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PR01289

Identifier
PROXISOMPAAR  [View Relations]  [View Alignment]  
Accession
PR01289
No. of Motifs
6
Creation Date
19-FEB-2000
Title
Peroxisome proliferator-activated receptor alpha 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). 

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]. 
 
PPAR alpha is thought to play an important role in lipid metabolism due to
its ability to activate transcription of a reporter gene through the 
promoter of the acyl-CoA oxidase (ACO) gene [4,5]. ACO catalyses the rate- 
limiting step in the peroxisomal beta-oxidation of fatty acids [5]. 
Activation is achieved by the binding of xPPAR alpha on a regulatory element
(DR1) found in the promoter region of this gene [4]. xPPAR beta and gamma
recognise the same type of element and, like PPAR alpha, form heterodimers
with retinoid X receptor [4].
 
PROXISOMPAAR is a 6-element fingerprint that provides a signature for 
peroxisome proliferator-activated alpha receptors. The fingeprint was 
derived from an initial alignment of 5 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the alpha receptors but distinguish them
from the rest of the PPAR family - motifs 1-4 lie N-terminal to the zinc
finger domain; motif 5 lies between the zinc fingers and the putative
ligand-binding domain; and motif 6 resides towards the C-terminus of the
latter domain. A single iteration on SPTR37_10f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
5 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
6555555
5000000
4000000
3000000
2000000
123456
True Positives
PPAR_CAVPO    PPAR_HUMAN    PPAR_MOUSE    PPAR_RAT      
PPAR_XENLA
Sequence Titles
PPAR_CAVPO  PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA (PPAR-ALPHA) - CAVIA PORCELLUS  
PPAR_HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA (PPAR-ALPHA) - HOMO SAPIENS (HU
PPAR_MOUSE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA (PPAR-ALPHA) - MUS MUSCULUS (MO
PPAR_RAT PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA (PPAR-ALPHA) - RATTUS NORVEGICU
PPAR_XENLA PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA (PPAR-ALPHA) - XENOPUS LAEVIS (
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
CPLSPLEADDLESPLSEEF PPAR_MOUSE 9 9 -
CPLSPLEADDLESPLSEEF PPAR_RAT 9 9 -
CPLSPLEAGDLESPLSEEF PPAR_HUMAN 9 9 -
CPLSPLEAEDLESPLSEYF PPAR_CAVPO 9 9 -
CILTPLDEDDLESPLSGEF PPAR_XENLA 13 13 -

Motif 2 width=22
Element Seqn Id St Int Rpt
LQEMGNIQEISQSIGEESSGSF PPAR_MOUSE 28 0 -
LQEMGNIQEISQSLGEESSGSF PPAR_RAT 28 0 -
LQEMGNIQEISQSIGEDSSGSF PPAR_HUMAN 28 0 -
LQEMGTIQDISRSLGEDSSGSF PPAR_CAVPO 28 0 -
LQDIVDIQDITQTIGDDGSTPF PPAR_XENLA 32 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
FGFADYQYLGSCPGSEGSVITD PPAR_MOUSE 49 -1 -
FSFADYQYLGSCPGSEGSVITD PPAR_RAT 49 -1 -
FGFTEYQYLGSCPGSDGSVITD PPAR_HUMAN 49 -1 -
FGFPEYQYLGSGPGSDGSVITD PPAR_CAVPO 49 -1 -
FGASEHQFFGNSPGSIGSVSTD PPAR_XENLA 53 -1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LSPASSPSSVSCPVIPAS PPAR_MOUSE 72 1 -
LSPASSPSSVSCPAVPTS PPAR_RAT 72 1 -
LSPASSPSSVTYPVVPGS PPAR_HUMAN 72 1 -
LSPASSPSSVSYPEVPCG PPAR_CAVPO 72 1 -
LSPASSPASITFPAASGS PPAR_XENLA 79 4 -

Motif 5 width=18
Element Seqn Id St Int Rpt
ETLCMAEKTLVAKMVANG PPAR_MOUSE 245 155 -
ETLCMAEKTLVAKMVANG PPAR_RAT 245 155 -
ETLCMAEKTLVAKLVANG PPAR_HUMAN 245 155 -
ETLCTAEKTLMAKVVSDG PPAR_CAVPO 245 155 -
ETLCMAEKTLVAKLVANG PPAR_XENLA 251 154 -

Motif 6 width=18
Element Seqn Id St Int Rpt
IEKLQEGIVHVLKLHLQS PPAR_MOUSE 397 134 -
IEKLQEGIVHVLKLHLQS PPAR_RAT 397 134 -
IEKMQEGIVHVLRLHLQS PPAR_HUMAN 397 134 -
IEKMQEAIVHVLKLHLQS PPAR_CAVPO 397 134 -
IEKMQESIVHVLKLHLQS PPAR_XENLA 403 134 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
CPLSPLEADDLESPLSEEF PPAR_MOUSE 9 9 -
CPLSPLEADDLESPLSEEF PPAR_RAT 9 9 -
CPLSPLEAGDLESPLSEEF PPAR_HUMAN 9 9 -
CPLSPLEAEDLESPLSEYF PPAR_CAVPO 9 9 -
CILTPLDEDDLESPLSGEF PPAR_XENLA 13 13 -

Motif 2 width=22
Element Seqn Id St Int Rpt
LQEMGNIQEISQSIGEESSGSF PPAR_MOUSE 28 0 -
LQEMGNIQEISQSLGEESSGSF PPAR_RAT 28 0 -
LQEMGNIQEISQSIGEDSSGSF PPAR_HUMAN 28 0 -
LQEMGTIQDISRSLGEDSSGSF PPAR_CAVPO 28 0 -
LQDIVDIQDITQTIGDDGSTPF PPAR_XENLA 32 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
FGFADYQYLGSCPGSEGSVITD PPAR_MOUSE 49 -1 -
FSFADYQYLGSCPGSEGSVITD PPAR_RAT 49 -1 -
FGFTEYQYLGSCPGSDGSVITD PPAR_HUMAN 49 -1 -
FGFPEYQYLGSGPGSDGSVITD PPAR_CAVPO 49 -1 -
FGASEHQFFGNSPGSIGSVSTD PPAR_XENLA 53 -1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LSPASSPSSVSCPVIPAS PPAR_MOUSE 72 1 -
LSPASSPSSVSCPAVPTS PPAR_RAT 72 1 -
LSPASSPSSVTYPVVPGS PPAR_HUMAN 72 1 -
LSPASSPSSVSYPEVPCG PPAR_CAVPO 72 1 -
LSPASSPASITFPAASGS PPAR_XENLA 79 4 -

Motif 5 width=18
Element Seqn Id St Int Rpt
ETLCMAEKTLVAKMVANG PPAR_MOUSE 245 155 -
ETLCMAEKTLVAKMVANG PPAR_RAT 245 155 -
ETLCMAEKTLVAKLVANG PPAR_HUMAN 245 155 -
ETLCTAEKTLMAKVVSDG PPAR_CAVPO 245 155 -
ETLCMAEKTLVAKLVANG PPAR_XENLA 251 154 -

Motif 6 width=18
Element Seqn Id St Int Rpt
IEKLQEGIVHVLKLHLQS PPAR_MOUSE 397 134 -
IEKLQEGIVHVLKLHLQS PPAR_RAT 397 134 -
IEKMQEGIVHVLRLHLQS PPAR_HUMAN 397 134 -
IEKMQEAIVHVLKLHLQS PPAR_CAVPO 397 134 -
IEKMQESIVHVLKLHLQS PPAR_XENLA 403 134 -