITOGEN INDUC 
NR43_RAT NUCLEAR HORMONE RECEPTOR NOR-1 (NEURON-DERIVED ORPHAN RECEPTOR 1) - RATTUS NORVE
O97726 NEURON-DERIVED ORPHAN RECEPTOR-1 ALFA - SUS SCROFA (PIG).

NOR2_RAT NUCLEAR HORMONE RECEPTOR NOR-2 (NEURON-DERIVED ORPHAN RECEPTOR 2) - RATTUS NORVE
O97727 NEURON-DERIVED ORPHAN RECEPTOR-1 BETA - SUS SCROFA (PIG).
Q14979 NUCLEAR RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_10f 1  15   NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RPLIKVEEGRAPSYHHH NR43_HUMAN 81 81 -
RPLIKMEEGREHGYHHH NR43_RAT 85 85 -

Motif 2 width=22
Element Seqn Id St Int Rpt
QPSIPPASSPEDEVLPSTSMYF NR43_HUMAN 114 16 -
QPSIPPPSGPEDEVLPSTSMYF NR43_RAT 116 14 -

Motif 3 width=22
Element Seqn Id St Int Rpt
LPSAPGCIAPGPLLDPPMKAVP NR43_HUMAN 160 24 -
LPSAPGCIAPGPLLDPQMKAVP NR43_RAT 162 24 -

Motif 4 width=18
Element Seqn Id St Int Rpt
HPPAPSPAGGHHLGYDPT NR43_HUMAN 199 17 -
HPPAPSPAGGHHLGYDPT NR43_RAT 201 17 -

Motif 5 width=22
Element Seqn Id St Int Rpt
AAAALSLPLGAAAAAGSQAAAL NR43_HUMAN 217 0 -
AAAALSLPLGAAAAAGSQAAAL NR43_RAT 219 0 -

Motif 6 width=18
Element Seqn Id St Int Rpt
EGHPYGLPLAKRAAPLAF NR43_HUMAN 239 0 -
EGHPYGLPLAKRTATLTF NR43_RAT 241 0 -

Motif 7 width=21
Element Seqn Id St Int Rpt
PLGLTPSPTASSLLGESPSLP NR43_HUMAN 258 1 -
PLGLTASPTASSLLGESPSLP NR43_RAT 260 1 -

Motif 8 width=20
Element Seqn Id St Int Rpt
PLQQEPSQPSPPSPPICMMN NR43_HUMAN 381 102 -
PLQQEPSQPSPPSPPICMMN NR43_RAT 383 102 -

Motif 9 width=17
Element Seqn Id St Int Rpt
YCPTDQAAAGTDAEHVQ NR43_HUMAN 419 18 -
YCPTDQATAGTDAEHVQ NR43_RAT 421 18 -

Motif 10 width=27
Element Seqn Id St Int Rpt
HQSKGQALEPTESKVLGALVELRKICT NR43_HUMAN 569 133 -
HQRKGQALEPSEPKVLRALVELRKICT NR43_RAT 571 133 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RPLIKVEEGRAPSYHHH NR43_HUMAN 81 81 -
RPLIKMEEGREHGYHHH NR43_RAT 85 85 -
RPLIKMEEGRAHGYHHH O97726 85 85 -

Motif 2 width=22
Element Seqn Id St Int Rpt
QPSIPPASSPEDEVLPSTSMYF NR43_HUMAN 114 16 -
QPSIPPPSGPEDEVLPSTSMYF NR43_RAT 116 14 -
QPSIPPPSGPEDEVLPSTSMYF O97726 126 24 -

Motif 3 width=22
Element Seqn Id St Int Rpt
LPSAPGCIAPGPLLDPPMKAVP NR43_HUMAN 160 24 -
LPSAPGCIAPGPLLDPQMKAVP NR43_RAT 162 24 -
LPSAQGCIAPGPLLDPPMKAVP O97726 172 24 -

Motif 4 width=18
Element Seqn Id St Int Rpt
HPPAPSPAGGHHLGYDPT NR43_HUMAN 199 17 -
HPPAPSPAGGHHLGYDPT NR43_RAT 201 17 -
HPPAPSPAGGHHLGYDPT O97726 211 17 -

Motif 5 width=22
Element Seqn Id St Int Rpt
AAAALSLPLGAAAAAGSQAAAL NR43_HUMAN 217 0 -
AAAALSLPLGAAAAAGSQAAAL NR43_RAT 219 0 -
AAAALGLPLGAAAAAAAAAAGS O97726 229 0 -

Motif 6 width=18
Element Seqn Id St Int Rpt
EGHPYGLPLAKRAAPLAF NR43_HUMAN 239 0 -
EGHPYGLPLAKRTATLTF NR43_RAT 241 0 -
EGHPYGLPLAKRAAALAF O97726 256 5 -

Motif 7 width=21
Element Seqn Id St Int Rpt
PLGLTPSPTASSLLGESPSLP NR43_HUMAN 258 1 -
PLGLTASPTASSLLGESPSLP NR43_RAT 260 1 -
PLGLTTSPTTSSLLGESPSLP O97726 275 1 -

Motif 8 width=20
Element Seqn Id St Int Rpt
PLQQEPSQPSPPSPPICMMN NR43_HUMAN 381 102 -
PLQQEPSQPSPPSPPICMMN NR43_RAT 383 102 -
PLQQEPSQPSPPSPPVCMMN O97726 398 102 -

Motif 9 width=17
Element Seqn Id St Int Rpt
YCPTDQAAAGTDAEHVQ NR43_HUMAN 419 18 -
YCPTDQATAGTDAEHVQ NR43_RAT 421 18 -
YCPADQAAAGTDAEHVQ O97726 436 18 -

Motif 10 width=27
Element Seqn Id St Int Rpt
HQSKGQALEPTESKVLGALVELRKICT NR43_HUMAN 569 133 -
HQRKGQALEPSEPKVLRALVELRKICT NR43_RAT 571 133 -
HQSKGQALEPTEPKVLRALVELRKICT O97726 586 133 -