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PR01291

Identifier
PROXISOMPAGR  [View Relations]  [View Alignment]  
Accession
PR01291
No. of Motifs
6
Creation Date
19-FEB-2000
Title
Peroxisome proliferator-activated receptor gamma 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. APERLO, C., POGNONEC, P., SALADIN, R., AUWERX, J. AND BOULUKOS, K.E.
cDNA cloning and characterization of the transcriptional activities of the 
hamster peroxisome proliferator-activated receptor haPPAR gamma.
GENE 162 297-302 (1995). 
 
7. LAMBE K.G., TUGWOOD J.D.
A human peroxisome-proliferator-activated receptor-gamma is activated by
inducers of adipogenesis, including thiazolidinedione drugs.
EUR.J.BIOCHEMISTRY 239 1-7 (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].
 
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 cDNA corresponding to the hamster PPAR (haPPAR) gamma has been isolated 
[6]. haPPAR gamma mRNA is highly expressed in adipose tissue, and to a
lesser extent in lung, heart, kidney, liver and spleen, and may thus 
function in activating the transcription of target genes in a variety of
tissues, including those not particularly subjected to peroxisomal beta-
oxidation [6]. haPPAR gamma binds efficiently in the presence of retinoid X
receptor alpha (RXR alpha) to a peroxisome proliferator response element
(PPRE) first identified in the acyl-CoA oxidase (ACO) promoter, the rate-
limiting enzyme of peroxisomal beta-oxidation [6]. 
 
A human cognate of the mouse PPAR-gamma (hPPAR gamma) has been cloned from
a placental cDNA library [7]. Sequence analysis reveals a high degree of
similarity to the mouse receptor (mPPAR) and, like other PPARs, hPPAR gamma
forms heterodimers with RXR alpha. hPPAR gamma is expressed strongly in 
adipose tissue, but significant levels are also detectable in placenta, lung
and ovary [7]. In vitro trans-activation data suggest hPPAR gamma is only
poorly activated by xenobiotic peroxisome proliferators, although certain
fatty acids and eicosanoids are potent activators of this receptor [7]. Both
mPARR and hPPAR gamma may be activated by thiazolidinedione drugs, although
the receptors appear to differ in their sensitivity to these compounds [7].
These data suggest a high degree of structural and functional similarity
between mPARR and hPPAR gamma, and provide evidence for variation in human
receptor structure that may result in differential sensitivity to 
activators [7]. 
 
PROXISOMPAGR is a 6-element fingerprint that provides a signature for 
peroxisome proliferator-activated gamma receptors. The fingeprint was 
derived from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the gamma 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 within this latter domain.
Two iterations on SPTR37_10f were required to reach convergence, at which
point a true set comprising 11 sequences was identified.
ANNOTATION
Summary Information
11 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
6111111111111
5000000
4000000
3000000
2000000
123456
True Positives
O18924        O18971        O62807        O77815        
O88275 PPAT_HUMAN PPAT_MOUSE PPAT_RABIT
PPAT_XENLA Q15180 Q15832
Sequence Titles
O18924      PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA 2 - MACACA MULATTA (RHESUS MACA 
O18971 PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA 2 (PEROXISOME PROLIFERATOR ACTI
O62807 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA 2 - SUS SCROFA (PIG).
O77815 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA 2 (PEROXISOME PROLIFERATOR-CCTI
O88275 PPAR-GAMMA PROTEIN - RATTUS NORVEGICUS (RAT).
PPAT_HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR-GAMMA) - HOMO SAPIENS (HU
PPAT_MOUSE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR-GAMMA) - MUS MUSCULUS (MO
PPAT_RABIT PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR-GAMMA) - ORYCTOLAGUS CUNI
PPAT_XENLA PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR-GAMMA) - XENOPUS LAEVIS (
Q15180 PPAR GAMMA2 (PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA) - HOMO SAPIENS (H
Q15832 PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA 2 - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
NFGISSVDLSVMEDH PPAT_MOUSE 12 12 -
NFGISSVDLSVMEDH PPAT_HUMAN 12 12 -
NFGIGSVDLSVMDDH PPAT_RABIT 12 12 -
NFGMNSMDMSALEDH PPAT_XENLA 13 13 -

Motif 2 width=14
Element Seqn Id St Int Rpt
FDIKPFTTVDFSSI PPAT_MOUSE 30 3 -
FDIKPFTTVDFSSI PPAT_HUMAN 30 3 -
FDIKPFTTVDFSSI PPAT_RABIT 30 3 -
YDIKPFTTVDFSSI PPAT_XENLA 31 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
RADPMVADYKYDLKLQEY PPAT_MOUSE 55 11 -
RTDPVVADYKYDLKLQEY PPAT_HUMAN 55 11 -
RADPMVADYKYDLKLQEY PPAT_RABIT 55 11 -
RNDQSPIDYKYDLKLQEC PPAT_XENLA 60 15 -

Motif 4 width=19
Element Seqn Id St Int Rpt
QSAIKVEPASPPYYSEKTQ PPAT_MOUSE 73 0 -
QSAIKVEPASPPYYSEKTQ PPAT_HUMAN 73 0 -
QSAIKVEPASPPYYSEKTQ PPAT_RABIT 73 0 -
QSSIKLEPPSPPYFSDKPQ PPAT_XENLA 78 0 -

Motif 5 width=17
Element Seqn Id St Int Rpt
QAEKEKLLAEISSDIDQ PPAT_MOUSE 185 93 -
QAEKEKLLAEISSDIDQ PPAT_HUMAN 185 93 -
QAEKEKLLAEISSDIDQ PPAT_RABIT 185 93 -
QAEKEKLLAEISSDIDQ PPAT_XENLA 189 92 -

Motif 6 width=14
Element Seqn Id St Int Rpt
DNLLQALELQLKLN PPAT_MOUSE 409 207 -
DNLLQALELQLKLN PPAT_HUMAN 409 207 -
DNLLQALELQLKLN PPAT_RABIT 409 207 -
DSLLQALELQLKLN PPAT_XENLA 411 205 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
NFGISSVDLSVMEDH PPAT_MOUSE 12 12 -
NFGISSVDLSVMEDH PPAT_HUMAN 12 12 -
NFGISSVDLSVMEDH Q15180 42 42 -
NFGISSVDLSVMEDH Q15832 42 42 -
NFGISSVDLSVMDDH O88275 12 12 -
NFGISSVDLSVMDDH O18924 42 42 -
NFGIGSVDLSVMDDH PPAT_RABIT 12 12 -
NFGISSVDLSVMDDH O62807 41 41 -
NFGISSVDLSVMDDH O77815 41 41 -
NFGISSVDLSMMDDH O18971 42 42 -
NFGMNSMDMSALEDH PPAT_XENLA 13 13 -

Motif 2 width=14
Element Seqn Id St Int Rpt
FDIKPFTTVDFSSI PPAT_MOUSE 30 3 -
FDIKPFTTVDFSSI PPAT_HUMAN 30 3 -
FDIKPFTTVDFSSI Q15180 60 3 -
FDIKPFTTVDFSSI Q15832 60 3 -
FDIKPFTTVDFSSI O88275 30 3 -
FDIKPFTTVDFSSI O18924 60 3 -
FDIKPFTTVDFSSI PPAT_RABIT 30 3 -
FDIKPFTTVDFSSI O62807 59 3 -
FDIKPFTTVDFSSI O77815 59 3 -
FDIKPFTTVDFSSI O18971 60 3 -
YDIKPFTTVDFSSI PPAT_XENLA 31 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
RADPMVADYKYDLKLQEY PPAT_MOUSE 55 11 -
RTDPVVADYKYDLKLQEY PPAT_HUMAN 55 11 -
RTDPVVADYKYDLKLQEY Q15180 85 11 -
RTDPVVADYKYDLKLQEY Q15832 85 11 -
RADPMVADYKYDLKLQEY O88275 55 11 -
RTDPMVADYKYDLKLQEY O18924 85 11 -
RADPMVADYKYDLKLQEY PPAT_RABIT 55 11 -
RADPMVADYKYDLKLQDY O62807 84 11 -
RADPMVADYKYDLKLQDY O77815 84 11 -
RADPMVADYKYDLKLQEY O18971 85 11 -
RNDQSPIDYKYDLKLQEC PPAT_XENLA 60 15 -

Motif 4 width=19
Element Seqn Id St Int Rpt
QSAIKVEPASPPYYSEKTQ PPAT_MOUSE 73 0 -
QSAIKVEPASPPYYSEKTQ PPAT_HUMAN 73 0 -
QSAIKVEPASPPYYSEKTQ Q15180 103 0 -
QSAIKVEPASPPYYSEKTQ Q15832 103 0 -
QSAIKVEPASPPYYSEKTQ O88275 73 0 -
QSAIKVEPASPPYYSEKTQ O18924 103 0 -
QSAIKVEPASPPYYSEKTQ PPAT_RABIT 73 0 -
QSAIKVEPVSPPYYSEKTQ O62807 102 0 -
QSAIKVEPVSPPYYSEKTQ O77815 102 0 -
QSAIKVEPVSPPYYSEKTQ O18971 103 0 -
QSSIKLEPPSPPYFSDKPQ PPAT_XENLA 78 0 -

Motif 5 width=17
Element Seqn Id St Int Rpt
QAEKEKLLAEISSDIDQ PPAT_MOUSE 185 93 -
QAEKEKLLAEISSDIDQ PPAT_HUMAN 185 93 -
QAEKEKLLAEISSDIDQ Q15180 215 93 -
QAEKEKLLAEISSDIDQ Q15832 215 93 -
QAEKEKLLAEISSDIDQ O88275 185 93 -
QAEKEKLLAEISSDIDQ O18924 215 93 -
QAEKEKLLAEISSDIDQ PPAT_RABIT 185 93 -
QAEKEKLLAEISSDIDQ O62807 214 93 -
QAEKEKLLAEISSDIDQ O77815 214 93 -
QAEKEKLLAEISSDIDQ O18971 215 93 -
QAEKEKLLAEISSDIDQ PPAT_XENLA 189 92 -

Motif 6 width=14
Element Seqn Id St Int Rpt
DNLLQALELQLKLN PPAT_MOUSE 409 207 -
DNLLQALELQLKLN PPAT_HUMAN 409 207 -
DNLLQALELQLKLN Q15180 440 208 -
DNLLQALELQLKLN Q15832 439 207 -
DNLLQALELQLKLN O88275 409 207 -
DNLLQALELQLKLN O18924 439 207 -
DNLLQALELQLKLN PPAT_RABIT 409 207 -
DNLLQALELQLKLN O62807 438 207 -
DNLLQALELQLKLN O77815 438 207 -
DNLLQALELQLKLN O18971 439 207 -
DSLLQALELQLKLN PPAT_XENLA 411 205 -