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PR01290

Identifier
PROXISOMPABR  [View Relations]  [View Alignment]  
Accession
PR01290
No. of Motifs
4
Creation Date
19-FEB-2000
Title
Peroxisome proliferator-activated receptor beta signature
Database References
PRINTS; PR00398 STRDHORMONER; PR01288 PROXISOMEPAR
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. KREY, G., KELLER, H., MAHFOUDI, A., MEDIN, J., OZATO, K., DREYER, C.
AND WAHLI, W. 
Xenopus peroxisome proliferator activated receptors: genomic organization,
response element recognition, heterodimer formation with retinoid X receptor
and activation by fatty acids.
J.STEROID BIOCHEM.MOL.BIOL. 47 65-73 (1993). 
 
5. DREYER, C., KREY, G., KELLER, H., GIVEL, F., HELFTENBEIN, G. 
AND WAHLI, W.
Control of the peroxisomal beta-oxidation pathway by a novel family
of nuclear hormone receptors.
CELL 68 879-887 (1992). 
 
6. KLIEWER, S.A., FORMAN, B.M., BLUMBERG, B., ONG, E.S., BORGMEYER, U.,
MANGELSDORF, D.J., UMESONO, K. AND EVANS, R.M.
Differential expression and activation of a family of murine peroxisome
proliferator-activated receptors.
PROC.NATL.ACAD.SCI.U.S.A. 91 7355-7359 (1994). 

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].
 
Peroxisome proliferator-activated receptors (PPAR) are ligand-activated
transcription factors that belong to the nuclear hormone receptor 
superfamily. Three cDNAs encoding PPARs have been isolated from Xenopus
laevis: xPPAR alpha, beta and gamma [4]. All three xPPARs appear to be
activated by both synthetic peroxisome proliferators and naturally occurring
fatty acids, suggesting a common mode of action for all members of this 
subfamily of receptors [4]. Furthermore, the multiplicity of the receptors
suggests the existence of hitherto unknown cellular signalling pathways for
xenobiotics and putative endogenous ligands [5]. 
 
A PPAR alpha-related cDNA from mouse (designated PPAR delta, and
subsequently renamed beta) has been cloned and characterised. The alpha, 
beta and gamma PPAR isoforms display widely divergent patterns of expression
during embryogenesis and in the adult [6]. PPAR gamma and beta are not 
activated by pirinixic acid, a potent peroxisome proliferator and activator
of PPAR alpha [6]; they are, however, activated by the structurally distinct
peroxisome proliferator LY-171883 and linoleic acid, respectively, 
indicating that each isoform can act as a regulated activator of
transcription [6]. Thus tissue-specific responsiveness to peroxisome
proliferators, including certain fatty acids, may be partly a consequence
of differential expression of multiple, pharmacologically distinct PPAR
isoforms [6]. 
 
PROXISOMPABR is a 4-element fingerprint that provides a signature for 
peroxisome proliferator-activated beta receptors. The fingeprint was 
derived from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the beta receptors but distinguish them
from the rest of the PPAR family - motif 1 lies N-terminal to the zinc 
finger domain; motifs 2 and 3 reside between the zinc fingers and the
putative ligand-binding domain; and motif 4 lies within this latter domain.
Two iterations on SPTR37_10f were required to reach convergence, at which
point a true set comprising 4 sequences was identified. 
Summary Information
4 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
44444
30000
20000
1234
True Positives
PPAS_HUMAN    PPAS_MOUSE    PPAS_XENLA    Q62879        
Sequence Titles
PPAS_HUMAN  PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR BETA (PPAR-BETA) (PPAR-DELTA) (NUCLEA 
PPAS_MOUSE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR BETA (PPAR-BETA) (PPAR-DELTA) (NUCLEA
PPAS_XENLA PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR BETA (PPAR-BETA) - XENOPUS LAEVIS (AF
Q62879 PPAR DELTA PROTEIN - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
LDQLQMGCDGASCGS PPAS_HUMAN 55 55 -
LDQLQMGCDGASGGS PPAS_MOUSE 54 54 -
LDEQPSTPLEHQETS PPAS_XENLA 12 12 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LWQAEKGLVWKQL PPAS_HUMAN 219 149 -
LWQAEKGLVWKQL PPAS_MOUSE 218 149 -
LWQAEQGTVWEQL PPAS_XENLA 174 147 -

Motif 3 width=11
Element Seqn Id St Int Rpt
EISVHVFYRCQ PPAS_HUMAN 240 8 -
EISVHVFYRCQ PPAS_MOUSE 239 8 -
EIGVHVFYRCQ PPAS_XENLA 195 8 -

Motif 4 width=11
Element Seqn Id St Int Rpt
LRALEFHLQAN PPAS_HUMAN 378 127 -
LRALEFHLQVN PPAS_MOUSE 377 127 -
LGALRRHLKAS PPAS_XENLA 333 127 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
LDQLQMGCDGASCGS PPAS_HUMAN 55 55 -
LDQLQMGCDGASGGS PPAS_MOUSE 54 54 -
LDQLQMGCDGASGGS Q62879 54 54 -
LDEQPSTPLEHQETS PPAS_XENLA 12 12 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LWQAEKGLVWKQL PPAS_HUMAN 219 149 -
LWQAEKGLVWKQL PPAS_MOUSE 218 149 -
LWQAEKGLVWKQL Q62879 218 149 -
LWQAEQGTVWEQL PPAS_XENLA 174 147 -

Motif 3 width=11
Element Seqn Id St Int Rpt
EISVHVFYRCQ PPAS_HUMAN 240 8 -
EISVHVFYRCQ PPAS_MOUSE 239 8 -
EISVHVFYRCQ Q62879 239 8 -
EIGVHVFYRCQ PPAS_XENLA 195 8 -

Motif 4 width=11
Element Seqn Id St Int Rpt
LRALEFHLQAN PPAS_HUMAN 378 127 -
LRALEFHLQVN PPAS_MOUSE 377 127 -
LQALEFHLQVN Q62879 377 127 -
LGALRRHLKAS PPAS_XENLA 333 127 -